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EVIDENCE FOR ADAPTER-MEDIATED SUBSTRATE SELECTION IN ENDOPLASMIC RETICULUM ASSOCIATED DEGRADATIONCorcoran, Kathleen M. January 2009 (has links)
Viruses have evolved a multitude of mechanisms, which allow immune evasion in both initial and persistent infection. Understanding the intricacies of these pathways is essential to our future ability to combat primary and reactive viral infections. The murine gamma-2 herpesvirus 68 (γHV68) encodes a protein mK3, which targets Major Histocompatibility Complex (MHC) class I heavy chains for ubiquitin-dependent proteasome degradation. MK3 is able to target and ubiquitinate MHC class I by binding to Endoplasmic Reticulum (ER) resident proteins tapasin, Transporter associated with antigen processing (TAP) 1 and TAP2 that are subunits in the complex known as the peptide-loading complex (PLC). The aforementioned characteristics of mK3 make this novel protein an excellent vehicle to study MHC class I assembly, immune evasion, and ER associated degradation (ERAD). Deepening our understanding of class I assembly and viral immune evasion will impact both the fields of immunology and virology. The homology between γHV68 and many of the human γ-herpesviruses makes this an indispensable model to clarify mechanisms that can then be applied to a broader spectrum of viruses. ERAD, an emerging field of study, is known to play a key role in numerous cellular housekeeping pathways as well as a number of disease states. Illuminating the mechanisms implicated in the mK3-mediated ubiquitination of MHC class I, specifically requirements for substrate recognition and degradation, will yield an increased understanding of cellular pathways involved in ERAD. The studies in this dissertation aim to expand our understanding of the relationship between mK3 and adapter proteins TAP/tapasin as well as mK3 and mK3-targeted substrates. The results show that TAP/tapasin act as adapter proteins by recruiting substrates for mK3. Further, mK3 ubiquitinates TAP/tapasin-associated substrates as long as the substrates have a tail greater than 6aa in length and the tail possesses an ubiquitin acceptor residue (lysine, serine or threonine). These studies also confirm that location of a protein within the PLC will determine the substrate’s susceptibility to mK3-mediated degradation. In the field of ubiquitin ligases and ERAD, these studies lend support to the concept of adapter mediated substrate recruitment.
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Obemannade system, ett hot mot marinen?Rönnqvist, Kim January 2023 (has links)
I en komplex miljö som skärgårdar väntar en del utmaningar. Detta tillsammans med den teknik som finns idag inom UAV området skapar nya hotbilder. Ett av fartygen som den svenska flottan använder är Visbykorvetten, som är ett komplext system med kompetent förmåga som ska kunna lösa många uppgifter. Rapporten avser att analysera vilket hot som drönare kan utgöra mot Visbykorvetten. Några UAV som används i kriget i Ukraina är Switchblade 300, 600 och Shahed-136. Arbetet syftar till att undersöka dessa UAV och vilket hot de kan utgöra mot en Visbykorvett, i syfte för att se om korvettens skydd är tillräckligt. Fartyget har ett bra egenskydd mot ankommande hot från luften, dock på grund av vapensystemens placering på fartyget uppstår en begränsning i möjligheterna att erhålla ett eget skydd runt hela fartyget. Detta kan även försvåras av den komplexa miljö som skärgården medför. Begränsningen i egenskyddet bedöms en UAV kunna nyttja och på så sätt få möjligheten att skada fartygets sensorer som sitter relativt oskyddade. Vilket medför att fartyget inte fullt ut kan lösa tilldelade uppgifter utan är behov av att repareras. För att undvika detta kan fyra olika åtgärder vidtas. Undvika trånga sund om det är möjligt, fråga externa marina förband om eskortmöjligheter, eller installera vapenstation på akterdäck för att öka egenskyddet, och ge fartyget signalstörningsförmåga. / The complex environments that the archipelago provides, alongside the technical developments of drones, create a new form of threat. The Visby class corvette is a complex platform that can fulfil many different tasks both above and below the surface. This thesis will look closer at its surface-to-air defense system, and capability to defend against drones. Some of the drones that are used in the Russo-Ukrainian war, are Switchblade 300, 600 and Shahed-136. The thesis aims to investigate these drones and what threat they may pose against a Visby Corvette, to see if the ship’s protection is sufficient. The ship has good self-protection against incoming threats from the air, but due to the location of the weapon systems on the ship, there is a limitation in obtaining full protection. The protection can also be hampered by the complex environment that the archipelago entails. A drone can exploit this limitation of self-protection and obtain the possibility of damaging the sensors of the ship that are relatively unprotected. This means that the ship cannot fully solve the assigned tasks due to its need for repairs. In conclusion, to prevent this, four different actions can be taken. Avoid narrow straits, if possible. Ask external units for escort. Install a weapon station in the stern to increase self-protection and provide the vessel with signal interference technology.
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