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Phosphatidylinositol (PI)regulating enzymes are frequently altered in cancer and have become a focus for drug development. Here, we explore the phosphatidylinositol-5-phosphate 4-kinases (PI5P4K), a family of lipid kinases that regulate pools of intracellular PI, and demonstrate that the PI5P4Kα isoform influences androgen receptor (AR) signaling, which supports prostate cancer (PCa) cell survival. The regulation of PI becomes increasingly important in the setting of metabolic stress adaptation of PCa during androgen deprivation (AD), as we show that AD influences PI abundance and enhances intracellular pools of PI-4,5-P 2 . We suggest that this PI5P4Kα-AR relationship is mitigated through mTORC1 dysregulation and show that PI5P4Kα colocalizes to the lysosome, the intracellular site of mTORC1 complex activation. Notably, this relationship becomes prominent in mouse prostate tissue following surgical castration. Finally, multiple PCa cell models demonstrate marked survival vulnerability following stable PI5P4Kα inhibition. These results nominate PI5P4Kα as a target to disrupt PCa metabolic adaptation to castrate resistance.

With the ratification of the Paris Agreement, Switzerland among many other countries, declared their ambition to limit global warming well below 2 °C, aiming for 1.5 °C. The increase in global temperature results from accumulated CO2 emissions in the atmosphere. There exist only a certain amount - a budget - of additional tolerable CO2 until we reach 1.5 °C. The governments need to quickly implement measures to reduce fossil CO2 emissions, also for passenger car transportation. The challenge to decarbonize passenger cars lies in the complexity of the system. Mobility is essential for a prosperous economy and cannot be eradicated. At the same time, different propulsion technologies exist, each with their advantages and limitations. Currently, there exists no single technology that unites all the benefits. Furthermore, the policy on vehicle emission limits relies on laboratory test values, but on-road emissions differ significantly. The assessment of the CO2 reduction of such a policy is not straight forward. This thesis presents a systematic approach to decarbonize passenger cars on the example of Switzerland. It spans the arc from the initial decarbonization intention to the exploration and quantification of different reduction measures. The ultimate results are possible strategies to achieve the set climate goals. The methodology is data-driven. The information for the modeling of propulsion technologies stems from an extensive measurement campaign designed to analyze real-world vehicle energy demand. Multiple cars of different technologies were monitored for two years on the road and simultaneously measured on a dynamometer test bench. The description of representative vehicle usage is based on national travel surveys and maintenance logs of a large car retailer. National vehicle register data builds the foundation to describe the fleet composition and substitution rate. The text underlines the relevance of new propulsion technologies, as the only measure to lead to zero CO2 emissions. However, we cannot rely on legislative vehicle emission values to asses effective emissions of conventional technologies and demanded electricity for pluggable cars, as they differ for on-road operation. The thesis presents an energy demand estimation tool to account for the discrepancy in on-road operation. The work further explores CO2 optimal technology solutions depending on the setup of the energy supply sector and daily travel distances. These analyses serve as bases to assess national reduction potentials, which account for technological feasibility to supply individual transportation demand. These explorations represent desirable, future solutions for strategic planning. In the last step, the thesis addresses the transformation timescales and strategies of the existing fleet. To remain within the 1.5 °C carbon budget, the thesis presents three paths. They all base on a penetration scenario of battery-electric cars and differ in the exploitation of non-battery electric technology and the deployment of renewable e-fuels. For Switzerland and the European Union, the electrification of passenger cars always results in a CO2 reduction. More than 80 % of the daily trips (but less concerning kilometer performance) can be covered by a small battery capacity vehicle like a plug-in hybrid. The additional electricity demand for the electrification of the entire fleet corresponds to about 35 % of today’s fuel energy content. Hydrogen is not needed for passenger cars and thus not considered in the decarbonization strategies. Current emission limits are not compatible with the 1.5 °C climate goal. To reach the target, the average emission of the new vehicles have to follow a linear decrease and reach zero by 2030. Unless we achieve a 100 % ramp-up in battery electric vehicles by 2030, synthetic, renewable e-fuels are crucial to staying within the CO2 budget. For a given ramp-up in battery electric vehicles, the necessary amount of e-fuels depends on the sold non-battery electric technology. The promotion of hybrid technologies, but also improvements in vehicle design bring the advantage of significantly reducing the peak demand of e-fuels and delaying their need for deployment. Thereby, they reduce the stress on infrastructure and fuel supply in the transformation period to a full-electric fleet and should be promoted.

Ambitions to mitigate climate change, increase the pressure to reduce greenhouse gas (GHG) emissions across all sectors of the economy, with significant implications for the energy landscape as well as other emissions sources. Switzerland has committed to reducing its annual direct emissions of GHG by 50% by 2030 compared to 1990. A major share of this reduction shall be achieved domestically while some emissions can be based on measures abroad through the use of international credits. The Swiss government has also formulated the long-term goal to reduce GHG emissions in 2050 by 70-85% compared to 1990 levels (including measures abroad), and to achieve climate neutrality after 2050. Today, domestic GHG emissions in Switzerland originate by about 60% from energy conversion in the transport and building sectors, and by 40 % from other sources including industry. Carbondioxide (CO2) is the major GHG that is emitted with the transport sector being the sector with largest contribution. Given this distribution of GHG emissions, particularly CO2 emissions in the demand sectors attributable to energy conversion and industrial production processes need to be avoided to achieve the climate goals. As of 2017, the Swiss electricity sector is already almost CO2-free as electricity is mainly generated from hydropower (60%), nuclear (32%) renewable and non-renewable combustible energy (5%) and other renewable energy (4%). Future pathways for the developments of the Swiss energy sector are framed by the Swiss Energy Strategy 2050, which aims at discontinuing energy supply from nuclear power plants in Switzerland, and promoting renewable energy and energy efficiency. The transformation of the Swiss energy economy calls for the deployment of new low-carbon energy solutions while maintaining the high level of energy supply reliability, which in particular applies to the electricity sector. One option to provide low-carbon energy services is an increased electrification of energy demand services while using low-carbon generation sources. Against the background of a growing share of variable renewable energy sources in the electricity mix, such as wind and solar energy, the challenges of temporal and spatial balancing of supply and demand is expected to increase in future. Temporal balancing arises due to the inevitable mismatch between renewable electricity production and demand as a consequence of day/night cycles, weather effects and seasonal differences, while spatial balancing is resulting from differences between the locations of electricity production and consumption. A future Swiss energy supply substantially relying on large shares of intermittent electricity generation (mainly photovoltaics and wind power) will need sufficient flexibility options. These must allow for shifting energy between day and night as well as from summer to winter: roof-top PV installations, which exhibit the largest potential for new renewable electricity generation in Switzerland by far, show a distinct seasonal peak in summer and daily peak at noon. These peaks in electricity generation – if not to be curtailed – must either be stored and re-used as electricity at times without sufficient generation, or transformed into other energy carriers such as gases and liquids, which can be used as e.g. transport or heating fuels. In addition to the flexible power plants operated in Switzerland already today, i.e. dam hydro plants and pump storage power plants, increasing the system’s flexibility and installing of further flexible power plants and storages becomes inevitable at very high shares of wind and solar PV electricity production in order to operate the electricity system cost-efficiently and to ensure the system’s secure operation. A related aspect concerning flexibility options is their location in the system, which, preferably, is close to the Solar-PV generation sites which are often embedded in the consumption centres. There are multiple technologies and measures to avoid CO2 emissions and to increase the energy system’s flexibility with Power-to-X (P2X) technologies representing one possible option of the technology portfolio. As defined in this White Paper, the terminology “P2X” refers to a class of technologies that use an electro-chemical process to convert electricity into a gaseous or liquid energy carrier or chemical product (and vice versa), and which may include energy storage. As such, P2X technology not only offers the possibility of enhanced sector coupling between the power sector and energy demand sectors but also to provide short and long-term supply and demand balancing. The objective of the White Paper its supplementary report is to collect the major existing P2X knowledge and to provide a synthesis and evaluation for the Swiss energy market. With the aim to derive a technical, economic and environmental assessment of P2X in the energy system, the gas market, the mobility sector and the electricity market are specifically investigated. Where possible, the White Paper also provides information on applications of P2X technologies in production industries. P2X technology stands for a cluster of technologies which use electricity and other inputs in order to produce other secondary energy carriers. Hence, P2X comprises multiple conversion pathways and energy carriers. In this White Paper we focus on the conversion to hydrogen as well as further gaseous and liquid energy carriers, such as methane, methanol, OME and FT-diesel, as well as the reelectrification where appropriate. For industrial P2X applications further energy carriers/conversion pathways might be included (depending on available information). Since this White Paper focusses on P2X technologies based on chemical conversion processes, technologies for the conversion of electricity with the purpose to produce heat as target product is not in the scope of this White Paper. The White Paper on Power-to-X Technology and its supplementary report emanate from the corresponding project of the Joint Activity of five Swiss Competence Centers for Energy Research (SCCER) funded by Innosuisse with complementary funding from the Swiss Federal Office of Energy (SFOE).

Mobility patterns define the energy demand of passengers, respectively of the used vehicles. The daily and annual distribution of those patterns are of particular relevance to electric mobility; they define both the daily peak charging power demand and the overall need for additional electricity generation capacity. These are crucial inputs for life cycle assessments and energy research in general. A common approach to describe mobility patterns on a national level is to categorize a limited amount of personal mobility information (e.g. microcensus) and extrapolate it onto the whole population. The quality of the mobility behaviour distribution is highly dependent on the size and quality of the sample data. We present a comparison of two different approaches for describing the vehicle annual mileage. To that end, we analyse the distribution of mileage with data collected at different scales, i.e. daily resolved data from microcensus and yearly resolved data from maintenance logs. We conclude with a discussion on the potential complementarity of both approaches to gain further insights into individual mobility.

Estimations of the future mobility demand are highly valuable for policymakers, transportation planners, and the automotive industry. Knowing mobility patterns allows for targeted and optimized decarbonization of the transport sector. This work provides a model order reduction approach for clustering mobility demand according to characteristic population groups that share similar travel behavior. Using Swiss household travel survey data and machine learning algorithms, the methodology developed in this paper allows for extrapolating future mobility demand based on socio-demographic information.

We present a method to simulate the charging (and battery swapping) energy demand of electrified trucks, and apply it to the example of Switzerland. We describe the daily mobility behavior of the Swiss fleet throughout a year, using governmental data sources. Based on this, we calculate the energy demand of each vehicle using vehicle and powertrain simulation. This then flows into a discrete event simulation, which we use to derive time-resolved charging power and battery swapping profiles. From that, we draw conclusions about the number of required swapping stations (respectively the average waiting time if there are not enough stations) and electrical loads they have to bear. We saw that, with better batteries and a maximum of three battery swaps per day, over 95% of heavy-duty vehicles can be electrified. This does not mean that every vehicle swaps its battery three times per day, and therefore the amount of extra batteries needed is not large. Nevertheless, to minimize the time loss for swapping, an adequate number and vehicle throughput of swapping stations should be guaranteed. For instance, to keep the waiting time under half an hour a day (duration of lunch break), a minimum of two swapping stations per large motorway fuel station and a throughput of at least eighteen vehicles per hour (per station) would be needed in Switzerland.

Energie für unser Europa: 14. Symposium Energieinnovation (EnInnov 2016), ISBN:978-3-85125-449-5, ISBN:978-3-85125-448-8, ISBN:978-3-85125-447-1