263134 research outputs found
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Macrofagenstreken Getemd: De Ontdekking van een Verborgen Regelaar in Tumormacrofagen
No full textTumour-associated macrophages (TAMs) are a major component of the tumour microenvironment and can be classified according to their major histocompatibility complex class II (MHC-II) expression in MHC-IIlow and MHC-IIhigh macrophages, having opposite effects on tumour growth. Since MHC-IIlow TAMs highly express pro-angiogenic factors and immune suppressive molecules which promote tumour progression, specific targeting of MHC-IIlow TAMs or repolarization to MHC-IIhigh TAMs are promising strategies to improve the response to cancer therapies and prevent relapse and therapy resistance. LncRNAs are transcripts longer than 200 nucleotides lacking coding potential. They have been implicated in many developmental pathways and because of their highly tissue- and cell-specificity they are considered as excellent biomarkers and potential therapeutic targets. Recent studies have shown that several lncRNAs have a role in regulating cancer immunity. However, their role in tumour-associated macrophages remains unclear. The aim of my PhD project will be to identify and study lncRNAs regulating TAM biology. The results of my study may bring to the identification of novel therapeutic opportunities.status: Publishe
ONTWIKKELING EN PREKLINISCHE EVALUATIE VAN DIAGNOSTISCHE EN THERAPEUTISCHE RADIOFARMACA GERICHT OP CXCR4
No full textIncreased understanding of the pivotal role of chemokine receptor type 4 (CXCR4) in tumor biology has resulted in the development of radiopharmaceuticals that can provide sensitive detection of CXCR4 expression and allow patient selection for CXCR4-targeted therapies. [68Ga]Pentixafor is the only CXCR4-targeted imaging agent that has found broad clinical applicability so far. However, due to the low production capacity, implementation of [68Ga]Pentixafor in clinical practice is still limited. Further, results with the therapeutic companion radiopharmaceutical [177Lu]Pentixather are promising, but there is still room for improvement regarding pharmacokinetics and dosimetry profile. Moreover, an CXCR4-targeted radiopharmaceutical labeled with an α-emitter might present a breakthrough in therapy of various CXCR4 expressing tumors such as multiple myeloma. Therefore, the aim of this project is to develop innovative CXCR4 radiopharmaceuticals, both for diagnostic and therapeutic purposes, starting from all D-amino acid peptide vector molecules that have not been explored yet for nuclear medicine applications.status: Publishe
Een Leuvens voorstander van de Katholieke Hervorming? Canoniekrechtelijke collegenotities en verhandelingen van Petrus Peckius (1529-1589) over herstel van kerken en kerkelijke tucht
No full textThis thesis examines the contributions of Petrus Peckius (1529-1589), a law professor at the University of Leuven, focusing on how he shaped canon law in response to the complexities of his era, including the rise of Protestantism, ongoing wars, and the new demands of Catholic Reform, particularly the changes instituted by the Council of Trent (1545-1563). The research utilizes Peckius's published works alongside lecture notes taken by one of his students during classes in Leuven from 1575 to 1577, providing insight into his dual role as both a jurist in print and an educator dedicated to mentoring the next generation of scholars. The study emphasizes two primary issues addressed by Peckius: (1) the restoration of churches that were damaged during the Iconoclastic Fury and (2) the regulation of clerical conduct and discipline. Ultimately, we explore how, while Peckius predominantly adhered to the authority of established canons and jurisprudence within the ius commune framework, he also actively engaged with Catholic Reform, introduced methodological innovations, and took into account the prevailing context when addressing canon law in Leuven.
This project is part of the @AULAM initiative at the Lectio Institute, or Innovation through Education. Pioneers of Change in Law and Theology during Leuven's Golden Age.status: Publishe
Speciale economische & geïnternationaliseerde jurisdicties: Een case-study van de Internationale Zone van Tangier, de Hong Kong Speciale Administratieve Regio & de Qatar Financial Centre
No full textThis doctoral thesis is a study of certain 'places in between' our common understanding of national and international law. More specifically, this is a study of certain special jurisdictions, i.e. semi-autonomous carve-outs from a hosting jurisdiction, that have a strong internationalised element in both their institutions and structure and that play an important economic role for that hosting jurisdiction. The idea of a special 'zone' or jurisdiction for foreign investors and merchants is not new: it has existed throughout history, and such jurisdictions continue to be established until today. However, such places are rarely compared in-depth, as their foundational basis is either in national or international law. Even so, they can and should be compared to each other, as they all have similar characteristics and perform the same function: they are special economic and internationalised jurisdictions ('SEIJs'). This work focuses on and compares three such examples from recent history and the present time: the International Zone of Tangier (1923/24-1956/60), the Hong Kong Special Administrative Region of the People's Republic of China (1997 - …) and the Qatar Financial Centre (2005 - …). This work finds many interesting and unexpected links and connections between these three case studies and beyond, such as the early European Union, leading to the confirmation of the concept. SEIJs are important places of cultural-, legal- and economic exchange, leading to an influence and impact far outside the boundaries of their limited territory.status: Publishe
Ontwikkeling van biofilmspecifieke magnetische ijzeroxide nanopartikels als drager voor 2-aminoimidazool biofilminhibitoren
No full textOver the years, multifunctional nanomaterials and in particular nanoparticles have been investigated thoroughly for their use in many applications, including catalysis, imaging, energy-based research and biomedical applications. Especially iron oxide nanoparticles are extensively used in hyperthermia treatment, medical imaging, cancer therapy and drug delivery thanks to their biocompatibility, chemical stability, low toxicity and superparamagnetic behavior.
In this dissertation the development of multifunctional superparamagnetic iron oxide nanoparticles is presented, which act as a magnetic carrier for in-house developed 5-aryl-2-amino-imidazole biofilm inhibitors to increase the practical applicability of biofilm inhibitors.
In the first part of this work, the synthesis and the possibility to control the size and magnetization of iron oxide nanoparticles in a forced hydrolysis synthesis method is described. Tuning the size of the nanoparticle by varying the surfactant/precursor ratio is a frequently used method and can be applied in various synthetic methods. This knowledge was used to determine the ideal nanoparticle size and applied in the thermal decomposition method, which was used in the following chapters due to the very good shape control, large scalability and the ability to produce high quality nanoparticles with very narrow size distribution.
In the second part of this research, a new ligand is designed and synthesized to connect in-house developed 5-Ar-2-AI-based biofilm inhibitors to the nanoparticle. Evaluation of the developed bioconjugated nanoparticles is tested against a broad panel of bacterial species, including Salmonella Typhimurium, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Since the substitution pattern of 5-Ar-2-AIs determines their activity and toxicity, N1-substituted, 2N-substituted as well as N1-2N-disubstituted 5-Ar-2-AIs are evaluated.
The effect of magnetic forces on the biofilm inhibition is analyzed in the final part of this dissertation. An alternating magnetic field is applied after incubation to determine the effect of magnetic nanoparticle heating. Furthermore, the nanoparticles are enriched at the surface by applying magnetic forces underneath a biofilm prior to incubation.status: Publishe
De kritische verbinding tussen metabolisme en het immuunsysteem tijdens malaria
No full textWith > 200 million clinical cases and over 400 thousands deaths each year, malaria remains a major health problem. In our research group, we focus on malaria complications, which are the main cause of death in malaria patients and arise from complex interactions between the parasite and the host immune and vascular systems. We investigate the pathogenesis of these complications and aim to develop improved therapies. Advanced mouse models, including transgenic parasites and conditional knockout mice, are combined with clinical studies and state-of-the-art technologies, including multicolor flow cytometry, histology and (confocal) microscopy, imaging technologies, transcriptomics and metabolomics. Both inflammatory markers and metabolic disturbances are highly associated with severity and mortality in malaria. In this PhD project, the aim is to investigate the regulation and mechanistic link between inflammation and metabolism in malaria and to determine how dysmetabolism may aggravate severe malaria and impede efficient therapy.status: Publishe
Battering RAM: Low-Cost Interposer Attacks on Confidential Computing via Dynamic Memory Aliasing
No full textConfidential computing, powered by trusted execution environments (TEEs) like Intel SGX/TDX and AMD SEV-SNP, is now widely available from major cloud providers. At the core of these technologies is hardware-level memory encryption to protect against privileged attackers and physical threats such as bus snooping and cold boot attacks. Recent extensions add access-control checks to defend against software-based ciphertext manipulation and aliasing attacks. In this work, we challenge the protection modern memory encryption technologies offer against physical adversaries by building a low-cost (\dollarcost) DDR4 interposer that dynamically tampers with address lines to bypass aliasing checks in current TEEs.
We demonstrate how the runtime nature of our interposer bypasses boot-time firmware mitigations introduced by AMD and Intel in response to software-based memory aliasing attacks. Using our interposer, we present the first attack on Scalable SGX's single-key domain, achieving arbitrary plaintext read/write access and extracting SGX's platform provisioning key, thereby dismantling trust in remote attestation. We further re-enable a full attestation breach on up-to-date AMD SEV-SNP platforms, bypassing recent firmware defenses against static aliases. Our results challenge core assumptions about encrypted memory security and highlight critical shortcomings in the performance-security trade-offs of current confidential computing systems. Costing orders of magnitude less than commercial DRAM interposers, our device underscores the need for stronger protections against low-cost physical attacks in scalable TEE designs.sponsorship: Fonds Wetenschappelijk Onderzoek|1261222N, Vlaamse Overheid|VOEWICS02, European Research Council|101020005, Engineering and Physical Sciences Research Council|EP/X03738X/1, Engineering and Physical Sciences Research Council|EP/V000454/1, Engineering and Physical Sciences Research Council|EP/R012598/1, Fonds Wetenschappelijk Onderzoek|11PFE24Nstatus: Accepte
De Europese Unie en de Bescherming van Cultureel Erfgoed in Derde Landen: Juridische en Beleidsmatige Aspecten
No full textThe European Union (EU) has set ambitious objectives for the protection and valorisation of cultural heritage, both within its borders and through its external action. However, a fundamental discrepancy exists between the EU's competence in culture—granted under Articles 6 and 167 TFEU—and its expansive policy goals regarding cultural heritage protection in third countries. Culture is designated as a supporting competence, meaning that the EU can only intervene to support, coordinate, or complement Member States' actions. Consequently, the EU lacks independent authority to implement cultural heritage policies abroad unless they are linked to policy areas where the EU has exclusive or shared competences.
Article 167(4) TFEU presents a significant mechanism for overcoming these constraints by allowing the integration of cultural heritage considerations into broader EU policies. This provision extends EU engagement beyond the procedural limitations of Article 167(5) TFEU, facilitating a more expansive role for cultural heritage in EU external relations. A key question thus emerges: how can the EU successfully integrate cultural heritage protection in third countries despite its supporting competence in culture?
This thesis explores how the EU, pursuant to Article 167(4) TFEU, utilises the accession process as a strategic instrument to protect, safeguard, and promote cultural heritage in third countries, with a specific focus on the Western Balkans and Turkey. Furthermore, the research assesses the EU's capacity to act as a coherent and influential player in global cultural heritage governance, particularly within the United Nations Educational, Scientific and Cultural Organization (UNESCO). While the EU itself does not hold a vote in UNESCO, its Member States participate as sovereign entities, raising the question of whether the EU can ensure policy coherence and avoid fragmented national positions. By examining the EU's external action - in particular through the accession process and through multilateral engagement within UNESCO, this doctoral research evaluates the extent to which the EU can achieve its cultural heritage objectives in its external action while navigating institutional and legal constraints.status: Publishe
Onderzoek naar het gebruik van elektrofysiologische opgewekte potentialen bij diepe hersenstimulatie
No full textDeep brain stimulation (DBS) is an established therapy for several neurological and psychiatric disorders, yet its optimization still largely relies on trial and error. Despite advances in imaging and stimulation hardware, robust physiological markers to guide electrode placement and programming are still lacking. Evoked potentials (EPs), measurable time-locked electrical responses to stimulation, represent an emerging approach for objectively assessing network engagement and clinical efficacy.
This thesis explores the utility of DBS-evoked potentials across three major indications: Parkinson's disease (PD), obsessive-compulsive disorder (OCD), and treatment-resistant depression (TRD). In PD, we investigated evoked resonant neural activity (ERNA) in the subthalamic nucleus. ERNA scaled with stimulation amplitude, varied systematically across directional contacts, and the derived electrophysiological sweet spot closely mapped onto previously established sites associated with clinical benefit. Comparative analyses across disorders further indicated that the presence of ERNA primarily reflects engagement of the STN-GPe circuitry, whereas its morphology appears to vary with disease-specific pathology. In OCD, we examined intraoperative electroencephalography (EEG) during anterior limb of the internal capsule (ALIC) stimulation. We showed that EP amplitude corresponded with white matter tracts connected to the prefrontal cortex, which have previously been implicated in clinical effectiveness, supporting their use as biomarkers of target engagement. In TRD, high-density EEG recordings during subcallosal cingulate cortex (SCC) stimulation revealed reproducible spatio-temporal patterns that differentiated therapeutic from non-therapeutic stimulation contacts, reflecting engagement of distinct white matter pathways implicated in mood regulation.
Together, these studies demonstrate that DBS-evoked potentials convey physiologically and clinically relevant information across disorders and targets. By linking evoked responses to anatomical lead placement derived from imaging, and in other targets by relating them to structural connectivity and clinical response, this work advances EPs as biomarkers for personalized DBS, with the potential to improve targeting accuracy, streamline programming, and enhance long-term clinical efficacy.status: Publishe
Depositum Irregulare en gelijkaardige types van bewaargevingsovereenkomsten in de Romeinsrechtelijke traditie
No full textThe objective of this thesis is to give a comprehensive overview of the evolution of the irregular deposit as well as some other types of deposit of fungibles, namely the aggregate deposit (reguläres Summendepot) and the mingled deposit (Sammeldepot). Economic aspect of the said institutions are also going to be considered. The irregular deposit existed already in Roman law as we may assert from the texts contained in the Digest and Code of Justinian. However, not only are some of these texts in mutual conflict, some are even outright internally contradictory. Accordingly, the author shall try to explain these contradictions and discover how the Romans dealt with the deposit of fungibles in classical as well later periods of Romal law. The glossators developed their own doctrine of depositum irregulare which was based on Roman legal texts, but also influenced by the reality of their day. This evolution was then continued by the commentators and other civilist in medieval and early modern period. At the same time the irregular deposit and banking in general was thoroughly studied by the scholars of the famed School of Salamanca. The development also continued in later ages. In the German legal science of the 19th century multiple concepts of the institution of depositum irregulare appeared, some of which can be found even in today's law.status: Publishe