Doctor of Philosophy

dissertationChemical protein synthesis, via solid-phase peptide synthesis and chemoselective ligation of peptides, is a powerful approach for preparing peptides and proteins. These techniques enable complete atomic control over protein composition with both mechanistic and practical applications for biochemistry. The foundation of this dissertation is formed by two ambitious chemical protein synthesis projects: DapA (Chapter 2) and Dpo4 (Chapter 5). DapA is a 312-residue protein whose folding depends on the well-studied chaperone GroEL/ES. The successful synthesis of DapA (in both L- and D- chirality) was used to demonstrate cross-chiral folding by GroEL/ES-a fundamental biological insight and potential tool for future mirror-image synthetic biology research. However, the record-breaking synthesis of DapA was an arduous process requiring tremendous human and technical resources. The lessons from this project were then applied to the synthesis of our next target, Dpo4 (352 residues). Dpo4 is one of the shortest DNA/RNA polymerases, providing an accessible synthetic tool to amplify DNA/RNA for future synthetic biology studies. A new concept termed DOPPEL (Diversity-based Optimization of Peptide Properties to Enhance Ligations) was used to simplify this synthesis. Furthermore, various synthesis strategies and general advice for completing ! ! iv mega-synthesis projects in the future are detailed in this chapter. In both the DapA and Dpo4 projects, one of the most prominent challenges was the handling of poorly soluble peptide segments. These poorly soluble peptides can lead to dramatic yield losses and additional complexities. In the third major synthesis project of this thesis, GroES, we overcame an even greater insolubility challenge. This 97-residue protein could not be synthesized due to extreme solubility challenges with its C-terminal half. In response to this challenge, a new chemical tool was developed to link a solubilizing peptide ("Helping Hand") to the C-terminal half of the protein. Key to this approach is a new synthetic building block, Fmoc-Ddae-OH, which is easy to synthesize, incorporate, and cleanly remove once the solubilizing function is complete. Overall, this dissertation pushes the limits of chemical peptide and protein synthesis, and provides exciting directions for the next wave of biochemists looking to use chemical protein synthesis to study interesting problems and engineering challenges

New Risks Ahead:The Eastward Enlargement of the Eurozone

Eastward enlargement is one of the hot topics in European economics. The accession of central and eastern European Countries (CEEC) into the European Union (EU) is accompanied by an extension of the eurozone to this region. This paper surveys likely outcomes and challenges of this specific feature of EU enlargement. Moreover, the ar-ticle represents the start of an international research project dealing with these ques-tions. Research is structured along different markets. Hence, the impact of an adoption of the euro is analysed for capital and labour markets as well as with respect to exchange rate and monetary policies. Our main position is that the euro has in general beneficiary ef-fects for the CEEC and the current EU in all examined markets. However, these bene-fits evolve mainly in the long run, whereas the short-term costs of adaptation to the new situation may be high. Although we believe that the present value of long-term benefits exceeds these costs, it is by no means clear that policy-makers will share this view. Due to the usual political-economy transformation, the assessment of costs and benefits may be different for politicians than compared to any overall perspective. If of-ficial policies become unforeseeable, so will private behaviour. International investors may reverse their capital flows, draining precious liquidity, and leading to currency and financial crises whenever they perceive the authorities’ commitment to EMU less credi-ble. This article highlights some thinkable mechanisms how any such crisis could evolve. It, thus, sets the agenda for further research, mainly, with the focus on appropriate policy strategies to keep adaptation costs as low as possible, minimise other external risks, without hampering the long-term benefits.EMU, EU enlargement, monetary integration

Transport in a three-terminal graphene quantum dot in the multi-level regime

We investigate transport in a three-terminal graphene quantum dot. All nine elements of the conductance matrix have been independently measured. In the Coulomb blockade regime accurate measurements of individual conductance resonances reveal slightly different resonance energies depending on which pair of leads is used for probing. Rapid changes in the tunneling coupling between the leads and the dot due to localized states in the constrictions has been excluded by tuning the difference in resonance energies using in-plane gates which couple preferentially to individual constrictions. The interpretation of the different resonance energies is then based on the presence of a number of levels in the dot with an energy spacing of the order of the measurement temperature. In this multi-level transport regime the three-terminal device offers the opportunity to sense if the individual levels couple with different strengths to the different leads. This in turn gives qualitative insight into the spatial profile of the corresponding quantum dot wave functions.Comment: 12 pages, 6 figure

Hvorfor vokser trafikken på vores veje?

Fra 2000 - 2015 voksede vejtrafikken i gennemsnit med 1,2 pct. om året, men det er gået langt hurtigere i de sidste par år, hvor der er kommet større afstand til finanskrisen. Det er forventningen, at trafikken også vil vedblive med at stige fremover. Landstrafikmodellens basisprognose lyder på en vækst på 14 pct. i vejtrafikken fra 2015 til 2030. For biltrafikken peges der på økonomi (ofte målt som BNP), befolkningens størrelse og sammensætning, priser på biler og kørselsomkostninger, rejsetider og vejkapacitet, erhvervs- og bystruktur, konkurrerende transportformer, såvel som sociale normer og nye teknologier – som de væsentligste drivkræfter. Mange af disse er dækket af de prognosemodeller der anvendes, mens andre falder uden for. Et overblik over trafikkens drivkræfter er med til at give et udgangspunkt for at forstå og foregribe udviklingen, samt overveje indikatorer, der kan understøtte arbejdet med at planlægge fremtidens infrastruktur og trafik