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Proper neuronal function requires the preservation of appropriate neural excitability. An adaptive increase in neural excitability after exposure to agents that depress neuronal signaling blunts the sedative drug effects upon subsequent drug exposure. This adaptive response to drug exposure leads to changes in drug induced behaviors such as tolerance, withdrawal and addiction. Here I use Drosophila melanogaster to study the cellular and neuronal components which mediate behavioral tolerance to the anesthetic benzyl alcohol. I demonstrate that rapid tolerance to benzyl alcohol is a pharmacodynamic mechanism independent of drug metabolism. Furthermore, tolerance is a cell autonomous response which occurs in the absence of neural signaling. Using genetic and pharmacological manipulations I find the synapse to play an important role in the development of tolerance. In addition, the neural circuits that regulate arousal and sleep also alter benzyl alcohol sensitivity. Beyond previously described transcriptional mechanisms I find a post-translational role of the Ca2+-activated K+-channel, slowpoke in the development of tolerance. Finally, I explore a form of juvenile onset tolerance, which may have origins that differ from rapid tolerance. The implications of this study go beyond tolerance in Drosophila melanogaster to benzyl alcohol and can shed light on human drug tolerance, withdrawal and addiction. / text

Three-dimensional (3D) integration of micro- and nano-electromechanical systems (MEMS/NEMS) with integrated circuits (ICs) is an emerging technology that offers great advantages over conventional state-of-the-art microelectronics. MEMS and NEMS are most commonly employed as sensor and actuator components that enable a vast array of functionalities typically not attainable by conventional ICs. 3D integration of NEMS and ICs also contributes to more compact device footprints, improves device performance, and lowers the power consumption. Therefore, 3D integration of NEMS and ICs has been proposed as a promising solution to the end of Moore’s law, i.e. the slowing advancement of complementary metal-oxide-semiconductor (CMOS) technology.In this Ph.D. thesis, I propose a comprehensive fabrication methodology for heterogeneous 3D integration of NEM devices directly on top of CMOS circuits. In heterogeneous integration, the NEMS and CMOS components are fully or partially fabricated on separate substrates and subsequently merged into one. This enables process flexibility for the NEMS components while maintaining full compatibility with standard CMOS fabrication. The first part of this thesis presents an adhesive wafer bonding method using ultra-thin intermediate bonding layers which is utilized for merging the NEMS components with the CMOS substrate. In the second part, a novel NEM switch concept is introduced and the performance of CMOS-integrated NEM switch circuits for logic and computation applications is discussed. The third part examines two different packaging approaches for integrated MEMS and NEMS devices with either hermetic vacuum cavities or low-cost glass lids for optical applications. Finally, a novel fabrication approach for through silicon vias (TSVs) by magnetic assembly is presented, which is used to establish an electrical connection from the packaged devices to the outside world. / Tredimensionell (3D) integration av mikro- och nano-elektromekaniska system (MEMS/NEMS) med integrerade kretsar (ICs) är en ny teknik som erbjuder stora fördelar jämfört med konventionell mikroelektronik. MEMS och NEMS används oftast som sensorer och aktuatorer då de möjliggör många funktioner som inte kan uppnås med vanliga ICs.3D-integration av NEMS och ICs bidrar även till mindre dimensioner, ökade prestanda och mindre energiförbrukning av elektriska komponenter. Den nuvarande tekniken för complementary metal-oxide-semicondictor (CMOS) närmar sig de fundamentala gränserna vilket drastiskt begränsar utvecklingsmöjligheten för mikroelektronik och medför slutet på Moores lag. Därför har 3D-integration identifierats som en lovande teknik för att kunna driva vidare utvecklingen för framtidens elektriska komponenter.I denna avhandling framläggs en omfattande fabrikationsmetodik för heterogen 3D-integration av NEMS ovanpå CMOS-kretsar. Heterogen integration betyder att både NEMS- och CMOS-komponenter byggs på separata substrat för att sedan förenas på ett enda substrat. Denna teknik tillåter full processfrihet för tillverkning av NEMS-komponenter och garanterar kompatibilitet med standardiserade CMOS-fabrikationsprocesser.I den första delen av avhandlingen beskrivs en metod för att sammanfoga två halvledarskivor med en extremt tunn adhesiv polymer. Denna metod demonstreras för 3D-integration av NEMS- och CMOS-komponenter. Den andra delen introducerar ett nytt koncept för NEM-switchar och dess användning i NEM-switch-baserade mikrodatorchip. Den tredje delen presenterar två olika inkapslingsmetoder för MEMS och NEMS. Den ena metoden fokuserar på hermetisk vakuuminkapsling medan den andra metoden beskriver en lågkostnadsstrategi för inkapsling av optiska komponenter. Slutligen i den fjärde delen presenteras en ny fabrikationsteknik för så kallade ”through silicon vias” (TSVs) baserad på magnetisk självmontering av nickeltråd på mikrometerskala. / <p>20170519</p>