The aim of this master thesis is to investigate the ideas about functions that public libraries have in the local society. We have used the method idea analysis on four municipal library plans, to find out which ideas about library functions that frequented each plan, and what similarities and differences there were between the ideas about functions in each plan. As a theoretic base, we have used a theory about three dynamic spheres in modern society: the state market and civil society, and examined how these three spheres influence and control the library functions. We have extracted six different ideas about library functions: educational, social, economical, entertaining, serving and democratic functions. The most dominating ideas in this study are ideas that the public library should be an educating and formative institution. As the public library is a public institution depending on the state, are the most ideas of functions connected to this sphere. We can also see a tendency that the public library is a service institution that acts on the demands from users and other authorities in society. This can be a result of influence from the market, just as ideas that the public library should be engaged in economic development, though this idea is scarce in the documents analysed. The civil society is mostly represented in the social ideas, that the public library is a public meeting place and a room for recreation and entertainment. We have found these ideas in all plans but as these are of a more voluntary character are they not as visible. / Uppsatsnivå: D

Antagonism of the activin receptor signaling pathway represents a promising potential therapy for the muscular dystrophies and other muscle wasting disorders (i.e., cachexia or sarcopenia). Previous research has shown that antagonism of activin signaling promotes muscle growth, attenuates muscle wasting, and restores function in both wild type and diseased animals. Our laboratory has recently developed a novel small molecule (SGI-1252) that inhibits activin downstream (i.e., Smad2/3 phosphorylation) signaling. Purpose: In this study we determined how eight weeks of orally administered SGI-1252 affected TGF-ß signaling, whole body mass, individual limb muscle mass, and muscle fiber cross sectional area (CSA). Methods: Wild-type (WT) mice were treated with SGI-1252 or a vehicle control (VC) via oral gavage (400 mg/kg 3 times per week) for 8 weeks. Body mass was measured twice per week during the 8-week treatment period. At the end of the treatment period, gastrocnemius and tibialis anterior (TA) muscles were excised, weighed, and prepared for histological and biochemical analyses. Results: Following 8 weeks of treatment, there was no difference in weight gain between SGI-1252 (24.8 ± 1.8g) and VC treated mice (23.2 ± 1.5g) (p = 0.06). Gastrocnemius whole muscle mass was significantly greater in the SGI-1252 treated group relative to the VC treated mice (139.6 ± 12.8 mg vs 128.8 ± 14.9 mg) (p = 0.04), although when normalized with body mass there was no difference in gastrocnemius mass. For the TA muscle, there were no significant differences in whole muscle mass between SGI-1252 and VC groups, yet TA muscles in the SGI-1252 treated group had a reduced muscle fiber CSA compared to controls (621 ± 44 µm2 vs 749 ± 36 µm2) (p = 0.0005). There was a statistical trend of decreasing Smad2 phosphorylation in the SGI-1252 treated TA muscles (mean SGI-1252 = 0.668 vs VC = 0.848) (p = 0.06), and no significant differences in Smad2 phosphorylation in the gastrocnemius. Conclusions: Contrary to our hypothesis, 8 weeks of orally administered SGI-1252 was not effective in promoting increases in whole body mass, limb whole muscle mass, or myofiber cross sectional area. This may be due to the inability of SGI-1252, at the administered dose, to effectively decrease signaling downstream of the activin receptor. Clearly, studies using a wider range of doses and delivery methods will be needed to ascertain the efficacy of SGI-1252 as a potential therapeutic.

Cell signaling is central to integration of internal and external cues that regulate development and homeostasis. Most development is thought of as pre-adult, but limited developmental processes occur in adults. Gametogenesis incorporates elements of both these facets, with a distinct developmental plan for gamete synthesis which is regulated by integration of homeostatic inputs such as nutrient status, and environmental cues. Signaling pathways integrate and transduce information from these cues to evoke a response. A decline in homeostasis and subsequent cues occurs over time, in the case of reproductive tissues leading to a progressive loss of fertility. The Janus Kinase and Signal Transducer and Activator of Transcription or Jak/Stat signaling pathway is conserved between vertebrates and invertebrates and is necessary for numerous functions needed to maintain organism and reproductive homeostasis, as well as contributing to various developmental events. The pathway in the fruit fly Drosophila melanogaster, is composed of a single receptor, Domeless, one Janus kinase, Hopscotch, one known effector, Stat92E, and the Unpaired family of ligands consisting of Upd, Upd2, and Upd3. Jak/Stat signaling is highly pleiotropic in both sexes with involvement in homeostasis and reproduction, making it an ideal model for studying the role of signaling in reproductive aging. Reduction of pathway activity in females results in a higher proportion of unfertilized eggs, which increases with age, and in males leads to a premature onset of infertility. Central to both is integration through cell signaling to evoke an appropriate response. This dissertation explores two of the requirements for Jak/Stat signaling: the pleiotropic requirement for Jak/Stat activity during oogenesis and male reproductive maintenance. Jak/Stat functions from the beginning of oogenesis, in the stem cell niche. From there it participates in multiple functions including specification of a subset of somatic cells called the border cells through the polar cells, a pair of cells at either pole of the egg. Pathway stimulation in the border cells drives their migration with the polar cells to the oocyte boundary, where the polar cells each form an extension in a coordinated manner into the micropyle, the means for sperm entrance during fertilization. Loss of Jak/Stat activity in the border cells prevents border cell migration. While border cell migration has been well studied, polar cell involvement after completion of border cell migration is less well known. To investigate the requirements for polar cell activity and Jak/Stat activity after the completion of border cell migration, we reduced Jak/Stat signaling in the polar cells which, while having no effect on border cell migration, results in blocked micropyles due to loss of coordination of extensions during their outgrowth. Reduced function in the polar cells did not significantly affect expression of adhesion molecules. But, the loss of Stat92E is phenocopied by loss of DE-cadherin. Hence, these results indicate a previously unknown autocrine requirement for Jak/Stat activity in the polar cells. The testes also have a continuous requirement for Jak/Stat activity for stem cell maintenance and differentiation of the germline into mature sperm. Reproductive maintenance not only requires sustained production of gametes, but reproductive tissues are also subject to deterioration of homeostatic functions that contribute to organismal aging. Males from thirty-nine lines of the Drosophila Genetic Reference Panel (DGRP), a panel of inbred, fully sequenced lines, were screened for age at infertility. Data were used to perform a genome-wide association study (GWAS) to identify the genetic architecture of reproductive aging. Candidate variants associated with cell signaling regulators, genes with functions in maintaining cell homeostasis, and organism behavior were uncovered. Notably, several SNPs fell in and near Ptp61F, a negative regulator of Jak/Stat activity. While variants in the primary components of the Jak/Stat pathway were not identified, the general classes of candidate loci functions reflect the requirements for homeostasis, metabolism, and development that have been shown by other studies examining the genetics of aging and fecundity. Thus, we show that Jak/Stat has an amazing amount of pleiotropy that encompasses both the real-time functions of fertility and the time related process of aging.

Les interférons (IFNs) de type I sont des cytokines qui jouent un rôle capital dans les défenses immunes, antivirales et antiprolifératives de l'organisme. En se liant à leur récepteur de surface, composé des deux sous-unités IFNAR1 et IFNAR2, ils induisent la cascade de signalisation JAK/STAT qui aboutit à leur effets biologiques. L'objectif de ma thèse était d'identifier des mécanismes de régulation de la signalisation des IFNs. Dans ce contexte, nous nous sommes intéressés à la palmitoylation du récepteur de l'IFN de type I, une modification lipidique souvent impliquée dans le trafic et la signalisation des protéines. Par marquage métabolique au palmitate tritié, nous avons montré qu'IFNAR1 et IFNAR2 sont palmitoylées. Le domaine cytoplasmique d'IFNAR1 contient deux cystéines, Cys463 et Cys502, qui sont des sites potentiels de palmitoylation. A l'aide de mutants sur chacune de ces cystéines, nous avons montré qu'IFNAR1 est palmitoylée uniquement sur sa cystéine la plus proche de la membrane plasmique, la Cys463. Un mutant non palmitoylé dans lequel cette cystéine a été remplacée par une alanine nous a permis de constater que la palmitoylation d'IFNAR1 n'est pas impliquée dans son trafic intracellulaire, dans son endocytose ni dans sa stabilité, mais qu'en revanche elle joue un rôle crucial dans l'activation de la voie de signalisation JAK/STAT. De façon concordante, la palmitoylation d'IFNAR1 est requise pour l'activation transcriptionnelle des gènes induits spécifiquement par l'IFN-a. Par contre, un défaut de palmitoylation n'influence nullement l'activité antiproliférative de l'IFN-a, en dépit du rôle de cette modification dans la signalisation.

<p>Syftet med undersökningen var att med hjälp av lämpliga statistiska metoder testa det så kallade ”Första petropolitiska lagen” med vilket menas en negativ korrelation mellan priset på råolja och graden av friheten hos petropolitiska länder. Med stöd av ett lämplig teoretisk referensram och diskussion över de kausala mekanismerna, har en hypotes över sambandet tagits fram. Trettio tre petropolitiska stater har identifierats vilket omfattar hela populationen. Demokratiska friheter och priset på råolja har definierats och omvandlats till en kvantifierbar form och sedan testats statistiskt. Samtliga variabler har kodats i form av tidsserieobservationer och en paneldata har konstruerats innehållande totalt 939 årliga observationer för de trettio tre petropolitiska länder. Den aggregerade sambandet över hela populationen har testats med en OLE regressionsanalys med så kallad ”first-order” autokorrelation med panelspecifika standardavvikelser. Den första petropolitiska lagen har även testats individuellt för varje petropolitisk land som ingick i urvalet. Erhållen resultat från aggregerat regressionsanalys tyder på att det föreligger ett svagt, med 95 % statistiskt signifikant, positiv samband mellan den beroende och den oberoende variabeln. När sambandet testades enskilt för varje land, har endast 16 av 33 länder fått signifikanta korrelationsnivåer. Fem av länder visade en negativ samband medan elva länder visade en positiv samband mellan beroende och oberoende variabler. Hypotesen har därmed kunnat falsifieras. Förklaringsgraden, samt autokorrelationsproblem tyder dock på att en mer omfattande analys krävs för att kunna säkerställa erhållna resultat.</p> / <p>The purpose of this study was to, with proper statistical methods, investigate so called ”The First Law of Petropolitics”. The First Law of Petropolitics postulates that there exists a negative correlation between price of oil and pace of freedom in the oil-rich petrolist states. A hypothesis has been formulated based on appropriate theoretical references and a discussion about its causal mechanisms. Thirty three petropolist states have been identified which comprises the whole population. The pace of freedom and the price of oil has been defined and transformed into a quantifiable measure and tested statistically. Variables were coded into a time-series panel-data form which included 939 annual observations for those thirty three petrolist states. The aggregated correlation between dependent and independent variables has been tested with an OLE regression analysis with so called “first-order autocorrelation with panel-specific standard errors”. The first law of petropolitics also has been individually tested for each petrolist state. The results from the aggregate regression suggest that there exists a weak, with 95 % statistically significant, positive correlation between a dependent and an independent variables. When each petrolist state has been regressed individually the results showed that only 16 of 33 states had significant levels of correlation. Five of those states had a negative correlation, while other eleven states had a positive correlation. The hypothesis has therefore been falsified. The low R2 –value obtained in both tests and autocorrelation problems suggest that a further investigation of the First Law of Petropolitics is necessary in order to secure the obtained results.</p>

<p>I uppsatsen analyseras remissförslaget till den nya skollagen (Ds 2009:25) samt Barnkonventionen med avsikt att formulera och jämföra hur föräldrar och stat positioneras gällande barnets fostran. Analysen syftar till att belysa likheter och skillnader mellan de båda texterna. Detta sker utifrån ett diskursanalytiskt perspektiv där subjektspositioner är ett nyckelbegrepp i analysen, samt med hjälp av politisk filosofi. Det filosofiska materialet är hämtat från John Rawls, Alasdair MacIntyre samt nutida utbildningsforskning främst representerat av Tomas Englund. De politiska filosofierna bidrar till utmejslandet av tre diskurser funna i den nya skollagen och Barnkonventionen.</p><p>Dessa diskurser är <em>de stödjande subjektens diskurs</em> vilken är den dominerande diskursen i de båda texterna och i vilken barnet självt ges ansvar för sin utveckling; denna diskurs ligger nära John Rawls politiska teorier. Vidare framkommer <em>isärhållandets diskurs</em> vilken återfinns i den nya skollagen och ligger närmast den nutida utbildningsforskningen; i denna diskurs framträder staten som garant för elevens väl. I den sista diskursen, <em>traditionens diskurs</em>, som utmejslas ur MacIntyre och Barnkonventionen ses istället föräldrarna som barnets garant.</p><p>Utifrån arbetet framkommer en förhållandevis stor likhet mellan den nya skollagen och Barnkonventionen även om en nyansskillnad kan urskiljas. Denna nyansskillnad visar sig genom att isärhållandets diskurs och traditionens diskurs, vilka står i polemik, återfinns i betydande grad enbart i en text var.</p>

Mammalian Scribble is a target for proteins encoded by human papilloma virus, retro- and flaviviruses. Tick-borne encephalitis virus (TBEV) is a flavivirus that have evolved distinct strategies to escape antiviral responses. Information of how flaviviruses intrude on cell integrity comes from understanding of the roles that host-factors play when they interfere with viruses. The first part of this thesis describes a novel interaction between the TBEVNS5 protein and Scribble. The importance of the interaction was demonstrated by RNAi-mediated depletion of Scribble, which prevented suppression of JAK-STAT signaling by NS5. Together, these results define Scribble as a novel target for NS5. TBEV is known to cause central nervous system disease TBE in humans that can lead to cognitive dysfunction. A unifying theme in CNS related diseases are defects in neuronal extensions. We therefore addressed the effects of TBEV expression in PC12 cell differentiation, which is characterized by extensive neurite growth. Our data show that TBEVNS5 suppresses neurite outgrowth through the Rho GTPase Rac1. These findings provide evidence that Rac1 is an indirect target of NS5 in neurite inhibition. Scribble was recently implicated in spine morphogenesis. Thus, we tested the role of Scribble in neurite elongation. Depletion of Scribble in PC12 cells, reduced neurite density but increased length of those remaining. Moreover, Scribble bound components in the Ras/ERK cascade in a growth factor dependent manner. Together, these results demonstrate that Scribble controls neurite elongation by scaffolding MAPK components. Moreover, as loss of dendritic spines, actin-rich protrusions on neurons, is a feature in cognitive dysfunction we speculate that cognitive dysfunction in TBE might involve disturbed Scribble expression by NS5. We also investigated the binding between NS1 of Influenza A virus and Scribble. The PDZ domains of Scribble are usually selective for specific C-terminal motifs in proteins. Because NS1 has a canonical PDZ motif we tested if binding to Scribble depends on this motif. We found that Scribble binds NS1; the association is dependent on the NS1 C-terminus that is recognized by PDZ3-4 of Scribble. Together, these results suggest that Scribble is a target for the H5N1 NS1 protein / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: In press. Paper 3: Manuscript. Paper 4: Manuscript.

I uppsatsen analyseras remissförslaget till den nya skollagen (Ds 2009:25) samt Barnkonventionen med avsikt att formulera och jämföra hur föräldrar och stat positioneras gällande barnets fostran. Analysen syftar till att belysa likheter och skillnader mellan de båda texterna. Detta sker utifrån ett diskursanalytiskt perspektiv där subjektspositioner är ett nyckelbegrepp i analysen, samt med hjälp av politisk filosofi. Det filosofiska materialet är hämtat från John Rawls, Alasdair MacIntyre samt nutida utbildningsforskning främst representerat av Tomas Englund. De politiska filosofierna bidrar till utmejslandet av tre diskurser funna i den nya skollagen och Barnkonventionen. Dessa diskurser är de stödjande subjektens diskurs vilken är den dominerande diskursen i de båda texterna och i vilken barnet självt ges ansvar för sin utveckling; denna diskurs ligger nära John Rawls politiska teorier. Vidare framkommer isärhållandets diskurs vilken återfinns i den nya skollagen och ligger närmast den nutida utbildningsforskningen; i denna diskurs framträder staten som garant för elevens väl. I den sista diskursen, traditionens diskurs, som utmejslas ur MacIntyre och Barnkonventionen ses istället föräldrarna som barnets garant. Utifrån arbetet framkommer en förhållandevis stor likhet mellan den nya skollagen och Barnkonventionen även om en nyansskillnad kan urskiljas. Denna nyansskillnad visar sig genom att isärhållandets diskurs och traditionens diskurs, vilka står i polemik, återfinns i betydande grad enbart i en text var.

La tesis ha quedado estructurada en dos partes. En la primera, se desarrolla y fundamenta el marco teórico de este trabajo de investigación, desde el que se presentan los principales planteamientos conceptuales que han ayudado y están contribuyendo a definir la alta habilidad intelectual, haciendo especial hincapié en enfoques amplios y variados, que permitan que la identificación de esos sujetos se realice considerando junto a su potencial intelectual otras muchas y diferentes variables. Y la segunda se centra en la explicación del estudio empírico realizado y en el análisis de los resultados y conclusiones más significativas obtenidas del mismo. / The thesis is divided into two parts. In the first part the theoretical framework underlying the research is described, as are the principal conceptual approaches which contribute to the definition of high intellectual ability. Special emphasis is laid on wide and varied approaches which enable gifted subjects to be identified by taking mary other variables into consideration besides intellectual potential. The second part describes the empirical studies carried out and analyses the must significant results and conclusions.

Abstract Denna uppsats ska utgå från den generella problematiken och komplexiteten om ansvarsfördelningen mellan stat och familj när det gäller barnets bästa. Mer specifikt vill jag närmare titta på vad som kan hända när denna fråga ställs på sin spets: i detta fall när barn befinner sig i någon form av krissituation och frågan om ett offentligt ingripande av något slag aktualiseras. Frågor om vad som är barnets bästa uppstår i sådana fall och den myndighet som har ansvar för att avgöra detta är Socialtjänsten. Socialtjänstens arbete handlar också om att undersöka om barnet får sina behov tillgodosedda i hemmamiljön. Utgångsläget skall vara att familjen ska kunna lösa sina problem på egen hand, men om det bedöms nödvändigt ska samhället ingripa. Här kan frågan om ett omhändertagande av barn vara aktuell. Med utgångspunkt i frågan om ansvarsfördelningen mellan det offentliga och familjen när det gäller barnets bästa, är syftet med min uppsats att undersöka hur en offentlig myndighet på lokal nivå agerar när det kommer till deras kännedom att ett barn far illa och behöver hjälp. Jag vill få en bild av och exempel på hur samhällets ansvar för barnets bästa kan tillgodoses. Det kan dock inte vara helt problemfritt med att veta vad barnets bästa är samt hur man ska gå tillväga för att på ett tillfredsställande sätt kunna tillgodose barnets behov. Undersökningen berör också utvecklingen på en nationell nivå när det gäller förskjutningar i ansvarsfördelningen mellan det privata och det offentliga. Följande behandlar jag i denna uppsats: - Vilka olika typer av fall hamnar på myndighetens bord? - Hur hanteras dessa fall?