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Fysiologie-gebaseerd farmacokinetisch modelleren in bijzondere patiëntenpopulaties: Inzichten in ouderen en volwassenen met obesitas
No full textThis research project aims to develop an open-source physiologically based biopharmaceutics (PBPK) model to support dose selection and improve pharmacotherapy for geriatric patients and older people. This model will integrate in vitro and in vivo data that focuses on the distinction between age and/or disease-related impact on drug absorption. Ultimately, the model could be implemented into PBB/PBPK modelling tools to predict and mechanistically inform changes in oral drug absorption in the elderly population.status: Publishe
Convolution-Friendly Image Compression with FHE
No full textDuring the past few decades, the field of image processing has grown to cradle hundreds of applications, many of which are outsourced to be computed on trusted remote servers. More recently, Fully Homomorphic Encryption (FHE) has grown in parallel as a powerful tool enabling computation on encrypted data, and transitively on untrusted servers. As a result, new FHE-supported applications have emerged, but not all have reached practicality due to hardware, bandwidth or mathematical constraints inherent to FHE. One example is processing encrypted images, where practicality is closely related to bandwidth availability. In this paper, we propose and implement a novel technique for FHE-based image compression and decompression. Our technique is a stepping stone towards practicality of encrypted image-processing and applications such as private inference, object recognition, satellite-image searching or video editing.
Inspired by the JPEG standard, and with new FHE-friendly compression/decompression algorithms, our technique allows a client to compress and encrypt images before sending them to a server, greatly reducing the required bandwidth. The server homomorphically decompresses a ciphertext to obtain an encrypted image to which generic pixel-wise processing or convolutional filters can be applied. To reduce the round-trip bandwidth requirement, we also propose a method for server-side post-processing compression.
Using our pipeline, we demonstrate that a high-definition grayscale image (1024 ⨯ 1024) can be homomorphically decompressed, processed and re-compressed in ∼8.1 s with a compression ratio of 100/34.4 on a standard personal computer without compromising on fidelity.sponsorship: This work was supported by the Flemish Government through the Cybersecurity Research Program with grant number: VOEWICS02 and by the FWO under an Odysseus project GOH9718N. This work was supported by the Spanish Ministry of Economy and Competitiveness with reference number RTI2018-102112-B-I00. Any opinions, findings and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of Cybersecurity Research Flanders, the FWO or the Spanish Ministry of Economy and Competitiveness. (Flemish Government through the Cybersecurity Research Program|VOEWICS02, FWO under an Odysseus project|GOH9718N, Spanish Ministry of Economy and Competitiveness|RTI2018-102112-B-I00)status: Publishe
Tumor Geabsorbeerde Dose-Respons Relaties in Gerichte Radionucliden Therapie. Een Preklinisch Onderzoek van Lutetium-177 en Terbium-161 Geradiolabelde Peptides.
No full textNeuroendocrine tumors (NETs) are a heterogeneous group of neoplasms that originate from cells of the neuroendocrine system. Targeted radionuclide therapy (TRT) has become the standard treatment in the management of patients with inoperable or metastasized well-differentiated NETs (up to 90% of symptomatic patients). Peptide receptor radionuclide therapy (PRRT) employs an exclusive feature of well-differentiated NETs that is the overexpression of somatostatin receptors (SST, subtype 2 or 5). This allows for the treatment with somatostatin analogs such as octreotide as well as radiolabeled somatostatin analogs (SSAs) such as 90Y-DOTATOC and 177Lu-DOTATATE. The basic principle of a radiopharmaceutical such as 177-Lu-DOTATATE is to chelate a vector molecule ((Tyr3)octreotate), which specifically targets the cancerous tissue, with a radionuclide (177Lu), which emits ionizing radiation, damaging the DNA of the cancer cells, thereby killing the cancerous cells, but not the surrounding healthy tissue. As an alternative to Lu-177, the recently introduced radiolanthanide Tb-161 has been proposed for NET therapeutic applications. It has a similar half-life (6.89 days) and chemical properties while emitting β- particles (Eβ-av=154 keV) for therapeutic purposes and γ-irradiation (Eγ = 49 keV, I = 17.0%; Eγ = 75 keV, I = 10.2%) suitable for SPECT imaging. Tb-161 also emits a substantial number of low-energy conversion and Auger electrons (≤ 50 keV; about 10x higher emission yield than Lu-177), which makes this radionuclide exceptionally interesting for the treatment of disseminated cancers, such as metastasized NETs, with multiple metastases ranging from a single cell (diameter: ~10 μm) to micro cell clusters (diameter: < 1 mm). Since the very beginning, researchers attempted to understand the radiobiologic effects of external beam radiotherapy (EBRT) and how this could be optimized to maximize therapeutic benefit. To correctly evaluate efficacy and safety of therapy modalities and in the framework of individualized treatment, for which prediction of outcome is important, appropriate biological/biophysical models are needed. The probability that a given therapy may eradicate or control the tumor, is indicated by the formalism 'tumor control probability' (TCP). Originally, TCP models have been developed to predict external beam radiotherapy outcomes, both across populations and on a patient-specific level. TRT however is highly different from conventional external beam radiotherapy since it is a form of protracted radiation delivery during which the dose-rate is variable (e.g. due to physical half-life of the radionuclide, its specific activity and vector pharmacokinetics) and the spatial activity distribution is often non-uniform on both cellular and tissue level. Thereby, vectors can be coupled to an abundance of radionuclides that emit beta, alpha or Auger electrons, associated or not with X or gamma rays. Consequently, commonly used assumptions for modeling of EBRT dose response cannot be generalized towards TRT as well. Despite frequent and successful use of Lu-177-DOTATATE in the clinic, little or no radiobiologic considerations are made at the time of treatment planning or delivery, nor is there an abundance of data from preclinical studies. Currently, treatment is usually administered as a standard dose and number of cycles without adjustment for peptide uptake, dosimetry or radiobiological and DNA damage effects in the tumor. Moreover, data on the influence of absorbed doses on the response and toxicity of treatment with radiopharmaceuticals, which are actually a prerequisite for evidence-based individualized therapy, are also still lacking. The aim of this PhD is to develop a framework for improved modeling of the dose-response, i.e. the tumor control probability, for specific TRT scenarios. We will determine the different parameters within the TCP model based on extensive experimental data, gained from well designed experimental studies, representing the specific TRT exposure characteristics. The radiopharmaceuticals of interest consist of the clinically relevant DOTATATE vector, combined with the Lu-177 or Tb-161 radionuclide, tested in well-characterized in vitro and in vivo NET models. Due to the fact that Tb-161 emits a higher percentage of internal conversion and Auger electrons, Tb-161-DOTATATE is expected to deliver a higher absorbed dose to the bound tumor cell and immediate neighboring cells. We aim with our established TCP model to illustrate the expected improved therapeutic efficacy of Tb-161 DOTATATE compared to Lu-177 DOTATATE.status: Publishe
Vermogenelektronische Betrouwbaarheid van Meerpoortsomvormers: Rekening Houdend met het Ontwerp en de Werking in Hernieuwbare Energietoepassingen
No full textElectrification is put forward as an important strategy to reduce greenhouse gas emissions. Hence, both energy sources and sinks need to be electrified as much as possible. All these new applications often have different voltage and power levels, requiring power converters at the interconnections. These converters should be cost effective, efficient, and reliable to make large scale adoption possible. Currently, mostly standardised converters are used which have a single input and output. When more than two terminals need to be combined, multiple converters are interconnected to a common bus. This provides an expandable solution which is easy to design. However, other solutions that provide even better characteristics might exist. Instead of using one converter per port, components could be shared between ports, leading to a final solution with less components. Next to reducing the cost, this might also improve the efficiency and reliability. Unfortunately, designing these multiport systems requires a lot of skill and creativity. The solution is also application specific, leading to the need for a redesign when ports need to be added. This makes the use of these converters impractical in most applications.
In order to solve this, the converter design should be automated. This work focuses on the first step, deriving the circuit topology. The proposed methodology makes use of the limited amount of valid connections that can be made between power electronic components. At different abstraction levels, the possibilities are explored and invalid configurations are eliminated, transferring only potentially viable solutions to the next round. Finally, the voltage relations and current flows in the remaining candidate converters are evaluated, allowing to identify the final valid solutions. The methodology is tested on a PV-battery use case and valid topologies are found, using less components than the reference topology with individual converters. The reliability improved as well due to the reduced power fluctuation in individual components caused by combining different port power flows. Less fluctuations also allow for the selection of smaller heat sinks, however, it could be decided to keep the heat sinks larger in order to retain a good efficiency.
Although the proposed methodology already allows to construct converters with an increased reliability, it remains an important goal to improve the reliability further. Failures in renewable energy applications do not only increase the overall maintenance cost, but also lead to costs linked to the loss of energy produced. Next to selecting reliable topologies during design, it is also possible to increase the reliability in the operational phase, by eliminating a strongly degraded component before catastrophic failure occurs. In order to make these decisions, the condition of the converter components needs to be known. To this end, damage sensitive parameters can be measured, linking an electrical parameter to the amount of damage present. Establishing this relation is difficult in applications with a highly varying mission profile, as these parameters are often also dependent on temperature. Hence, in this work a dual approach is proposed, estimating both the temperature and degradation level using two independent measurements. A PV-battery application is used to demonstrate that it is possible to eliminate a component and form new circuits using the topology derivation methodology. The resulting back-up converter potentially has reduced capabilities, however, operation can be resumed.status: Publishe
De academische samenwerking met Israël meteen stopzetten? Zo simpel is het niet
No full textstatus: Publishe
Reinforcement corrosion assessment through Bayesian parameter updating with spatially distributed inspection data
No full textsponsorship: The authors would like to express their gratitude to Research Foundation Flanders for their financial support (FWO PhD-grant no. 1SC1921N and FWO-SBO LifeMACS project no. S001021N). (Research Foundation Flanders, 1SC1921N, FWO-SBO LifeMACS, S001021N)status: Published onlin
Nanomaterialen met hoge entropie voor elektrokatalytische stikstofcycli
No full textElectrocatalytic nitrogen cycling, such as the nitrogen oxidation reaction (NOR) and the nitrate reduction to ammonia (NRA), offers an attractive low-energy route for transforming inert atmospheric N2 or nitrate pollutants into valuable products such as nitrates or ammonia. These reactions hold significant promise for sustainable ammonia synthesis and nitrate remediation but are hindered by sluggish kinetics, competing side reactions, and stability challenges under operating conditions. Addressing these issues requires electrocatalysts that combine high activity, selectivity, and durability while operating under complex, multistep reaction pathways. Since the advent of high-entropy alloys (HEAs) in 2004, high-entropy materials (HEMs), particularly in nanoscale form, have emerged as a promising electrocatalyst platform due to their unique physicochemical properties. Their tunable electronic structure, lattice distortion, excellent stability, and multi-element synergy offer unique opportunities for tailoring adsorption energies, stabilizing key intermediates, and suppressing competing reactions, thereby addressing the kinetic and selectivity bottlenecks in nitrogen-based electrochemical transformations. However, their application in NOR and NRA remains in its infancy, with only a few reported studies, leaving substantial room for exploration in both fundamental understanding and practical performance optimization.status: Publishe
Eco-evolutionaire dynamiek en prioriteitseffecten in de gemeenschapsassemblage van het darmmicrobioom van Daphnia
No full textThe gut microbiome exerts a profound effect on the development, physiology and behaviour of its host and plays an important role in the rapid adaptation of host individuals to changing environmental conditions. While much research has been done in recent years in evaluating the mechanisms driving community assembly in gut microbiomes, there is a very limited understanding of the underlying eco-evolutionary processes involved in shaping the gut microbiota composition. Using the water flea Daphnia as a model system, this thesis aims at investigating the importance of eco-evolutionary processes, more specifically evolution-mediated and microbiome-mediated priority effects in gut microbiome community assembly, to explore the consequences of the resulting variation in microbiome composition on host adaptation to environmental stressors. This project thus seeks to generate unique insights on microbiome community assembly with profound relevance for general gut microbiome studies.status: Publishe
Causal Effects of an Ecologically Valid Home Numeracy Intervention on Preschoolers' Numeracy Skills
No full textThe home numeracy environment is suggested to influence children's numerical development, but causal evidence for this assertion remains limited. Addressing this gap, we randomly assigned 117 predominantly White 4-5-year-olds (M = 4.68 years, SD = 0.2, 47% girls) attending preschool in Flanders (Belgium) to either an experimental (numeracy) or an active control (language) condition. The 6-week intervention (pretest-March 2023; posttest-May 2023) consisted of an ecologically valid implementation, with parents integrating flexible activities into their routines. Pre- and post-intervention assessments measured children's numerical skills. Medium effects were observed on transcoding and ordering skills, providing causal evidence for the impact of the home numeracy environment on children's numeracy. This study highlights the potential of ecologically valid interventions to support early numeracy in daily life.sponsorship: This work was supported by Fondation Fyssen, post-doctoral study grant to C.G. (Fondation Fyssen)status: Published onlin
De ontwikkeling van XNA ligases als tool voor de synthetische biologie
No full textBeyond storing the complete genetic blueprint for all life on Earth, DNA and RNA also function as sensors, regulators, and even catalysts. Attempts have been made to expand their functionality towards pharmaceutical and biotechnological applications, but limited (biological) stability makes them ineffective candidates. Xenobiotic nucleic acids (XNAs) are artificial analogues of DNA and RNA with increased chemical and biological stability due to altered chemical moieties.
XNA oligonucleotides can be made using the same solid-chemistry methodology as DNA. Due to the limited coupling efficiencies of the phosphoramidites and complex purification, the chemical synthesis of XNA oligonucleotides suffers from size limitations. Enzymatic synthesis methods can be promising alternatives to generate longer, more diverse XNAs in a more sustainable, solvent-free environment. However, the XNA research field was, and still is, primarily focused on the development of XNA polymerases. While tremendous advancements have been achieved, the XNA polymerases still suffer from low efficiency, high error rates and cannot deliver the same chemical diversity as chemical synthesis.
The main goal of this thesis was to develop XNA ligases for synthesising chemically diverse and extended XNA fragments, previously unreachable with chemical or polymerase-driven synthesis methods. This will be a new step towards the maturation of the XNA research field, while simultaneously gaining insight into XNA (and by extension DNA) ligation.status: Publishe