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Die bedarfsgerechte Versorgung im Alter zukünftig sicherzustellen, gehört zu den entscheidenden Aufgaben unserer Zeit. Der in Deutschland bestehende Fachkräftemangel sowie der demografische Wandel belasten das Pflegesystem in mehrfacher Hinsicht: In einer alternden Gesellschaft sind immer mehr Menschen auf eine anhaltende Unterstützung angewiesen. Niedrige Geburtenraten und damit verbunden ein sinkender Bevölkerungs-anteil von Menschen im erwerbsfähigen Alter bringen einen bereits heute spürbaren Mangel an beruflich Pflegenden mit sich.
Um eine menschenwürdige Pflege anhaltend zu gewährleisten, müssen vorhandene Ressourcen gezielter eingesetzt und zusätzliche Reserven freigelegt werden. Viele Hoffnungen liegen hier auf technologischen Innovationen. Die Digitalisierung soll das Gesundheitswesen effizienter gestalten und beispielsweise durch Künstliche Intelligenz zeitraubende Prozesse vereinfachen oder sogar automatisieren. Im Kontext der Pflege wird der Einsatz von robotischen Assistenzsystemen diskutiert.
Aus diesem Grund wurde die die Potsdamer Bürger:innenkonferenz „Robotik in der Altenpflege?“ initiiert. Um die Zukunft der Pflege gemeinsam zu gestalten, wurden 3.500 Potsdamer Bürgerinnen und Bürger kontaktiert und schließlich fünfundzwanzig Teilnehmende ausgewählt. Im Frühjahr 2024 kamen sie zusammen, um den verantwortlichen Einsatz von Robotik in der Pflege zu diskutieren.
Die hier vorliegende Erklärung ist das Ergebnis der Bürger:innenkonferenz. Sie enthält die zentralen Positionen der Teilnehmenden.
Die Bürger:innenkonferenz ist Teil des Projekts E-cARE („Ethics Guidelines for Socially Assistive Robots in Elderly Care: An Empirical-Participatory Approach“), welches die Juniorprofessur für Medizinische Ethik mit Schwerpunkt auf Digitalisierung der Fakultät für Gesundheitswissenschaften Brandenburg, Universität Potsdam, durchgeführt hat.
Genome-scale metabolic models are mathematical representations of all known reactions occurring in a cell. Combined with constraints based on physiological measurements, these models have been used to accurately predict metabolic fluxes and effects of perturbations (e.g. knock-outs) and to inform metabolic engineering strategies. Recently, protein-constrained models have been shown to increase predictive potential (especially in overflow metabolism), while alleviating the need for measurement of nutrient uptake rates. The resulting modelling frameworks quantify the upkeep cost of a certain metabolic flux as the minimum amount of enzyme required for catalysis. These improvements are based on the use of in vitro turnover numbers or in vivo apparent catalytic rates of enzymes for model parameterization. In this thesis several tools for the estimation and refinement of these parameters based on in vivo proteomics data of Escherichia coli, Saccharomyces cerevisiae, and Chlamydomonas reinhardtii have been developed and applied. The difference between in vitro and in vivo catalytic rate measures for the three microorganisms was systematically analyzed. The results for the facultatively heterotrophic microalga C. reinhardtii considerably expanded the apparent catalytic rate estimates for photosynthetic organisms. Our general finding pointed at a global reduction of enzyme efficiency in heterotrophy compared to other growth scenarios. Independent of the modelled organism, in vivo estimates were shown to improve accuracy of predictions of protein abundances compared to in vitro values for turnover numbers. To further improve the protein abundance predictions, machine learning models were trained that integrate features derived from protein-constrained modelling and codon usage. Combining the two types of features outperformed single feature models and yielded good prediction results without relying on experimental transcriptomic data. The presented work reports valuable advances in the prediction of enzyme allocation in unseen scenarios using protein constrained metabolic models. It marks the first successful application of this modelling framework in the biotechnological important taxon of green microalgae, substantially increasing our knowledge of the enzyme catalytic landscape of phototrophic microorganisms.
During the last decades, therapeutical proteins have risen to great significance in the pharmaceutical industry. As non-human proteins that are introduced into the human body cause a distinct immune system reaction that triggers their rapid clearance, most newly approved protein pharmaceuticals are shielded by modification with synthetic polymers to significantly improve their blood circulation time. All such clinically approved protein-polymer conjugates contain polyethylene glycol (PEG) and its conjugation is denoted as PEGylation. However, many patients develop anti-PEG antibodies which cause a rapid clearance of PEGylated molecules upon repeated administration. Therefore, the search for alternative polymers that can replace PEG in therapeutic applications has become important. In addition, although the blood circulation time is significantly prolonged, the therapeutic activity of some conjugates is decreased compared to the unmodified protein. The reason is that these conjugates are formed by the traditional conjugation method that addresses the protein's lysine side chains. As proteins have many solvent exposed lysines, this results in a somewhat uncontrolled attachment of polymer chains, leading to a mixture of regioisomers, with some of them eventually affecting the therapeutic performance.
This thesis investigates a novel method for ligating macromolecules in a site-specific manner, using enzymatic catalysis. Sortase A is used as the enzyme: It is a well-studied transpeptidase which is able to catalyze the intermolecular ligation of two peptides. This process is commonly referred to as sortase-mediated ligation (SML). SML constitutes an equilibrium reaction, which limits product yield. Two previously reported methods to overcome this major limitation were tested with polymers without using an excessive amount of one reactant.
Specific C- or N-terminal peptide sequences (recognition sequence and nucleophile) as part of the protein are required for SML. The complementary peptide was located at the polymer chain end. Grafting-to was used to avoid damaging the protein during polymerization. To be able to investigate all possible combinations (protein-recognition sequence and nucleophile-protein as well as polymer-recognition sequence and nucleophile-polymer) all necessary building blocks were synthesized. Polymerization via reversible deactivation radical polymerization (RDRP) was used to achieve a narrow molecular weight distribution of the polymers, which is required for therapeutic use.
The synthesis of the polymeric building blocks was started by synthesizing the peptide via automated solid-phase peptide synthesis (SPPS) to avoid post-polymerization attachment and to enable easy adaptation of changes in the peptide sequence. To account for the different functionalities (free N- or C-terminus) required for SML, different linker molecules between resin and peptide were used.
To facilitate purification, the chain transfer agent (CTA) for reversible addition-fragmentation chain-transfer (RAFT) polymerization was coupled to the resin-immobilized recognition sequence peptide. The acrylamide and acrylate-based monomers used in this thesis were chosen for their potential to replace PEG.
Following that, surface-initiated (SI) ATRP and RAFT polymerization were attempted, but failed. As a result, the newly developed method of xanthate-supported photo-iniferter (XPI) RAFT polymerization in solution was used successfully to obtain a library of various peptide-polymer conjugates with different chain lengths and narrow molar mass distributions.
After peptide side chain deprotection, these constructs were used first to ligate two polymers via SML, which was successful but revealed a limit in polymer chain length (max. 100 repeat units). When utilizing equimolar amounts of reactants, the use of Ni2+ ions in combination with a histidine after the recognition sequence to remove the cleaved peptide from the equilibrium maximized product formation with conversions of up to 70 %.
Finally, a model protein and a nanobody with promising properties for therapeutical use were biotechnologically modified to contain the peptide sequences required for SML. Using the model protein for C- or N-terminal SML with various polymers did not result in protein-polymer conjugates. The reason is most likely the lack of accessibility of the protein termini to the enzyme. Using the nanobody for C-terminal SML, on the other hand, was successful. However, a similar polymer chain length limit was observed as in polymer-polymer SML. Furthermore, in case of the synthesis of protein-polymer conjugates, it was more effective to shift the SML equilibrium by using an excess of polymer than by employing the Ni2+ ion strategy.
Overall, the experimental data from this work provides a good foundation for future research in this promising field; however, more research is required to fully understand the potential and limitations of using SML for protein-polymer synthesis. In future, the method explored in this dissertation could prove to be a very versatile pathway to obtain therapeutic protein-polymer conjugates that exhibit high activities and long blood circulation times.
Zum dreißigjährigen Bestehen des Kommunalwissenschaftlichen Instituts an der Universität Potsdam vereint dieser Jubiläumsband kurze Aufsätze von ehemaligen und aktuellen Vorstandsmitgliedern, von Ehrenmitgliedern des Vorstands, langjährigen wissenschaftlichen Mitarbeitern des Instituts und aktuellen wissenschaftlichen Kooperationspartnern. Die insgesamt zwölf Beiträge befassen sich mit den Kommunalwissenschaften und der Geschichte des Kommunalwissenschaftlichen Instituts, mit aktuellen kommunalwissenschaftlichen Fragestellungen und wissenschaftlichen Kooperationen des KWI. Der vom KWI-Vorstand herausgegebene Band soll einen breiten Blick auf 30 Jahre Kommunalwissenschaften in Brandenburg und an der Universität Potsdam werfen und einen Ausblick auf zukünftige kommunalwissenschaftliche Forschung geben.
We analyze how conventional emissions trading schemes (ETS) can be modified by introducing “clean-up certificates” to allow for a phase of net-negative emissions. Clean-up certificates bundle the permission to emit CO2 with the obligation for its removal. We show that demand for such certificates is determined by cost-saving technological progress, the discount rate and the length of the compliance period. Introducing extra clean-up certificates into an existing ETS reduces near-term carbon prices and mitigation efforts. In contrast, substituting ETS allowances with clean-up certificates reduces cumulative emissions without depressing carbon prices or mitigation in the near term. We calibrate our model to the EU ETS and identify reforms where simultaneously (i) ambition levels rise, (ii) climate damages fall, (iii) revenues from carbon prices rise and (iv) carbon prices and aggregate mitigation cost fall. For reducing climate damages, roughly half of the issued clean-up certificates should replace conventional ETS allowances. In the context of the EU ETS, a European Carbon Central Bank could manage the implementation of cleanup certificates and could serve as an enforcement mechanism.
Das Forschungsprojekt „Workflow-Management-Systeme für Open-Access-Hochschulverlage (OA-WFMS)” ist eine Kooperation zwischen der HTWK Leipzig und der Universität Potsdam. Ziel ist es, die Bedarfe von Universitäts- und Hochschulverlagen und Anforderungen an ein Workflow-Management-Systeme (WFMS) zu analysieren, um daraus ein generisches Lastenheft zu erstellen. Das WFMS soll den Publikationsprozess in OA-Verlagen erleichtern, beschleunigen sowie die Verbreitung von Open Access und das nachhaltige, digitale wissenschaftliche Publizieren fördern.
Das Projekt baut auf den Ergebnissen der Projekte „Open-Access-Hochschulverlag (OA-HVerlag)“ und „Open-Access-Strukturierte-Kommunikation (OA-STRUKTKOMM)“ auf. Der diesem Bericht zugrunde liegende Auftaktworkshop fand 2024 in Leipzig mit Vertreter:innen von zehn Institutionen statt. Der Workshop diente dazu, Herausforderungen und Anforderungen an ein WFMS zu ermitteln sowie bestehende Lösungsansätze und Tools zu diskutieren.
Im Workshop wurden folgende Fragen behandelt:
a. Wie kann die Organisation und Überwachung von Publikationsprozessen in wissenschaftlichen Verlagen durch ein WFMS effizient gestaltet werden?
b. Welche Anforderungen muss ein WFMS erfüllen, um Publikationsprozesse optimal zu unterstützen?
c. Welche Schnittstellen müssen berücksichtigt werden, um die Interoperabilität der Systeme zu garantieren?
d. Welche bestehenden Lösungsansätze und Tools sind bereits im Einsatz und welche Vor- und Nachteile haben diese?
Der Workshop gliederte sich in zwei Teile : Teil 1 behandelte Herausforderungen und Anforderungen (Fragen a. bis c.), Teil 2 bestehende Lösungen und Tools (Frage d.). Die Ergebnisse des Workshops fließen in die Bedarfsanalyse des Forschungsprojekts ein.
Die im Bericht dokumentierten Ergebnisse zeigen die Vielzahl der Herausforderungen der bestehenden Ansätze bezüglich des OA-Publikationsmanagements . Die Herausforderungen zeigen sich insbesondere bei der Systemheterogenität, den individuellen Anpassungsbedarfen und der Notwendigkeit der systematischen Dokumentation. Die eingesetzten Unterstützungssysteme und Tools wie Dateiablagen, Projektmanagement- und Kommunikationstools können insgesamt den Anforderungen nicht genügen, für Teillösungen sind sie jedoch nutzbar. Deshalb muss die Integration bestehender Systeme in ein zu entwickelndes OA-WFMS in Betracht gezogen und die Interoperabilität der miteinander interagierenden Systeme gewährleistet werden. Die Beteiligten des Workshops waren sich einig, dass das OA-WFMS flexibel und modular aufgebaut werden soll. Einer konsortialen Softwareentwicklung und einem gemeinsamen Betrieb im Verbund wurde der Vorrang gegeben.
Der Workshop lieferte wertvolle Einblicke in die Arbeit der Hochschulverlage und bildet somit eine solide Grundlage für die in Folge zu erarbeitende weitere Bedarfsanalyse und die Erstellung des generischen Lastenheftes.
We study the effect of energy and transport policies on pollution in two developing country cities. We use a quantitative equilibrium model with choice of housing, energy use, residential location, transport mode, and energy technology. Pollution comes from commuting and residential energy use. The model parameters are calibrated to replicate key variables for two developing country cities, Maputo, Mozambique, and Yogyakarta, Indonesia. In the counterfactual simulations, we study how various transport and energy policies affect equilibrium pollution. Policies may be induce rebound effects from increasing residential energy use or switching to high emission modes or locations. In general, these rebound effects tend to be largest for subsidies to public transport or modern residential energy technology.
We examine how the gender of business-owners is related to the wages paid to female relative to male employees working in their firms. Using Finnish register data and employing firm fixed effects, we find that the gender pay gap is – starting from a gender pay gap of 11 to 12 percent - two to three percentage-points lower for hourly wages in female-owned firms than in male-owned firms. Results are robust to how the wage is measured, as well as to various further robustness checks. More importantly, we find substantial differences between industries. While, for instance, in the manufacturing sector, the gender of the owner plays no role for the gender pay gap, in several service sector industries, like ICT or business services, no or a negligible gender pay gap can be found, but only when firms are led by female business owners. Businesses in male ownership maintain a gender pay gap of around 10 percent also in the latter industries. With increasing firm size, the influence of the gender of the owner, however, fades. In large firms, it seems that others – firm managers – determine wages and no differences in the pay gap are observed between male- and female-owned firms.
The Arctic is the hot spot of the ongoing, global climate change. Over the last decades, near-surface temperatures in the Arctic have been rising almost four times faster than on global average. This amplified warming of the Arctic and the associated rapid changes of its environment are largely influenced by interactions between individual components of the Arctic climate system. On daily to weekly time scales, storms can have major impacts on the Arctic sea-ice cover and are thus an important part of these interactions within the Arctic climate. The sea-ice impacts of storms are related to high wind speeds, which enhance the drift and deformation of sea ice, as well as to changes in the surface energy budget in association with air mass advection, which impact the seasonal sea-ice growth and melt.
The occurrence of storms in the Arctic is typically associated with the passage of transient cyclones. Even though the above described mechanisms how storms/cyclones impact the Arctic sea ice are in principal known, there is a lack of statistical quantification of these effects. In accordance with that, the overarching objective of this thesis is to statistically quantify cyclone impacts on sea-ice concentration (SIC) in the Atlantic Arctic Ocean over the last four decades. In order to further advance the understanding of the related mechanisms, an additional objective is to separate dynamic and thermodynamic cyclone impacts on sea ice and assess their relative importance. Finally, this thesis aims to quantify recent changes in cyclone impacts on SIC. These research objectives are tackled utilizing various data sets, including atmospheric and oceanic reanalysis data as well as a coupled model simulation and a cyclone tracking algorithm.
Results from this thesis demonstrate that cyclones are significantly impacting SIC in the Atlantic Arctic Ocean from autumn to spring, while there are mostly no significant impacts in summer. The strength and the sign (SIC decreasing or SIC increasing) of the cyclone impacts strongly depends on the considered daily time scale and the region of the Atlantic Arctic Ocean. Specifically, an initial decrease in SIC (day -3 to day 0 relative to the cyclone) is found in the Greenland, Barents and Kara Seas, while SIC increases following cyclones (day 0 to day 5 relative to the cyclone) are mostly limited to the Barents and Kara Seas.
For the cold season, this results in a pronounced regional difference between overall (day -3 to day 5 relative to the cyclone) SIC-decreasing cyclone impacts in the Greenland Sea and overall SIC-increasing cyclone impacts in the Barents and Kara Seas. A cyclone case study based on a coupled model simulation indicates that both dynamic and thermodynamic mechanisms contribute to cyclone impacts on sea ice in winter. A typical pattern consisting of an initial dominance of dynamic sea-ice changes followed by enhanced thermodynamic ice growth after the cyclone passage was found. This enhanced ice growth after the cyclone passage most likely also explains the (statistical) overall SIC-increasing effects of cyclones in the Barents and Kara Seas in the cold season.
Significant changes in cyclone impacts on SIC over the last four decades have emerged throughout the year. These recent changes are strongly varying from region to region and month to month. The strongest trends in cyclone impacts on SIC are found in autumn in the Barents and Kara Seas. Here, the magnitude of destructive cyclone impacts on SIC has approximately doubled over the last four decades. The SIC-increasing effects following the cyclone passage have particularly weakened in the Barents Sea in autumn. As a consequence, previously existing overall SIC-increasing cyclone impacts in this region in autumn have recently disappeared. Generally, results from this thesis show that changes in the state of the sea-ice cover (decrease in mean sea-ice concentration and thickness) and near-surface air temperature are most important for changed cyclone impacts on SIC, while changes in cyclone properties (i.e. intensity) do not play a significant role.