System-wide approaches to uncover Th2 cell lineage commitment

T helper (Th) cells are vital regulators of the adaptive immune system. When activated by presentation of cognate antigen, Th cells demonstrate capacity to differentiate into functionally distinct effector cell subsets. The Th2 subset is required for protection against extracellular parasites, such as helminths, but is also closely linked to pathogenesis of asthma and allergies. The intracellular molecular signal transduction pathways regulating T helper cell subset differentiation are still incompletely known. Moreover, great majority of studies regarding Th2 differentiation have been conducted with mice models, while studies with human cells have been fewer in comparison. The goal of this thesis was to characterize molecular mechanisms promoting the development of Th2 phenotype, focusing specifically on human umbilical cord blood T cells as an experimental model. These primary cells, activated and differentiated to Th2 cells in vitro, were investigated by complementary system-wide approaches, targeting levels of mRNA, proteins, and lipid molecules. Specifically, the results indicated IL4-regulated recruitment of nuclear protein, and described novel components of the Th2-promoting STAT6 enhanceosome complex. Furthermore, the development of the activated effector cell phenotype was found to correlate with remodeling of the cellular lipidome. These findings will hopefully advance the understanding of human Th2 cell lineage commitment and development of Th2-associated disease states.

Qualitative Characteristics and Quantitative Measures of Solution's Reliability in Discrete Optimization: Traditional Analytical Approaches, Innovative Computational Methods and Applicability

The purpose of this thesis is twofold. The first and major part is devoted to sensitivity analysis of various discrete optimization problems while the second part addresses methods applied for calculating measures of solution stability and solving multicriteria discrete optimization problems. Despite numerous approaches to stability analysis of discrete optimization problems two major directions can be single out: quantitative and qualitative. Qualitative sensitivity analysis is conducted for multicriteria discrete optimization problems with minisum, minimax and minimin partial criteria. The main results obtained here are necessary and sufficient conditions for different stability types of optimal solutions (or a set of optimal solutions) of the considered problems. Within the framework of quantitative direction various measures of solution stability are investigated. A formula for a quantitative characteristic called stability radius is obtained for the generalized equilibrium situation invariant to changes of game parameters in the case of the H¨older metric. Quality of the problem solution can also be described in terms of robustness analysis. In this work the concepts of accuracy and robustness tolerances are presented for a strategic game with a finite number of players where initial coefficients (costs) of linear payoff functions are subject to perturbations. Investigation of stability radius also aims to devise methods for its calculation. A new metaheuristic approach is derived for calculation of stability radius of an optimal solution to the shortest path problem. The main advantage of the developed method is that it can be potentially applicable for calculating stability radii of NP-hard problems. The last chapter of the thesis focuses on deriving innovative methods based on interactive optimization approach for solving multicriteria combinatorial optimization problems. The key idea of the proposed approach is to utilize a parameterized achievement scalarizing function for solution calculation and to direct interactive procedure by changing weighting coefficients of this function. In order to illustrate the introduced ideas a decision making process is simulated for three objective median location problem. The concepts, models, and ideas collected and analyzed in this thesis create a good and relevant grounds for developing more complicated and integrated models of postoptimal analysis and solving the most computationally challenging problems related to it.

"It's Barack Obama Who's Soft" Political Bias on BBC, CNN, and Fox News: A Critical Discourse Analysis of News Websites

Tutkielmassa analysoidaan kolmen internetsivuston uutisartikkeleita kielitieteen näkökulmasta. Tavoitteena on selvittää esiintyykö internetsivustojen BBC, CNN ja Fox News uutisoinnissa politiikkaan liittyviä ennakkoasenteita tai puolueellisuuksia ja miten ne käytännössä näkyvät uutisartikkeleiden kielessä. Kriittiseen diskurssianalyysiin pohjautuen tutkielma esittelee jokaisen uutissivuston taustaan (esimerkiksi rakenteeseen ja rahoitukseen) liittyviä seikkoja sekä mediadiskurssiin ja politiikkaan liittyvät taustatiedot, jolla taataan Norman Fairclough'n kolmivaiheisen menetelmän mahdollisimman perusteellinen toteuttaminen. Uutissivustoja analysoidaan kriittiselle diskurssianalyysille sopivan funktionaalisen kieliopin ja muiden lingvististen välineiden avulla. Koko aineiston (404 artikkelia) otsikot analysoidaan ensin, minkä jälkeen analysoidaan yhdeksän kokonaista artikkelia kolmeen eri aihealueeseen liittyen niin, että jokaiselta internetsivustolta analysoidaan yksi artikkeli jokaista aihetta kohden. Analyysikeinoina käytetään ensisijaisesti systeemis-funktionaalisen kieliopin tekstuaalisen metafunktion välineitä (thematic structure). Myös ideationaalisen metafunktion välineitä (transitivity), referenssiketjuja (referential identity chains) ja leksikaalista analyysia käytetään hyväksi. Lähtökohtaisesti tavoitteena on analysoida uutissivustoja vertailevasti, jolloin analyysin tulokset ovat paremmin havainnoitavissa ja perusteltavissa. Hypoteesi aikaisempien tutkimusten ja yleisen mielikuvan perusteella on, että CNN uutisoi demokraattipuolueelle ja Fox News taas republikaanipuolueelle edulliseen sävyyn. Tutkimustulokset vaihtelivat hypoteesia tukevista ja sen vastaisista tuloksista niihin, jotka eivät olleet tarpeeksi tuettuja kumpaankaan suuntaan. Vahvimmat tulokset ovat kuitenkin hypoteesia tukevia, joten tässä tutkielmassa todetaan, ettei uutisointi ole puolueetonta ainakaan näiden kolmen internetsivuston kohdalla. Lisäksi muutaman aihealueen kohdalla uutisointi on niin toistuvaa tietystä näkökulmasta, että luonnollistumisteorian mukaista aatteiden luonnollistumista saattaa tapahtua. Tutkielmassa käytettyjen menetelmien menestyksen perusteella suositellaan, että tekstuaalisen metafunktion analyysivälineitä käytetään enemmän. Lisäksi suositellaan meta-analyysin harkitsemista, jotta voitaisiin selvittää, mitkä analyysimetodit parhaiten sopivat minkäkinlaisen aineiston analysointiin.

Adaptive Routing Approaches for Networked Many-Core Systems

Through advances in technology, System-on-Chip design is moving towards integrating tens to hundreds of intellectual property blocks into a single chip. In such a many-core system, on-chip communication becomes a performance bottleneck for high performance designs. Network-on-Chip (NoC) has emerged as a viable solution for the communication challenges in highly complex chips. The NoC architecture paradigm, based on a modular packet-switched mechanism, can address many of the on-chip communication challenges such as wiring complexity, communication latency, and bandwidth. Furthermore, the combined benefits of 3D IC and NoC schemes provide the possibility of designing a high performance system in a limited chip area. The major advantages of 3D NoCs are the considerable reductions in average latency and power consumption. There are several factors degrading the performance of NoCs. In this thesis, we investigate three main performance-limiting factors: network congestion, faults, and the lack of efficient multicast support. We address these issues by the means of routing algorithms. Congestion of data packets may lead to increased network latency and power consumption. Thus, we propose three different approaches for alleviating such congestion in the network. The first approach is based on measuring the congestion information in different regions of the network, distributing the information over the network, and utilizing this information when making a routing decision. The second approach employs a learning method to dynamically find the less congested routes according to the underlying traffic. The third approach is based on a fuzzy-logic technique to perform better routing decisions when traffic information of different routes is available. Faults affect performance significantly, as then packets should take longer paths in order to be routed around the faults, which in turn increases congestion around the faulty regions. We propose four methods to tolerate faults at the link and switch level by using only the shortest paths as long as such path exists. The unique characteristic among these methods is the toleration of faults while also maintaining the performance of NoCs. To the best of our knowledge, these algorithms are the first approaches to bypassing faults prior to reaching them while avoiding unnecessary misrouting of packets. Current implementations of multicast communication result in a significant performance loss for unicast traffic. This is due to the fact that the routing rules of multicast packets limit the adaptivity of unicast packets. We present an approach in which both unicast and multicast packets can be efficiently routed within the network. While suggesting a more efficient multicast support, the proposed approach does not affect the performance of unicast routing at all. In addition, in order to reduce the overall path length of multicast packets, we present several partitioning methods along with their analytical models for latency measurement. This approach is discussed in the context of 3D mesh networks.

Irruptive discourse and conflicted curiosity

Kirjallisuusarvostelu

Strategic communication : practice, ideology and dissonance

This dissertation approaches the manifestations of ideology in U.S. Strategic Communication. The discussion approaches Strategic Communication by relating it to the Enlightenment narratives and suggesting these narratives maintain similar social and political functions. This dissertation aims to address the key contents and mechanisms of Strategic Communication by covering the perspectives of (i) communication as leadership as well as (ii) communication as discourse , i.e. practice and contents. Throughout the empirical part of the dissertation, the communication theoretical discussion is supported by a methodological framework that bridges Critical Discourse Analysis (CDA) and functional language theory. According to the principles of CDA, Strategic Communication is treated as ideological, hegemonic discourse that impacts social order. The primary method of analysis is transitivity analysis, which is concerned with how language and its patterns construe reality. This analysis is complemented with a discussion on the rituals of production and interpretation, which can be treated as visual extensions of textual transitivity. The concept of agency is the key object of analysis. From the perspective of leadership, Strategic Communication is essentially a leadership model through which the organization defines itself, its aims and legitimacy. This dissertation arrives to the conclusion that Strategic Communication is used not only as a concept for managing Public Relations and information operations. It is an esse ntial asset in the inter-organization management of its members. The current developments indicate that the concept is developing towards even heavier measures of control. From the perspective of language and discourse, the key narratives of Strategic Communication are advocated with the intrinsic values of democracy and technological progress as the prerequisites of ethics and justice. The transitivity patterns reveal highly polarized agency. The agency of the Self is typically outsourced to technology. Further, the transitivity pa tterns demonstrate how the effects-centric paradigm of warfare has created a lexicon that is ideologically exclusive. It has led to the development of two mutually exclusive sets of vocabulary, where the desc riptions of legitimate ac tion exclude Others by default. These ideological discourses have become naturalized in the official vocabulary of strategic planning and le adership. Finally, the analysis of the images of the captures and deaths of Saddam Hussein, Osama bin Laden and Muammar Gaddafi bring the discussion back to the themes of the Enlightenment by demonstrating how democracy is framed to serve political purposes. The images of democracy are essentially images of violence. Contrary to the official, instrumental and humanitari an narratives of Strategic Communication, it is the grammar of expressive, violent rituals that serve as the instrument of unity.

Perspectives on narrative discourse markers : focus on Old English þa

Ett element som har intresserat forskarna av fornengelska sedan början av filologiska studier är adverbet þa ’då’, som är högfrekvent i många berättande texter. Utöver ordföjldsregeln enligt vilken satsinitialt þa följs av omvänd ordföljd, finns det redan tidigt kommentarer om användningen av þa för emfas, livlighet och konnektivitet. Även om sådana karakteriseringar tar den textuella kontexten i beaktande, är deras fokus inte på diskursfunktioner utan på satsgrammatik. Denna avhandling betraktar användningen av þa från diskursstrukturens perspektiv och undersöker dess funktioner i markeringen av berättelsens huvudlinje (eng. grounding), kohesiva kontinuiter (eng. continuities), samt vändpunkter och spänning (eng. peak, tension) i texten. I stället för att fokusera på bara en funktion som har associerats med þa, undersöks denna frekventa element från olika perspektiv. Genom både kvantitativa och kvalitativa analyser av narrativt material, visar de inkluderade delstudierna att detta ord spelar en viktig roll i struktureringen av fornengelska berättelser. Parallellt med kärnfunktionen att markera berättelsens huvudlinje, används þa i samspel med andra strukturerande element för att uttrycka den hierarkiska strukturen och spänning i berättelsen. Jämförelser med andra uttryck av temporal kontinuitet visar att þa skiljer sig från dem i sina användningsmönster, vilket vidare bekräftar dess status som en narrativ diskursmarkör.

Functional Genomic Approaches for Deciphering Plant-Virus Interactions

Plant-virus interactions are very complex in nature and lead to disease and symptom formation by causing various physiological, metabolic and developmental changes in the host plants. These interactions are mainly the outcomes of viral hijacking of host components to complete their infection cycles and of host defensive responses to restrict the viral infections. Viral genomes contain only a small number of genes often encoding for multifunctional proteins, and all are essential in establishing a viral infection. Thus, it is important to understand the specific roles of individual viral genes and their contribution to the viral life cycles. Among the most important viral proteins are the suppressors of RNA silencing (VSRs). These proteins function to suppress host defenses mediated by RNA silencing and can also serve in other functions, e.g. in viral movement, transactivation of host genes, virus replication and protein processing. Thus these proteins are likely to have a significant impact on host physiology and metabolism. In the present study, I have examined the plant-virus interactions and the effects of three different VSRs on host physiology and gene expression levels by microarray analysis of transgenic plants that express these VSR genes. I also studied the gene expression changes related to the expression of the whole genome of Tobacco mosaic virus (TMV) in transgenic tobacco plants. Expression of the VSR genes in the transgenic tobacco plants causes significant changes in the gene expression profiles. HC-Pro gene derived from the Potyvirus Y (PVY) causes alteration of 748 and 332 transcripts, AC2 gene derived from the African cassava mosaic virus (ACMV) causes alteration of 1118 and 251transcripts, and P25 gene derived from the Potyvirus X (PVX) causes alterations of 1355 and 64 transcripts in leaves and flowers, respectively. All three VSRs cause similar up-regulation in defense, hormonally regulated and different stress-related genes and down-regulation in the photosynthesis and starch metabolism related genes. They also induce alterations that are specific to each viral VSR. The phenotype and transcriptome alterations of the HC-Pro expressing transgenic plants are similar to those observed in some Potyvirus-infected plants. The plants show increased protein degradation, which may be due to the HC-Pro cysteine endopeptidase and thioredoxin activities. The AC2-expressing transgenic plants show a similar phenotype and gene expression pattern as HC-Pro-expressing plants, but also alter pathways related to jasmonic acid, ethylene and retrograde signaling. In the P25 expressing transgenic plants, high numbers of genes (total of 1355) were up-regulated in the leaves, compared to a very low number of down-regulated genes (total of 5). Despite of strong induction of the transcripts, only mild growth reduction and no other distinct phenotype was observed in these plants. As an example of whole virus interactions with its host, I also studied gene expression changes caused by Tobacco mosaic virus (TMV) in tobacco host in three different conditions, i.e. in transgenic plants that are first resistant to the virus, and then become susceptible to it and in wild type plants naturally infected with this virus. The microarray analysis revealed up and down-regulation of 1362 and 1422 transcripts in the TMV resistant young transgenic plants, and up and down-regulation of a total of 1150 and 1200 transcripts, respectively, in the older plants, after the resistance break. Natural TMV infections in wild type plants caused up-regulation of 550 transcripts and down-regulation of 480 transcripts. 124 up-regulated and 29 down-regulated transcripts were commonly altered between young and old TMV transgenic plants, and only 6 up-regulated and none of the down-regulated transcripts were commonly altered in all three plants. During the resistant stage, the strong down-regulation in translation-related transcripts (total of 750 genes) was observed. Additionally, transcripts related to the hormones, protein degradation and defense pathways, cell division and stress were distinctly altered. All these alterations may contribute to the TMV resistance in the young transgenic plants, and the resistance may also be related to RNA silencing, despite of the low viral abundance and lack of viral siRNAs or TMV methylation activity in the plants.

Impact of reliability of supply on long-term development approaches to electricity distribution networks

The Finnish electricity distribution sector, rural areas in particular, is facing major challenges because of the economic regulation, tightening supply security requirements and the ageing network asset. Therefore, the target in the distribution network planning and asset management is to develop and renovate the networks to meet these challenges in compliance with the regulations in an economically feasible way. Concerning supply security, the new Finnish Electricity Market Act limits the maximum duration of electricity supply interruptions to six hours in urban areas and 36 hours in rural areas. This has a significant impact on distribution network planning, especially in rural areas where the distribution networks typically require extensive modifications and renovations to meet the supply security requirements. This doctoral thesis introduces a methodology to analyse electricity distribution system development. The methodology is based on and combines elements of reliability analysis, asset management and economic regulation. The analysis results can be applied, for instance, to evaluate the development of distribution reliability and to consider actions to meet the tightening regulatory requirements. Thus, the methodology produces information for strategic decision-making so that DSOs can respond to challenges arising in the electricity distribution sector. The key contributions of the thesis are a network renovation concept for rural areas, an analysis to assess supply security, and an evaluation of the effects of economic regulation on the strategic network planning. In addition, the thesis demonstrates how the reliability aspect affects the placement of automation devices and how the reserve power can be arranged in a rural area network.

Enseigner l'interculturel dans le supérieur: quels discours et approches d'un concept ambigu à l'heure de l'internationalisation? Le cas de la Finlande

L‘interculturel est un concept souvent partagé mais rarement défini dans la recherche alors que ses compréhensions, interprétations et applications sont variées, ce qui mène à des malentendus et des positionnements épistémologiques et méthodologiques ambigus. En parallèle, de nombreuses critiques et propositions de réorientations de la notion voient le jour. Nous entendons faire le point sur la notion et son intégration potentielle dans l‘enseignement de la communication interculturelle (ECI). Notre étude se base sur l‘analyse de six groupes focalisés d‘enseignants (-chercheurs) impliqués dans l‘enseignement de l‘interculturel du niveau supérieur en Finlande, pays du nord de l‘Europe. Nous avons recours aux paradigmes postmodernes et aux sciences du langage (analyse du discours inspirée d‘auteurs français, et plus particulièrement de l‘école française de la deuxième génération (les théories de l‘énonciation (Kerbrat-Orecchioni, 2002 ; Marnette, 2005) et une approche du dialogisme inspirée par Bakhtine (1977))). Ces méthodes permettent de mettre en avant la complexité identitaire en posant l‘hétérogénéité du discours comme principe, c‘est-à-dire qu‘elles considèrent que tout discours inclut la « voix » de l‘autre. Repérer la présence de ces voix dans les discours des enseignants/chercheurs nous a permis de démontrer comment celles-ci participaient à la construction de leur identité pendant l‘interaction. Nous avons pu observer comment les relations entre ces interactions verbales donnaient lieu à des instabilités (contradictions, omissions), dont l‘étude nous a aidée à déduire leur(s) façon(s) de concevoir l‘interculturel. Les discours analysés révèlent a) que la définition de l‘interculturel est partagée sans être perçue de la même manière et b) que les différentes représentations du concept peuvent varier dans le discours d‘un même enseignant, mettant en évidences des contradictions qui posent problème s‘il s‘agit de communiquer un savoir-être aux apprenants. Nous nous sommes efforcée de trouver la place d‘un interculturel renouvelé parmi ces discours et de dissocier l‘image de l‘éducation interculturelle qui est promue en Finlande de ce qui est proposé en réalité : les changements actuels semblent avoir un minimum d‘impact sur la façon dont les enseignants traitent l‘interculturel. Nous nous demandons alors comment l‘Etat finlandais peut promouvoir un enseignement interculturel cohérent sans proposer aux enseignants/chercheurs une formation qui leur permettrait de reconnaitre les diverses diversités impliquées par l‘interculturel. Mots clés : Communication interculturelle, diversité, culture, enseignement supérieur finlandais.

Litteratur och livskunskap : modersmålslärarens berättelse om undervisningen i årkurs 7-9

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Providing Discourse Services for Researchers in a Repository Setting

Poster at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014