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
This thesis describes a dissimilarity-based classification tool, the δ-machine, which gives an alternative way of statistical modeling compared to the conventional ones that directly use predictor... Show moreThis thesis describes a dissimilarity-based classification tool, the δ-machine, which gives an alternative way of statistical modeling compared to the conventional ones that directly use predictor variables. We use the symbol δ, because it is commonly used as a symbol for dissimilarities in multidimensional scaling.In this thesis, we discuss the properties of the δ-machine, and extend the δ-machine from handling continuous predictor variables only to handle different types of predictor variables, including continuous, ordinal, nominal, and binary predictor variables via the two tailored dissimilarity functions. Furthermore, we study the classification performance of the δ-machine in high dimensional data. We propose a Majorization-Minimization algorithm to interpolate new data points coherently into previously constructed classical multidimensional scaling (CMDS) configurations, and use the proposed algorithm in the δ-machine in high dimensional data scenario, where CMDS is applied to reduce the original high dimensional predictor variables. In order to make predictions for new data points, therefore, needs to interpolate them into the constructed CMDS.The δ-machine shows promising predictive performance in general and is able to find informative exemplars/prototypes, which bring extra insights of data. The informative exemplars could be used in the further study. Show less
This dissertation focuses on the overall study, as well as the nuances, of bullying behaviours among school-going youth in India. A systematic review of past literature from India is presented by... Show moreThis dissertation focuses on the overall study, as well as the nuances, of bullying behaviours among school-going youth in India. A systematic review of past literature from India is presented by synthesizing 37 empirical studies examining psychometric properties of the instruments adopted, methodological characteristics, sample size and procedures, and characteristics of bullying behaviour. Results show that bullying is widely spread, and certain factors, like caste and religion, and their association with bullying behaviours are typical to the Indian culture. This dissertation also examines if dimensions of psychopathy, namely callous-unemotional traits, narcissism, and impulsivity, can differentiate between, bullies, victims, and bully-victims in a longitudinal capacity. Using a multi-informant approach and multinomial logistic regression analyses, it was found that psychopathy dimensions taken together provide a better fit in predicting bullying than the independent psychopathic subscales. The dissertation further investigates the structure and context of the relationship between victimization and Body Mass Index through a transactional model. Key results of structural equation modeling analyses yielded mainly concurrent relations between BMI and victimization, emphasizing that results from western countries may not generalize to India. Finally, bullying behaviours among youth as a function of their socio-economic status (SES) in classroom and self-perceptions of minority status are examined using a moderated-mediation growth model. Results show classroom level SES plays a significant role in predicting victimization cross-sectionally, and is mediated through perceptions of self. However, in the long run, being part of a minority, and perceiving self as such, leads to decreased victimization among youth in India. Show less
The increasing popularity of Twitter in both scholarly communication and public engagement with science has triggered widespread Twitter interactions around scientific information, thus giving rise... Show moreThe increasing popularity of Twitter in both scholarly communication and public engagement with science has triggered widespread Twitter interactions around scientific information, thus giving rise to the emergence of scholarly Twitter metrics which aim to measure and characterize Twitter interactions related to scholarly objects. For the sake of more advanced scholarly Twitter metrics, the overarching aim of this PhD dissertation is to characterize diverse forms of Twitter interactions around scientific papers to understand in greater-depth the Twitter reception of scientific information and improve scholarly Twitter metrics. To this end, this dissertation starts with large-scale analyses of how many and how fast scientific papers are mentioned on Twitter in comparison with other types of social media metric data sources, to unravel the broadness and speed of Twitter presence of scientific papers. Then, focusing on scholarly tweets of scientific papers per se, this dissertation investigates the characteristics of diverse user interaction behaviors around scholarly tweets, shedding light on their potential value in developing more advanced indicators for measuring deeper levels of Twitter reception of scientific information. Finally, based on the main findings, this dissertation further discusses the possibility to approach a more fine-grained indicator system of scholarly Twitter metrics. 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
In essence, airport slots are planning tools for the rationing of capacity at airports where available capacity falls short of air travel demand. Since the availability of slots is directly... Show moreIn essence, airport slots are planning tools for the rationing of capacity at airports where available capacity falls short of air travel demand. Since the availability of slots is directly connected to the capacity of an airport at a particular date and time, a slot is by definition a scarce resource. The extent of. Slot scarcity depends on the congestion level of an airport. Excess demand for slots has substantial implications for airlines, coordinators and airports alike, as well as for society as a whole. This dissertation is designed to explore the compatibility of the global and specific legal regimes governing airport slot coordination with the particular socio-economic challenges that international organizations, governments and air transport industry stakeholders are experiencing today. A multitude of socio-economic objectives are identified, including but not limited to the environment in terms of noise and carbon reduction policies, growing airport access issues and general debates on airport functions to society. The number of so-called 'super-congested' airports in terms of the full slot capacity being historically 'occupied' by incumbent carriers are on the rise and are carefully studied from a policy and legal point of view. 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 corpus of Æsopian fables books has been taught to French children and teenagers for centuries. Yet little analysis looks at the production in its entirety. Therefore, within this corpus, I... Show moreThe corpus of Æsopian fables books has been taught to French children and teenagers for centuries. Yet little analysis looks at the production in its entirety. Therefore, within this corpus, I evaluated the relationship between the text, the images, and the educational purpose of various fable authors using 252 visuals, published between 1500 and 2020. Sources include picture books, board games, sheet music, posters, school materials, and even application software. All have in common the aim of pursuing or promoting an educational use of the fables. My research focuses on the role that illustrated fables play in French education.Through a sociological approach that features the concept of médiation littéraire, book history, literary analysis, the study of the layout of the books and intermedial analysis, I conclude that Æsopian fables are used as a social link between generations of French people.They became essential across primary schools in the mid-19th century. Before that, they were mostly intended for socially privileged children whose families could afford a secondary education.Regardless of the century, the illustrations which accompany fables play a role in the text’s adoption across French schools: they participate in the transmission of the genre and other kinds of knowledge 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 increasing amount and complexity of data over the past decades have given rise to new sorts of questions, also in the field of infectious disease epidemiology. This thesis proposes methods to... Show moreThe increasing amount and complexity of data over the past decades have given rise to new sorts of questions, also in the field of infectious disease epidemiology. This thesis proposes methods to analyze data available at multiple resolution levels and to combine different data types in infectious disease surveillance. Hereby using techniques central to data science. Show less
The heart is innervated by the autonomic nervous system, which can be divided into sympathetic and parasympathetic parts. The balance between cardiac sympathetic and parasympathetic innervation is... Show moreThe heart is innervated by the autonomic nervous system, which can be divided into sympathetic and parasympathetic parts. The balance between cardiac sympathetic and parasympathetic innervation is critical for maintaining normal cardiac function. After myocardial infarction, sympathetic hyperinnervation has been discovered in patients as well as in animal models, which has raised growing awareness in relation to arrhythmogenesis. However the mechanism is not clear yet. In this thesis, we hypothesize a role for epicardium-derived cells (EPDCs) in this process. In addition, we aimed to study ganglia remodeling after myocardial infarction. We explored: i) the role of EPDCs in promoting cardiac sympathetic re-/hyperinnervation after cardiac damage in vitro, ii) the impact of sex of EPDCs on cardiac innervation, iii) the generation of inducible proliferative human EPDCs (iEPDCs), iv) neuronal remodeling of superior cervical ganglia after myocardial infarction and v) the molecular signature of SCG revealed by single nucleus RNA sequencing. Show less
Sugammadex (Bridion®, laboratory code Org 25969) encapsulates neuromuscular blocking agents rocuronium and vecuronium and reverses their pharmacological effect in the post-operative setting. During... Show moreSugammadex (Bridion®, laboratory code Org 25969) encapsulates neuromuscular blocking agents rocuronium and vecuronium and reverses their pharmacological effect in the post-operative setting. During the development trajectory of this first selective relaxant binding agent, it was found that sugammadex has an effect on standard coagulation laboratory coagulation assays. However, this off-target effect was not further evaluated in clinical studies. This raised safety concerns by the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) during their review of the application for marketing authorization for sugammadex.This thesis is comprised of a variety of in vitro, ex vivo and in vivo (clinical) pharmacology studies to provide more insight into the off-target effect of sugammadex on coagulation. The research involved the search for a mechanism, but also the clinical consequences on both primary and secondary hemostasis in clinical studies that included healthy volunteers. This evaluation was indispensable to overcome the bleeding safety concerns raised by both the EMA and the FDA. Show less
This thesis addresses several pathophysiological and clinical aspects of both the Lambert-Eaton myasthenic syndrome (LEMS, introduced in chapter 1) and myasthenia gravis (MG).In chapter 2, the... Show moreThis thesis addresses several pathophysiological and clinical aspects of both the Lambert-Eaton myasthenic syndrome (LEMS, introduced in chapter 1) and myasthenia gravis (MG).In chapter 2, the search for new LEMS associated small cell lung cancer (SCLC) markers is described, leading to the discovery of ERC1 as a new antigen associated with LEMS.In chapter 3, a literature review of screening methods for SCLC in LEMS is presented, aswell as the role of associated SOX1 antibodies in SCLC-LEMS patients.In chapter 4 long-term follow-up, functional impairment and quality of life in LEMSpatients are described. We also report a normal survival in LEMS patients without associated tumour as well as an improved tumour survival in SCLC-LEMS patients.In chapter 5, we report that lowering the cut-off value for increment from 100% to 60% increases sensitivity for diagnosis of LEMS, without a negative effect on the specificity.Chapter 6 reports that a lower initial compound muscle action potential amplitude is a marker of more severe disease in AChR MG.In chapter 7, we show a small symptomatic effect of ephedrine as a symptomatic treatment in MG patients, in a placebo-controlled, double-blind, randomised, multiple crossover series of n-of-1 trials. Show less
In this research project I analyze and reflect on taqsīm recordings by two leading figures of ‘ūd playing who were pillars of modern Arabic music, namely the Egyptians Muḥammad al-Qaṣabjī (1898... Show moreIn this research project I analyze and reflect on taqsīm recordings by two leading figures of ‘ūd playing who were pillars of modern Arabic music, namely the Egyptians Muḥammad al-Qaṣabjī (1898-1964) and Riyāḍ al-Sunbāṭī (1906-1981). I decode and underline their most significant traits in order to:1) enrich and develop my melodic-rhythmic vocabulary;2) deepen my understanding of the structural, melodic and rhythmic processes underlying the genre;3) design a structural framework or a model for pre-composing taqsīm-like pieces of music.To put it another way, the dissertation discusses the creation of pre-composed taqāsīm. The pieces follow a specific model of pre-composition that was designed while taking al-Qaṣabjī and al-Sunbāṭī’s taqsīm practice as a reference and a source of inspiration. This model contributes to both artistic research and practical knowledge, and provides new insights into structural, melodic and rhythmical processes of the genre. The artistic outcome of this project includes five new works for solo ‘ūd. 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
Due to the increased incidence of breast cancer and improved survival, more women are at risk of developing contralateral breast cancer (CBC). The aim of this thesis was to explore risk factors... Show moreDue to the increased incidence of breast cancer and improved survival, more women are at risk of developing contralateral breast cancer (CBC). The aim of this thesis was to explore risk factors associated with CBC. We observed significant associations for a polygenic risk score of common germline variants (PRS313) and for different adjuvant systemic therapy regimens with (subtype-specific) CBC risk. These factors may be incorporated in CBC risk prediction models together with other known and available risk factors. For support of clinical decision making more biological information is needed to understand CBC development in women with invasive breast cancer and DCIS. As a first step towards implementation of a risk prediction model, we performed an exploratory interview study, which showed that patients had varying preferences for graphical presentation of probabilities in a CBC prediction model. In future studies, the prediction model should be incorporated in a decision support tool and implemented in clinical practice. This tool can then help to better identify women at high risk of CBC who may benefit from prophylactic surgery, while the estimates can also be used to reassure patients who are at low risk of developing CBC. Show less
In the field of Western art music, improvisation has become a much discussed topic. In this interdisciplinary study Mooiman argues that in this context, improvisation is not to be seen as a quasi... Show moreIn the field of Western art music, improvisation has become a much discussed topic. In this interdisciplinary study Mooiman argues that in this context, improvisation is not to be seen as a quasi-autonomous skill or art form, but as an aspect of music-making in general. With this research, Mooiman offers a ‘panorama’ of nineteenth-century styles and situations of music-making that together sketch a picture of improvisatory aspects of nineteenth-century music. Music was generally experienced as a wordless language, and he argues that making music was understood as a rhetorical act: performers strove for musical persuasion. This study focuses on the performer: it explores how performers in the nineteenth century might have thought during the real-time act of music-making, and how performers today might learn to use musical languages from the past actively again. For this last aspect, the area of music theory is relevant; Mooiman concludes his dissertation with a discussion of how traditional music theory is challenged by improvisatory music-making. Show less
