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  • Kivipuro, Suvi (2001)
    This essay aims at providing a framework for evaluating the desirability of stronger intellectual property rights in developing countries. Instead of assuming that product imitation in the developing countries happens through observation and reverse engineering, the emphasis is on active technology transfer. Foreign direct investment and technology licensing are evaluated here in a unified outline to find out the growth effect of intellectual property protection regime change. The main sources are articles by E. L.-C. Lai (1998) and G. Yang and K. Maskus (2001). By assumption the model consists of two countries, North and South, and all innovations are carried out in North. Innovative Northern companies choose to outsource production to South to gain from lower production costs. Due to inexistent or weak intellectual property protection the Northern foreign direct investment or licensing venture faces the threat of imitation. Choosing licensing allows innovators to combat the problem with costly licensing contracts. Yet naturally both types of technology transfer would benefit from better intellectual property protection and less imitation. If technology transfer to South occurs either through licensing or foreign direct investment, South should strengthen its intellectual property rights protection, as both countries will gain. Improved protection curbs the imitation activity and thus encourages more Northern companies to invest in South. As resources are freed in North and the expected return from innovations rises, new incentives to innovate emerge. Increased innovation corresponds to economic growth not only in North but also in South via technology transfer. Southern workers learn while employed by the multinational enterprises or licensees. The resulting knowledge spillovers support worldwide gain from better intellectual property protection.
  • Kivipuro, Suvi (2001)
    Tämä essee pohtii, pitäisikö kehitysmaiden parantaa immateriaalioikeussuojaansa. Sen sijaan, että oletettaisiin kehitysmaiden suoraan kopioivan ulkomaisia innovaatiota, painotus on aktiivisessa teknologian leviämisessä. Yhtenäistetyssä kehikossa tarkastellaan sekä lisensointia että suoria ulkomaisia investointeja teknologian leviämisen muotoina. Tarkoituksena on selvittää, olisiko immateriaalioikeuksien parantamisella talouskasvuvaikutuksia kehitysmaissa. Päälähteet ovat E.L.-C. Lain (1998) ja G. Yangin ja K. Maskuksen (2001) artikkelit. Malli olettaa, että on vain kaksi maata: Pohjoinen ja Etelä. Ainoastaan Pohjoisessa kehitetään uusia tuotteita. Innovatiiviset Pohjoisen yritykset ulkoistavat tuotantonsa Etelään hyötyäkseen matalammista tuotantokustannuksista. Koska Etelässä suojellaan huonosti Pohjoisen patentteja, Pohjoisen suorat investoinnit tai lisensointisopimus kohtaavat kopiointiuhan. Valitessaan lisensoinnin, Pohjoisen yritys voi estää kopioinnin sopimuksen hinnoittelulla. Silti molemmat ulkoistamistavat hyötyisivät parannetusta immateriaalioikeussuojasta. Jos teknologia leviää Etelään suorien ulkomaisten investointien tai lisensoinnin kautta, Etelän kannattaa parantaa immateriaalioikeussuojaansa. Siitä hyötyvät sekä Pohjoinen että Etelä. Parempi oikeussuoja vähentää kopiointiuhkaa ja lisää Pohjoisen investointeja Etelään. Silloin Pohjoisessa vapautuu resursseja tuotekehitykseen ja syntyy uusia innovaatioita. Suurempi innovaatioiden määrä johtaa nopeampaan talouskasvuun. Työskennellessään Pohjoisen lisensoimassa tai perustamassa tuotantolaitoksessa Etelän työntekijät oppivat uusimpia teknologioita. Tiedon ja teknologian leviäminen on hyväksi koko maailmalle.
  • Kojonen, Erkki Vesa Rope (Helsingin yliopisto, 2014)
    Intelligent Design (ID) is a contemporary attempt to defend the idea that the order of nature bears marks of its Creator. The movement began in the U.S.A. during the 1980´s and 1990´s, and its claims about the relationship of theology and science, and its critique of evolutionary theory have caused much controversy. This study is a theological and philosophical analysis of ID s design argument and its presuppositions. ID is contrasted with naturalistic evolutionism and theistic evolutionism, and related to the broader discussion of natural theology. The study attempts to provide a more balanced and nuanced view of both the strengths and weaknesses of ID s argumentation than much of the previous discussion. The study s main focus is on increasing understanding of the ID movement s argumentation, but some evaluation of the arguments of the discussion is also included and criticisms are developed. ID s design arguments are quite minimalistic, not aspiring to prove the existence of God, but merely of an unidentified intelligent designer of cosmic and biological teleology. It also emphasizes the scientific nature of its design argument. Consequently, much discussion has focused on the question of whether ID is better understood as part of the natural sciences, or as philosophical-theological idea. Though this study also considers this philosophical question, it also emphasis that it is not the central question of the debate, since good arguments are not restricted to science. So, it is more interesting to ask why people believe or do not believe in the designedness of the cosmos and how good the arguments for each view are. The definition of natural science is a side-issue in the discussion of these questions. The study argues that ID s design argument is best understood as an inference to the best explanation that is supported by the analogy between nature s teleological order and the teleological capabilities of minds. The credibility of this design argument depends not only on our philosophical and theological background beliefs, but also on the empirical evidence. Theological and philosophical a priori -considerations arguments are not sufficient to settle the debate on ID apart from empirical study of what the world is like. Nevertheless, the theistic and naturalistic worldviews that have been defended in the discussion are not based merely on scientific data, but also on philosophical, metaphysical and theological considerations. While emphasizing its scientific nature, the ID movement also seeks to build bridges between science and religion. Rather than conflicting with each other, ID argues that science and theology support each other, when they are rightly understood. Though this study supports the basic premise that there can be mutually beneficial dialogue between science and theology, it also warns against emphasizing the importance of scientific arguments to such an extent that the broader metaphysical, philosophical and theological nature of the doctrine of creation and the value of non-scientific arguments is forgotten. The study also argues that contrary to some of ID s argumentation, one can believe both in divine design and Darwinian evolution at the same time. This compatibility thesis can surprisingly be argued not only on the basis of broader theological and philosophical arguments, but also on the basis of the ID movement s own ideas.
  • Huotari, Salla-Maaria (Helsingin yliopisto, 2015)
    Aims. The purpose of this single-case study was to investigate the effects of intensive tablet-based treatment in overall language performance level and in reading and writing processes in mild aphasia. The communicative effectiveness and task performances on the tablet software were also studied. The tablet software included tasks where semantic, syntactic and phonological processing were required; written naming, sentence writing and reading comprehension. Previous studies have indicated improvements in language skills after computer-based treatment (Katz & Wertz, 1997; Wade, Mortley & Enderby, 2003). Especially reading and writing skills can be treated by the computer-based softwares (Katz, 2008). Methods & Procedures. In this single subject research the ABA design was used. The participant in this study was a 47 year old man who had a stroke 2.5 years earlier. He had a mild chronic aphasia with difficulties in writing, reading and naming. The data of this study was formed by linguistic tests and by a self-assessment method as the participant evaluated his communicative effectiveness (CETI). The methods used in the analysis of written and read narratives included assessing rate, authenticity and the types of errors. The analysis of written narratives also included assessing word classes and type-token –ratio. Based on the data by the tablet-based software the rate and the share of errors of task performances were assessed. Results & Conclusions. Based on the Western Aphasia Battery (WAB) results, the severity of the aphasia decreased but the change was not clinically significant. Naming improved but the change wasn’t stable until the follow-up. The participant showed positive development in his written and reading production; he made less spelling and reading errors after the treatment. At the same time reading and writing processes became slower. The share of lexical verbs, adjectives, pronouns and numerals increased in written narratives. The communicative effectiveness improved. The task performance on the tablet software was faster during the fourth week compared to the first week. Also the amount of incorrect performances decreased or remained the same. Based on the results, an intensive self-monitored tablet-based language treatment was effective to the subject.
  • Orpana, Terttu (1973)
  • Orpana, Terttu (1973)
  • Orpana, Terttu (1972)
  • Bäckman, Stefan (2008)
    The purpose of this study was to evaluate intensity, productivity and efficiency in agriculture in Finland and show implications for N and P fertiliser management. Environmental concerns relating to agricultural production have been and still are focused on arguments about policies that affect agriculture. These policies constrain production while demand for agricultural products such as food, fibre and energy continuously increase. Therefore the importance of increasing productivity is a great challenge to agriculture. Over the last decades producers have experienced several large changes in the production environment such as the policy reform when Finland joined the EU 1995. Other and market changes occurred with the further EU enlargement with neighbouring countries in 2005 and with the decoupling of supports over the 2006-2007 period. Decreasing prices a decreased number of farmers and decreased profitability in agricultural production have resulted from these changes and constraints and of technological development. It is known that the accession to the EU 1995 would herald changes in agriculture. Especially of interest was how the sudden changes in prices of commodities on especially those of cereals, decreased by 60%, would influence agricultural production. The knowledge of properties of the production function increased in importance as a consequence of price changes. A research on the economic instruments to regulate productions was carried out and combined with earlier studies in paper V. In paper I the objective was to compare two different technologies, the conventional farming and the organic farming, determine differences in productivity and technical efficiency. In addition input specific or environmental efficiencies were analysed. The heterogeneity of agricultural soils and its implications were analysed in article II. In study III the determinants of technical inefficiency were analysed. The aspects and possible effects of the instability in policies due to a partial decoupling of production factors and products were studied in paper IV. Consequently connection between technical efficiency based on the turnover and the sales return was analysed in this study. Simple economic instruments such as fertiliser taxes have a direct effect on fertiliser consumption and indirectly increase the value of organic fertilisers. However, fertiliser taxes, do not fully address the N and P management problems adequately and are therefore not suitable for nutrient management improvements in general. Productivity of organic farms is lower on average than conventional farms and the difference increases when looking at selling returns only. The organic sector needs more research and development on productivity. Livestock density in organic farming increases productivity, however, there is an upper limit to livestock densities on organic farms and therefore nutrient on organic farms are also limited. Soil factors affects phosphorous and nitrogen efficiency. Soils like sand and silt have lower input specific overall efficiency for nutrients N and P. Special attention is needed for the management on these soils. Clay soils and soils with moderate clay content have higher efficiency. Soil heterogeneity is cause for an unavoidable inefficiency in agriculture.
  • Rudanko, Mikko (2015)
    Pro gradu -tutkielmassani tarkastellaan ja vertaillaan rikosoikeudellista tahallisuutta ja sen alarajaa eri valtioiden oikeusjärjestelmissä, erityisesti kahden vakavan rikostyypin, seksuaali- ja henkirikosten kohdalla. Tutkielmaani varten olen keskittynyt tarkastelemaan ja vertailemaan Suomen ja Ruotsin, Saksan ja Alankomaiden sekä Englannin ja Yhdysvaltojen oikeusjärjestelmissä käytettyä rikosoikeudellista tahallisuutta käsitteineen sekä näissä maissa rangaistavaksi säädettyjä tahallisia seksuaali- ja henkirikoksia niiden tunnusmerkistössä kuvaillun teon tekijän tahallisuudelta edellyttämine vaatimuksineen. Tutkielmassani olen vertaillut tahallisuutta muun muassa lapseen kohdistuvissa seksuaalirikoksissa, HIV-tartuntaan liittyvissä rikoksissa sekä niin sanottua venäläistä rulettia koskevissa henkirikoksissa. Tahallisuuden alarajalla on usein hyvin merkityksellinen asema teon rikosoikeudellisen arvioinnin osalta. Kuten olen tutkielmassani havainnut, pääsääntö rikosoikeudessa usein on, että teot ovat rangaistavia vain tahallisina. Osa teoista on rangaistavia myös tuottamuksellisina, esimerkiksi toisen henkilön surmaaminen ilman tahallisuutta on silti tuomittavissa kuolemantuottamuksena. Englannissa osa rikoksista on jopa säädetty ankaran vastuun alaisiksi, jolloin jo pelkkä laissa kuvatun teon suorittaminen riittää rikosvastuuseen ilman erityisiä tietoisuus- tai tahtovaatimuksia. Tällaisia tekoja ovat muun muassa seksuaalirikokset alle 13- vuotiaita lapsia kohtaan. Tarkastelemissani oikeusjärjestelmissä useimmista teoista ei kuitenkaan ole säädetty rangaistavaksi tällaisia tahallisuutta alempia vastineita, jolloin tahallisuuden alaraja on myös rikosoikeudellisen vastuun alaraja ja sen merkitys korostuu. Tarkastelemissani oikeusjärjestelmissä tahallisuuden alarajalla on omat painopisteensä tietoisuuden ja tahtomisen osalta. Erityisesti Saksassa on esitetty alarajasta erilaisia teorioita, joista nykyään vallassa on korkeimman tuomioistuimen BGH:n käyttämä malli, jossa lähes mikä tahansa todennäköisyys riittää, jos tekijä on hyväksynyt siihen liittyvän seurauksen. Henkirikoksissa alaraja on kuitenkin korkeammalla. Alankomaissa on painotettu tilastollisia todennäköisyyksiä ja asetettu esimerkiksi HIV-tapauksista annettaville tuomioille korkeampi kynnys kuin Saksassa, mutta vaadittu todennäköisyys on kuitenkin alempi kuin Suomessa. Englannissa on annettu moraalisille ja muille lain ulkopuolisille sosiaalisille ulottuvuuksille selkeästi enemmän painoarvoa kuin muissa tarkastelemissani maissa. Englannissa ja Yhdysvalloissa käytetty recklessness-käsite myös vastaa vain osittain muiden tarkastelemieni maiden dolus eventualis -tahallisuuden tasoa. Ruotsi on siirtynyt 2000-luvulla käyttämään tekijän välinpitämättömyyteen perustuvaa tahallisuutta, josta Suomessakin on ollut keskustelua. Suomen korkein oikeus on kuitenkin pitäytynyt ratkaisuissaan siinä, että tekijän tulee olla mieltänyt sekä seuraus että olosuhteet varsin todennäköisiksi.
  • Xu, Enjun (Helsingin yliopisto, 2015)
    Regulation of cellular homeostasis is crucial for proper development, survival, defense responses, programmed cell death and ultimately survival. Maintaining cellular homeostasis requires tight regulation of multiple highly interactive signaling pathways. The apoplast lies at the frontier between the cell and the environment, where the plant perceives environmental cues. Since the apoplast is also a site for cell-to-cell communication, it has an important role in mediating plant-environment interactions. Reactive oxygen species (ROS) are known as both toxic agents and indispensable signaling molecules in all aerobic organisms. A ROS burst in the apoplast is one of the first measurable events produced in response to different biotic and abiotic stresses, eventually leading to the initiation of signal transduction pathways and altered gene expression. Apoplastic ROS signaling is well known to dynamically coordinate multiple signaling pathways in the activation of defense responses in plants. Dissection of the signaling crosstalk within such a signaling network could therefore reveal the molecular mechanisms underlying defense responses. Treatments with ozone (O3) have been adopted as an efficient tool to study apoplastic ROS signaling. Plants exposed to O3 trigger a ROS burst in the apoplast and induce extensive changes in gene expression and alteration of defense hormones, such as salicylic acid (SA), jasmonic acid (JA), and ethylene. Genetic variation in O3 sensitivity among Arabidopsis thaliana accessions or mutants highlights the complex genetic architecture of plant responses to ROS. To gain insight into the genetic basis of apoplastic ROS signaling, a recombinant inbred line (RIL) population from a reciprocal cross between two Arabidopsis accessions C24 (O3 tolerant) and Tenela (O3 sensitive) was used for quantitative trait loci (QTL) mapping. Through a combination of QTL mapping and transcriptomic analyses in the response to apoplastic-ROS treatment, three QTL regions containing several potential candidate genes were identified in this study. In addition, multiple mutants with varying O3-sensitivities were employed to dissect the signaling components involved in the early apoplastic ROS signaling and O3-triggered cell death. A combination of global and targeted gene expression profiling, genetic analysis, and cell death assays was performed to dissect the contribution of hormone signaling and various transcription factors to the regulation of apoplastic ROS-triggered gene expression and cell death. The contributions of SA, JA and ethylene were assessed through analysis of mutants deficient in these hormones, mutants with constitutively activated hormone signaling and the exogenous application of hormones. Plants with elevated SA levels were found to be associated with an attenuated O3 response, whereas simultaneous elimination of SA-dependent and SA- independent signaling components enhanced the response to apoplastic ROS treatment. JA could act as both a positive and negative modifier of apoplastic ROS signaling, which was enhanced when ethylene signaling was also impaired. However, transcriptome analysis of a triple mutant deficient in SA, JA and ethylene revealed that these hormones signaling only contributed part (about 30%) of early-apoplastic ROS-triggered changes in gene expression, suggesting multiple signaling pathways could be required to regulate the apoplastic ROS response via combinatorial or overlapping mechanisms.
  • Saad, Elyana (Helsingin yliopisto, 2015)
    The relationship between mental representations based on external visual percepts (i.e., information held in short-term memory or via mental imagery) and the encoding of visual input remains unsettled. What stimulates this debate is the share of overlapping neural resources between visual short-term memory (VSTM), mental imagery and visual perception in the realm of the early visual cortex (EVC). This overlap raises a number of questions: how do the internal memory and imagery representations affect the perception of incoming visual information? What happens to imagery and VSTM abilities when cognitive resources need to be shared with the encoding of visual input? In short: how do visual memory/imagery and visual perception interact? This work addressed these questions by the use of behavioral paradigms coupled with transcranial magnetic stimulation (TMS) in situations where the encoding of the visual percept (measured via the tilt after effect (TAE) magnitude) happens either simultaneously or subsequently to holding information in VSTM/imagery. Therefore, when VSTM and the encoding of external input occurred concurrently, VSTM maintenance was found to inhibit visual encoding, reflected as a reduction of the TAE. Using TMS, it was shown that this inhibition takes place at the level of EVC. This reduction was found when the VSTM content matched the visual input, and when they were incongruent. However, when the encoding of external input occurred after VSTM maintenance phase had ended, VSTM maintenance was found to facilitate the former when the VSTM content matched the visual input. The subjective strength and the contrast of VSTM and mental imagery content (as reported by participants) affect visual detection of a briefly presented masked target. The reported visual contrast was positively associated with reporting target presence for both VSTM and mental imagery, in other words, inducing a more liberal bias. However, a differential effect was found for the subjective strength of the representations. Whereas the subjective VSTM strength was positively associated with the visual detection of the target, the opposite effect was observed for imagery. Finally, TMS applied at the EVC revealed a partial dissociation in the neural basis of VSTM and mental imagery by inducing delayed responses for the former selectively. Thus, while VSTM and mental imagery share neural resources, their neural mechanisms are partly dissociable at the level of early visual cortex.
  • Venäläinen, Salla (Helsingin yliopisto, 2010)
    Continuous growth in the number of immigrant students has changed the Finnish school environment. The resulting multicultural school environment is new for both teachers and students. In order to develop multicultural learning environments, there is a need to understand immigrant students everyday lives in school. In this study, home economics is seen as a fruitful school subject area for understanding these immigrant students lives as they cope with school and home cultures that may be very different from each other. Home economics includes a great deal of knowledge and skills that immigrant students need during their everyday activities outside of school. -- The main aim of the study is to clarify the characteristics of multicultural home economics classroom practices and the multicultural contacts and interaction that take place between the students and the teacher. The study includes four parts. The first part, an ethnographical prestudy, aims to understand the challenges of multicultural schoolwork with the aid of ethnographical fieldwork done in one multicultural school. The second part outlines the theoretical frames of the study and focuses on the sociocultural approach. The third part of the study presents an analysis of videodata collected in a multicultural home economics classroom. The teacher s and students interaction in the home economics classroom is analyzed through the concepts of the sociocultural approach and the cultural-historical activity theory. Firstly, this is done by analyzing the focusedness of the teacher s and the students actions as well as the questions presented and apparent disturbances during classroom interaction. Secondly, the immigrant students everyday experiences and cultural background are examined as they appear during discussions in the home economics lessons. Thirdly, the teacher s tool-use and actions as a human mediator are clarified during interaction in the classroom. The fourth part presents the results, according to which a practice-based approach in the multicultural classroom situation is a prerequisite for the teacher s and the students shared object during classroom interaction. Also, the practice-based approach facilitates students understanding during teaching and learning situations. Practice in this study is understood as collaborative teaching and learning situations that include 1) guided activating learning, 2) establishing connections with students everyday lives and 3) multiple tool-use. Guided activating learning in the classroom is defined as situations that occur and assignments that are done with a knowledgeable adult or peer and include action. The teacher s demonstrations during the practical part of the lessons seemed to be fruitful in the teaching and learning situations in the multicultural classroom. Establishing connections with students everyday lives motivated students to follow the lesson and supported understanding of meaning. Furthermore, if multiple tools (both psychological and material) were used, the students managed better with new and sometimes difficult concepts and different working habits, and accomplished the practical work more smoothly . The teacher s tool-use and role as a mediator of meaning are also highlighted in the data analysis. Hopefully, this study can provide a seedbed for situations in which knowledge produced together, as well as horizontally oriented tool-use, can make school-learned knowledge more relevant to immigrant students everyday lives, and help students to better cope with both classroom work and outside activities. KEY WORDS: home economics education, multicultural education, sociocultural perspective, classroom interaction, videoanalysis
  • Salaspuro, Ville (Helsingin yliopisto, 2006)
    Background: Alcohol consumption and smoking are the main causes of upper digestive tract cancers. These risk factors account for over 75% of all cases in developed countries. Epidemiological studies have shown that alcohol and tobacco interact in a multiplicative way to the cancer risk, but the pathogenetic mechanism behind this is poorly understood. Strong experimental and human genetic linkage data suggest that acetaldehyde is one of the major factors behind the carcinogenic effect. In the digestive tract, acetaldehyde is mainly formed by microbial metabolism of ethanol. Acetaldehyde is also a major constituent of tobacco smoke. Thus, acetaldehyde from both of these sources may have an interacting carcinogenic effect in the human upper digestive tract. Aims: The first aim of this thesis was to investigate acetaldehyde production and exposure in the human mouth resulting from alcohol ingestion and tobacco smoking in vivo. Secondly, specific L-cysteine products were prepared to examine their efficacy in the binding of salivary acetaldehyde in order to reduce the exposure of the upper digestive tract to acetaldehyde. Methods: Acetaldehyde levels in saliva were measured from human volunteers during alcohol metabolism, during tobacco smoking and during the combined use of alcohol and tobacco. The ability of L-cysteine to eliminate acetaldehyde during alcohol metabolism and tobacco smoking was also investigated with specifically developed tablets. Also the acetaldehyde production of Escherichia coli - an important member of the human microbiota - was measured in different conditions prevailing in the digestive tract. Results and conclusions: These studies established that smokers have significantly increased acetaldehyde exposure during ethanol consumption even when not actively smoking. Acetaldehyde exposure was dramatically further increased during active tobacco smoking. Thus, the elevated aerodigestive tract cancer risk observed in smokers and drinkers may be the result of the increased acetaldehyde exposure. Acetaldehyde produced in the oral cavity during ethanol challenge was significantly decreased by a buccal L-cysteine -releasing tablet. Also smoking-derived acetaldehyde could be totally removed by using a tablet containing L-cysteine. In conclusion, this thesis confirms the essential role of acetaldehyde in the pathogenesis of alcohol- and smoking-induced cancers. This thesis presents a novel experimental approach to decrease the local acetaldehyde exposure of the upper digestive tract with L-cysteine, with the eventual goal of reducting the prevalence of upper digestive tract cancers.
  • Ahmed, Imtiaj (2013)
    This thesis explores interaction paradigms for virtual 3D models on large displays. We explored three distant freehand interaction paradigms and for each paradigm we implemented a prototype system. Among these paradigms, it has been found that pointing by hand/eye with selection gesture is the ideal technique to interact with such interfaces. In the pointing technique we reduced the 3D interaction into 2D interaction to explore the 3D contents presented on the large displays. We propose a pinch gesture to select items effortlessly: a gesture of touching index finger with the thumb. Also we found a user-friendly way to present content meta-information of the virtual 3D models and its interactive units during interaction.
  • Palva, J. Matias (Helsingin yliopisto, 2005)
  • Pernu, Tuomas (Helsingin yliopisto, 2013)
    The notion of causal explanation is an essential element of the naturalistic world view. This view is typically interpreted to claim that we are only licensed to postulate entities that make a causal difference , or have causal power . The rest are epiphenomena and hence eliminable from the correct view of reality. The worry that some entities and phenomena that we take for granted mental properties in particular turn out to be epiphenomenal, can be seen as stemming from this sort of naturalistic attitude. This thesis reviews the issue of causal explanation within the context of the naturalistic philosophy of mind. It is argued that there is no single monolithic, unanimously accepted notion of causation that the naturalist should be committed to. Views vary on what this notion amounts to exactly, and fields of science vary with respect to their causal commitments. However, the naturalist can still presume that a scientifically informed philosophical account of causation exists, an account that is fundamentally philosophical, but also sensitive to actual scientific practice and its view of reality. The central issue of the current naturalistic philosophy of mind is the so-called problem of causal exclusion. According to this, the assumption that mental states could have genuine and autonomous effects on the physical world is inconsistent with physical commitments, namely the idea that mental states are necessarily neurally based and the idea that the physical world is causally complete. The causal exclusion argument claims that mental causes must be reduced to physical causes, as there remains no role for independent mental causes. The thesis reviews some central responses to the causal exclusion argument. It is shown that within the context of the interventionist notion of causation, inter-level causation can be ruled out. The causal exclusion argument would thus find support, contrary to what the proponents of the interventionist view typically claim. However, the result is also shown to have the corollary that purely higher-level, mental-to-mental causation is possible. The thesis suggests that this offers a consistent view of mental causation for a naturalist to hold.
  • von Nandelstadh, Pernilla (Helsingin yliopisto, 2010)
    The striated muscle sarcomere is a force generating and transducing unit as well as an important sensor of extracellular cues and a coordinator of cellular signals. The borders of individual sarcomeres are formed by the Z-disks. The Z-disk component myotilin interacts with Z-disk core structural proteins and with regulators of signaling cascades. Missense mutations in the gene encoding myotilin cause dominantly inherited muscle disorders, myotilinopathies, by an unknown mechanism. In this thesis the functions of myotilin were further characterized to clarify the molecular biological basis and the pathogenetic mechanisms of inherited muscle disorders, mainly caused by mutated myotilin. Myotilin has an important function in the assembly and maintenance of the Z-disks probably through its actin-organizing properties. Our results show that the Ig-domains of myotilin are needed for both binding and bundling actin and define the Ig domains as actin-binding modules. The disease-causing mutations appear not to change the interplay between actin and myotilin. Interactions between Z-disk proteins regulate muscle functions and disruption of these interactions results in muscle disorders. Mutations in Z-disk components myotilin, ZASP/Cypher and FATZ-2 (calsarcin-1/myozenin-2) are associated with myopathies. We showed that proteins from the myotilin and FATZ families interact via a novel and unique type of class III PDZ binding motif with the PDZ domains of ZASP and other Enigma family members and that the interactions can be modulated by phosphorylation. The morphological findings typical of myotilinopathies include Z-disk alterations and aggregation of dense filamentous material. The causes and mechanisms of protein aggregation in myotilinopathy patients are unknown, but impaired degradation might explain in part the abnormal protein accumulation. We showed that myotilin is degraded by the calcium-dependent, non-lysosomal cysteine protease calpain and by the proteasome pathway, and that wild type and mutant myotilin differ in their sensitivity to degradation. These studies identify the first functional difference between mutated and wild type myotilin. Furthermore, if degradation of myotilin is disturbed, it accumulates in cells in a manner resembling that seen in myotilinopathy patients. Based on the results, we propose a model where mutant myotilin escapes proteolytic breakdown and forms protein aggregates, leading to disruption of myofibrils and muscular dystrophy. In conclusion, the main results of this study demonstrate that myotilin is a Z-disk structural protein interacting with several Z-disk components. The turnover of myotilin is regulated by calpain and the ubiquitin proteasome system and mutations in myotilin seem to affect the degradation of myotilin, leading to protein accumulations in cells. These findings are important for understanding myotilin-linked muscle diseases and designing treatments for these disorders.