857 resultados para pacs: human aspacts of it
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We present here a calculation of the inertial mass of a moving vortex in cuprate superconductors. This is a poorly known basic quantity of obvious interest in vortex dynamics. The motion of a vortex causes a dipolar density distortion and an associated electric field which is screened. The energy cost of the density distortion as well as the related screened electric field contributes to the vortex mass, which is small because of efficient screening. As a preliminary, we present a discussion and calculation of the vortex mass using a microscopically derivable phase-only action functional for the far region which shows that the contribution from the far region is negligible and that most of it arises from the (small) core region of the vortex. A calculation based on a phenomenological Ginzburg-Landau functional is performed in the core region. Unfortunately such a calculation is unreliable; the reasons for it are discussed. A credible calculation of the vortex mass thus requires a fully microscopic non-coarse-grained theory. This is developed, and results are presented for an s-wave BCS-like gap, with parameters appropriate to the cuprates. The mass, about 0.5m(e) per layer, for a magnetic field along the c axis arises from deformation of quasiparticle states bound in the core and screening effects mentioned above. We discuss earlier results, possible extensions to d-wave symmetry, and observability of effects dependent on the inertial mass. [S0163-1829(97)05534-3].
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The authors report an in vivo human examination of carotid atheroma by using the inversion-recovery ON resonance (IRON) sequence, which is able to produce positive contrast after the infusion of an ultrasmall super paramagnetic iron oxide (USPIO) contrast medium. This technique provides a method of potentially identifying inflammatory burden within carotid atheroma. This may be particularly useful in patients who currently do not meet criteria for intervention (ie, moderate symptomatic stenosis or <70% asymptomatic stenosis) to further risk-stratify this important patient cohort. A 63-year-old man was imaged at 1.5 T before and 36 hours after USPIO infusion by using the IRON sequence. Regions of interest showing profound signal loss at T2*-weighted imaging corresponded well with regions of positive contrast at IRON imaging after the administration of USPIO. These regions also showed a profound decrease in T2* measurements after USPIO infusion, whereas surrounding tissue did not. It has been shown that such strong signal loss on T2*-weighted images after USPIO infusion is indicative of USPIO uptake.
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This study examines both theoretically an empirically how well the theories of Norman Holland, David Bleich, Wolfgang Iser and Stanley Fish can explain readers' interpretations of literary texts. The theoretical analysis concentrates on their views on language from the point of view of Wittgenstein's Philosophical Investigations. This analysis shows that many of the assumptions related to language in these theories are problematic. The empirical data show that readers often form very similar interpretations. Thus the study challenges the common assumption that literary interpretations tend to be idiosyncratic. The empirical data consists of freely worded written answers to questions on three short stories. The interpretations were made by 27 Finnish university students. Some of the questions addressed issues that were discussed in large parts of the texts, some referred to issues that were mentioned only in passing or implied. The short stories were "The Witch à la Mode" by D. H. Lawrence, "Rain in the Heart" by Peter Taylor and "The Hitchhiking Game" by Milan Kundera. According to Fish, readers create both the formal features of a text and their interpretation of it according to an interpretive strategy. People who agree form an interpretive community. However, a typical answer usually contains ideas repeated by several readers as well as observations not mentioned by anyone else. Therefore it is very difficult to determine which readers belong to the same interpretive community. Moreover, readers with opposing opinions often seem to pay attention to the same textual features and even acknowledge the possibility of an opposing interpretation; therefore they do not seem to create the formal features of the text in different ways. Iser suggests that an interpretation emerges from the interaction between the text and the reader when the reader determines the implications of the text and in this way fills the "gaps" in the text. Iser believes that the text guides the reader, but as he also believes that meaning is on a level beyond words, he cannot explain how the text directs the reader. The similarity in the interpretations and the fact that the agreement is strongest when related to issues that are discussed broadly in the text do, however, support his assumption that readers are guided by the text. In Bleich's view, all interpretations have personal motives and each person has an idiosyncratic language system. The situation where a person learns a word determines the most important meaning it has for that person. In order to uncover the personal etymologies of words, Bleich asks his readers to associate freely on the basis of a text and note down all the personal memories and feelings that the reading experience evokes. Bleich's theory of the idiosyncratic language system seems to rely on a misconceived notion of the role that ostensive definitions have in language use. The readers' responses show that spontaneous associations to personal life seem to colour the readers' interpretations, but such instances are rather rare. According to Holland, an interpretation reflects the reader's identity theme. Language use is regulated by shared rules, but everyone follows the rules in his or her own way. Words mean different things to different people. The problem with this view is that if there is any basis for language use, it seems to be the shared way of following linguistic rules. Wittgenstein suggests that our understanding of words is related to the shared ways of using words and our understanding of human behaviour. This view seems to give better grounds for understanding similarity and differences in literary interpretations than the theories of Holland, Bleich, Fish and Iser.
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The purpose of this study is to analyze and develop various forms of abduction as a means of conceptualizing processes of discovery. Abduction was originally presented by Charles S. Peirce (1839-1914) as a "weak", third main mode of inference -- besides deduction and induction -- one which, he proposed, is closely related to many kinds of cognitive processes, such as instincts, perception, practices and mediated activity in general. Both abduction and discovery are controversial issues in philosophy of science. It is often claimed that discovery cannot be a proper subject area for conceptual analysis and, accordingly, abduction cannot serve as a "logic of discovery". I argue, however, that abduction gives essential means for understanding processes of discovery although it cannot give rise to a manual or algorithm for making discoveries. In the first part of the study, I briefly present how the main trend in philosophy of science has, for a long time, been critical towards a systematic account of discovery. Various models have, however, been suggested. I outline a short history of abduction; first Peirce's evolving forms of his theory, and then later developments. Although abduction has not been a major area of research until quite recently, I review some critiques of it and look at the ways it has been analyzed, developed and used in various fields of research. Peirce's own writings and later developments, I argue, leave room for various subsequent interpretations of abduction. The second part of the study consists of six research articles. First I treat "classical" arguments against abduction as a logic of discovery. I show that by developing strategic aspects of abductive inference these arguments can be countered. Nowadays the term 'abduction' is often used as a synonym for the Inference to the Best Explanation (IBE) model. I argue, however, that it is useful to distinguish between IBE ("Harmanian abduction") and "Hansonian abduction"; the latter concentrating on analyzing processes of discovery. The distinctions between loveliness and likeliness, and between potential and actual explanations are more fruitful within Hansonian abduction. I clarify the nature of abduction by using Peirce's distinction between three areas of "semeiotic": grammar, critic, and methodeutic. Grammar (emphasizing "Firstnesses" and iconicity) and methodeutic (i.e., a processual approach) especially, give new means for understanding abduction. Peirce himself held a controversial view that new abductive ideas are products of an instinct and an inference at the same time. I maintain that it is beneficial to make a clear distinction between abductive inference and abductive instinct, on the basis of which both can be developed further. Besides these, I analyze abduction as a part of distributed cognition which emphasizes a long-term interaction with the material, social and cultural environment as a source for abductive ideas. This approach suggests a "trialogical" model in which inquirers are fundamentally connected both to other inquirers and to the objects of inquiry. As for the classical Meno paradox about discovery, I show that abduction provides more than one answer. As my main example of abductive methodology, I analyze the process of Ignaz Semmelweis' research on childbed fever. A central basis for abduction is the claim that discovery is not a sequence of events governed only by processes of chance. Abduction treats those processes which both constrain and instigate the search for new ideas; starting from the use of clues as a starting point for discovery, but continuing in considerations like elegance and 'loveliness'. The study then continues a Peircean-Hansonian research programme by developing abduction as a way of analyzing processes of discovery.
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This study concentrates on the contested concept of pastiche in literary studies. It offers the first detailed examination of the history of the concept from its origins in the seventeenth century to the present, showing how pastiche emerged as a critical concept in interaction with the emerging conception of authorial originality and the copyright laws protecting it. One of the key results of this investigation is the contextualisation of the postmodern debate on pastiche. Even though postmodern critics often emphasise the radical novelty of pastiche, they in fact resuscitate older positions and arguments without necessarily reflecting on their historical conditions. This historical background is then used to analyse the distinction between the primarily French conception of pastiche as the imitation of style and the postmodern notion of it as the compilation of different elements. The latter s vagueness and inclusiveness detracts from its value as a critical concept. The study thus concentrates on the notion of stylistic pastiche, challenging the widespread prejudice that it is merely an indication of lack of talent. Because it is multiply based on repetition, pastiche is in fact a highly ambiguous or double-edged practice that calls into question the distinction between repetition and original, thereby undermining the received notion of individual unique authorship as a fundamental aesthetic value. Pastiche does not, however, constitute a radical upheaval of the basic assumptions on which the present institution of literature relies, since, in order to mark its difference, pastiche always refers to a source outside itself against which its difference is measured. Finally, the theoretical analysis of pastiche is applied to literary works. The pastiches written by Marcel Proust demonstrate how it can become an integral part of a writer s poetics: imitation of style is shown to provide Proust with a way of exploring the role of style as a connecting point between inner vision and reality. The pastiches of the Sherlock Holmes stories by Michael Dibdin, Nicholas Meyer and the duo Adrian Conan Doyle and John Dickson Carr illustrate the functions of pastiche within a genre detective fiction that is itself fundamentally repetitive. A.S. Byatt s Possession and D.M. Thomas s Charlotte use Victorian pastiches to investigate the conditions of literary creation in the age of postmodern suspicion of creativity and individuality. The study thus argues that the concept of pastiche has valuable insights to offer to literary criticism and theory, and that literary pastiches, though often dismissed in reviews and criticism, are a particularly interesting object of study precisely because of their characteristic ambiguity.
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This paper concentrates on Heraclitus, Parmenides and Lao Zi. The focus is on their ideas on change and whether the world is essentially One or if it is composed of many entities. In the first chapter I go over some general tendences in Greek and Chinese philosophy. The differences in the cultural background have an influence in the ways philosophy is made, but the paper aims to show that two questions can be brought up when comparing the philosophies of Heraclitus, Parmenides and Lao Zi. The questions are; is the world essentially One or Many? Is change real and if it is, what is the nature of it and how does it take place? For Heraclitus change is real, and as will be shown later in the chapter, quite essential for the sustainability of the world-order (kosmos). The key-concept in the case of Heraclitus is Logos. Heraclitus uses Logos in several senses, most well known relating to his element-theory. But another important feature of the Logos, the content of real wisdom, is to be able to regard everything as one. This does not mean that world is essentially one for Heraclitus in the ontological sense, but that we should see the underlying unity of multiple phenomena. Heraclitus regards this as hen panta: All from One, One from All. I characterize Heraclitus as epistemic monist and an ontological pluralist. It is plausible that the views of Heraclitus on change were the focus of Parmenides’ severe criticism. Parmenides held the view that the world is essentially one and that to see it as consisting of many entities was the error of mortals, i.e. the common man and his philosophical predecessors. For Parmenides what-is, can be approached by two routes; The Way of Truth (Aletheia) and The Way of Seeming (Doxa). Aletheia essentially sees the world as one, where even time is an illusion. In Doxa Parmenides is giving an explanation of the world seen as consisting of many entities and this is his contribution to the line of thought of his predecessors. It should be noted that a strong emphasis is given to the Aletheia, whereas the world-view given is in Doxa is only probable. I go on to describe Parmenides as ontological monist, who gives some plausibility to pluralistic views. In the work of Lao Zi world can be seen as One or as consisting of Many entities. In my interpretation, Lao Zi uses Dao in two different senses; Dao is the totality of things or the order in change. The wu-aspect (seeing-without-form) attends the world as one, whereas the you-aspect attends the world of many entities. In wu-aspect, Dao refers to the totality of things, when in you-aspect Dao is the order or law in change. There are two insights in Lao Zi regarding the relationship between wu- and- you-apects; in ch.1 it is stated that they are two separate aspects in seeing the world, the other chapters regarding that you comes from wu. This naturally brings in the question whether the One is the peak of seeing the world as many. In other words, is there a way from pluralism to monism. All these considerations make it probable that the work attributed to Lao Zi has been added new material or is a compilation of oral sayings. In the end of the paper I will go on to give some insights on how Logos and Dao can be compared in a relevant manner. I also compare Parmenides holistic monism to Lao Zi’s Dao as nameless totality (i.e. in its wu-aspect). I briefly touch the issues of Heidegger and the future of comparative philosophy.
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The study approaches two modern novels using the conceptual frame of Lacanian psychoanalysis, especially the Lacanian notion of subject. The novels can be described as subversive “Bildungsromans” (development novels) highly influenced by psychoanalytic thought. Anaïs Nin’s (1903—1977) “poetic novel” House of Incest (1936) is a story of sexual and artistic awakening while Hélène Cixous’s (b. 1937) first novel Dedans (1969) depicts the growth of a little girl whose father dies. Both are first novels and first person narratives. Concentrating in the narrator’s internal life the novels writings break with the realistic conventions of narrative, bringing forth the themes of anguish, alienation from the world and escape into the prison like realm of the self. The study follows roughly the Lacanian process of becoming a subject. Each chapter opens up with a quick introduction to the Lacanian concepts used in the following part that analyses the novels. The study can thus also be used as a brief introduction to Lacanian theory in finnish. The psychoanalytic narrative/story of the birth of the subject and the novels stories can be seen as mirroring each other. The method of the study is thus based on a dialogue between the theoretical concepts and the analyses. Novels are being approached as texts that break with the Cartesian notion of an autonomous subject making room for a dialectics of self and other, for a movement in which the “I” builds an identity mirroring itself with others. While both of the novels recount the birth of a character called I, they also have a first person narrator apart from the character “I”. Having constituted the self’s identity, the narrator finds from inside of the self also an other or “you” – this discovery is the final clue to the coffin of the autonomous self. From the Lacanian perspective man’s great Other is the order of language, Symbolic, which constitutes the individual, the speaking subject. Using this perspective the novels are interpreted as describing the process of becoming a subject of the Symbolic; subjected to Symbolic order. This “birth process” happens in particular in the Imaginary register, where the self’s identity is built. In the Imaginary or Mirror phase the “I” mirrors himself with different others (e.g. with his mirror image and the family members, the surrounding others) learning to see his body and his selfhood both as familiar and strange, other. In the Imaginary phase the novels’ characters are also trying to deal with the opposite realm of the Symcolic, the Real. The Lacanian Real is not the reality “before words” but a reality left over from the Symbolic, aside of it but constituted by the Symbolic, to be deducted only from within it. In the novels the Real is experienced as a womblike state where the self is immersed in the other’s body. The process of coming a subject of the Symbolic is depicted also as a process of renouncing the “dream of the womb”, which, if realized, could only mean the non-existence of the subject, i.e. death. The study concentrates on analysing the novels’ writing, where meanings are constantly changing: “I” becomes you, the father becomes a mother, inside becomes outside. This technique enables also the deconstruction of certain opposing notions in the novels. The Lacanian point of view exposes language as a constantly moving universe where the subject has no more stability than the momentary meanings language creates. The self’s identity depicted in the novels is a Lacanian fixed identity, whose growth is necessary but opposes the flux imminent to the Symbolic. The anguish experienced in the novels, in the “house of incest” or “inside”, is due to clinging on the unchanging “I”. However, the writing of the novels shows how the meaning of the “I” changes constantly and the fixity thus becomes movement. This way House of Incest and Dedans, despite their pessimistic stories, manage to create an image of a new, moving subject.
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Paropsis atomaria is a recently emerged pest of eucalypt plantations in subtropical Australia. Its broad host range of at least 20 eucalypt species and wide geographical distribution provides it the potential to become a serious forestry pest both within Australia and, if accidentally introduced, overseas. Although populations of P. atomaria are genetically similar throughout its range, population dynamics differ between regions. Here, we determine temperature-dependent developmental requirements using beetles sourced from temperate and subtropical zones by calculating lower temperature thresholds, temperature-induced mortality, and day-degree requirements. We combine these data with field mortality estimates of immature life stages to produce a cohort-based model, ParopSys, using DYMEX™ that accurately predicts the timing, duration, and relative abundance of life stages in the field and number of generations in a spring–autumn (September–May) field season. Voltinism was identified as a seasonally plastic trait dependent upon environmental conditions, with two generations observed and predicted in the Australian Capital Territory, and up to four in Queensland. Lower temperature thresholds for development ranged between 4 and 9 °C, and overall development rates did not differ according to beetle origin. Total immature development time (egg–adult) was approximately 769.2 ± S.E. 127.8 DD above a lower temperature threshold of 6.4 ± S.E. 2.6 °C. ParopSys provides a basic tool enabling forest managers to use the number of generations and seasonal fluctuations in abundance of damaging life stages to estimate the pest risk of P. atomaria prior to plantation establishment, and predict the occurrence and duration of damaging life stages in the field. Additionally, by using local climatic data the pest potential of P. atomaria can be estimated to predict the risk of it establishing if accidentally introduced overseas. Improvements to ParopSys’ capability and complexity can be made as more biological data become available.
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Artist statement – Artisan Gallery I have a confession to make… I don’t wear a FitBit, I don’t want an Apple Watch and I don’t like bling LED’s. But, what excites me is a future where ‘wearables’ are discreet, seamless and potentially one with our body. Burgeoning E-textiles research will provide the ability to inconspicuously communicate, measure and enhance human health and well-being. Alongside this, next generation wearables arguably will not be worn on the body, but rather within the body…under the skin. ‘Under the Skin’ is a polemic piece provoking debate on the future of wearables – a place where they are not overt, not auxiliary and perhaps not apparent. Indeed, a future where wearables are under the skin or one with our apparel. And, as underwear closets the skin and is the most intimate and cloaked apparel item we wear, this work unashamedly teases dialogue to explore how wearables can transcend from the overt to the unseen. Context Wearable Technology, also referred to as wearable computing or ‘wearables’, is an embryonic field that has the potential to unsettle conventional notions as to how technology can interact, enhance and augment the human body. Wearable technology is the next-generation for ubiquitous consumer electronics and ‘Wearables’ are, in essence, miniature electronic devices that are worn by a person, under clothing, embedded within clothing/textiles, on top of clothing, or as stand-alone accessories/devices. This wearables market is predicted to grow somewhere between $30-$50 billion in the next 5 years (Credit Suisse, 2013). The global ‘wearables’ market, which is emergent in phase, has forecasted predictions for vast consumer revenue with the potential to become a significant cross-disciplinary disruptive space for designers and entrepreneurs. For Fashion, the field of wearables is arguably at the intersection of the second and third generation for design innovation: the first phase being purely decorative with aspects such as LED lighting; the second phase consisting of an array of wearable devices, such as smart watches, to communicate areas such as health and fitness, the third phase involving smart electronics that are woven into the textile to perform a vast range of functions such as body cooling, fabric colour change or garment silhouette change; and the fourth phase where wearable devices are surgically implanted under the skin to augment, transform and enhance the human body. Whilst it is acknowledged the wearable phases are neither clear-cut nor discreet in progression and design innovation can still be achieved with first generation decorative approaches, the later generation of technology that is less overt and at times ‘under the skin’ provides a uniquely rich point for design innovation where the body and technology intersect as one. With this context in mind, the wearable provocation piece ‘Under the Skin’ provides a unique opportunity for the audience to question and challenge conventional notions that wearables need to be a: manifest in nature, b: worn on or next to the body, and c: purely functional. The piece ‘Under the Skin’ is informed by advances in the market place for wearable innovation, such as: the Australian based wearable design firm Catapult with their discreet textile biometric sports tracking innovation, French based Spinali Design with their UV app based textile senor to provide sunburn alerts, as well as opportunities for design technology innovation through UNICEF’s ‘Wearables for Good’ design challenge to improve the quality of life in disadvantaged communities. Exhibition As part of Artisan’s Wearnext exhibition, the work was on public display from 25 July to 7 November 2015 and received the following media coverage: WEARNEXT ONLINE LISTINGS AND MEDIA COVERAGE: http://indulgemagazine.net/wear-next/ http://www.weekendnotes.com/wear-next-exhibition-gallery-artisan/ http://concreteplayground.com/brisbane/event/wear-next_/ http://www.nationalcraftinitiative.com.au/news_and_events/event/48/wear-next http://bneart.com/whats-on/wear-next_/ http://creativelysould.tumblr.com/post/124899079611/creative-weekend-art-edition http://www.abc.net.au/radionational/programs/breakfast/smartly-dressed-the-future-of-wearable-technology/6744374 http://couriermail.newspaperdirect.com/epaper/viewer.aspx RADIO COVERAGE http://www.abc.net.au/radionational/programs/breakfast/wear-next-exhibition-whats-next-for-wearable-technology/6745986 TELEVISION COVERAGE http://www.abc.net.au/radionational/programs/breakfast/wear-next-exhibition-whats-next-for-wearable-technology/6745986 https://au.news.yahoo.com/video/watch/29439742/how-you-could-soon-be-wearing-smart-clothes/#page1
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New Internet and Web-based technology applications have meant significant cost and time efficiencies to many American businesses. However, many employers have not yet fully grasped the impact of these new information and communication technologies on applicants and employees with certain disabilities such as vision impairments, hearing problems or limited dexterity. Although not all applicants and employees who have a disability may experience IT-access problems, to select groups it can pose a needless barrier. The increasing dominance of IT in the workplace presents both a challenge and an opportunity for workers with disabilities and their employers. It will be up to HR professionals to ensure that Web-based HR processes and workplace technologies are accessible to their employees with disabilities. .
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The aim of the thesis was to compare the correspondence of the outcome a computer assisted program appearance compared to the original image. The aspect of the study was directed to embroidery with household machines. The study was made from the usability point of view with Brother's PE-design 6.0 embroidery design programs two automatic techniques; multicoloured fragment design and multicoloured stitch surface design. The study's subject is very current because of the fast development of machine embroidery. The theory is based on history of household sewing machines, embroidery sewing machines, stitch types in household sewing machines, embroidery design programs as well as PE-design 6.0 embroidery design program's six automatic techniques. Additionally designing of embroidery designs were included: original image, digitizing, punching, applicable sewing threads as well as the connection between embroidery designs and materials used on embroidery. Correspondences of sewn appearances were examined with sewing experimental methods. 18 research samples of five original image were sewn with both techniques. Experiments were divided into four testing stages in design program. Every testing stage was followed by experimental sewing with Brother Super Galaxie 3100D embroidery machine. Experiments were reported into process files and forms made for the techniques. Research samples were analysed on images syntactic bases with sensory perception assessment. Original images and correspondence of the embroidery appearances were analysed with a form made of it. The form was divided into colour and shape assessment in five stage-similarity-scale. Based on this correspondence analysis it can be said that with both automatic techniques the best correspondence of colour and shape was achieved by changing the standard settings and using the makers own thread chart and edited original image. According to the testing made it is impossible to inform where the image editing possibilities of the images are sufficient or does the optimum correspondence need a separate program. When aiming at correspondence between appearances of two images the computer is unable to trace by itself the appearance of the original image. Processing a computer program assisted embroidery image human perception and personal decision making are unavoidable.
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Purpose This study focused on craft from a standpoint of phenomenological philosophy and craft was interpreted through Maurice Merleau-Ponty’s phenomenology of the body. The main focus was the physical phase of the craft process, wherein a product is made from material. The aim was to interpret corporality in craft. There is no former research focusing on lived body in craft science. Physical, bodily making is inalienable in craft, but it is not articulated. Recent discussion has focused on craft as ”whole”, which emphasizes designing part in the process, and craft becomes conceptualized with the theories of art and design. The axiomatic yet silenced basis of craft, corporality, deserves to become examined as well. That is why this study answers the questions: how craft manifests in the light of phenomenology of the body and what is corporality in craft? Methods In this study I cultivated a phenomenological attitude and turned my exploring eye on craft ”in itself”. In addition I restrained myself from mere making and placed myself looking at the occurrence of craft to describe it verbally. I read up Maurice Merleau-Ponty’s phenomenology of the body on his principal work (2002) and former interpretations of it. Interpreting and understanding textual data were based on Gadamer’s hermeneutics, and the four-pronged composition of the study followed Koski’s (1995) version of the Gadamerian process of textual interpretation. Conclusions In the construction of bodily phenomenology craft was to be contemplated as a mutual relationship between the maker and the world materializing in bodily making. At the moment of making a human being becomes one with his craft, and the connection between the maker, material and the equipment appears as communication. Operational dimension was distinctive in the intentionality of craft, which operates in many ways, also in craft products. The synesthesia and synergy of craft were emphasized and craft as bodily practice came to life through them. The moment of making appeared as situation generating time and space, where throwing oneself into making may give the maker an experience of upraise beyond the dualism of mind and body. The conception of the implicit nature of craft knowledge was strengthened. In the light of interpretation it was possible to conceptualize craft as a performance and making ”in itself” as a work of art. In that case craft appeared as bodily expression, which as an experience approaches art without being it after all. The concept of aesthetic was settled into making as well. Bodily and phenomenological viewpoint on craft gave material to critically contemplate the concept of “whole craft” (kokonainen käsityö) and provided different kind of understanding of craft as making.
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Neurofibromatosis 2 (NF2) is a dominantly inherited disorder, which predisposes to multiple tumours of the nervous system, typically schwannomas and meningiomas. Biallelic inactivation of the NF2 gene occurs both in sporadic and NF2-related schwannomas and in most meningiomas. The NF2 gene product merlin (or schwannomin) is structurally related to the ERM proteins, ezrin, radixin and moesin, which act as molecular linkers between the actin cytoskeleton and the plasma membrane. Merlin is a tumor suppressor that participates in cell cycle regulation. Merlin s phosphorylation status appears to be associated with its tumour suppressor activity, i.e. non-phosphorylated merlin functions as a tumour suppressor, whereas protein phosphorylation results in loss of functional activity. This thesis study was initiated to investigate merlin s role as a tumor suppressor and growth inhibitor. These studies show, that like many other tumor suppressors, also merlin is targeted to the nucleus at some stages of the cell cycle. Merlin s nuclear localization is regulated by cell cycle phase, contact inhibition and adhesion. In addition, a potential nuclear binding partner for merlin was identified, Human Enhancer of Invasion 10 (HEI10), a cyclin B interacting protein. Many tumor suppressors interact with microtubules and this thesis work shows that also merlin colocalizes with microtubules in mitotic structures. Merlin binds microtubules directly, and increases their polymerization in vitro and in vivo. In addition, primary mouse Schwann cells lacking merlin displays disturbed microtubule cytoskeleton. Fourth part of this thesis work began from the notion that PKA phosphorylates an unidentified site from the merlin N-terminus. Our studies show that serine 10 is a target for PKA and modulation of this residue regulates cytoskeletal organization, lamellipodia formation and cell migration. In summary, this thesis work shows that merlin s role is much more versatile than previously thought. It has a yet unidentified role in the nucleus and it participates in the regulation of both microtubules and the actin cytoskeleton. These studies have led to a better understanding of this enigmatic tumor suppressor, which eventually will aid in the design of specific drugs for the NF2 disease.
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Sindbis virus (SINV) (genus Alphavirus, family Togaviridae) is an enveloped virus with a genome of single-stranded, positive-polarity RNA of 11.7 kilobases. SINV is widespread in Eurasia, Africa, and Australia, but clinical infection only occurs in a few geographically restricted areas, mainly in Northern Europe. In Europe, antibodies to SINV were detected from patients with fever, rash, and arthritis for the first time in the early 1980s in Finland. It became evident that the causative agent of this syndrome, named Pogosta disease, was closely related to SINV. The disease is also found in Sweden (Ockelbo disease) and in Russia (Karelian fever). Since 1974, for unknown reason, the disease has occurred as large outbreaks every seven years in Finland. This study is to a large degree based on the material collected during the 2002 Pogosta disease outbreak in Finland. We first developed SINV IgM and IgG enzyme immunoassays (EIA), based on highly purified SINV, to be used in serodiagnostics. The EIAs correlated well with the hemagglutination inhibition (HI) test, and all individuals showed neutralizing antibodies. The sensitivities of the IgM and IgG EIAs were 97.6% and 100%, and specificities 95.2% and 97.6%, respectively. E1 and E2 envelope glycoproteins of SINV were shown to be recognized by IgM and IgG in the immunoblot early in infection. We isolated SINV from five patients with acute Pogosta disease; one virus strain was recovered from whole blood, and four other strains from skin lesions. The etiology of Pogosta disease was confirmed by these first Finnish SINV strains, also representing the first human SINV isolates from Europe. Phylogenetic analysis indicated that the Finnish SINV strains clustered with the strains previously isolated from mosquitoes in Sweden and Russia, and seemed to have a common ancestor with South-African strains. Northern European SINV strains could be maintained locally in disease-endemic regions, but the phylogenetic analysis also suggests that redistribution of SINV tends to occur in a longitudinal direction, possibly with migratory birds. We searched for SINV antibodies in resident grouse (N=621), whose population crashes have previously coincided with human SINV outbreaks, and in migratory birds (N=836). SINV HI antibodies were found for the first time in birds during their spring migration to Northern Europe, from three individuals: red-backed shrike, robin, and song thrush. Of the grouse, 27.4% were seropositive in 2003, one year after a human outbreak, but only 1.4% of the grouse were seropositive in 2004. Thus, grouse might contribute to the human epidemiology of SINV. A total of 86 patients with verified SINV infection were recruited to the study in 2002. SINV RNA detection or virus isolation from blood and/or skin lesions was successful in eight patients. IgM antibodies became detectable within the first eight days of illness, and IgG within 11 days. The acute phase of Pogosta disease was characterized by arthritis, itching rash, fatigue, mild fever, headache, and muscle pain. Half of the patients reported in self-administered questionnaires joint symptoms to last > 12 months. Physical examination in 49 of these patients three years after infection revealed persistent joint manifestations. Arthritis (swelling and tenderness in physical examination) was diagnosed in 4.1% (2/49) of the patients. Tenderness in palpation or in movement of a joint was found in 14.3% of the patients in the rheumatologic examination, and additional 10.2% complained persisting arthralgia at the interview. Thus, 24.5% of the patients had joint manifestations attributable to the infection three years earlier. A positive IgM antibody response persisted in 3/49 of the patients; both two patients with arthritis were in this group. Persistent symptoms of SINV infection might have considerable public health implications in areas with high seroprevalence. The age-standardized seroprevalence of SINV (1999-2003, N=2529) in the human population in Finland was 5.2%. The seroprevalence was high in North Karelia, Kainuu, and Central Ostrobothnia. The incidence was highest in North Karelia. Seroprevalence in men (6.0%) was significantly higher than in women (4.1%), however, the average annualized incidence in the non-epidemic years was higher in women than in men, possibly indicating that infected men are more frequently asymptomatic. The seroprevalence increased with age, reaching 15.4% in persons aged 60-69 years. The incidence was highest in persons aged 50-59 years.