Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
Kölner UniversitätsPublikationsServerNot a member yet
25460 research outputs found
Sort by
Economic Essays on the Energy Transition
No full textThis dissertation contributes to the debate on how to achieve a cost-efficient energy transition in Germany. It explores open questions related to coordination issues in electricity grids and markets, and the decarbonization of residential heating. It consists of four papers, each addressing a distinct aspect of the energy transition:
Chapter 2 analyzes coordination issues in a power system with a high share of renewables and spatial imbalances that lead to transmission grid congestion. Using both a theoretical benchmark (nodal pricing) and a numerical partial‐equilibrium model of Germany’s grid, it shows that under uniform pricing randomly sited batteries incur a 9.3 % cost premium versus the theoretical first-best nodal pricing benchmark, while optimal siting (south of the north–south bottleneck, near solar) narrows this to 8.6 %. Simple policy rules (e.g. solar-tied siting or targeted site auctions) could potentially recover most of the theoretical gain.
Chapter 3 examines static welfare effects of splitting the German bidding zone under fricitions in flow-based market coupling and redispatch. In a 2030 scenario, a two-zone split yields a 1.6 % welfare loss, whereas a three-zone split delivers a 4.4 % gain. Both options, however, entail higher consumer costs and subsidy expenditures, and results are sensitive to assumptions on redispatch frictions and the scenario.
To tackle climate change, residential heating must become climate-neutral. Which technologies have the potential to achieve this goal in a cost-efficient manner is a complex question, given the heterogeneity of buildings and existing infrastructure, as well as the uncertainty regarding future energy prices and infrastructure costs. Chapter 4 compares levelized costs of eleven decentralized and centralized heating technologies across a wide range of input parameters. It finds that heat pumps dominate most scenarios—decentralized in rural areas, district heat in urban settings—while hydrogen boilers and synthetic methane compete only under very low fuel-price assumptions. These findings are highly relevant for the ongoing municipal heat planning process.
Chapter 4 uses a building-level mixed‐integer model to assess how subsidies, renewable mandates, and CO₂ pricing shape household investments in decentralized energy technologies across a representative German stock. Under renewable energy requirements, subsidies, CO2 pricing, high medium-term gas prices, and moderate electricity price increases, many buildings switch early to heat pumps and benefit from subsidies. At the same time, buildings with recently installed gas or oil systems, or single-story systems face high costs—highlighting significant distributional effects of the energy transition.
Across these four chapters, the dissertation demonstrates that refining price signals and potentially complementing them with well-targeted policy instruments is essential to guide investment and dispatch decisions toward a least-cost, equitable German energy transition
Examining Farnesyltransferase Interaction With Cell‐Permeable CaaX Peptides and the Role of the CaaX Motif in Biological Activity
No full textRecently, we presented cell‐permeable CaaX peptides as versatile tools to study intracellular prenylation of proteins. These peptides consist of a cell‐penetrating peptide (CPP) and a C ‐terminal CaaX motif derived from Ras proteins and demonstrated high cellular accumulation and the ability to influence Ras signaling in cancerous cells. Here, we aimed to gain a deeper insight into how such cell‐permeable CaaX peptides, particularly the KRas4B‐derived CaaX‐1 peptide, interact with farnesyltransferase (FTase) and likely influence further intracellular processes. We show that CaaX‐1 is farnesylated by FTase ex cellulo and that an intact CaaX motif is required for modification. A competition experiment revealed a slower farnesylation of CaaX‐1 by FTase compared to a CaaX motif‐containing control peptide. CaaX‐1 inhibited farnesylation of this control peptide at considerably lower concentrations; thus, a higher affinity for FTase is hypothesized. Notably, AlphaFold3 not only predicted interactions between CaaX‐1 and FTase but also suggested interactions between the peptide and geranylgeranyltransferase type I. This finding encourages further investigation, as cross‐prenylation is a well‐known drawback of FTase inhibitors. Our results are further evidence for the usefulness of CaaX peptides as tools to study and manipulate the prenylation of proteins. They offer real potential for the development of novel inhibitors targeting the prenylation pathway
Modelling the impact of environmental and social determinants on mental health using generative agents
No full textMental health is shaped by socio-environmental determinants, yet traditional research approaches struggle to capture their complex interactions. This review explores the potential of generative agents, powered by large language models, to simulate human-like behaviour in virtual environments for mental health research. We outline potential applications including the modelling of adverse life events, urbanicity, climate change, discuss potential challenges and describe how generative agents could transform mental health research
Einfluss des Alters auf die Krankenhausletalität nach aortokoronarer Bypass-Operation bei Patienten mit akutem Koronarsyndrom
No full textEinführung:
Die aortokoronare Bypass-Operation (CABG) wird routinemäßig zur Behandlung von Patienten mit koronarer Herzkrankheit (KHK) durchgeführt. Besonders bei KHK-Patienten mit akutem Koronarsyndrom (ACS) ist die chirurgische Myokardrevaskularisation weiterhin ein zentraler Bestandteil der möglichen Therapiestrategien. Die perioperative Morbidität und Mortalität von bypassoperierten Patienten wird durch zahlreiche Faktoren beeinflusst. Eine
möglicher Einflussfaktor für den Erfolg einer Operation, der zunehmend in unserer alternden Gesellschaft an Bedeutung gewinnt, ist das Alter der Patienten. Die Frage, inwieweit das Alter die Krankenhausletalität nach einer CABG bei Patienten mit ACS beeinflusst, hat eine hohe klinische Relevanz und ist derzeit wenig erforscht. Ältere Patienten zeigen häufig ein höheres Risiko für schwerwiegende perioperative Komplikationen nach Herzoperationen aufgrund von altersbedingten Begleiterkrankungen und dem Vorliegen von mehreren Systemerkrankungen.
Aus diesem Grund ist eine differenzierte perioperative Risikobewertung älterer Patienten mit ACS von entscheidender Bedeutung, um das optimale Therapieverfahren für dieses Hochrisiko-Kollektiv zu identifizieren.
Zielsetzung und Methodik:
Das Ziel dieser monozentrischen, retrospektiven Studie ist es, den Einfluss des Alters auf die perioperative Morbidität und Krankenhausletalität nach aortokoronarer Bypass-Operation bei Patienten mit ACS zu analysieren. Dabei wurden relevante prä-, intra- und postoperativen Merkmale in verschiedenen Altersgruppen (Gruppe 1: bis 65 Jahre; Gruppe 2: 66-79 Jahre, Gruppe 3: 80 Jahre oder älter) miteinander verglichen, um mögliche Risikofaktoren für eine
erhöhte perioperative Komplikationsrate zu identifizieren. Als übergeordneter klinischer Endpunkt wurde die Mortalität im Krankenhaus definiert und eine Regressionsanalyse zur Bestimmung von unabhängigen Prädiktoren, inklusive des Patientenalters, durchgeführt. Dies erfolgte über die retrospektive Analyse von insgesamt 1064 Patienten, die im Zeitraum zwischen Januar 2010 und Dezember 2016 an der Klinik für Herz- und Thoraxchirurgie des Universitätsklinikums Köln, aufgrund eines ACS eine Bypass-Operation erhalten haben. Die statistische Analyse erfolgte mittels SPSS, wobei relevante prä-, intra- und postoperative
Parameter univariat verglichen wurden. Zur Identifikation unabhängiger Prädiktoren für die perioperative Mortalität und für das Auftreten von schwerwiegenden Komplikationen wurde eine multivariate logistische Regressionsanalyse durchgeführt.
Ergebnisse und Diskussion
Die Altersgruppenverteilung des untersuchten Kollektivs zeigte, dass 37,6 % der Patienten der Gruppe 1 (≤65 Jahre) angehörten – also dem jüngsten Drittel mit vergleichsweise geringerer Komorbiditätslast –, während 53,7 % der Patienten in Gruppe 2 (66–79 Jahre) und 8,7 % in Gruppe 3 (≥80 Jahre) fielen. Das Durchschnittsalter des gesamten Patientenkollektivs betrug 67±11 Jahre, mit einem Anteil von 77,8 % männlicher Patienten. Häufige Begleiterkrankungen
waren arterielle Hypertonie (83,7%), Hyperlipidämie (47,7%) und ein Diabetes mellitus (31,9%). Die meisten Patienten litten an einer Dreigefäßerkrankung (78,8%) und circa die Hälfte (49,9%) hatten einen NSTEMI. Patienten über 80 Jahre hatten häufiger einen NSTEMI, eine koronare Dreigefäßerkrankung, eine Hauptstammstenose, einen Diabetes, ein Vorhofflimmern, einen Schlaganfall, eine periphere arterielle Verschlusskrankheit (pAVK) und einen höheren präoperativen Kreatininwert. Mit steigendem Alter war eine häufigere Gabe von Betablockern präoperativ zu beobachten, während Statine und ASS altersunabhängig
eingesetzt wurden. Die Operation wurde bei älteren Patienten seltener als OPCAB durchgeführt und es wurden mehr venöse Grafts verwendet. Mit steigendem Alter erhöhte sich die postoperative Reintubationsrate, die Dauer einer postoperativen Katecholamintherapie und die Notwendigkeit für eine Dialyse. Die Krankenhausletalität war in der ältesten Patientengruppe (≥80 Jahre) 20,4% und somit signifikant höher als in den beiden anderen Gruppen. Die Rate der schwerwiegenden Komplikationen (MACCE) war ebenfalls in der ältesten Patientengruppe mit 31,2% deutlich höher im Vergleich zu den beiden jüngeren Altersgruppen. Als unabhängiger Prädiktor für die Krankenhausletalität wurden das Alter (≥80 Jahre; OR: 2,59; 95%-KI: 1,32-5,10; p=0,006), der Einsatz von Katecholaminen (OR: 4,22; 95%-KI: 2,27-7,85; p<0,001), das Vorliegen einer pAVK (OR: 2,07; 95%-KI: 1,14-3,74; p=0,017) und Niereninsuffizienz (CKD-EPI Grad III-IV; OR: 1,73; 95%-KI: 1,02-2,93; p=0,043) identifiziert.
Für das Auftreten von schwerwiegenden kardiozerebralen Komplikationen (MACCE) waren eine Reanimation (OR: 2,04; 95%-KI: 1,16-3,60; p=0,014), der Einsatz von Katecholaminen (OR: 5,85; 95%-KI: 3,57-9,57; p<0,001), eine pAVK (OR: 1,85; 95%-KI: 1,16-2,97; p=0,010) und eine Niereninsuffizienz (CKD-EPI Grad III-IV; OR: 1,69; 95%-KI: 1,15-2,47; p=0,007) signifikant unabhängige Prädiktoren.
Die Ergebnisse unserer retrospektiven Analyse zeigen, dass das Alter ein entscheidender Prädiktor für die Krankenhausletalität nach einer Bypass-Operation bei Patienten mit akutem Koronarsyndrom ist, insbesondere bei Patienten ≥80 Jahren. Die höhere Mortalität in dieser Altersgruppe ist aufgrund von begleitenden Komorbiditäten zu erklären. Patienten ≥80 Jahren hatten häufiger einen NSTEMI und eine koronare Dreigefäßerkrankung. Die älteste Patientenkohorte wies eine signifikant höhere Rate an präoperativen Begleiterkrankungen wie Diabetes mellitus und Vorhofflimmern auf. Zusammenfassend könnten wir in unserer retrospektiven Analyse demonstrieren, dass bei Patienten mit ACS mit Indikation zur Bypass-Operation das Patientenalter (≥80 Jahre) ein unabhängiger Prädiktor für eine erhöhte Krankenhausletalität ist. Insgesamt ist eine aortokoronare Bypass-Operation aufgrund eines ACS in diesem Hochrisiko-Patientenkollektiv mit einer 20,2% Mortalität und 31,2% MACCE Rate vergesellschaftet. Interessanterweise
zeigte das Alter jedoch keinen signifikanten Einfluss auf das Auftreten von MACCE. Neben dem Alter müssen weitere Risikofaktoren wie unter anderem eine pAVK und eine Niereninsuffizienz bei der präoperativen Risikostratifizierung berücksichtigt werden
Catalytic Asymmetric Reduction of Alkenes
No full textOver the past two decades, organocatalytic asymmetric transfer hydrogenation of alkenes has seen significant advances. Inspired by enzymes, chemists have developed catalytic strategies that employ small organic chiral molecules as catalysts and biomimetic dihydrogen donors as reducing agents, to achieve high levels of enantioselectivity. Beyond classical steric and electronic effects, it is now well recognized that noncovalent interactions, such as hydrogen bonding, ion pairing and London dispersion, play a decisive role in determining reactivity and selectivity. This understanding has opened new avenues for rational catalyst design in asymmetric transfer hydrogenation reactions.
The first part of this dissertation investigates the first report of asymmetric counteranion-directed catalysis (ACDC) describing the transfer hydrogenation of α,β-unsaturated aldehydes. Particular emphasis is placed on the role of noncovalent interactions, especially London dispersion, in governing stereocontrol. Computational studies revealed that an isopropyl group in the reducing agent engages in key dispersion interactions, contributing significantly to enantioselectivity. Building on this insight, a second-generation catalyst was designed, incorporating analogous dispersion energy donors into the catalyst scaffold. This modified system overcame limitations of the original, and mechanistic analysis confirmed that the enhanced enantioselectivity resulted directly from intended dispersion interactions.
The second part of this work focuses on the development of an enantioselective reduction of α-alkyl styrenes. While activated alkenes such as enals, enones, nitroolefins, and α-(2-hydroxyphenyl) styrenes can be reduced enantioselectively using established organocatalytic methods, analogous asymmetric transformations of less functionalized substrates remain underdeveloped. Here, a Brønsted acid-catalyzed, chemo- and enantioselective ionic hydrogenation of α-alkyl styrenes was established using silanes in combination with benzoic acid. Mechanistic investigations support a pathway proceeding via a stabilized carbocation intermediate and a transient silylated catalyst species, with catalyst turnover dependent on the presence of a protic additive. Density functional theory highlights key noncovalent interactions, including cation–π interactions, that govern enantioselectivity
Proteomic characterization of MET-amplified esophageal adenocarcinomas reveals enrichment of alternative splicing- and androgen signaling-related proteins
No full text[Article No. 112] Background: Esophageal adenocarcinomas (EACs) represent an evolving tumor entity with high mortality rates. MET amplification is a recurrent driver in EACs and is associated with decreased patient survival. However, the response to MET inhibitors is limited. Recent studies have identified several mechanisms that lead to resistance against MET inhibitors in different tumor entities. Nonetheless, a characterization of additional vulnerable targets beyond MET has not been conducted in MET-amplified EACs. Methods: In this study, we determined the MET amplification status in a cohort of more than 900 EACs using fluorescence in situ hybridization (FISH) and compared the proteomes of MET-amplified ( n = 20) versus non-amplified tumors ( n = 39) by mass spectrometry. Results: We identified a phenotype, present in almost all MET-amplified tumors, which shows an enrichment of alternative RNA splicing, and androgen receptor signaling proteins, as well as decreased patient survival. Additionally, our analyses revealed a negative correlation between MET expression and patient survival in MET-amplified EACs, indicating biological heterogeneity with clinical relevance despite the presence of MET amplification as the predominant oncogenic driver. Furthermore, quantitative immunohistochemical analysis of the inflammatory tumor microenvironment showed that an increased percentage of M2 macrophages is associated with lower overall survival in MET-amplified EACs. Conclusions: Our results provide valuable insights into possible new therapeutic approaches for MET-amplified EACs for further research
Psychopathological symptoms in school-aged children after a traumatic event
No full text[Article number 12] Background: Traumatic experiences in childhood can have far-reaching and serious consequences for the development of those affected. Little is known about the age- and sex-specific symptom patterns in children and adolescents following a traumatic event. These do not always manifest in symptoms that meet the diagnostic criteria for post-traumatic stress disorder according to ICD 10. Methods: In an outpatient cohort of 84 children and adolescents aged 6 to 18 years, we utilised the dimensional Child Behaviour Checklist (CBCL) to analyse symptoms occurring within twelve months of a traumatic event as defined in ICD 10. Regression models were applied to examine the effects of sex, age, and their interaction. CBCL (sub-)scales from caregivers served as the outcome variables. Results: The most severe symptoms were externalising symptoms found in boys aged six to below twelve years, while girls of the same age showed the fewest symptoms. No fully consistent picture regarding age- and sex-effects was found across the (sub-)scales, however, the most consistent finding for all scales was an interaction between age and sex, resulting in a convergence between boys and girls with age. Adolescent males and females were affected to a similar extent. Conclusion: Knowledge of age- and sex-specific patterns in children and adolescents following a traumatic event is essential to recognise possibly trauma-related symptoms at an early stage, initiate adequate treatment. Considering that trauma can exacerbate or complicate externalising symptoms, and vice versa, it is crucial to integrate trauma-specific interventions into the treatment plan for those affected. Developing comprehensive, age- and sex-specific diagnostic criteria for trauma-related disorders might not only improve early detection and treatment but also ensure that interventions address both emotional and behavioural dimensions effectively. Future research should focus on refining these criteria and exploring the interplay between trauma and co-occurring conditions to enhance treatment outcomes
Which tariff to choose? How individual attitudes and preferences explain demand for flexible electricity tariffs in Germany
No full text[Artikel-Nr. 103978] Time-variant pricing and voluntary flexibility in private energy consumption have the potential to enhance demand sensitivity in electricity markets, playing crucial roles in the transition towards a greener energy system. This paper uses survey methods to examine the determinants of the stated willingness to adopt time-variant electricity tariffs. Based on a large population sample (N = 1200) from the most populous German federal state, North Rhine-Westphalia, we differentiate between the general willingness to adopt such tariffs and specific types, including time-of-use (TOU), critical-peak-pricing (CPP), and real-time-pricing (RTP) tariffs. Additionally, participants provide information on their willingness to adjust their electricity consumption in a timely manner. Our findings reveal that the stated willingness to adopt time-variant tariffs decreases as the potential price volatility increases. Moreover, there is a strong positive correlation between the willingness to adopt time-variant tariffs and the willingness to provide energy demand flexibility. The results of our analysis further indicate that early adopters of energy-efficient technologies and supporters of climate policies are more inclined towards time- variant pricing and providing flexibility in their electricity consumption. Economic preferences, such as loss aversion and present bias, appear to be particularly relevant for adopting the RTP tariff. These insights offer valuable guidance for promoting time-variant tariffs and flexible energy consumption, facilitating the adoption of efficient and sustainable energy systems
Mapping Groundwater Potential Zones in the Widyan Basin, Al Qassim, KSA: Analytical Hierarchy Process-Based Analysis Using Sentinel-2, ASTER-DEM, and Conventional Data
No full text[Artikel-Nr. 766] Groundwater availability in semi-arid regions like the Widyan Basin, the Kingdom of Saudi Arabia (KSA), is a critical challenge due to climatic, topographic, and hydrological variations. The accurate identification of groundwater zones is essential for sustainable development. Therefore, this study combines remote-sensing datasets (Sentinel-2 and ASTER-DEM) with conventional data using Geographic Information System (GIS) and analytical hierarchy process (AHP) techniques to delineate groundwater potential zones (GWPZs). The basin’s geology includes Pre-Cambrian rock units of the Arabian Shield in the southwest and Cambrian–Ordovician units in the northeast, with the Saq Formation serving as the main groundwater aquifer. Six soil types were identified: Haplic and Calcic Yermosols, Calcaric Regosols, Cambic Arenosols, Orthic Solonchaks, and Lithosols. The topography varies from steep areas in the southwest and northwest to nearly flat terrain in the northeast. Hydrologically, the basin is divided into 28 sub-basins with four stream orders. Using GIS-based AHP and weighted overlay methods, the GWPZs were mapped, achieving a model consistency ratio of 0.0956. The zones were categorized as excellent (15.21%), good (40.85%), fair (43.94%), and poor (0%). The GWPZ model was validated by analyzing data from 48 water wells distributed in the study area. These wells range from fresh water to primary saline water, with water depths varying between 13.98 and 130 m. Nine wells—with an average total dissolved solids (TDS) value of 597.2 mg/L—fall within the excellent zone, twenty-one wells are categorized in the good zone, fifteen wells are classified in the fair zone, and the remaining wells fall into the poor zone, with TDS values reaching up to 2177 mg/L. The results indicate that the central zone of the study area is suitable for drilling new water wells
Transcatheter edge-to-edge repair for mitral regurgitation
No full textMitral valve transcatheter edge-to-edge repair (M-TEER) has emerged as a transformative therapy for mitral regurgitation (MR), addressing the unmet needs of patients unsuitable for surgery. Landmark trials such as EVEREST II, COAPT, and MITRA-FR have established the safety and efficacy of M-TEER, in both patients with primary (PMR) and secondary MR (SMR). Recent trials, including RESHAPE-HF2 and MATTERHORN, have expanded our understanding and refueled discussions regarding patient selection and appropriate treatment indications in SMR. These trials have also contributed to the discussion regarding SMR phenotypes most appropriate for M-TEER. This review summarizes the evidence from pivotal trials, discusses patient selection, device advancements, potential future directions, and outlines ongoing trials that may shape future clinical practice