Ephrins and Eph receptors have been implicated in a number of developmental processes including axon growth and guidance. One important guidepost is the central nervous system midline, where ephrins and Eph receptors have been implicated. At the embryonic midline, axons either cross into the contralateral central nervous system (CNS) targeting appropriate partners on the opposite side or remain ipsilateral extending either rostrally or caudally. In these studies, we examine a major forebrain commissure called the corpus callosum (CC). Agenesis of the CC is a rare birth defect that occurs in isolated conditions and in combination with other developmental cerebral abnormalities. Recent identification of families of growth and guidance molecules has generated interest in the mechanisms that regulate callosal growth. One family, ephrins and Eph receptors, has been implicated in mediating midline pathfinding decisions; however, the complexity of these interactions has yet to be unraveled. This dissertation sheds light on which B-class ephrins and Eph receptors function to regulate CC midline growth, and how these molecules interact with important guideposts during development. We also show that multiple Eph receptors (B1, B2, B3, and A4) and B-class ephrins (B1, B2, and B3) are present and function in developing forebrain callosal fibers based on both spatial and temporal expression patterns and analysis of gene-targeted knockout mice. Defects are most pronounced in the combination double knockout mice, suggesting that compensatory mechanisms exist for several of these family members. Furthermore, these CC defects range from mild hypoplasia to complete agenesis and Probst's bundle formation. Further analysis of the ephrinB3 gene revealed that Probst's bundle formation may reflect aberrant glial formations which alter the normal architecture of midline glia resulting in one potential mechanism of this abnormal phenotype. Another potential mechanism we discovered is a role for EphB1 receptor in the altered sensitivity of CC axons to midline guidance cues. Removal of this receptor resulted in cortical axons responding to GW guidepost cells with increased sensitivity. Our results support a significant role for ephrins and Eph receptors in CC development and may provide insight to possible mechanisms involved in axon midline crossing as well how failed molecular and genetic mechanisms may contribute to human CC disorders. Lastly, we show that one fiber tract that remains ipsilateral in the forebrain may use distinct midline guideposts to regulate proper growth and guidance. These findings implicate additional ephrins and Eph receptors in CC midline guidance than previously known and reveal novel mechanisms in mice, which may be pertinent to human disease states that result in agenesis of the CC.

G-protein coupled receptors (GPCRs) have been shown to act as part of GPCR associated protein complexes (GAPCs) which are required to appropriately transduce downstream signaling pathways leading to specific cellular actions. I hypothesize that there are distinct molecular effectors that couple to the glucagon superfamily of B-class GPCRs (glucagon, GLP-1, GLP-2, GIP receptors) to effect the myriad of reported actions in numerous target cells including regulation of insulin secretion, intestinal growth and appetite suppression. GLP-1R, GIPR, GLP-2R and GCGR were screened using a newly developed membrane-based split-ubiquitin yeast two-hybrid (MYTH) system to reveal 181 novel candidate protein interactors associated with signal transduction, transport, metabolism and cell survival. Each candidate was validated using yeast two-hybrid prey retransformation tests and by co-purification to confirm coupling to each receptors. The present work is the first demonstration of a split-ubiquitin interaction screen using in situ membrane expressed GPCRs of the secretin-like B class.

G-protein coupled receptors (GPCRs) have been shown to act as part of GPCR associated protein complexes (GAPCs) which are required to appropriately transduce downstream signaling pathways leading to specific cellular actions. I hypothesize that there are distinct molecular effectors that couple to the glucagon superfamily of B-class GPCRs (glucagon, GLP-1, GLP-2, GIP receptors) to effect the myriad of reported actions in numerous target cells including regulation of insulin secretion, intestinal growth and appetite suppression. GLP-1R, GIPR, GLP-2R and GCGR were screened using a newly developed membrane-based split-ubiquitin yeast two-hybrid (MYTH) system to reveal 181 novel candidate protein interactors associated with signal transduction, transport, metabolism and cell survival. Each candidate was validated using yeast two-hybrid prey retransformation tests and by co-purification to confirm coupling to each receptors. The present work is the first demonstration of a split-ubiquitin interaction screen using in situ membrane expressed GPCRs of the secretin-like B class.

This diploma thesis is focused on design of high frequency power amplifiers in UHF band, specifically at 435 MHz. Amplifiers are designed in different classes of operation. The thesis deals with the comparison of main parameters in each class of operation, the most important parameter is effeciency. The amplifying part is unipolar transistor which is working in Single-stage mode. The results were simulated in Advanced Design Systems Software.

I centrum för den här avhandlingen står det tidiga 1900-talets diskussion om skola, begåvning och social organisering. Tidsperioden som omfattas är 1910– 1950. Det är skolan i de större städerna Stockholm, Göteborg och Malmö som har stått i fokus. Det övergripande syftet har varit att analysera den betydelse som begåvning och intelligens fick i relation till skolväsendets förändring. Med utgångspunkt i detta syfte diskuteras hur uppfattningar om samhällets begåvningsresurser och individers förmågor har format 1900-talets samhällsliv. Betoningen på begåvning förde med sig primärt två saker: Att tillvarata god begåvning och att motverka låg begåvning. Avhandlingen har främst syftat till att granska de sociala och institutionella sammanhang i vilka intelligensmätningarna kom att uppfattas som användbara. Det innebär att intresset har riktats mot det inflytande som olika professionella via förhandlingar, professionalisering och vetenskapliggörande fick över skolans utformning. Teoretisk har undersökningen hämtat inspiration hos Michel Foucault, vilket ger en utgångspunkt som betonar sambandet mellan kunskapsbildning och makt. Genom olika gränsdragningar och uteslutningar – ”åtskiljande praktiker” – i utbildningssystemet blir individerna synliga i förhållande till olika institutionella arrangemang och konstrueras därmed både som individer och som grupper. Avhandlingen använder ett historiskt perspektiv för att studera hur makt och vetande i en given tid formulerar vad som är att betrakta som ett problem i samhället. / At the centre of this thesis is the early 20th century’s discussion on school, talent and social organisation. The period that is covered is 1910 – 1950. It is schools in the cities Stockholm, Gothenburg and Malmö that have been focused on. The overall purpose has been to analyse the importance that talent and intelligence had in relationship with the changes in the educational system. Using this as a starting point, it was discussed how views on society’s talent resources and the abilities of individuals have formed 20th century social life. Emphasis on talent led to primarily two things: to utilise good talent and counteract poor talent. The thesis has mainly aimed at examining the social and institutional contexts in which intelligence testing came to be seen as usable. This means that interest has been directed at the influence that different professionals had via deliberations, professionalizing and scientificating had on the forming of schools. Theoretically the study has been inspired by Michel Foucault, which provided an excellent starting point that emphasises the connection between education and power. Through different boundaries and conclusions – “separating practices” – in the education system the individuals become visible in relation to different institutional arrangements and can therefore be construed both as individuals and groups. The thesis uses an historic perspective to study how power and knowledge in a given time formulate what is considered as a problem in society.