Decarbonizing the building stock is critical for realizing the climate-neutral target for the Netherlands. This thesis uses multi-source data, mainly including GIS data of building footprints and... Show moreDecarbonizing the building stock is critical for realizing the climate-neutral target for the Netherlands. This thesis uses multi-source data, mainly including GIS data of building footprints and the archetypes representative of Dutch residential buildings, to develop a series of bottom-up building stock models to track future material stock and flows, energy demand, electricity generation, and GHG emissions. Results demonstrate the great potential for decarbonizing the Dutch residential building sector, while decarbonization strategies should be effectively and extensively implemented. Saving space heating energy consumption is the most direct way to reduce annual GHG emissions. Considering that most existing residential buildings will still be in use in 2050, renovating them with high energy performance standards is required. Despite the great potential of renovation, it alone is not enough to realize the climate-neutral target in the residential building stock because the upstream fossil fuel-based energy systems still emit large amounts of GHG. Replacing fossil fuels with renewable energy sources is a critical path, mainly involving onsite natural gas combustion for space heating and offsite natural gas and coal combustion for electricity and heat (in heat networks) generation. Urban mining cannot contribute to as much GHG emission reduction as energy transition strategies, though, should still be implemented as it can reduce the primary material consumption and CDW landfill. In addition to the technical aspects considered in this thesis, it is also necessary to develop feasible policies in terms of socioeconomic aspects to guarantee the effective and quick deployment of these technical strategies. Show less
Most small-molecule drugs are designed to interact with their biological targets under equilibrium binding conditions, whereby the desired drug-protein interaction is a rapid and reversible (non... Show moreMost small-molecule drugs are designed to interact with their biological targets under equilibrium binding conditions, whereby the desired drug-protein interaction is a rapid and reversible (non-covalent) process. As an extension to maximizing the strength of these noncovalent molecular interactions, a less conventional strategy termed ‘covalent interactions’ has recently gained reputation in the field of drug discovery. In this thesis a covalent strategy is applied and shown to be compatible with a target-directed, structure-guided discovery paradigm, with a focus on adenosine receptors as drug targets. The development and application of chemical tools and strategies are described to study three subtypes of ARs, A1R, A2AR and A3R. We set up a work flow of in vitro pharmacological assays as a robust tool for measuring and quantifying covalent modulation. Besides, we developed affinity-based probes, which allow monitoring of GPCR expression in cell fragments. Combined, this research approach may ultimately aid in the discovery and development of novel adenosine receptor-based therapeutics that lack potential side effects as much as possible. Show less
