The underlying goal of neuroscience research is to understand how the nervous system functions to bring about behavior. A detailed map of neural circuits is required for scientists to tackle this question. To this purpose, we developed a synthetic and genetically-encoded system, TRanscellular ACtivation of Transcription (TRACT) to monitor cell-cell contact. Upon ligand-receptor interaction at sites of cell-cell contact, the transmembrane domain of an engineered Notch receptor is cleaved by intramembrane proteolysis and releases a fragment that regulates transcription in the receptor-expressing cell. We demonstrate that in cultured cells, the synthetic receptor can be activated to drive reporter gene expression by co-incubation with ligand-expressing cell or by growth on ligand-coated surfaces. We further show that TRACT can detect interactions between neurons and glia in the Drosophila brain; expressing the ligand in spatially-restricted subsets of neurons leads to transcription of a reporter in the glial cells that interact with those neurons. To optimize TRACT for neural tracing, we attempted to target the synthetic receptor to post-synaptic sites by fusion with the intracellular domain of Drosophila neuroligin2. However, this modification only facilitate the receptor to be localized homogeneously throughout the neurites. The induction data of the modified receptor shows that the new receptor has better sensitivity compared to the original receptor, but the ligand-receptor interaction still happened at non-synaptic sites of membrane contact. To further target the ligand to pre-synaptic sites, we fused the ligand to different pre-synaptic markers. We found the one fused with synaptobrevin is likely located at axon terminals, but only able to trigger moderate induction. Therefore, more examinations are required to further characterize the capability of this ligand. In summary, TRACT is useful for monitoring cell-cell interactions in animals and could also be used to genetically manipulate cells based on contact. Moreover, we believe that proper targeting of the ligand to synaptic sites will improve the specificity of TRACT for synaptic connections in the future.

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The discovery of solidus coins on the islands of Öland and Gotland, propose a contactbetween Scandinavia and the Roman Empire during the Migration Period (AD 400-550), buthow did the Scandinavians get access to these coins? In this essay, I will study thestampidentity and coin embossing from 572 coins found on Öland and Gotland. The aim is tounderstand where the coins were minted and during which periods there was a big influx ofsolidus coins to Scandinavia. But also, to understand what European regions the people ofÖland and Gotland were in contact with. This essay will also map certain events that are vitalfor understanding why the solidus coins are found in Scandinavia.

Autophagy is the delivery of cytoplasmic cargo to lysosomes for degradation. Defects in autophagy are responsible for various diseases, including neurodegenerative diseases and cancer. While studies in yeast have largely characterized autophagy in response to nutrient starvation, these elegant studies do not account for autophagy in other contexts, including selective autophagy of organelles. A previous screen identified Vps13D as a gene required for the autophagic removal of mitochondria, mitophagy. Vps13D is highly conserved and essential in animals, and Vps13d loss-of-function mutants have enlarged mitochondria and mitophagy deficiencies in both cell and animal models. However, the mechanism by which Vps13D regulates these processes has not been defined. Here, I use mitochondrial clearance in the developing Drosophila intestine and fibroblasts from VPS13D mutant patients as experimental models to investigate the function of Vps13D. I discover that Vps13D is a regulator of ubiquitin and Atg8a/LC3/GABARAP localization around mitochondria. These functions are dependent on Pink1, a ubiquitin kinase, and the core autophagy machinery, respectively. Furthermore, Vps13D regulates mitochondria and endoplasmic reticulum (ER) contact sites downstream of Vmp1, a repressor of mitochondria and ER contact sites. I find that Marf, a mitochondria and ER tether and regulator of mitochondrial fusion, acts downstream of both Vmp1 and Vps13D. These findings explain the phenotypes in Vps13d mutants, as dysregulation of ubiquitin, Atg8a, and mitochondria and ER membrane contact sites impair regulation of both autophagy and mitochondria morphology.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第19710号 / 工博第4165号 / 新制||工||1642(附属図書館) / 32746 / 京都大学大学院工学研究科材料工学専攻 / (主査)教授 酒井 明, 教授 河合 潤, 教授 中村 裕之 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

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It is challenging to achieve low-resistive ohmic contacts to III-nitride semiconductors due to their wide bandgap. A common way to reduce the contact resistance is to recess the ohmic area prior to metallization. In the minimization of the contact resistance, parameters like the recess depth, anneal temperature and design of the metal stack are commonly optimized. In this work, three other approaches have been evaluated. All experiments were performed on AlGaN/GaN heterostructures. The fabricated ohmic contacts were recess etched, metallized with a Ta/Al/Ta stack, and annealed at 550-575◦C.Firstly, it is shown that the laser writer intensity, transmittance and focus offset during optical lithography affect the contact resistance. The reason is believed to be the variation in the resist profile, which has an impact on the metal coverage. At the optimum intensity/transmittance/focus condition, which generates a relatively medium undercut, a contact resistance of 0.23 Ωmm was obtained.In the second approach, the metal layer of annealed contacts was removed by wet etching, followed by the re-deposition of a metal stack and annealing. The purpose was to increase the amount of N vacancies in the AlGaN, which are responsible for the contact formation. A minimum contact resistance of 0.41 Ωmm was achieved with this method, compared to 0.28 Ωmm with the regular method (without remetallization).In the last approach, the bottom Ta layer was sputtered, whereas evaporation was used in all other cases. The minimum contact resistance was found to be 0.6 Ωmm, which was higher than for the evaporated contacts. The reason was assumed that the thickness of sputtered Ta should be thinner than the evaporated Ta due to its higher density. Moreover, the obtained lower sheet resistance is assumed to caused by the atomic scale damage due to the high energy ions during sputtering. / En utmaning med III-nitrid-halvledare är att uppnå låg-resistivitetskontakter, på grund av deras breda bandgap. Ett konventionellt tillvägagångsätt för att reducera kontaktresistansen är att fördjupa ohmska ytan före metallisering. I strävandet av att minska den ohmska resistansen sker vanligtvis en optimering av följande parametrar, recessddjup, anlöpningstemperatur och metallagersdesign. I detta arbete så har samtliga tre parametrar evaluerats. Alla experiment utfördes på AlGaN/GaNheterostrukturer. De tillverkade ohmska kontakterna var recesssetsade, metalliserade med ett Ta/Al/Ta lager och anlöpt vid 550-575◦C.Den primära undersökningen, visar att laserritar-intensitet, -transmission och fokusförskjutning under optisk litografi inverkar på kontaktresistansen. Anledningen antas vara variation i resistprofilen, vilket påverkar metallbeläggningen. Vid optimal intensitet/transmission/fokus-förhållanden, (som genererar en underskärning), blev den resulterande kontaktresistansen 0.23 Ωmm uppmätt.I en sekundär undersökning, avlägsnas ohmska kontaktens metallager genom våtetsning, följt av en återdeponering av ett nytt metallager, samt anlöpning. Syftet var att öka mängden N-vakanser i AlGaN-lagret, som formar ohmska kontakten. Minsta kontaktresistansen uppmätt var 0.41Wmm, att jämföras med 0.28 Ωmm, som uppnåddes genom den konventionella metoden (utan återmetallisering).Den sista undersökningen jämförde sputtrade med evaporerade bottenlager av Ta, (evaporation användes som standardmetod i de tidigare undersökningarna). Med sputtrning blev den minsta kontakresistansen 0.6 Ωmm, (högre än de evaporerade kontakterna). En hypotetisk förklarning kan vara att det sputtrade Ta-lagret är tunnare än det evaporerade Ta-lagret, på grund av en dess högre densitet. Därutöver, den uppmätta lägre skiktresistansen antas bero på den skada i atomskala som sker vid de höga energi-kollisioner som joner skapar vid sputtrning.

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The roman coins on the islands of Bornholm, Öland and Gotland have shownarchaeologist and historians that a connection between Scandinavia and the RomanEmpire existed. But what did the roman coins mean to the inhabitants of these islands?This essay will study the coins found on the islands and the context in which they havebeen found. The aim for this essay is to understand in what context the coins werefound and what they meant for the inhabitants. The essay also strive towardsconducting a discussion around theories, speculations and facts to form an idea of whatthe coins may have meant to the inhabitants.

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