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A Benchmark of Cryo-CMOS Dynamic Comparators in a 40 nm Bulk CMOS Technology
No full textsponsorship: This work was supported by the Research Foundation-Flanders (FWO) under Grant 11N0523N. (Research Foundation-Flanders (FWO)|11N0523N)status: Publishe
Organoïde modellen voor het bestuderen van mucoviscidose-geassocieerde endometriale pathobiologie
No full textCystic fibrosis (CF) is a burdening genetic disorder, caused by mutations in the CF transmembrane conductance regulator (CFTR) protein that regulates ion and fluid transport and pH in epithelial tissues, including the reproductive tract. Women with CF (wwCF) face significant fertility challenges, showing a higher prevalence of subfertility compared to healthy women. The underlying cause is multifactorial but far from understood. In particular, the endometrium, the uterus' inner lining which is essential for pregnancy and dynamically expresses CFTR during the menstrual cycle, is largely unexplored in CF. Furthermore, in this era of CFTR modulator therapy, it is essential to start unraveling the impact of modulators on CF patients' endometrium and thus fertility, which is currently unknown. Since not relevant in previous decades when CF was mainly a pediatric disease, we are currently lacking appropriate, reliable and accessible study models to investigate the endometrium (and other reproductive tissues) in the context of CF fertility deficiency.
Therefore, in this thesis I aimed to establish the first CF endometrial organoids (CFEO) to study potential endometrium-related causes of decreased fertility in wwCF.
Endometrial organoids (EO) represent a robust research model recapitulating endometrial epithelium biology, including its physiological responsiveness to the menstrual cycle-regulating hormones, thereby reliably mimicking the cycle phases 'in the dish'. Moreover, in this thesis, I showed that EO recapitulate cycle phase-associated hormonal regulation of CFTR and other relevant ion channels, such as the epithelial sodium channel (ENaC), thereby demonstrating that the EO model provides a useful tool to study CFTR, ENaC and other ion channel involvement in endometrial (patho)biology.
I successfully developed organoids from endometrial biopsies obtained from wwCF. We focused in this first study on the most prevalent F508del mutation. I confirmed CFTR functional deficiency in the CFEO and showed (partial) rescue by CFTR modulators, being the first demonstration of direct 'highly effective modulator therapy' (HEMT) impact on the endometrium, as revealed here by its organoids.
By applying bulk RNA sequencing (RNA-seq) analysis, I found that CFEO recapitulated CF characteristics and revealed molecular and pathway differences in cycling hormone responses compared to healthy endometrial organoids (HEO). Aberrant behavior of CFEO appeared most pronounced in the proliferative phase, as instigated in the organoids by estradiol (E2) exposure. Enriched pathways in CFEO were related to enhanced endoplasmic reticulum (ER) stress, unfolded protein response (UPR) and cell cycle arrest. E2 exposure also induced apoptosis in part of the CFEO, together suggesting that E2 exposure in combination with retained, misfolded F508del CFTR protein causes stress levels above the threshold that endometrial cells can still cope with and resolve. These aberrations seemed (visually) restored by HEMT, providing the first indication that HEMT may improve fertility at the level of the endometrium.
To further complement the human organoid model for unraveling endometrial pathobiology in CF and expand the experimental toolbox to study CF-associated fertility deficiency, I also developed organoids from a genetic CF mouse model, which were shown to exhibit CFTR dysfunction and respond to CFTR modulator treatment. Moreover, single-cell RNA sequencing (scRNA-seq) analysis of the CF mouse uterus revealed molecular traits in the endometrium similar to those in the human CF endometrium (as evidenced by its organoid model). This finding reinforces our observations in human CF endometrium as well as validates the translatability of the CF mouse model to the human setting, which will be highly useful in future studies.
Taken together, our study presents a novel powerful research model to enhance our understanding of CF-associated endometrial pathobiology, particularly regarding menstrual cycle abnormalities that affect fertility. This research is timely since improved CF therapeutics result in increased life expectancy, allowing more people with CF (PwCF) to consider starting a family. Moreover, PwCF strongly desire increased attention to their reproductive well-being and problems, which our study provides. Furthermore, knowing the impact of the new-era CFTR modulator therapy on this key reproductive organ will help to guide clinical care of PwCF in the context of fertility and pregnancy.status: Publishe
All is fish that comes to the net. Vissende boeren op de Engelse zuidkust in de turbulente late middeleeuwen
No full textPeasants living on the coastlines of late medieval England could rely on more than their farmland alone: although not all peasants had equal access to the sea, a sizeable group was actively involved in small-scale maritime fisheries. This dissertation wants to shed light on these pluriactive coastal dwellers that have been overlooked by most of recent historiography. Despite the length and variety of the English coast, research into the agricultural- and peasant history of medieval England has remained predominantly landlocked. Meanwhile studies on medieval fisheries tend to focus on the scale enlargement and commercialisation that took place throughout the Middle Ages, assuming small-scale fishing lost importance over time. Coastal inhabitants are instead more often considered in disaster studies, which has led to an image of the medieval coast as a dangerous place. The coasts also boasted resources and opportunities, however, of which fish are a prime example. Adding peasant fishing to the picture broadens our understanding of the diversity of "medieval fishermen" beyond the specialists who left the shores for months on end. More importantly, it highlights peasant strategies and mindsets, especially in the face of the various turbulences the Late Medieval period is known for.
Relying on administrative documents of multiple manors and other estates across three regions on the English South Coast, this research compiles numerous traces of peasant fishing activities, highlighting their commonplace nature even at the end of the Middle Ages. The dissertation details how the combination of fishing and agriculture could occur in a variety of ways depending on local circumstances. It was also culturally embedded, as access to knowledge and technology ran along networks of kin and community. Finally, coastal peasants fished not as a matter of coercion or desperation, but because it was desirable to them. It was a systematically practiced means of income diversification, which its participants valued in particular for its capacity to minimise risk and generate stability. In this way, where peasant fisheries continued and at times flourished, this should not be regarded as a failure of these fisheries to commercialise. Instead, for those able to participate, it was a matter of utilising the available resources in the ways that supported them best.status: Publishe
Voorbij verklaringen: het ontwerpen van interactieve verklaarbare AI-systemen voor eindgebruikers
No full textWith the rapid adoption of Artificial Intelligence (AI) across critical domains, the need for transparency, user trust, and effective human-AI collaboration has never been more urgent. While Explainable AI (XAI) and Interactive Machine Learning (IML) have made notable progress in improving model interpretability and user involvement, most existing approaches treat explainability and interactivity in isolation. Such approaches involve either providing static, one-off explanations or limiting user input to model training phases. However, recent literature in XAI underscores that static explanations alone are often insufficient for meaningful understanding or trustworthy decision-making.
This thesis addresses this gap by investigating the design and utility of interactive Explainable AI (iXAI) systems that integrate explanation and interactivity to help end users with minimal AI knowledge (such as domain experts and non-experts) to better understand, evaluate, and guide AI-driven decisions. By adopting a user-centric design and development methodology, the research focuses on three core questions:
RQ1. How do iXAI systems influence end users' understanding of AI and calibrate trust in its outputs?
RQ2. In what ways can domain experts contribute to refining AI workflows through iXAI interfaces?
RQ3. How can iXAI support end users in taking informed action for achieving their end goals?
To explore these questions, the thesis presents a series of application-grounded studies in healthcare and recruitment in Chapters 4 to 6. Across these research studies, several iXAI systems were developed that combine diverse explanation types (model-centric, data-centric, and outcome-centric) with interactive mechanisms (such as what-if explorations, conversational interactions, steering and debiasing of prediction models). These systems were evaluated through a combination of quantitative, qualitative, and mixed-method user studies involving both expert and non-expert participants.
Through the individual research studies included in this thesis, this thesis offers the following key contributions:
Empirical contributions that help us understand how different explanatory and interactive strategies in iXAI system can support user understanding, trust calibration, and actionable insights.
Artifact contributions in the form of system designs, source code of the iXAI systems, study procedure and the data collected through the application-grounded user studies.
Theoretical contributions through several design guidelines proposed in the research studies for the design of multifacted explanatory systems to involve non-experts and facilitate domain experts for steering and debiasing prediction models without impacting the model performance.
Methodological contributions outlining practical approaches for evaluating iXAI systems through application-grounded user studies.
The thesis concludes with a critical reflection on the practical challenges encountered and proposes future research directions to address open questions at the intersection of explainability, interactivity, and human-centred AI.status: Publishe
On calibration procedures and selective powder deposition uncertainty of a multi-material laser powder bed fusion machine
No full textstatus: Accepte
Prikkelanalyse in toestemmingsloze blockchains
No full textIn recent years, permissionless blockchains have emerged as the foundation for a wide range of decentralized applications, including cryptocurrency management, decentralized finance, auctions, voting systems, digital ownership, and more. The reliability of these applications depends on the security guarantees offered by the underlying blockchain protocols. Although prominent permissionless blockchains often base their security on formal analyses and claims, these assessments typically rely on simplifying assumptions, such as the existence of an honest majority, or overlook critical factors, like the influence of reward distribution on system security.
Permissionless blockchains incentivize their participants, referred to as miners or validators, by rewarding them with cryptocurrency to encourage active participation in the protocol. The incentive mechanism plays a crucial role in maintaining the security of the blockchain by motivating participants to follow the desired, or honest, behavior. Since validators and miners are typically rational actors seeking to maximize profit, any flaw in the incentive design may motivate them to deviate from honest behavior in pursuit of an unfair advantage. Such exploitation of the incentive mechanism can lead to a destabilizing situation in which disadvantaged participants may choose either to deviate from honest behavior or to eventually abandon the network, with both possibilities threatening the blockchain's continued progress and stability.
In this thesis, we analyze the incentive mechanisms behind several prominent permissionless blockchains, including Bitcoin, Cardano, and Ethereum. Our focus is primarily on potential fairness attacks that allow adversarial miners or validators to increase their profits by capturing an unfair share of blocks. As a first step, we analyze the incentive structure in Bitcoin, the pioneering Proof-of-Work (PoW) blockchain. Specifically, we examine the temporal aspects of profitability associated with one of the most well-known fairness attacks, namely selfish mining, which aims to exclude honest blocks from the longest chain. Building on this, we assess the role of Bitcoin's difficulty adjustment mechanism in mitigating such attacks. We then explore the implications of mining pool rationality for Bitcoin's security and propose novel attack vectors that could further increase an adversary's profit in a rational setting. Additionally, we investigate how upcoming Bitcoin reward halvings and the transition toward a transaction-fee era can impact Bitcoin's security by lowering the security threshold and increasing the potential for immediate profitability.
As a next step, we analyze the incentive mechanisms of Proof-of-Stake (PoS) protocols. We examine longest-chain PoS protocols, such as Cardano, and show that due to the block proposer predictability inherent in PoS systems, the selfish mining attack can be even more destructive in this context. We also analyze Ethereum as a voting-based PoS protocol. These protocols are susceptible to block reorganization attacks, in which an adversarial validator attempts to exclude blocks with weak voting support from the canonical chain. We identify a vulnerability in Ethereum's reward mechanism that results from the centralized distribution of vote rewards. If exploited, this vulnerability can lead to both short- and long-range reorganization attacks. To address this issue, we propose a fairer and more decentralized reward mechanism for Ethereum.
We hope the insights learned from this thesis will help identify potential incentive-based vulnerabilities in permissionless blockchains and contribute to the design of fairer blockchain protocols.status: Publishe
Efficiënte bewegingsplanning voor robottoepassingen: een aanpak op basis van optimale controle
No full textDue to their autonomous capabilities and their large potential to replace and
support humans in all aspects of life, robots, the situations where they are
deployed and the tasks that they have to perform are becoming increasingly
complex. This pushes control algorithms to evolve similarly in complexity,enabling robots to autonomously handle a large variety of tasks while meeting
expectations of high performance and reliability. The performance of robotic
applications is not only determined by several performance metrics but also by
the robots adhering to their inherent limitations and the requirements imposed
by the task. Optimal control problems (OCPs) and their reactive component -
model predictive control (MPC) - handle these requirements naturally through
their formulation of the control problem as an optimisation problem, allowing
to balance desired performance objectives with hard constraints that must
be satisfied. It enables control engineers to extract high performance out of
a robotic system while guaranteeing adherence to the constraints and task
requirements.
However, despite their attractive properties, the adoption of optimal control and
MPC for these complex applications is limited for various reasons. Firstly, the
inherent computational complexity of solving an optimisation problem hinders
the use of these techniques for complex systems as the low-level controllers of
these systems often require control updates between 50 Hz and 1 kHz which are
hard to meet for MPC. Secondly, due to its optimisation-based nature, optimal
control is restricted in the representation and the size of the environments
where the robot has to perform its task. These restrictions exist due to the
disadvantageous scalability of the computational performance towards cluttered
environments and the dependency on differentiable constraint and objective
formulations. Lastly, implementing performant optimal control strategies
requires a large engineering effort and a deep knowledge of optimisation. This
thesis addresses those limitations by (1) reducing the computational complexity
of optimal control for cluttered environments, (2) by facilitating the use of
optimal control in an industrial context and (3) by lowering the computational requirements of MPC algorithms for complex systems.
First of all, it introduces a technique that reduces the amount of constraints
in an OCP through only considering the most critical one at a time. It
also reformulates a generic obstacle avoidance constraint to simplify the
formulation of collision avoidance for a set of obstacle geometries. Through
extensive experimentation, both techniques are shown to significantly reduce the
computational complexity of solving an OCP with a negligible loss in optimality.
The complexity reduction does not come at the expense of constraint satisfaction.
Secondly, this thesis covers a methodology to relax the hard requirement on high
control rates for MPC by asynchronously computing MPC updates at a slower
rate and tracking those control updates with a low-level feedback controller at
a high rate. The efficacy of this methodology, extended with a safety controller
in case of MPC failure, is validated for autonomous agile quadrotor navigation
in partially known, obstacle-rich environments.
Lastly, this dissertation presents a computationally efficient motion planner
for object picking in industry. The focus of the planner is on low computation
complexity and easy-to-tune constraints that guarantee reaching a desired pick
pose accuracy and that computes trajectories that are on average 30% faster
than the state-of-the-art.status: Publishe
De lange weg naar Fiducia Supplicans: Wat kan een verklaring over relatiezegeningen betekenen voor homokoppels in Vlaanderen?
No full textsponsorship: Fonds Wetenschappelijk Onderzoek|1129625Nstatus: Publishe