Rapid technological breakthroughs originating from fundamental microbiology research have yielded novel genome engineering tools that greatly facilitate our ability to modify specific genomic... Show moreRapid technological breakthroughs originating from fundamental microbiology research have yielded novel genome engineering tools that greatly facilitate our ability to modify specific genomic sequences in living cells and organisms. As a corollary, these technologies are also starting to permeate the realm of medicine when applied as a form of “genomic surgery”. These genetic therapies aim at tacking the root cause of human pathologies, inherited or acquired, by correcting or modulating the genetic content or expression, respectively, present in target cells, tissues and organs. To this end, delivery vehicles capable of introducing, in an efficient and safe manner, the increasingly sophisticated (epi)genome editing reagents are in demand, especially when considering in vivo genetic therapies. The research presented in this thesis reveals the feasibility and utility of using regular and high-specificity nicking RGNs for achieving efficient and accurate genetic modification of human cells involving targeted gene knockouts and knock-ins. Moreover, it establishes the suitability of the HC-AdV platform for the versatile investigation of prime editing systems. Finally, this thesis establishes causal relationships between specific chromatin states and the activities and fidelities attained by base editing and prime editing complexes in human cells, which has consequences for their further development and optimal deployment. Show less
We first investigate the microscopic working principle of the nanowire superconducting single-photon detectors (SSPDs), and we find that the edge of the nanowire is much more sensitive than the... Show moreWe first investigate the microscopic working principle of the nanowire superconducting single-photon detectors (SSPDs), and we find that the edge of the nanowire is much more sensitive than the central part. The experimental results agree quantitatively with the theory based on a photon-assisted vertex- entry model. We then explore its potential to be used as a probe for near-field detection. Our calculations show that the SSPDs have a much higher signal collection efficiency than the conventional near-field optical microscopy, and that their spacial resolution can reach 20 nm. With photon number resolving ability, a SSPD fabricated on a micro-pillar can be used to investigate the quantum information of the optical near-field at subwavelength scales. Show less
Anicius Manlius Severinus Boethius (480-525 A.D.) is regarded as a great thinker of the early Middle Ages. Indeed, Boethius is a man of immense erudition and his works touch upon many philosophical... Show moreAnicius Manlius Severinus Boethius (480-525 A.D.) is regarded as a great thinker of the early Middle Ages. Indeed, Boethius is a man of immense erudition and his works touch upon many philosophical fields, including mathematics, logic and theology. In Boethius’ classification system, mathematics and theology belong to speculative philosophy, and logic is both a part of philosophy and an instrument of philosophy. However, scholars from different fields tend to focus only on the part of Boethius’ thoughts that relate to their own disciplines. The result is a lack of understanding Boethius as a whole. In my dissertation, I will reassess Boethius’ mathematics and logic, and their roles in philosophy, and on the basis of these, I will explore the connections between mathematics and logic in Boethius and their applications to theological or philosophical topics. However, I will not focus on the applications of al l his mathematical and logical knowledge but only on his basic ideas of arithmetic and music, and basic logic including knowledge of categories, theories of division and definition Show less
