Material circularity and energy efficiency are highly relevant and intertwined issues for the transition towards a carbon-neutral and circular built environment. In the Netherlands, the building... Show moreMaterial circularity and energy efficiency are highly relevant and intertwined issues for the transition towards a carbon-neutral and circular built environment. In the Netherlands, the building sector has been rendered a priority towards a circular and low-carbon society. This thesis explored potential solutions for these twin issues in light of a novel technological system. This system presents an energy–material efficiency solution for energy renovation of building stocks with prefabricated concrete elements (PCEs) with recycled CDW as feedstock. Life cycle assessment (LCA) and life cycle costing (LCC) were combined with dynamic material flow analysis (MFA) to estimate the economic and environmental implications at both a product level and a national level. Show less
A structural investigation of coiled coil peptides used as membrane fusogens, mimicing naturally occuring coiled-coil fusion proteins. Synthetic modifications have been made to alter lipid... Show moreA structural investigation of coiled coil peptides used as membrane fusogens, mimicing naturally occuring coiled-coil fusion proteins. Synthetic modifications have been made to alter lipid attachment, secondary structure and to insert photoactive azobenzene moieties for active control over coiled coil structure. Finally, the underlying photocontrol mechanism investigated in coiled coil peptides is extended to beta-structured peptides, and was shown to be universally applicable. Show less
The rapidly increasing commercial application of metallic nanoparticles within products will inevitably enhance the amount of NPs being released into soil. Assessment of the impact of metallic... Show moreThe rapidly increasing commercial application of metallic nanoparticles within products will inevitably enhance the amount of NPs being released into soil. Assessment of the impact of metallic nanoparticles (NPs) in soil ecosystems is a necessity for ensuring their safe and sustainable application. In this thesis, we integrated exposure routes and exposure dynamics of NPs to investigate the uptake, translocation and impacts of metallic NPs in plants upon long-term exposure. We furthermore investigated the long-term impacts of NPs on the rhizosphere soil bacterial community and the potential transfer and biomagnification within the lettuce - terrestrial snails food chain. Our results demonstrate that 1) root exposure induced more phytotoxicity than foliar exposure at equal exposure concentrations; 2) the phytotoxicity and accumulation of AgNPs in plants was shape- and size-dependent; 3) nanoparticulate Ag present in AgNPs suspensions that predominantly drive their impacts on green leafy plants; 4) the dissolution of AgNPs in soil is the dominant process influencing Ag uptake and translocation in lettuce; 5) long-term exposure to high concentrations of AgNPs altered the structure and composition of rhizosphere bacterial community; 6) NPs can be transferred from lettuce leaves to snails, as associated with increased potential risks to higher trophic level organisms. Show less
The function of TLRs in innate immunity has aroused worldwide attention soon after its discovery. Because of the broad functions of TLR2 in innate immunity, the drive for the development of TLR2... Show moreThe function of TLRs in innate immunity has aroused worldwide attention soon after its discovery. Because of the broad functions of TLR2 in innate immunity, the drive for the development of TLR2-targeted vaccines or therapeutic treatments has accelerated in the last decades. However, its dual role in both activation and suppression of innate immune responses makes it very difficult to use the available results from basic research for the development of clinical trials. In addition, it is still not clear what is the function of TLR2 in regulating phagocytic cell migration. Therefore, we aimed to determine the function of TLR2 in mycobacterial infection and explore its role in regulating phagocytic cell migration in inflammatory tissue by using a zebrafish larval model in this thesis. We showed that infection of a tlr2 mutant in zebrafish larvae leads to a higher mycobacterial burden, accompanied by a lower number of granulomas and increased extracellular bacterial growth. Through a tail fin wounding and tail fin infection zebrafish model, we demonstrated that tlr2 is involved in modulating leukocyte migration. This thesis provides a better understanding of the functions of TLR2 in innate immune responses to infection and tissue wounding. Show less
The Standard Model (SM) of particle physics fails to explain several observed phenomena and is incomplete. In order to resolve this problem, one may extend the SM by adding new particles. However,... Show moreThe Standard Model (SM) of particle physics fails to explain several observed phenomena and is incomplete. In order to resolve this problem, one may extend the SM by adding new particles. However, yet they have not been observed, and currently, the scientific community tries to find a signature that manifests the existence and properties of such particles. This thesis is devoted to exploring the parameter space of Feebly Interacting new physics Particles (FIPs) in a model-independent fashion using two complementary approaches. The first one is searching for FIPs at next-generation accelerator experiments called Intensity Frontier experiments. The second one is constraining the parameter space of FIPs by considering their possible impact on the observables coming from the Early Universe - Big Bang Nucleosynthesis and Cosmic Microwave Background, which are in good agreement with the predictions of the cosmological models with SM particles. They are, therefore, very sensitive to the possible existence of FIPs in the primordial plasma. As a result of the researches constituting this thesis, novel model-independent results, as well as constraints on particular models of FIPs such as Heavy Neutral Leptons, have been obtained in both of these areas. Show less
Barrier function is the natural role of the skin. The lipid matrix present in the outermost layer of the skin, the stratum corneum is important for this function. Barrier impairment and altered... Show moreBarrier function is the natural role of the skin. The lipid matrix present in the outermost layer of the skin, the stratum corneum is important for this function. Barrier impairment and altered lipid composition are observed in several inflammatory skin diseases including atopic dermatitis and psoriasis. However, the relationship between the lipid properties and barrier function is not comprehended.In this project, a lipid model was prepared from synthetic lipids that closely resemble the stratum corneum lipid composition and organization. Subsequently, diseased skin models were developed to mimic various abnormalities in lipid composition observed in atopic dermatitis patients’ skin. Biophysical methods were used to monitor the changes in lipid organization in these models. Diffusion studies and trans-epidermal water loss measurements were performed to monitor the barrier function. This allowed the determination of the changes in lipid properties that were most instrumental in reducing the lipid barrier.This thesis further describes the use of simple skin lipid model membranes incorporating fewer components to provide a detailed insight into the relationship between lipid composition, lipid organization, and the skin barrier. The information gained in this project offers the opportunity to develop a new generation of formulations to treat these patients. Show less
The clinical potential of applying synthetic lethality to cancer treatment is famously demonstrated by the BRCA1/PARP1 paradigm: a tumor specific defect in BRCA1 – a component of the DNA double... Show moreThe clinical potential of applying synthetic lethality to cancer treatment is famously demonstrated by the BRCA1/PARP1 paradigm: a tumor specific defect in BRCA1 – a component of the DNA double-strand break (DSB) repair pathway homologous recombination (HR) – results in a remarkable sensitivity to PARP1 inhibition (PARPi). Despite spectacular initial responses in patients, resistance to PARPi treatment may develop and must be overcome to maximally exploit this interaction in the clinic. Genetically engineered (mouse) model systems have shown that PARPi resistance may arise through inactivation of the 53BP1 pathway. The 53BP1 pathway normally protects DSB ends from resection and the removal of this “brake” restores HR in the absence of BRCA1. However, how the 53BP1 pathway protects DSB ends from resection has remained elusive. In this thesis, advances in 3D tumor organoid culture protocols and CRISPR/Cas9 (screening) technology were applied to identify and validate new components of the 53BP1 pathway that render BRCA1 deficient cells resistant to PARPi upon their loss. Furthermore, a new acquired vulnerability that can be therapeutically exploited to deplete such PARPi resistant cells is described. Together, this thesis provides mechanistic insight in DSB repair and illustrates how such fundamental knowledge may stand at the basis to combat resistance. Show less
This thesis is an experimental study of the UV irradiation of the interstellar ice analogues, relevant for the different stages of the star and planet formation sequence. It describes in detail... Show moreThis thesis is an experimental study of the UV irradiation of the interstellar ice analogues, relevant for the different stages of the star and planet formation sequence. It describes in detail photodesorption and photoconversion processes, and as such, contributes to worldwide efforts that aim at understanding how chemistry in space could have contributed to the origin of life on Earth and possibly planets around other stars. Show less
Dit proefschrift beschrijft een collectie aan alternatieve strategieën voor het begrijpen, ontwerpen en toepassen van lipide nanosystemen, waarin de rol van de bio-nano interacties centraal staan.... Show moreDit proefschrift beschrijft een collectie aan alternatieve strategieën voor het begrijpen, ontwerpen en toepassen van lipide nanosystemen, waarin de rol van de bio-nano interacties centraal staan. In het bijzonder wordt gekeken naar de interactie van RNA-lipide nanosystemen, bekend van de toepassing als vaccins en andere medicatie. Het onderzoeksgebied van de nanomedicatie kan gebruik maken van de specifieke voorbeelden die worden beschreven, maar er kan ook inspiratie worden opgedaan om de aanpak van onderzoek doen te verschuiven van een kostbare empirische aanpak naar rationeel gedreven ontwerpstrategie. Dit alles zal helpen in de ontwikkelen van nieuwe RNA therapieen in de toekomst. Show less
The role of material production as a driver of environmental impacts is increasing, which calls for a better understanding of global material flows. This thesis explores the role of in-use stocks... Show moreThe role of material production as a driver of environmental impacts is increasing, which calls for a better understanding of global material flows. This thesis explores the role of in-use stocks of products, buildings and infrastructure as a key driver of global material demand and discusses the implications with regards to availability of waste flows. The method based on detailed product compositions and lifetimes is applied to generate material use scenario’s towards 2050 for appliances, vehicles, buildings and electricity infrastructure. Under most of the developed scenarios, a growing population and increasing affluence are expected to lead to higher demand for products, and consequentially leads to a continued growth in annual material demand worldwide. While the results can be used to identify sector specific challenges and opportunities for achieving a more circular economy, the method also provides a starting point to incorporate material cycles and resource efficiency strategies more explicitly and consistently in integrated assessment models. This would allow for a more comprehensive assessment of resource use in relation to other global challenges such as climate change. Show less
This thesis aims to improve the detection from ultra-weak single emitter by enhancing their emission properties with plasmonic nanostructures. We exploit the wet-chemically synthesized single... Show moreThis thesis aims to improve the detection from ultra-weak single emitter by enhancing their emission properties with plasmonic nanostructures. We exploit the wet-chemically synthesized single crystalline gold nanorods (GNRs) as our basic frameworks in the whole studies, simply because of their unique optical properties, such as the intense electromagnetic fields enhancement near the tips, and the narrow, tunable resonance with light. We first explore the lower limit of fluorescence quantum yield for single-molecule detection by enhancing the fluorescence with a single gold nanorod. Later, we develop a method to synthesize end-to-end gold nanorod dimers on glass substrates with the aid of molecular linkers, and then apply these strong plasmon coupling systems to enhance the single-molecule fluorescence under two-photon excitation. Show less
In astronomy, the interpration of observations and measurements plays a crucial role: we rely purely and fundamentally on the information that reaches us as observers. And 80% of all matter in the... Show moreIn astronomy, the interpration of observations and measurements plays a crucial role: we rely purely and fundamentally on the information that reaches us as observers. And 80% of all matter in the universe is undetectable directly.This so called 'dark matter' can be observed indirectly, by the gravitational effect on its surroundings and the curvature of spacetime predicted by the theory of relativity.In this thesis, we combine scientific research, a description of our universe, with theoretical considerations of the statistical methods used for that research, or how we can deduce that description from the 'reflections' that we see. In this work, we focus on the matter distribution in groups and clusters of galaxies, and consider the intricacies of the method of weak gravitational lensing that we use, respectively. Show less
In this thesis, I study 1) metabolic alterations in tuberculosis related to wasting syndrome in human patients as well as in rodent and fish animal models. 2) effects of the mutation of the leptin... Show moreIn this thesis, I study 1) metabolic alterations in tuberculosis related to wasting syndrome in human patients as well as in rodent and fish animal models. 2) effects of the mutation of the leptin gene on cachexia and diabetes in rodent and zebrafish animal models. 3) how tuberculosis infection and resulting metabolic reprogramming are dependent on leptin signaling in mice and zebrafish larvae. Show less
In this thesis it is posed that the central object of preference discovery is a co-creative process in which the Other can be represented by a machine. It explores efficient methods to enhance... Show moreIn this thesis it is posed that the central object of preference discovery is a co-creative process in which the Other can be represented by a machine. It explores efficient methods to enhance introverted intuition using extraverted intuition's communication lines. Possible implementations of such processes are presented using novel algorithms that perform divergent search to feed the users' intuition with many examples of high quality solutions, allowing them to take influence interactively. The machine feeds and reflects upon human intuition, combining both what is possible and preferred. The machine model and the divergent optimization algorithms are the motor behind this co-creative process, in which machine and users co-create and interactively choose branches of an ad hoc hierarchical decomposition of the solution space.The proposed co-creative process consists of several elements: a formal model for interactive co-creative processes, evolutionary divergent search, diversity and similarity, data-driven methods to discover diversity, limitations of artificial creative agents, matters of efficiency in behavioral and morphological modeling, visualization, a connection to prototype theory, and methods to allow users to influence artificial creative agents. This thesis helps putting the human back into the design loop in generative AI and optimization. Show less
In today's volatile market environments, companies must be able to continuously innovate. In this context, innovation does not only refer to the development of new products or business models but... Show moreIn today's volatile market environments, companies must be able to continuously innovate. In this context, innovation does not only refer to the development of new products or business models but often also affects the entire organization, which has to transform its structures, processes, and ways of working.Corporate entrepreneurship (CE) programs are often used by established companies to address these innovation and transformation challenges. In general, they are understood as formalized entrepreneurial activities to (1) support internal corporate ventures or (2) work with external startups. The organizational design and value creation of CE programs exhibit a high degree of heterogeneity. On the one hand, this heterogeneity makes CE programs a valuable management tool that can be used for many purposes. On the other hand, it can be seen as a reason for the current challenges that companies experience in effectively using and managing CE programs.By systematically analyzing 54 different cases in established companies in Germany, Switzerland, and Austria, this study contributes to a better understanding of the heterogeneity of CE programs. The taxonomic approach provides clearly defined types of CE programs that are distinguished according to their organizational design and the outputs they generate. Show less
Systems with local constraints is a new finding in recent researches on complex systems. The heterogeneous spatial interactions and the temporal dependencies among those numerous units make it... Show moreSystems with local constraints is a new finding in recent researches on complex systems. The heterogeneous spatial interactions and the temporal dependencies among those numerous units make it difficult to describe by traditional statistical physics.These complex structures also make information storage and transmission in it is impossible to describe by the random variables with finite outcomes in the classical information theory. In this thesis, we use the statistical ensemble with local constraints to describe those complex systems with heterogeneous interactions and dependencies. This description also helps us find the new information-theoretical bounds in the systems with local constraints, even when the temporal dependencies among numerous units break the asymptotic equipartition property in the classical information theory.Furthermore, we find that the breaking of ensemble equivalence generally exists in systems with local constraints even without the presence of phase transition, and this ensemble nonequivalence in the systems with local constraints without phase transition can be the same strong as the one that only appears on the boundary of phase transitions caused by the long-range interactions. We also find that this breaking of ensemble equivalence will affect the limit of information storage and transmission in systems with local constraints.These results in this thesis extend our understanding of complex systems and information theory. Show less
This thesis takes steps toward understanding the interaction between gas-phase and solid-state molecules in star- and planet-forming regions. Chapter 1 and 2 provide the reader with an introduction... Show moreThis thesis takes steps toward understanding the interaction between gas-phase and solid-state molecules in star- and planet-forming regions. Chapter 1 and 2 provide the reader with an introduction and in-depth description of methods used in subsequent chapters. Chapter 3 and 4 present the spectroscopic infrared characterization of acetaldehyde, dimethyl ether, ethanol, and methyl formate in the solid state, both pure and mixed in astronomically relevant matrices. This characterization will allow for probing of the solid-state organic inventory of star- and planet-forming regions with the upcoming James Webb Space Telescope. Interferometric observations of the protoplanetary disk around TW Hya with the Atacama Large Millimeter/submillimeter Array are presented in Chapter 5. These results hint that the observed gas-phase formaldehyde is formed in the gas phase, contrary to the generally accepted solid-state formation. Chapter 6 provides an insight to the interaction between gas-phase carbon monoxide and solid-state hydroxyl radicals on the surface of vacuum-UV irradiated water ice. Even tough residence times of carbon monoxide are short, they are sufficient to allow reactions with hydroxyl radicals and produce carbon dioxide. This process could explain the lack of gas-phase carbon monoxide in protoplanetary disks and the presence of carbon dioxide mixed in solid-state water. Show less
Freshwater and brackish water ecosystems are arguably the most vulnerable ecosystems on earth, due to concentrated human developments in and around them. The Pontocaspian (PC) region located at the... Show moreFreshwater and brackish water ecosystems are arguably the most vulnerable ecosystems on earth, due to concentrated human developments in and around them. The Pontocaspian (PC) region located at the border of Europe and Asia contains a variety of brackish water ecosystems and unique inhabitants, known as the PC biota. The current status and trends in PC biodiversity are poorly known, however, deterioration of PC habitats is evident in the Black Sea and Caspian Sea Basins. This thesis aims to support an establishment of effective PC biodiversity conservation regime. I use the Black Sea Basin as a study system and outline current status and trends in PC biodiversity and assess the direct and indirect anthropogenic drivers of the PC biodiversity change. I show that PC biodiversity is severely declining as a result of human action. Identified direct drivers of decline include damming of rivers; habitat modifications; pollution and eutrophication; invasive alien species and climate change. Indirect drivers of PC biodiversity decline include current suboptimal legal arrangements, inadequate institutional design of environmental stakeholder organizations and non-inclusive governance systems, as well as the limited funding availability for PC biodiversity conservation, institutional instability and low recognition of the need for PC biodiversity conservation. Show less
In this thesis we use Josephson and noise scanning tunneling microscopy for the study of conventional, unconventional (iron-based) and disordered superconductors. On the one hand, Josephson... Show moreIn this thesis we use Josephson and noise scanning tunneling microscopy for the study of conventional, unconventional (iron-based) and disordered superconductors. On the one hand, Josephson scanning tunneling microscopy allows us to directly visualize the superfluid density with high spatial resolution. On the other hand, noise scanning tunneling microscopy is employed for measuring the shot noise which detects the charge of the carriers forming a superconducting condensate. Show less
