16 resultados para SILENT SYNAPSES
em Doria (National Library of Finland DSpace Services) - National Library of Finland, Finland
Resumo:
Opinnäytetyössäni tarkastellaan Internet-elokuvan historiaa sekä nykyistä tilaa. Käyn läpi yleisimmät katseluohjelmat: QuickTime Player, Windows Media Player, RealPlayer ja Flash Player sekä Internet-elokuvasivustot: YouTube, IFILM, AtomFilm ja Pixoff.net. Kerron myös Flash-elokuvista ja siitä miten Internet on luonut kokonaan uuden elokuvan muodon sekä Internetissä julkaistuista Dogma 2001 The New Rules for Internet Cinema -säännöistä. Käsittelen myös lyhyesti miten Internet-elokuva on vaikuttanut perinteiseen elokuvaan. Käsittelen perinteisen, isolta ruudulta katsottavaksi tehdyn, elokuvan julkaisemista Internetissä. Tarkastelen kahta verkossa julkaistua elokuvaa: Star Wreck ja The Silent City ja käyn läpi miksi ne on julkaistu Internetissä. Star Wreck on tamperelainen poikkeuksellisen kunnianhimoinen amatööriprojekti. The Silent City on taas irlantilaisen 3D-animaattorin, Ruairi Robinsonin, lyhytelokuva, jonka hän on tehnyt työnäytteeksi Hollywoodiin. Käsittelen myös ohjaaja David Lynchin verkkosivut, koska ne ovat Internetissä ainoaa laatuaan ja mainio ympäristö elokuvan julkaisemiseen. Kerron oman Uhripuu-kauhuelokuvani synnystä ja tekoprosessista. Uhripuun idea sai alkunsa Iso-Britanniassa vuoden 2004 alussa. Käsikirjoitus sai lopullisen muotonsa keväällä 2006. Käsittelen miksi ja miten se julkaistaan Internetissä. Kerron elokuvan Internet-sivujen sisällöstä ja sen jaosta eri osiin: Tarina, Rooleissa, Tekijät, Uhripuista, Traileri, Näin tehtiin, Kuvagalleria, E-kortti, Näe/Katso elokuva. Koska olen saanut koulutukseni nimenomaan verkkoviestinnän enkä audiovisuaalisen viestinnän puolella, Uhripuu-elokuvan tekoprosessi on ollut minulle elokuvakoulu. Sen tekemisen aikana olen oppinut elokuvan tekemisestä paljon. Elokuva kuvattiin HD-tarkkuuksilla, jotta kuva ei kärsisi liikaa jälkikäsittelyssä. Mitä tulee elokuvan ja Internetin yhteiseen tulevaisuuteen, näyttää siltä, että nämä kaksi mediaa ovat yhdistymässä yhä enemmän toisiinsa.
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Moderni liiketoiminta kohtaa uusia haasteita. Haasteiden aiheuttajia ovat mm. alenevat tuotantokustannukset ja kiihtyvä kilpailu. Jotta yritys kykenisi vastaamaan näihin moderneihin haasteisiin, sen tulee toimissaan hyödyntää tehokkaasti omat resurssit. Yrityksen suurimmat resurssit sijaitsevat henkilöstössä, heihin sitoutuneessa tiedossa. Tästä tiedosta iso osa on ns. hiljaista tietoa, jota ei voida perinteisin keinoin tallentaa. Tämä työ, tutkimus keskittyy tuon hiljaisen tiedon tallentamiseen. Tutkimuksen tavoitteena oli luoda malli, joka sisältää hiljaisen tiedon keruun, analyysin ja siirtämisen. Kokonaisuus muodostaa työkalun jolla teettävän yrityksen eläkkeelle jäävä henkilöstön hiljainen tieto tallennetaan yritykseen. Mallin lisäksi tutkimuksessa tuodaan esille aihetta koskevat erilaiset kehitysmahdollisuudet ja visiot.
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Tässä opinnäytetyössä tutkittiin onko mentorointia Sokos Hyvä Olo -kampaamoissa. Kuinka mentorointi näkyy tai ilmenee? Onko mentoroinnista hyötyä Sokos Hyvä Olo -kampaamon työntekijöiden omasta mielestä? Tutkimus tehtiin Sokoksen omassa omistuksessa oleviin Hyvä Olo -kampaamoihin. Näitä kampaamoja on Suomessa yhteensä kuusi kappaletta. Tutkimus toteutettiin postikyselynä. Tutkimuslomakkeita lähetettiin yhteensä 57 kappaletta. Lomakkeet lähetettiin tutkimuksen koko perusjoukolle. Tutkimukseen vastasi 13 henkilöä eli vastausprosentti oli 33 %. Tutkimuksen vastaukset tulivat kahdesta eri toimipisteestä. Analysointi tapahtui toimipisteittäin, ja lopuksi kaikista tutkimuksen vastauksista tehtiin yhteenveto. Tuloksista oli havaittavissa, että mentorointia ei ole Sokos Hyvä Olo -kampaamoissa. Tutkimuksesta kävi myös ilmi, että työntekijät eivät erityisesti myöskään kaipaa mentoria. Viidelle henkilölle vastanneista voisi olla apua mentorointisuhteesta, sillä nämä henkilöt ovat ammatilliselta kokemukseltaan nuoria parturi-kampaajia, jotka kaipaavat enemmän ohjausta työhönsä kuin pidempään ammatissa toimineet henkilöt.
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Members of the bacterial genus Streptomyces are well known for their ability to produce an exceptionally wide selection of diverse secondary metabolites. These include natural bioactive chemical compounds which have potential applications in medicine, agriculture and other fields of commerce. The outstanding biosynthetic capacity derives from the characteristic genetic flexibility of Streptomyces secondary metabolism pathways: i) Clustering of the biosynthetic genes in chromosome regions redundant for vital primary functions, and ii) the presence of numerous genetic elements within these regions which facilitate DNA rearrangement and transfer between non-progeny species. Decades of intensive genetic research on the organization and function of the biosynthetic routes has led to a variety of molecular biology applications, which can be used to expand the diversity of compounds synthesized. These include techniques which, for example, allow modification and artificial construction of novel pathways, and enable gene-level detection of silent secondary metabolite clusters. Over the years the research has expanded to cover molecular-level analysis of the enzymes responsible for the individual catalytic reactions. In vitro studies of the enzymes provide a detailed insight into their catalytic functions, mechanisms, substrate specificities, interactions and stereochemical determinants. These are factors that are essential for the thorough understanding and rational design of novel biosynthetic routes. The current study is a part of a more extensive research project (Antibiotic Biosynthetic Enzymes; www.sci.utu.fi/projects/biokemia/abe), which focuses on the post-PKS tailoring enzymes involved in various type II aromatic polyketide biosynthetic pathways in Streptomyces bacteria. The initiative here was to investigate specific catalytic steps in anthracycline and angucycline biosynthesis through in vitro biochemical enzyme characterization and structural enzymology. The objectives were to elucidate detailed mechanisms and enzyme-level interactions which cannot be resolved by in vivo genetic studies alone. The first part of the experimental work concerns the homologous polyketide cyclases SnoaL and AknH. These catalyze the closure of the last carbon ring of the tetracyclic carbon frame common to all anthracycline-type compounds. The second part of the study primarily deals with tailoring enzymes PgaE (and its homolog CabE) and PgaM, which are responsible for a cascade of sequential modification reactions in angucycline biosynthesis. The results complemented earlier in vivo findings and confirmed the enzyme functions in vitro. Importantly, we were able to identify the amino acid -level determinants that influence AknH and SnoaL stereoselectivity and to determine the complex biosynthetic steps of the angucycline oxygenation cascade of PgaE and PgaM. In addition, the findings revealed interesting cases of enzyme-level adaptation, as some of the catalytic mechanisms did not coincide with those described for characterised homologs or enzymes of known function. Specifically, SnoaL and AknH were shown to employ a novel acid-base mechanism for aldol condenzation, whereas the hydroxylation reaction catalysed by PgaM involved unexpected oxygen chemistry. Owing to a gene-level fusion of two ancestral reading frames, PgaM was also shown to adopt an unusual quaternary sturucture, a non-covalent fusion complex of two alternative forms of the protein. Furthermore, the work highlighted some common themes encountered in polyketide biosynthetic pathways such as enzyme substrate specificity and intermediate reactivity. These are discussed in the final chapters of the work.
Resumo:
Tässä tutkielmassa tarkasteltiin keskijohtajien ja työntekijöiden psykologisia sopimuksia OP-Pohjola-ryhmässä. Tutkielman tarkoituksena oli tuottaa uutta ymmärrystä henkilöstön ja organisaation suhteesta. Tavoitteena oli selvittää, millaisia psykologisia sopimuksia keskijohtajat ja työntekijät muodostavat, rikotaanko näitä sopimuksia ja kuinka haastateltavat reagoivat mahdollisiin rikkomuksiin. Lisäksi eri organisaatiotasojen käsityksiä ja näkemyksiä psykologisesta sopimuksesta vertailtiin keskenään. Tutkielma on laadullinen tutkielma, jonka tutkimusmenetelmänä käytettiin puolistrukturoitua haastattelua. Tutkimusaineisto kerättiin tekemällä kahdeksan haastattelua. Tutkimusta varten haastateltiin neljää keskijohtajaa ja neljää työntekijää. Empiirisen aineiston analyysissa tulkinta pohjautuu tutkimuksen teoreettiseen viitekehykseen. Tutkimustulosten mukaan haastateltujen keskijohtajien psykologiset sopimukset ovat luonteeltaan relationaalisia ja työntekijöiden sopimukset puolestaan transaktionaalisia. Molempien sopimukset sisältävät kuitenkin kumpiakin sopimusehtoja. Haastateltujen psykologisia sopimuksia on rikottu harvakseltaan. Rikkomuksiin on reagoitu keskustelemalla työnantajan kanssa tai olemalla vaiti ja sopeutumalla tilanteeseen. Tulokset myös osoittavat, että organisaatiossa vallitsee suuri luottamus ja asioista keskustellaan hyvin avoimesti.
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Kirjallisuusarvostelu
Resumo:
The action of the neurotransmitters dopamine (DA) and serotonin (5-HT) at synapses is terminated by their rapid reuptake into presynaptic nerve endings via plasma membrane dopamine (DAT) and serotonin (SERT) transporters. Alterations in the function of these transporters have been suggested as a feature of several neurological and neuropsychiatric diseases, such as Parkinson’s disease (PD), depression, and anxiety. A suitable clinical method for studying these transporters non-invasively in vivo is positron emission tomography (PET) utilizing radiopharmaceuticals (tracers) labelled with short-lived positron-emitting radionuclides. The aim of this study was to evaluate in rats two novel radiotracers, [18F]beta -CFT-FP and 18FFMe-McN, for imaging DAT and SERT, respectively, using in vitro, ex vivo and in vivo methods. Substituting an N-methyl in [18F]beta-CFT, a well known DAT tracer, with a 18Ffluoropropyl group significantly changed the properties of the tracer. [18F]beta- CFT showed slow kinetics and metabolism, and a high specific uptake in the striatum, whereas [18F]beta-CFT-FP showed fast kinetics and metabolism, and a moderate specific uptake in the striatum. [18F]betaCFT-FP was selective for DAT; but [18F]beta-CFT also bound to the noradrenaline transporter. [18F]beta-CFT-FP may be a suitable PET tracer for imaging the striatal DAT sites, but a tracer with a higher affinity is needed for imaging extrastriatal DAT sites. In rats, 18FFMe-McN showed high target-to-non-target ratios, specificity and selectivity for SERT, but slow kinetics. However, 18FFMe-McN reveals potential for imaging SERT, at least in pre-clinical studies. In addition, the sensitivities of [18F]beta CFT and [18 F]FDOPA (a precursor of DA) for detecting mild nigrostriatal hypofunction were compared in an animal model of PD. The uptake of [18F]FDOPA was significantly affected by compensatory effects in dopaminergic cells, whereas [18F]beta-CFT was more sensitive and therefore more suitable for PET studies of mild dopaminergic symptoms. In conclusion, both novel tracers, [18F]-CFT-FP and 18FFMe-McN, have potential, but are not optimal PET tracers for DAT and SERT imaging in rats, respectively. [18F]beta-CFT is superior to [18F]FDOPA for imaging mild nigral lesions in rat brains.
Resumo:
Ride comfort of elevators is one of the quality criteria valued by customers. The objective of this master’s thesis was to develop a process to measure the ride comfort of automatic elevator doors. The door’s operational noise was chosen as a focus area and other kinds of noise for example caused by pressure differences in the elevator shaft were excluded. The thesis includes a theory part and an empirical part. In the first part theories of quality management, measuring of quality and acoustics are presented. In the empirical part the developed ride comfort measuring process is presented, different operational noise sources are analyzed and an example is presented of how this measuring process can be used to guide product development. To measure ride comfort a process was developed where a two-room silent room was used as a measuring environment and EVA-625 device was used in the actual measuring of door noise. A-weighted decibels were used to scale noise pressure levels and the door movement was monitored with an accelerometer. This enabled the connection between the noise and noise sources which in turn helped to find potential ride comfort improvement ideas. The noise isolation class was also measured with the Ivie-measuring system. Measuring of door ride comfort gives feedback to product development and to managing current product portfolio. Measuring enables the continuous improvement of elevator door ride comfort. The measuring results can also be used to back up marketing arguments for doors.
Resumo:
This dissertation examined skill development in music reading by focusing on the visual processing of music notation in different music-reading tasks. Each of the three experiments of this dissertation addressed one of the three types of music reading: (i) sight-reading, i.e. reading and performing completely unknown music, (ii) rehearsed reading, during which the performer is already familiar with the music being played, and (iii) silent reading with no performance requirements. The use of the eye-tracking methodology allowed the recording of the readers’ eye movements from the time of music reading with extreme precision. Due to the lack of coherence in the smallish amount of prior studies on eye movements in music reading, the dissertation also had a heavy methodological emphasis. The present dissertation thus aimed to promote two major issues: (1) it investigated the eye-movement indicators of skill and skill development in sight-reading, rehearsed reading and silent reading, and (2) developed and tested suitable methods that can be used by future studies on the topic. Experiment I focused on the eye-movement behaviour of adults during their first steps of learning to read music notation. The longitudinal experiment spanned a nine-month long music-training period, during which 49 participants (university students taking part in a compulsory music course) sight-read and performed a series of simple melodies in three measurement sessions. Participants with no musical background were entitled as “novices”, whereas “amateurs” had had musical training prior to the experiment. The main issue of interest was the changes in the novices’ eye movements and performances across the measurements while the amateurs offered a point of reference for the assessment of the novices’ development. The experiment showed that the novices tended to sight-read in a more stepwise fashion than the amateurs, the latter group manifesting more back-and-forth eye movements. The novices’ skill development was reflected by the faster identification of note symbols involved in larger melodic intervals. Across the measurements, the novices also began to show sensitivity to the melodies’ metrical structure, which the amateurs demonstrated from the very beginning. The stimulus melodies consisted of quarter notes, making the effects of meter and larger melodic intervals distinguishable from effects caused by, say, different rhythmic patterns. Experiment II explored the eye movements of 40 experienced musicians (music education students and music performance students) during temporally controlled rehearsed reading. This cross-sectional experiment focused on the eye-movement effects of one-bar-long melodic alterations placed within a familiar melody. The synchronizing of the performance and eye-movement recordings enabled the investigation of the eye-hand span, i.e., the temporal gap between a performed note and the point of gaze. The eye-hand span was typically found to remain around one second. Music performance students demonstrated increased professing efficiency by their shorter average fixation durations as well as in the two examined eye-hand span measures: these participants used larger eye-hand spans more frequently and inspected more of the musical score during the performance of one metrical beat than students of music education. Although all participants produced performances almost indistinguishable in terms of their auditory characteristics, the altered bars indeed affected the reading of the score: the general effects of expertise in terms of the two eye- hand span measures, demonstrated by the music performance students, disappeared in the face of the melodic alterations. Experiment III was a longitudinal experiment designed to examine the differences between adult novice and amateur musicians’ silent reading of music notation, as well as the changes the 49 participants manifested during a nine-month long music course. From a methodological perspective, an opening to research on eye movements in music reading was the inclusion of a verbal protocol in the research design: after viewing the musical image, the readers were asked to describe what they had seen. A two-way categorization for verbal descriptions was developed in order to assess the quality of extracted musical information. More extensive musical background was related to shorter average fixation duration, more linear scanning of the musical image, and more sophisticated verbal descriptions of the music in question. No apparent effects of skill development were observed for the novice music readers alone, but all participants improved their verbal descriptions towards the last measurement. Apart from the background-related differences between groups of participants, combining verbal and eye-movement data in a cluster analysis identified three styles of silent reading. The finding demonstrated individual differences in how the freely defined silent-reading task was approached. This dissertation is among the first presentations of a series of experiments systematically addressing the visual processing of music notation in various types of music-reading tasks and focusing especially on the eye-movement indicators of developing music-reading skill. Overall, the experiments demonstrate that the music-reading processes are affected not only by “top-down” factors, such as musical background, but also by the “bottom-up” effects of specific features of music notation, such as pitch heights, metrical division, rhythmic patterns and unexpected melodic events. From a methodological perspective, the experiments emphasize the importance of systematic stimulus design, temporal control during performance tasks, and the development of complementary methods, for easing the interpretation of the eye-movement data. To conclude, this dissertation suggests that advances in comprehending the cognitive aspects of music reading, the nature of expertise in this musical task, and the development of educational tools can be attained through the systematic application of the eye-tracking methodology also in this specific domain.
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Tutkimus käsittelee viranomaisten ja asukkaiden välistä vuorovaikutusta kaavaprosessin aikana. Tutkimusalueena on valtakunnallisesti merkittäväksi kulttuuriympäristöksi luokiteltu Porin Kuudes osa, joka on yksi laajimmista yhtenäisenä säilyneistä 1800-luvun lopun puukaupunkialueista Suomessa. Hermeneuttis-fenomenologista otetta soveltava tutkimus perustuu muistitietoaineistoon, joka avaa näkökulman paikallisen kulttuuriperinnön syntymiseen, periytymiseen ja muutokseen. Kuudennen osan vuonna 2012 voimaan tulleessa asemakaavamuutoksessa suojeltiin 405 rakennusta. Sekä viranomaiset että asukkaat haluavat säilyttää arvokkaan ympäristön jälkipolville. Asukkaiden ja viranomaisten lähtökohdat arvottamiselle ovat kuitenkin erilaiset. Asiantuntijoiden näkemys kulttuuriympäristön arvoista perustuu eksplisiittiseen viralliseen tietoon, joka heijastaa positivistista käsitystä maailmasta mitattavista objekteista koostuvana kokonaisuutena. Asukkaiden arvostus asuinaluetta ja sen rakennuksia kohtaan puolestaan nousee sukupolvelta toiselle siirretyn aineettoman perinnön yhteisöllisestä merkityksestä. Heidän kokemuksensa kiteytyy kodin ja kotiseudun käsitteissä ja se tuodaan esiin rakennuksiin liittyvissä tarinoissa. Tulkinta on virallista tietoa haastavaa ja täydentävää. Kestäviä suojelupäätöksiä voidaan tehdä vain viranomaisten ja asukkaiden väliseen tasa-arvoiseen vuoropuheluun perustuen. Tutkimus nostaa asukkaiden kokemuksellisen, paikkaan sitoutuneen hiljaisen tiedon virallisen tiedon rinnalle, kulttuurisesti kestävän maankäytön suunnittelun perustaksi. Koska ihminen toimii sellaisten asioiden puolesta, jotka hän kokee arvokkaaksi, asukaslähtöinen rakennussuojelu on lähtökohtaisesti yhteisön omakseen kokeman aineettoman kulttuuriperinnön suojelua.
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Kirjallisuusarvostelu
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Työn tavoitteena oli kuvata kotimaisia lääkemarkkinoita koko arvoketjun alueelta, lähtien lääketehtaista ja päättyen vähittäismyyntiin tai sairaalajakeluun. Lisäksi työssä kuvattiin julkisen terveydenhuollon ostopalveluiden tilaa erityisesti logistiikkapalveluiden osalta. Markkinoiden kuvausta hyödynnettiin työssä Suomalaisen logistiikkayrityksen markkinapotentiaalin määrittämisessä kyseisille markkinoille. Työn toinen tavoite oli tarkastella markkinoita tulevaisuustutkimuksen työkaluja käyttämällä, ja luoda kyseisille markkinoille skenaarioita 10–15 vuoden päähän nykyhetkestä. Skenaarioiden ja markkinapotentiaaliselvityksen perusteella on työn lopputulemana luotu toimintaehdotuksia asiakasyritykselle koskien selvityksen alla olevien markkinoiden houkuttelevuutta yrityksen kannalta. Selvityksessä käytettävä tieto on kerätty julkisten raporttien ja selvitysten pohjalta, sekä tuottamalla laajamittainen haastattelututkimus yksityisten ja julkisten toimijoiden kautta läpi kotimaisen lääkkeen ja sairaalatarvikkeen arvoketjun. Haastattelututkimus on työn kannalta merkittävin tiedon lähde ja työssä hyödynnetty hiljaisten signaalien tulkinta perustuu haastatteluiden kautta saatuihin tietoihin.
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This study examines the aftermath of mass violence in local communities. Two rampage school shootings that occurred in Finland are analyzed and compared to examine the ways in which communities experience, make sense of, and recover from sudden acts of mass violence. The studied cases took place at Jokela High School, in southern Finland, and at a polytechnic university in Kauhajoki, in western Finland, in 2007 and 2008 respectively. Including the perpetrators, 20 people lost their lives in these shootings. These incidents are part of the global school shooting phenomenon with increasing numbers of incidents occurring in the last two decades, mostly in North America and Europe. The dynamic of solidarity and conflict is one of the main themes of this study. It builds upon previous research on mass violence and disasters which suggests that solidarity increases after a crisis, and that this increase is often followed by conflict in the affected communities. This dissertation also draws from theoretical discussions on remembering, narrating, and commemorating traumatic incidents, as well as the idea of a cultural trauma process in which the origins and consequences of traumas are negotiated alongside collective identities. Memorialization practices and narratives about what happened are vital parts of the social memory of crises and disasters, and their inclusive and exclusive characteristics are discussed in this study. The data include two types of qualitative interviews; focused interviews with 11 crisis workers, and focused, narrative interviews with 21 residents of Jokela and 22 residents of Kauhajoki. A quantitative mail survey of the Jokela population (N=330) provided data used in one of the research articles. The results indicate that both communities experienced a process of simultaneous solidarity and conflict after the shootings. In Jokela, the community was constructed as a victim, and public expressions of solidarity and memorialization were promoted as part of the recovery process. In Kauhajoki, the community was portrayed as an incidental site of mass violence, and public expressions of solidarity by distant witnesses were labeled as unnecessary and often criticized. However, after the shooting, the community was somewhat united in its desire to avoid victimization and a prolonged liminal period. This can be understood as a more modest and invisible process of “silent solidarity”. The processes of enforced solidarity were partly made possible by exclusion. In some accounts, the family of the perpetrator in Jokela was excluded from the community. In Kauhajoki, the whole incident was externalized. In both communities, this exclusion included associating the shooting events, certain places, and certain individuals with the concept of evil, which helped to understand and explain the inconceivable incidents. Differences concerning appropriate emotional orientations, memorialization practices and the pace of the recovery created conflict in both communities. In Jokela, attitudes towards the perpetrator and his family were also a source of friction. Traditional gender roles regarding the expression of emotions remained fairly stable after the school shootings, but in an exceptional situation, conflicting interpretations arose concerning how men and women should express emotion. The results from the Jokela community also suggest that while increased solidarity was seen as important part of the recovery process, some negative effects such as collective guilt, group divisions, and stigmatization also emerged. Based on the results, two simultaneous strategies that took place after mass violence were identified; one was a process of fast-paced normalization, and the other was that of memorialization. Both strategies are ways to restore the feeling of security shattered by violent incidents. The Jokela community emphasized remembering while the Kauhajoki community turned more to the normalization strategy. Both strategies have positive and negative consequences. It is important to note that the tendency to memorialize is not the only way of expressing solidarity, as fast normalization includes its own kind of solidarity and helps prevent the negative consequences of intense solidarity.
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In this work, the feasibility of the floating-gate technology in analog computing platforms in a scaled down general-purpose CMOS technology is considered. When the technology is scaled down the performance of analog circuits tends to get worse because the process parameters are optimized for digital transistors and the scaling involves the reduction of supply voltages. Generally, the challenge in analog circuit design is that all salient design metrics such as power, area, bandwidth and accuracy are interrelated. Furthermore, poor flexibility, i.e. lack of reconfigurability, the reuse of IP etc., can be considered the most severe weakness of analog hardware. On this account, digital calibration schemes are often required for improved performance or yield enhancement, whereas high flexibility/reconfigurability can not be easily achieved. Here, it is discussed whether it is possible to work around these obstacles by using floating-gate transistors (FGTs), and analyze problems associated with the practical implementation. FGT technology is attractive because it is electrically programmable and also features a charge-based built-in non-volatile memory. Apart from being ideal for canceling the circuit non-idealities due to process variations, the FGTs can also be used as computational or adaptive elements in analog circuits. The nominal gate oxide thickness in the deep sub-micron (DSM) processes is too thin to support robust charge retention and consequently the FGT becomes leaky. In principle, non-leaky FGTs can be implemented in a scaled down process without any special masks by using “double”-oxide transistors intended for providing devices that operate with higher supply voltages than general purpose devices. However, in practice the technology scaling poses several challenges which are addressed in this thesis. To provide a sufficiently wide-ranging survey, six prototype chips with varying complexity were implemented in four different DSM process nodes and investigated from this perspective. The focus is on non-leaky FGTs, but the presented autozeroing floating-gate amplifier (AFGA) demonstrates that leaky FGTs may also find a use. The simplest test structures contain only a few transistors, whereas the most complex experimental chip is an implementation of a spiking neural network (SNN) which comprises thousands of active and passive devices. More precisely, it is a fully connected (256 FGT synapses) two-layer spiking neural network (SNN), where the adaptive properties of FGT are taken advantage of. A compact realization of Spike Timing Dependent Plasticity (STDP) within the SNN is one of the key contributions of this thesis. Finally, the considerations in this thesis extend beyond CMOS to emerging nanodevices. To this end, one promising emerging nanoscale circuit element - memristor - is reviewed and its applicability for analog processing is considered. Furthermore, it is discussed how the FGT technology can be used to prototype computation paradigms compatible with these emerging two-terminal nanoscale devices in a mature and widely available CMOS technology.
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JNK1 is a MAP-kinase that has proven a significant player in the central nervous system. It regulates brain development and the maintenance of dendrites and axons. Several novel phosphorylation targets of JNK1 were identified in a screen performed in the Coffey lab. These proteins were mainly involved in the regulation of neuronal cytoskeleton, influencing the dynamics and stability of microtubules and actin. These structural proteins form the dynamic backbone for the elaborate architecture of the dendritic tree of a neuron. The initiation and branching of the dendrites requires a dynamic interplay between the cytoskeletal building blocks. Both microtubules and actin are decorated by associated proteins which regulate their dynamics. The dendrite-specific, high molecular weight microtubule associated protein 2 (MAP2) is an abundant protein in the brain, the binding of which stabilizes microtubules and influences their bundling. Its expression in non-neuronal cells induces the formation of neurite-like processes from the cell body, and its function is highly regulated by phosphorylation. JNK1 was shown to phosphorylate the proline-rich domain of MAP2 in vivo in a previous study performed in the group. Here we verify three threonine residues (T1619, T1622 and T1625) as JNK1 targets, the phosphorylation of which increases the binding of MAP2 to microtubules. This binding stabilizes the microtubules and increases process formation in non-neuronal cells. Phosphorylation-site mutants were engineered in the lab. The non-phosphorylatable mutant of MAP2 (MAP2- T1619A, T1622A, T1625A) in these residues fails to bind microtubules, while the pseudo-phosphorylated form, MAP2- T1619D, T1622D, Thr1625D, efficiently binds and induces process formation even without the presence of active JNK1. Ectopic expression of the MAP2- T1619D, T1622D, Thr1625D in vivo in mouse brain led to a striking increase in the branching of cortical layer 2/3 (L2/3) pyramidal neurons, compared to MAP2-WT. The dendritic complexity defines the receptive field of a neuron and dictates the output to the postsynaptic cells. Previous studies in the group indicated altered dendrite architecture of the pyramidal neurons in the Jnk1-/- mouse motor cortex. Here, we used Lucifer Yellow loading and Sholl analysis of neurons in order to study the dendritic branching in more detail. We report a striking, opposing effect in the absence of Jnk1 in the cortical layers 2/3 and 5 of the primary motor cortex. The basal dendrites of pyramidal neurons close to the pial surface at L2/3 show a reduced complexity. In contrast, the L5 neurons, which receive massive input from the L2/3 neurons, show greatly increased branching. Another novel substrate identified for JNK1 was MARCKSL1, a protein that regulates actin dynamics. It is highly expressed in neurons, but also in various cancer tissues. Three phosphorylation target residues for JNK1 were identified, and it was demonstrated that their phosphorylation reduces actin turnover and retards migration of these cells. Actin is the main cytoskeletal component in dendritic spines, the site of most excitatory synapses in pyramidal neurons. The density and gross morphology of the Lucifer Yellow filled dendrites were characterized and we show reduced density and altered morphology of spines in the motor cortex and in the hippocampal area CA3. The dynamic dendritic spines are widely considered to function as the cellular correlate during learning. We used a Morris water maze to test spatial memory. Here, the wild-type mice outperformed the knock-out mice during the acquisition phase of the experiment indicating impaired special memory. The L5 pyramidal neurons of the motor cortex project to the spinal cord and regulate the movement of distinct muscle groups. Thus the altered dendrite morphology in the motor cortex was expected to have an effect on the input-output balance in the signaling from the cortex to the lower motor circuits. A battery of behavioral tests were conducted for the wild-type and Jnk1-/- mice, and the knock-outs performed poorly compared to wild-type mice in tests assessing balance and fine motor movements. This study expands our knowledge of JNK1 as an important regulator of the dendritic fields of neurons and their manifestations in behavior.