Synthesis of Short Oligonucleotides on a Soluble Support by the Phosphoramidite Method

In the last decades, the chemical synthesis of short oligonucleotides has become an important aspect of study due to the discovery of new functions for nucleic acids such as antisense oligonucleotides (ASOs), aptamers, DNAzymes, microRNA (miRNA) and small interfering RNA (siRNA). The applications in modern therapies and fundamental medicine on the treatment of different cancer diseases, viral infections and genetic disorders has established the necessity to develop scalable methods for their cheaper and easier industrial manufacture. While small scale solid-phase oligonucleotide synthesis is the method of choice in the field, various challenges still remain associated with the production of short DNA and RNA-oligomers in very large quantities. On the other hand, solution phase synthesis of oligonucleotides offers a more predictable scaling-up of the synthesis and is amenable to standard industrial manufacture techniques. In the present thesis, various protocols for the synthesis of short DNA and RNA oligomers have been studied on a peracetylated and methylated β-cyclodextrin, and also on a pentaerythritol-derived support. On using the peracetylated and methylated β-cyclodextrin soluble supports, the coupling cycle was simplified by replacement of the typical 5′-O-(4,4′-dimethoxytrityl) protecting group with an acid-labile acetal-protected 5′-O-(1-methoxy-1-methylethyl) group, which upon acid-catalyzed methanolysis released easily removable volatile products. For this reason monomeric building blocks 5′-O-(1-methoxy-1-methylethyl) 3′-(2-cyano-ethyl-N,N-diisopropylphosphoramidite) were synthesized. Alternatively, on using the precipitative pentaerythritol support, novel 2´-O-(2-cyanoethyl)-5´-O-(1-methoxy-1-methylethyl) protected phosphoramidite building blocks for RNA synthesis have been prepared and their applicability by the synthesis of a pentamer was demonstrated. Similarly, a method for the preparation of short RNAs from commercially available 5´-O-(4,4´-dimethoxytrityl)-2´-O-(tert-butyldimethyl-silyl)ribonucleoside 3´-(2-cyanoethyl-N,N-diisopropylphosphoramidite) building blocks has been developed

Distributed energy resources in an electricity retailer’s short-term profit optimization

Liberalization of electricity markets has resulted in a competed Nordic electricity market, in which electricity retailers play a key role as electricity suppliers, market intermediaries, and service providers. Although these roles may remain unchanged in the near future, the retailers’ operation may change fundamentally as a result of the emerging smart grid environment. Especially the increasing amount of distributed energy resources (DER), and improving opportunities for their control, are reshaping the operating environment of the retailers. This requires that the retailers’ operation models are developed to match the operating environment, in which the active use of DER plays a major role. Electricity retailers have a clientele, and they operate actively in the electricity markets, which makes them a natural market party to offer new services for end-users aiming at an efficient and market-based use of DER. From the retailer’s point of view, the active use of DER can provide means to adapt the operation to meet the challenges posed by the smart grid environment, and to pursue the ultimate objective of the retailer, which is to maximize the profit of operation. This doctoral dissertation introduces a methodology for the comprehensive use of DER in an electricity retailer’s short-term profit optimization that covers operation in a variety of marketplaces including day-ahead, intra-day, and reserve markets. The analysis results provide data of the key profit-making opportunities and the risks associated with different types of DER use. Therefore, the methodology may serve as an efficient tool for an experienced operator in the planning of the optimal market-based DER use. The key contributions of this doctoral dissertation lie in the analysis and development of the model that allows the retailer to benefit from profit-making opportunities brought by the use of DER in different marketplaces, but also to manage the major risks involved in the active use of DER. In addition, the dissertation introduces an analysis of the economic potential of DER control actions in different marketplaces including the day-ahead Elspot market, balancing power market, and the hourly market of Frequency Containment Reserve for Disturbances (FCR-D).