15 resultados para MULTIPLICITY
em Helda - Digital Repository of University of Helsinki
Resumo:
The study is a philosophical analysis of Israel Scheffler’s philosophy of education, focusing on three crucial conceptions in his philosophy: the conception of rationality, the conception of human nature, and the conception of reality. The interrelations of these three concepts as well as their relations to educational theorizing are analysed and elaborated. A conceptual problem concerning Scheffler’s ideal of rationality derives from Scheffler’s supposition of the strong analogy between science education and moral education in terms of the ideal of rationality. This analogy is argued to be conceptually problematic, since the interconnections of rationality, objectivity, and truth, appear to differ from each other in the realms of ethics and science, given the presuppositions of ontological realism and ethical naturalism, to which Scheffler explicitly subscribes. This study considers two philosophical alternatives for solving this problem. The first alternative relates the analogy to the normative concept of personhood deriving from the teleological understanding of human nature. Nevertheless, this position turns out to be problematic for Scheffler, since he rejects all teleological thinking in his philosophy. The problem can be solved, as it is argued, by limiting Scheffler’s rejection of teleology – in light of his philosophical outlook on the whole – in a manner that allows a modest version of a teleological conception of human nature. The second alternative, based especially on Scheffler’s later contributions, is to suggest that reality is actually more complex and manifold than it appears to be in light of a contemporary naturalist worldview. This idea of plurealism – Scheffler’s synthesis of pluralism and realism – is represented especially in Scheffler’s contributions related to his debate with Nelson Goodman dealing with both constructivism and realism. The idea of plurealism is not only related to the ethics-science-distinction, but is more widely related to the relationship between ontological realism and the incommensurable systems of description in diverse realms of human understanding. The Scheffler-Goodman debate is also analysed in relation to the contemporary constructivism-realism debate in educational philosophy. In terms of educational questions, Scheffler’s plurealism is argued as offering a fruitful perspective. Scheffler’s philosophy of education can be interpreted as searching for solutions to the problems deriving from the tension between the tradition of analytical philosophy and the complexity and multiplicity of educational reality. The complexity of reality combined with the supposition of the limitedness of human knowledge does not lead Scheffler to relativism or particularism, but, in contrast, Schefflerian formulations of rationality and objectivity preserve the possibility for critical inquiry in all realms of educational reality. In light of this study, Scheffler’s philosophy of education provides an exceptional example of combining ontological realism, epistemological fallibilism, and the defence of the ideal of rationality, combined with a wide-ranging understanding of educational reality.
Resumo:
Kasvainten, ajatellaan syntyvän yksittäisen solun perimän mutaatioista, jonka seurauksena tuon solun kasvu häiriintyy. Ruoansulatuskanavan polyyppien syntyä käytetään usein mallina siitä, miten nämä epiteelisoluun kerääntyvät mutaatiot aiheuttavat asteittain pahenevan kasvuhäiriön. Peutz–Jeghersin oireyhtymä (PJS) on perinnöllinen polypoosisyndrooma, jossa oireita aiheuttavat erityisesti maha-suolikanavan hamartomatoottiset polyypit. Noin puolella PJS potilaista havaitaan mutaatioita LKB1 kasvunrajoite geenissä. Hiirille joilta toinen Lkb1 alleeli on poistettu (Lkb1+/-) kehittyy PJS-tyypin maha-suolikanavan polyyppeja, joissa on epiteelin liikakasvun lisäksi merkittävä sileälihaskomponentti, aivan kuten PJS polyypeissa. Kuten myös muissa ruoansulatuskanavan polypooseissa, sekä PJS että hiirten polyypeissa Cyclo-oxygenaasi-2:n (COX-2) määrä on usein kohonnut. PJS-polyyppien kehittymisen molekulaarinen mekanismi on kuitenkin selvittämättä. Koska vain osa PJS potilaista kantaa LKB1 mutaatioita, mutaatiot jossakin toisessa lokuksessa saattaisivat selittää osan PJS tapauksista. Jotta PJS:n geneettinen tausta selviäisi, seulottiin kolmen LKB1:n kanssa interaktoivan proteiinin (BRG1, STRADα ja MO25α) geenit PJS potilaista joilla ei ole havaittu LKB1 mutaatioita. Yhdessäkään tutkituista geeneistä ei havaittu tautia aiheuttavia mutaatioita. Näiden kolmen geenin pois sulkeminen, ja uusien menetelmien ansiosta kasvanut havaittujen Lkb1 mutaatioden määrä viittaavat LKB1:n olevan useimpien PJS tapausten taustalla. COX-2:n estäjien käyttö on tehokkaasti vähentänyt polyyppien määrää familiaarisessa adenomatoottisessa polypoosissa. Tästä johtuen COX-2:n eston tehokkuutta tutkittiin PJS polypoosissa. PJS-tyypin polypoosin havaittin pienenevän merkittävästi Lkb1+/- hiirissä, joilta oli lisäksi poistettu toinen tai molemmat COX-2:n alleeleista. Lisäksi farmakologinen COX-2:n esto Celecoxib:lla vähensi polypoosia tehokkaasti. Näin ollen COX-2:n eston tehokkuutta tutkittiin seuraavaksi PJS potilaissa. Kuuden kuukauden Celecoxib hoidon jälkeen polypoosin havaittiin vähentyneen merkittävästi osalla potilaista (2/6). Nämä tulokset osoittavat COX-2:n roolin PJS-polyyppien kehityksessä, ja viittaavat COX-2:n eston vähentävän polypoosia. Kasvunrajoitegeenin klassisen määritelmän mukaan kasvaimen kehitys vaatii perinnöllisen mutaation lisäksi geenin toisenkin alleelin mutaation, mutta PJS-polyyppien häiriintyneestä epiteelistä ei kuitenkaan systemaattisesti löydy toista LKB1:n mutaatiota. Havainto johti tutkimukseen, jossa selvitettiin voisiko LKB1:n kasvun rajoitus välittyäkin epäsuorasti tukikudokseksi ajatelluista sileälihassoluista. Tätä tutkittiin kehittämällä poistogeeninen hiirimalli jossa Lkb1 on mutatoitunut vain sileälihassoluissa. Näille hiirille kehittyi polyyppeja, jotka ovat kaikin tavoin PJS-polyyppien kaltaisia. Lkb1:n menettäneiden solujen havaittiin tuottavan vähemmän transformoivaa kasvutekijä beetaa (TGFß), joka aiheutti solujen välisen viestinnän heikentymisen ja mahdollisesti viereisten epiteelisolujen liikakasvun. Vastaava häiriö havaittiin myös PJS-potilaiden polyypeissa, mikä viittaa siihen, että potilaillakin sileälihassolujen häiriö on polyyppien taustalla. Havainto suuntaa täten hoitokohteiden etsintää ja osoittaa että LKB1 toimii kasvunrajoittajana epätyypillisellä tavalla pitäen naapurisolujen kasvun kurissa.
Resumo:
Taking the appropriation of objects as a theoretical starting point, this study makes a distinction between a conceptual and practical level of adopting new objects and products in everyday life. The study applies the concept of appropriation in social food research and examines consumers appropriation of functional foods, i.e., foods developed to improve health and well-being or reduce the risk of disease beyond the usual nutritional effects of foods. The study uses the concept of appropriation to understand the adoption and the process of making functional foods our own . First, the study focuses on the conceptual appropriation by analysing consumers interpretations and opinions on functional foods. Second, it analyses the use of functional foods and examines the role of sociodemographic and food- and health-related background factors in the use of functional foods. Both quantitative and qualitative data were used in the study. Altogether 1210 Finns representative of the population took part in a survey carried out in 2002 as computer-assisted telephone interviews (CATI). The survey examined the acceptability and use of functional foods in Finland. In 2004, eight focus group discussions were organised for 45 users and non-users of cholesterol-lowering spreads. The qualitative study focused on consumers interpretative perspectives on healthy eating and functional foods. The findings are reported in four original articles and a summary article. The results show that the appropriation of functional foods is a multifaceted phenomenon. The conceptual appropriation is related to consumers interpretations of functional foods in the context of healthy foods and healthy eating; their trust in the products, their manufacturers, research and control; and the relationship of functional foods and the ideal of natural foods. The analysis of the practical appropriation of four different types of foods marketed as functional showed that there are sociodemographic differences between users and non-users of the products, but more importantly, the differences are related to consumers food- and health-related views and practices. Consumers ways of appropriating functional foods in the conceptual and practical sense take shape in a complex web of ideas and everyday practices concerning food, health and eating as a whole. The results also indicate that the conceptual and practical appropriation are not necessarily uniform or coherent processes. Consumers interpret healthy eating and functional foods from a variety of perspectives and there is a multiplicity of rationales of using functional foods. Appropriation embraces many opposing dimensions simultaneously: good experiences and doubts, approval and criticism, expectations and things taken for granted.
Resumo:
Cervical cancer is the second most common cancer among women globally. Most, probably all cases, arise through a precursor, cervical intraepithelial neoplasia (CIN). Effective cytological screening programmes and surgical treatments of precancerous lesions have dramatically reduced its prevalence and related mortality. Although these treatments are effective, they may have adverse effects on future fertility and pregnancy outcomes. The aim of this study was to evaluate the effects of surgical treatment of the uterine cervix on pregnancy and fertility outcomes, with the focus particularly on preterm birth. The general preterm birth rates and risk factors during 1987–2005 were studied. Long-term mortality rates of the treated women were studied. In this study, information from The Medical Birth Register (MBR), The Hospital Discharge Register (HDR), The Cause-of-Death Register (CDR), and hospital records were used. Treatments were performed during 1987–2003 and subsequent deliveries, IVF treatments and deaths were analyzed. The general preterm birth rate in Finland was relatively stable, varying from 5.1% to 5.4% during the study period (1987 to 2005), although the proportion of extremely preterm births had decreased substantially by 12%.The main risk factor as regards preterm birth was multiplicity, followed by elective delivery (induction of delivery or elective cesarean section), primiparity, in vitro fertilization treatment, maternal smoking and advanced maternal age. The risk of preterm birth and low birth weight was increased after any cervical surgical treatment; after conization the risk of preterm birth was almost two-fold (RR 1.99, 95% CI 1.81– 2.20). In the conization group the risk was the highest for very preterm birth (28–31 gestational weeks) and it was also high for extremely preterm birth (less than 28 weeks). In this group the perinatal mortality was also increased. In subgroup analysis, laser ablation was not associated with preterm birth. When comparing deliveries before and after Loop conization, we found that the risk of preterm birth was increased 1.94-fold (95% CI 1.10–3.40). Adjusting for age, parity, or both did not affect our results. Large or repeat cones increased the risk of preterm birth when compared with smaller cones, suggesting that the size of the removed cone plays a role. This was corroborated by the finding that repeat treatment increased the risk as much as five-fold when compared with the background preterm birth rate. We found that the proportion of IVF deliveries (1.6% vs. 1.5%) was not increased after treatment for CIN when adjusted for year of delivery, maternal age, or parity. Those women who received both treatment for CIN and IVF treatment were older and more often primiparous, which explained the increased risk of preterm birth. We also found that mortality rates were 17% higher among women previously treated for CIN. This excess mortality was particularly seen as regards increased general disease mortality and alcohol poisoning (by 13%), suicide (by 67%) and injury death (by 31%). The risk of cervical cancer was high, as expected (SMR 7.69, 95% CI 4.23–11.15). Women treated for CIN and having a subsequent delivery had decreased general mortality rate (by -22%), and decreased disease mortality (by -37%). However, those with preterm birth had increased general mortality (SMR 2.51, 95% CI 1.24–3.78), as a result of cardiovascular diseases, alcohol-related causes, and injuries. In conclusion, the general preterm birth rate has not increased in Finland, as in many other developed countries. The rate of extremely preterm births has even decreased. While other risk factors of preterm birth, such as multiplicity and smoking during pregnancy have decreased, surgical treatments of the uterine cervix have become more important risk factors as regards preterm birth. Cervical conization is a predisposing factor as regards preterm birth, low birth weight and even perinatal mortality. The most frequently used treatment modality, Loop conization, is also associated with the increased risk of preterm birth. Treatments should be tailored individually; low-grade lesions should not be treated at all among young women. The first treatment should be curative, because repeat treatments are especially harmful. The proportion of IVF deliveries was not increased after treatment for CIN, suggesting that current treatment modalities do not strongly impair fertility. The long-term risk of cervical cancer remains high even after many years post-treatment; therefore careful surveillance is necessary. In addition, accidental deaths and deaths from injury were common among treated women, suggesting risk-taking behavior of these women. Preterm birth seems be associated with extremely high mortality rates, due to cardiovascular, alcohol-related and injury deaths. These women could benefit from health counseling, for example encouragement in quitting smoking.
Resumo:
This thesis describes methods for the reliable identification of hadronically decaying tau leptons in the search for heavy Higgs bosons of the minimal supersymmetric standard model of particle physics (MSSM). The identification of the hadronic tau lepton decays, i.e. tau-jets, is applied to the gg->bbH, H->tautau and gg->tbH+, H+->taunu processes to be searched for in the CMS experiment at the CERN Large Hadron Collider. Of all the event selections applied in these final states, the tau-jet identification is the single most important event selection criterion to separate the tiny Higgs boson signal from a large number of background events. The tau-jet identification is studied with methods based on a signature of a low charged track multiplicity, the containment of the decay products within a narrow cone, an isolated electromagnetic energy deposition, a non-zero tau lepton flight path, the absence of electrons, muons, and neutral hadrons in the decay signature, and a relatively small tau lepton mass compared to the mass of most hadrons. Furthermore, in the H+->taunu channel, helicity correlations are exploited to separate the signal tau jets from those originating from the W->taunu decays. Since many of these identification methods rely on the reconstruction of charged particle tracks, the systematic uncertainties resulting from the mechanical tolerances of the tracking sensor positions are estimated with care. The tau-jet identification and other standard selection methods are applied to the search for the heavy neutral and charged Higgs bosons in the H->tautau and H+->taunu decay channels. For the H+->taunu channel, the tau-jet identification is redone and optimized with a recent and more detailed event simulation than previously in the CMS experiment. Both decay channels are found to be very promising for the discovery of the heavy MSSM Higgs bosons. The Higgs boson(s), whose existence has not yet been experimentally verified, are a part of the standard model and its most popular extensions. They are a manifestation of a mechanism which breaks the electroweak symmetry and generates masses for particles. Since the H->tautau and H+->taunu decay channels are important for the discovery of the Higgs bosons in a large region of the permitted parameter space, the analysis described in this thesis serves as a probe for finding out properties of the microcosm of particles and their interactions in the energy scales beyond the standard model of particle physics.
Resumo:
This is an ethnographic study, in the field of medical anthropology, of village life among farmers in southwest Finland. It is based on 12 months of field work conducted 2002-2003 in a coastal village. The study discusses how social and cultural change affects the life of farmers, how they experience it and how they act in order to deal with the it. Using social suffering as a methodological approach the study seeks to investigate how change is related to lived experiences, idioms of distress, and narratives. Its aim has been to draw a locally specific picture of what matters are at stake in the local moral world that these farmers inhabit, and how they emerge as creative actors within it. A central assumption made about change is that it is two-fold; both a constructive force which gives birth to something new, and also a process that brings about uncertainty regarding the future. Uncertainty is understood as an existential condition of human life that demands a response, both causing suffering and transforming it. The possibility for positive outcomes in the future enables one to understand this small suffering of everyday life both as a consequence of social change, which fragments and destroys, and as an answer to it - as something that is positively meaningful. Suffering is seen to engage individuals to ensure continuity, in spite of the odds, and to sustain hope regarding the future. When the fieldwork was initiated Finland had been a member of the European Union for seven years and farmers felt it had substantially impacted on their working conditions. They complained about the restrictions placed on their autonomy and that their knowledge was neither recognised, nor respected by the bureaucrats of the EU system. New regulations require them to work in a manner that is morally unacceptable to them and financial insecurity has become more prominent. All these changes indicate the potential loss of the home and of the ability to ensure continuity of the family farm. Although the study initially focused on getting a general picture of working conditions and the nature of farming life, during the course of the fieldwork there was repeated mention of a perceived high prevalence of cancer in the area. This cancer talk is replete with metaphors that reveal cultural meanings tied to the farming life and the core values of autonomy, endurance and permanence. It also forms the basis of a shared identity and a means of delivering a moral message about the fragmentation of the good life; the loss of control; and the invasion of the foreign. This thesis formed part of the research project Expressions of Suffering. Ethnographies of Illness Experiences in Contemporary Finnish Contexts funded by the Academy of Finland. It opens up a vital perspective on the multiplicity and variety of the experience of suffering and that it is particularly through the use of the ethnographic method that these experiences can be brought to light. Keywords: suffering, uncertainty, phenomenology, habitus, agency, cancer, farming
Resumo:
Since the 1990s, European policy strategies have stressed the mutual responsibility and joint action of all societal branches in preventing social problems. Network policy is an integral part of the new governance that generates a new kind of dependency between the state and civil society in formulating and adhering to policy goals. Using empirical group interview data collected in Helsinki, the capital of Finland, this case study explores local multi-agency groups and their efforts to prevent the exclusion of children and young people. These groups consist mainly of professionals from the social office, youth clubs and schools. The study shows that these multi-agency groups serve as forums for professional negotiation where the intervention dilemma of liberal society can be addressed: the question of when it is justified and necessary for an authority or network to intervene in the life of children and their families, and how this is to be done. An element of tension in multi-agency prevention is introduced by the fact that its objectives and means are anchored both in the old tradition of the welfare state and in communitarian rhetoric. Thus multi-agency groups mend deficiencies in wellbeing and normalcy while at the same time try to co-ordinate the creation of the new community, which will hopefully reduce the burden on the public sector. Some of the professionals interviewed were keen to see new and even forceful interventions to guide the youth or to compel parents to assume their responsibilities. In group discussions, this approach often met resistance. The deeper the social problems that the professionals worked with, the more solidarity they showed for the families or the young people in need. Nothing seems to assure professionals and to legitimise their professional position better than advocating the under-privileged against the uncertainties of life and the structural inequalities of society. The groups that grappled with the clear, specific needs of certain children and families were the most capable of co-operation. This requires the approval of different powers and the expertise of distinct professions as well as a forum to negotiate case-specific actions in professional confidentiality. The ideals of primary prevention for everyone and value discussions alone fail to inspire sufficient multiagency co-operation. The ideal of a network seems to give word and shape to those societal goals that are difficult or even impossible to reach, but are nevertheless yearned for: mutual understanding of the good life, close social relationships, mutual trust and active agency for all citizens. Individualisation, the multiplicity of life styles and the possibility to choose have come true in such a way that the very idea of a mutual and binding network can be attained only momentarily and between restricted participants. In conclusion, uniting professional networks that negotiate intervention dilemmas with citizen networks based on changing compassions and feelings of moral superiority seems impossible. Rather, one should encourage openness to scrutiny among tangential or contradicting groups, networks and communities. Key words: network policy, prevention of exclusion, multi-agency groups, young people
Resumo:
Body: The foundation for the formation of the knowledge and conception of gender identity among the transgendered The purpose of this study is to increase the understanding of the experiential formation of the knowledge and conception of one's gender and the foundation of that experience. This study is based on qualitative method and phenomenological approach. The research material consists: Herculine Barbin's Herculine Barbin, Christine Jorgensen's Christine Jorgensen. A Personal Autobiography Kate Bornstein's Gender Outlaw and Deirdre McCloskey's Crossing. A Memoir. The theoretical frame of reference for the study is Michel Henry's phenomenology of the body. The most important relations regarding the formation of the knowledge and conception of gender identity at which the sensing of the body is directed are human being's own subjective, organic and objective bodily form and other people and representatives of institutions. The concept of resistance reveals that gender division and the stereotypes and accountability related to it have dual character in culture. As a resistance they contain the potential for triggering the reflections about one's own gender. As an instrument they may function as means of exercising power and, as such, of monitoring gender normality. According to the research material the sources for the knowledge and conception of gender identity among the transgendered are literature, medical articles and books, internet, clerical and medical professionals, friends and relatives, and the peer group, that is, other transgendered. The transgendered are not only users of gender knowledge, but many of them are also active producers and contributors of gender knowledge and especially of knowledge about transgenderness. The problem is that this knowledge is unevenly distributed in society. The users of gender knowledge are mainly the transgendered, researchers of different disciplines specialized in gender issues, and medical and healthcare professionals specialized in gender adjustments. Therefore not everyone has the sufficient knowledge to support one's own or someone other's life as a gendered being in a society and ability to achieve gender autonomy. The quality of this knowledge is also rather narrow from the gender multiplicity point of view. The feeling of strangeness and the resulting experience of enstrangement have, like stereotypes, dual character in culture. They may be the reason for people's social disadvantage or exclusion, but the experiences may just as well be a resource for people's gender maturity and culture. As a cultural resource in gender issue this would mean innovativity in creating, upholding and changing cultural gender division, stereotypes and accounting customs. A transgendered may then become a liminal that aspires to change the limits related to resistances in society. Transgenderness is not only a medical issue but, first and foremost, an issue bearing upon human situation as a whole, or, in other words, related to the art of life. The subject of gender adjustment treatments is not only gender itself but the art of life as a gendered being. Transgenderness would then require multi-discipline co-operation.
Resumo:
We report a set of measurements of particle production in inelastic pbar{p} collisions collected with a minimum-bias trigger at the Tevatron Collider with the CDF II experiment. The inclusive charged particle transverse momentum differential cross section is measured, with improved precision, over a range about ten times wider than in previous measurements. The former modeling of the spectrum appears to be incompatible with the high particle momenta observed. The dependence of the charged particle transverse momentum on the event particle multiplicity is analyzed to study the various components of hadron interactions. This is one of the observable variables most poorly reproduced by the available Monte Carlo generators. A first measurement of the event transverse energy sum differential cross section is also reported. A comparison with a Pythia prediction at the hadron level is performed. The inclusive charged particle differential production cross section is fairly well reproduced only in the transverse momentum range available from previous measurements. At higher momentum the agreement is poor. The transverse energy sum is poorly reproduced over the whole spectrum. The dependence of the charged particle transverse momentum on the particle multiplicity needs the introduction of more sophisticated particle production mechanisms, such as multiple parton interactions, in order to be better explained.
Resumo:
We report a set of measurements of particle production in inelastic pbar{p} collisions collected with a minimum-bias trigger at the Tevatron Collider with the CDF II experiment. The inclusive charged particle transverse momentum differential cross section is measured, with improved precision, over a range about ten times wider than in previous measurements. The former modeling of the spectrum appears to be incompatible with the high particle momenta observed. The dependence of the charged particle transverse momentum on the event particle multiplicity is analyzed to study the various components of hadron interactions. This is one of the observable variables most poorly reproduced by the available Monte Carlo generators. A first measurement of the event transverse energy sum differential cross section is also reported. A comparison with a Pythia prediction at the hadron level is performed. The inclusive charged particle differential production cross section is fairly well reproduced only in the transverse momentum range available from previous measurements. At higher momentum the agreement is poor. The transverse energy sum is poorly reproduced over the whole spectrum. The dependence of the charged particle transverse momentum on the particle multiplicity needs the introduction of more sophisticated particle production mechanisms, such as multiple parton interactions, in order to be better explained.
Resumo:
Close to one half of the LHC events are expected to be due to elastic or inelastic diffractive scattering. Still, predictions based on extrapolations of experimental data at lower energies differ by large factors in estimating the relative rate of diffractive event categories at the LHC energies. By identifying diffractive events, detailed studies on proton structure can be carried out. The combined forward physics objects: rapidity gaps, forward multiplicity and transverse energy flows can be used to efficiently classify proton-proton collisions. Data samples recorded by the forward detectors, with a simple extension, will allow first estimates of the single diffractive (SD), double diffractive (DD), central diffractive (CD), and non-diffractive (ND) cross sections. The approach, which uses the measurement of inelastic activity in forward and central detector systems, is complementary to the detection and measurement of leading beam-like protons. In this investigation, three different multivariate analysis approaches are assessed in classifying forward physics processes at the LHC. It is shown that with gene expression programming, neural networks and support vector machines, diffraction can be efficiently identified within a large sample of simulated proton-proton scattering events. The event characteristics are visualized by using the self-organizing map algorithm.
Resumo:
Prostate cancer is the most common cancer in males. Although many patients with localized disease can be cured with surgery and radiotherapy, advanced disease and especially castration resistant metastatic disease remains incurable, with a median life expectancy of less than 18 months. Oncolytic adenoviruses (Ads) are a new promising treatment against cancer due to their innate capacity to kill cancer cells. Viral replication in tumor cells leads to oncolysis and production of a multiplicity of new virions that are capable of further destroying cancerous tissue. Oncolytic Ads can be modified for tumor targeted infection and replication and be armed with therapeutic transgenes to maximize the oncolytic effect. Worldwide, clinical trials with oncolytic Ads have demonstrated good safety while the antitumor efficacy remains to be improved. Importantly, the best responses have been reported when oncolytic adenoviruses have been combined with standard cancer treatments, such as chemotherapy and radiation. Further, a challenge in many virotherapy approaches has been the monitoring of virus replication in vivo. Reporter genes have been extensively used as transgenes to evaluate the biodistribution of the virus and activity of specific promoters. However, these techniques are often limited to preclinical evaluation and not amenable to human use. The aim of the thesis was to find and develop new oncolytic Ads with maximum efficacy against metastatic, castration resistant prostate cancer and study them in vitro and in vivo combined to different forms of radiation therapy. Using combination therapy, we were aiming for better antitumor efficacy with reduced side effects. Capsid modified Ads for enhanced transduction were studied. Serotype 3 targeted chimera, Ad5/3, was found to have enhanced infectivity for prostate cancer and was used for developing new viruses for the study. Correlation between Ad-encoded marker peptide secretion and simultaneous viral replication was evaluated and the effects of radiotherapy on viral replication were studied in detail. We found that the repair of double strand breaks caused by ionizing radiation was inhibited by adenoviral proteins and led to autophagic cell death. Both subcutaneous models and intrapulmonary tumor models mimicking metastatic, aggressive disease were used in vivo. Virus efficacy was evaluated by intratumoral injections. Also, intravenous administration was evaluated to study the effectiveness in metastatic disease. Oncolytic adenovirus treatment led to significant tumor growth control and increased the survival rate of the mice. These results were further improved when oncolytic Ads were combined with radiation therapy. Oncolytic Ads expressing human sodium/iodide transporter (hNIS) as a transgene were evaluated for their oncolytic potency and for the functionality of hNIS in vitro and in vivo. Monitoring of viral replication was also assessed using different imaging modalities relative to clinical use. SPECT imaging of tumor-bearing mice was evaluated and combined with simultaneous CT-scanning to obtain important anatomical information on biodistribution, also in a three-dimensional form. It was shown that hNIS-expressing adenoviruses could harbour a bi-functional transgene allowing for localization and imaging of viral replication. Targeted radiotherapy was applied by systemic radioiodide administration and resulted in iodide accumulation into Ad-infected tumor. The combination treatment showed significantly enhanced antitumor efficacy in mice bearing prostate cancer tumors. In summary, the results presented above aim to provide new treatment modalities for castration resistant prostate cancer. Molecular insights were provided for better understanding of the benefits of combined radiation therapy and oncolytic adenoviruses, which will hopefully facilitate the translation of the approach into clinical use for humans.
Resumo:
Tourism is one of important livelihoods in Lapland. Christmas tourism was launched in the early 1980s and it became a success story - being labelled as the most epochal tourism product in Finland. Hence, today Christmas tourists are one of the most significant foreign groups arriving to Lapland during the winter season and contributing considerably to the economics of the northeastern periphery of the EU. Christmas tourism concentrates around Father Christmas who uses reindeer for transportation. The Sämi are the only indigenous people in the EU. They are all stereotypically perceived to be reindeer herders. Somehow these three, that is, Santa Claus, reindeer and the Sämi, have been incorporated into same fairytale dominion. In practice, this has happened by using the most visible cultural but also significant identity marker of the Sämi, the Sämi costume. This, in turn, has created controversy over authenticity due to manners in which the costume is used in tourism - often in imitational, mismatched forms by non-Sämi. In this thesis, after relevant literature review I intend to establish how the Sâmi are represented in Christmas tourism through visual data consisting of ten images from three foreign sources. Then I clarify why and to whom it matters of how the Sâmi are represented in Christmas tourism with the aid of 65 questionnaires and nineteen expert interviews collected mainly in the Finnish Sâmi Home Region in October 2009. Through the multiplicity of the voices of various interest and ethnic groups and by using critical discourse analysis I attempt to give an overview of the respondents' opinions and look at some preliminary solutions to the controversy. Based on my data, the non-Sami appear to accept the Sami costume usage in Christmas tourism most readily. Consequently, respect and attitudinal changes have become the respondents' propositions in addition to common set of rules of how the Sami image could be appropriated without violating the integrity of the Sami people, or a similar system of S¿m¡ Duodji trademark guaranteeing the authenticity of the tourism products. Additionally, though half of the interviewees explicate Sami presence in Christmas tourism by adding local flavour to otherwise commercial enterprise, the other half see no rationale to connect facts with fiction, that is, the Sami with Santa Claus.
Resumo:
Tourism is one of important livelihoods in Lapland. Christmas tourism was launched in the early 1980s and it became a success story - being labelled as the most epochal tourism product in Finland. Hence, today Christmas tourists are one of the most significant foreign groups arriving to Lapland during the winter season and contributing considerably to the economics of the northeastern periphery of the EU. Christmas tourism concentrates around Father Christmas who uses reindeer for transportation. The Sämi are the only indigenous people in the EU. They are all stereotypically perceived to be reindeer herders. Somehow these three, that is, Santa Claus, reindeer and the Sämi, have been incorporated into same fairytale dominion. In practice, this has happened by using the most visible cultural but also significant identity marker of the Sämi, the Sämi costume. This, in turn, has created controversy over authenticity due to manners in which the costume is used in tourism - often in imitational, mismatched forms by non-Sämi. In this thesis, after relevant literature review I intend to establish how the Sâmi are represented in Christmas tourism through visual data consisting of ten images from three foreign sources. Then I clarify why and to whom it matters of how the Sâmi are represented in Christmas tourism with the aid of 65 questionnaires and nineteen expert interviews collected mainly in the Finnish Sâmi Home Region in October 2009. Through the multiplicity of the voices of various interest and ethnic groups and by using critical discourse analysis I attempt to give an overview of the respondents' opinions and look at some preliminary solutions to the controversy. Based on my data, the non-Sami appear to accept the Sami costume usage in Christmas tourism most readily. Consequently, respect and attitudinal changes have become the respondents' propositions in addition to common set of rules of how the Sami image could be appropriated without violating the integrity of the Sami people, or a similar system of S¿m¡ Duodji trademark guaranteeing the authenticity of the tourism products. Additionally, though half of the interviewees explicate Sami presence in Christmas tourism by adding local flavour to otherwise commercial enterprise, the other half see no rationale to connect facts with fiction, that is, the Sami with Santa Claus.