Title Promoter Affiliations Abstract "Improving the EOL test process for wind turbine gearboxes" "Elke Deckers" "Mecha(tro)nic System Dynamics (LMSD)" "The aim of this research is to advance the end-of-line (EOL) test process for wind turbine gearboxes.  A decrease in test rig related measurement spread is strived for, together with (improved) correlations between different test runs. The EOL evaluation of the gearboxes will so become more stable and reliable, leading to a smaller amount of physical performed tests. Techniques such as mulitbody simulation and machine learning will be used. The eventual reduction in (re)test time will be valorized. " "Robotic Reuse, Repair, Remanufacturing, Repurposing and Recycling for Electrical Vehicles Batteries." "Jef Peeters" "Industrial Management/Traffic and Infrastructure (CIB)" "The electrification of the transport system and the transition to renewable energy sources is resulting in a rapid growth in the market for batteries. Hence, an exponential growth in Electric Vehicle (EV) battery production, as well as in end-of-(first)-life (EoL) batteries is expected. This will lead to the emergence of various opportunities to upscale circular businesses targeting their repair, reuse, remanufacturing, repurposing and/or recycling. One of the main challenges is that EoL batteries are not standardized and can widely vary in their design. In addition, when reaching their EoL the condition and integrity of the battery pack is no longer guaranteed, which increases the complexity of the EoL treatment and the related risks. Due to all these factors, the pre-processing, including the testing, discharging and disassembly of EoL EV batteries, is nowadays a costly manual process. Moreover, due to this labor intensity it will not be feasible to upscale the EoL treatment of EV batteries to the level needed to optimize the full lifecycle of EV batteries from an economic and environmental perspective and to secure the resources that are essential for upscaling various ecotechnologies. To overcome this challenge, the current battery value chain will be reconsidered where the opportunities of interlinking novel technologies, such as artificial intelligence (AI), robotics, innovative business models, such as product Ecodesigns will be investigated. Therefore, this project aims to develop a smart automatic platform for testing, discharging, disassembling and re-assembling EV batteries targeting repair, reuse, remanufacturing, repurposing and/or recycling." "Acoustic metamaterials: towards practical realisations" "Elke Deckers" "Mecha(tro)nic System Dynamics (LMSD)" "Human exposure to noise has increased over centuries and is recognized as the second largest environmental cause of ill health in today’s Western Europe. Common sound sources - e.g. traffic and machinery noise - are low frequent (< 2 000 Hz) and the thick sound absorbing panels, which are required to efficiently absorb these sound waves, conflict with the strive towards compact and lightweight design.Acoustic metamaterials (AMs) that target high absorption coefficients at low frequencies are omnipresent in today's academic literature. These structures are based on conventional acoustic resonators, but are geometrically modified to obtain thin and performant solutions. However, due to their complexity, AM designs are often only theoretically studied, using a variety of prediction models, or validated using small-scale samples, typically produced by additive manufacturing. To bring AMs to industrial practice, there is thus a clear need for (i) performant absorber designs, which are manufacturable by high-throughput production processes, and (ii) supporting design tools.This project will therefore develop a versatile and computationally efficient modelling framework to predict the AMs’ performance, whilst accounting for production related limitations. Using this framework, design trade-offs will be evaluated and compact absorbing structures will be optimized, manufactured and validated. The potential of these structures will be demonstrated in selected real life applications, e.g. thin sound absorption panels for landscape offices." "Striking Essential Oil: Novel tools and new insights to study the biological activities of essential oils (EOs) and their components (EOCs)" "Patrick Van Dijck" "Molecular Biotechnology of Plants and Micro-organisms, Animal Physiology and Neurobiology" "The increasing level of antimicrobial resistance poses the threat that no suitable antimicrobials will be available for systematic treatment of common diseases. More and more Candida infections are caused by intrinsically and multi-resistant Candida isolates. There is clearly renewed scientific interest in  discovering drugs from natural sources, although natural product-based drug discovery is considered intrinsically complex and requires a highly integrated interdisciplinary approach. Medicinal plants that are used to treat infectious diseases appear to be an abundant source of new bioactive secondary metabolites. One such class of plant-based molecules are essential oils which have been used therapeutically for millennia as they have a broad range of biological activities.Reanalyzing the data of a large antimicrobial screening (2012) of essential oils in microtiter plates systematically showed false-positive hits. We discovered that these false-positives were mediated by the vapor-phase of some essential oils in adjacent wells. The challenge was to circumvent this problem before we could start screening our latest essential oil (component) collection against two potentially disease-causing fungi i.e. C. albicans and C. glabrata. We developed an alternative plate set-up for the new screening in a way that it intrinsically does not modify the standardized protocol, while controlling for false positive results caused by the vapor-phase-mediated antimicrobial activity of the tested essential oils and their components. However, the alternative plate set-up and its derivatives are not limited to the testing of essential oils and their components but can be used with any volatile compound; nor is the set-up limited to testing antimicrobial activity but can essentially be extended to any biological activity tested in a microtiter plate. Therefore, we recommend these adaptations as good laboratory practices when working with volatiles in microtiter plates.An in vitro assay to test the vapor-phase-mediated antimicrobial activity of volatiles did not exist. From a drug discovery point such an assay is interesting as a model for testing compounds for e.g. the treatment of tract-related infections. We hypothesized that if we can detect false-positives in microtiter plates caused by the vapor-phase of volatiles, it should be possible to develop a microtiter plate-based assay. We developped the qualitative vapor-phase-mediated patch assay, a relatively simple test to detect the vapor-phase-mediated activity of volatiles such as essential oils and their components. We conceptualized a quantitative version of the aforementioned assay, i.e. the vapor-phase-mediated susceptibility assay, which we then developed further. Subsequently we quantified with this assay the vapor-phase-mediated antimicrobial activity of a collection of 175 commercial essential oils and 37 reference essential oil components against C. albicans and C. glabrata. About half of the essential oils and their components had a growth-inhibitory vapor-phase-mediated antimicrobial activity. On average, a stronger activity was observed against the intrinsically more resistant C. glabrata, with essential oil component citronellal showing the largest  significant difference in vapor-phase-mediated antimicrobial activity. In contrast, representatives of each class of antifungals currently used in clinical practice did not exhibit any vapor-phase-mediated antimicrobial activity. The vapor-phase-mediated susceptibility assay can advance the search for novel (applications of existing) antimicrobials. Furthermore, our study is the first comprehensive characterization of essential oils and their components as a unique class of antifungals with properties distinct from existing antifungal classes. We conducted a pairwise comparison between the inhibitory vapor-phase-mediated anti-Candida activity of 33 certified organic essential oils and as many equivalent essential oils without such certification. It is believed among essential oil consumers that essential oils from organic cultivation, which includes plants that are harvested in the wild, are therapeutically more potent than those from conventional cultivation. However, we did not discern a significant difference in inhibitory vapor-phase-mediated anti-Candida activity between certified organic essential oils and those without such certification.Although essential oils have been used therapeutically for millennia they continue to be considered as products mainly used in complementary and alternative medicine. Few have made the transition to drugs despite a shared Nobel Prize in 2015 for essential oil-related research of Dr. Youyou Tu for her discoveries concerning a novel therapy against malaria. In the past decades, natural products such as essential oils and their components have somehow been avoided in drug discovery because of inter alia possible technical problems during processing. However, is this still justified with our current understanding of drug discovery? Therefore, we studied selected physicochemical parameters, used in conventional drug discovery, from the components of a collection of 142 essential oils. We demonstrated that, contrary to generally held belief, most essential oil components satisfy current-day requirements of medicinal chemistry for good drug candidates. Therefore, their therapeutic potential remains vastly under-used and should be more vigorously explored with modern methods. Furthermore, it seems that they offer striking opportunities for lead optimization or even fragment-based drug discovery." "The role of the COL4A2 NC1-domain in cerebrovascular and aneurysmal disorders: a functional approach." "Medical Genetics (MEDGEN), Medical Genetics (MEDGEN)" "COL4A1- and COL4A2-related disorders cause a broad spectrum of problems comprising abnormal brain development, brain hemorrhage at any age, aneurysms (local dilatations) of the brain arteries, but also eye or renal problems. In addition, COL4A1 was recently identified as a genetic modifier in Marfan syndrome. We studied the presence of COL4A1 and COL4A2 variants in two patient cohorts; a cerebral palsy (CP) and a TAA (thoracic aortic aneurysm) cohort. This led to a specific interest in the COL4A2 NC1 domain. A burden analysis demonstrated a statistically significant overrepresentation of COL4A2 NC1 variants in the CP cohort. Furthermore, we identified the NC1 variant p.Arg1662His in 3 TAA patients and 3 CP patients of Moroccan descent. In 5 cases in combination with the helical variant p.Met1355Thr. The latter is suggestive of a shared ""risk haplotype"". The p.Arg1662His variant was significantly overrepresented in Moroccan patients in our cohorts compared to a Moroccan control cohort. In addition, We will study the cellular effects of NC1 variants using patient fibroblasts in order to assess (1) the levels of endoplasmatic reticulum stress and activation of the unfolded protein response and (2) alterations in Akt-FAK-mTOR signaling and procaspase 8 and 9 expression. Fibroblasts were collected from patients harboring (1) the COL4A2 variant p.Arg1662His, (2) the COL4A2 variant p.Arg1662His in combination with the COL4A2 variant p.Met1355Thr and (3) the pathogenic COL4A2 p.Gly1353Ala as a positive control. Three wild-type fibroblasts are used as negative controls. Secondly, we will develop a zebrafish model to study the effect of COL4A2 NC1 variants. We will start with the introduction of the pathogenic COL4A2 p.Gly1353Ala variant and study the effect on zebrafish development using a fish that has fluorescent blood vessels in order to easily pick up abnormal vessels. We will study the occurrence of brain haemorrhage, changes in movement patterns and the basement membrane, a structure that stabilizes the wall of blood vessels and measure the aortic diameter. When a reliable read-out is identified, we will introduce NC1 variants in the zebrafish model to assess their effect. This project is the first study to investigate the contibution of specific COL4A2 NC1-domain variants in pathology. When our findings are corroborated by functional studies, it would also be the first identification of a population-specific COL4A2-related risk haplotype associated with cerebral and aortic vascular pathology, which is an important finding in the age of personalized medicine. Another novelty is the development and use of a zebrafish model to study functional effects of COL4A2 variants using (CRISPR)/Cas9 technology. The model would enable not only functional analysis of additional variants of unknown significance in cerebrovascular pathology and TAA, but additionally allows studies regarding the pathogenic mechanisms underlying different types of COL4A2-mutations. This will help in identifying potential therapeutic strategies. Eventually, the model is suited for testing of potential treatment strategies in vivo, enabling monitoring of the therapeutic effect, as well as unwanted side-effects." "In search for chaperone-agonizing drugs for skeletal dysplasias attributed to dominant-negative COL2A1 mutations." "Aline Verstraeten" "Medical Genetics (MEDGEN), Medical Genetics (MEDGEN)" "Heterozygous missense mutations in the collagen type II-encoding gene COL2A1 explain about 95% and 70% of the hypochondrogenesis and spondyloepiphyseal dysplasia congenita patients, respectively, as well as a smaller fraction of patients with closely related phenotypes. Prior functional characterization of iPSC-derived and transdifferentiated chondrocytes of carriers of COL2A1 missense mutations revealed increased expression of endoplasmatic reticulum (ER) stress and apoptosis markers in addition to reduced levels of cartilage matrix proteins. Abnormal procollagen folding is considered a key pathogenic skeletal dysplasia mechanism, rendering chaperone-oriented therapy an interesting pharmacological avenue. Subjecting iPSC-chondrocytes of a COL2A1 glycine substitution carrier to a drug library comprising roughly 2,400 chaperone agonists and antagonists, we aim to identify a highly potent novel drug for skeletal dysplasias attributed to COL2A1 missense mutations. To evaluate the compounds' efficiency in restoring the cellular phenotype, integrated high content quantification of collagen type II as well as apoptosis and ER stress markers will be done. The most interesting compounds will be tested in knock-in COL2A1 mice to establish in vivo performance." "Mast cell activation tests (MAT): from an innovative diagnostic to the expansion of a service facility." "Didier Ebo" Immunology "Drug hypersensitivity constitutes a significant health problem with serious consequences of both mis- and overdiagnosis. nfortunately, correct diagnosis of drug hypersensitivity can pose significant challenges, mainly because of our knowledge gaps in the molecular and pathophysiological processes underlying immediate and non-immediate drug hypersensitivity reactions but also, most importantly, because of the unavailability of reliable in vitro tests and uncertainties associated with skin testing 1-3. This ""proof-of-concept project"" is an apex of our ongoing overarching research on the cellular processes, pathophysiology and diagnosis of immediate drug hypersensitivity reactions resulting from mast cell and basophil degranulation 1-30. Likely, this project will deepen our insights and shift paradigms in the mechanisms that govern mast cell degranulation finally culminating in immediate drug hypersensitivity reactions. However, our proposal primarily focuses on i) the confirmation of our innovative MAT (mast cell activation test) to be a performant diagnostic and ii) to expand capacity of our service platform to offer these tests to colleagues and industry. With respect to the valorisation, this POC-proposal should promote our services and offering our MAT (amongst other diagnostics) to more colleagues and industry. Today, our laboratory has already created a restricted service platform. In other words, this POC-project will not restrict to confirmation of the MAT, but will also invest, via several initiatives, in the expansion and promotion of our services (inter)nationally, application for a full patent, and in the set-up of a business model. In this context, communication of the data, analyses of demands and market studies are critical. Clearly, the potential of the MAT, which we already filed a priority application for and necessitates only patients' sera, is broad. Moreover, preliminary results from our market analysis, and the potential of additional indications, could result in industrial interest and the creation of a spin-off." "Mitochondrial and endoplasmic reticulum stress in oocytes and embryos as treatment targets for infertile patients with metabolic diseases." "Waleed Marei" "Veterinary physiology and biochemistry" "Oxidative stress, mitochondrial and endoplasmic reticulum (ER) stress have been recently postulated as main drivers of altered pathways in the oocyte linking maternal metabolic disorders to low fertility outcomes. Upregulated lipolysis, commonly associated with obesity and other metabolic disorders, increases the concentrations of lipotoxic fatty acids in the follicular fluid, which were shown to have a direct detrimental impact on oocyte quality and subsequent embryo development. Oocyte maturation involves complex nuclear, cytoplasmic, and molecular changes that determines its developmental competence. In human IVF clinics, oocytes are usually collected after hormonal stimulation and thus after exposure to metabolic stress during maturation in the follicle in affected mothers. It is not known if the deterioration in developmental competence of these metabolically-compromised oocytes can be rescued by alleviating mitochondrial and endoplasmic stress during or after fertilization, or should the stress be prevented during maturation. This project aims to test sensitive windows for preventative or reparative measures that may improve in vitro embryo production from metabolically-compromised oocytes, and examine the intrinsic quality of the embryos produced after treatment. A well-established bovine in vitro model will be used to generate metabolically-compromised oocytes by exposure to elevated pathophysiological levels of palmitic acid. MitoQ, a highly efficient mitochondria-targeted antioxidant, and Sirolimus, a specific ER-stress inhibitor, will be used to alleviate cellular stress either during fertilization or embryo culture, or during maturation. Embryo development will be recorded and blastocysts quality will be assessed by examining their metabolism, cell proliferation, cell lineage, DNA damage, markers for cellular stress and apoptosis. RNA-seq will be used to detect any persistent alterations in the transcriptomic profile. These studies will help defining windows of sensitivity and efficiency of targeting intracellular stress as a treatment option for infertile patients suffering from metabolic diseases." "New processes for the fermentative production of glycolipid biosurfactants and specialised carbohydrates" "Wim Soetaert" "Department of Biotechnology, Department of Biochemical and microbial technology, Institutszentrum Schloss Birlinghoven, Bio Base Europe, INBIOSE, EOC BELGIUM NV, Carbosynth Limited, Evonik (Germany), Croda (United Kingdom), IMD NATURAL SOLUTIONS GMBH, Evonik Stiftung, CRODA EUROPE LTD, Flemish Institute for Technological Research, Compagnie Industrielle de la Matière Végétale (France)" "CARBOSURF aims to develop new biobased processes and products. Specifically, it targets the fermentative production of different glycolipid biosurfactants with a wide range of application fields, and specialty carbohydrates, i.e. complex human milk oligosaccharides, whith applications as neutraceutical, pharmaceutical and cosmetic ingredients. Sufficient amounts of new products will be produced for application testing, in order to evaluate their market potential." "Quantitative approach to assess function and apoptosis changes in the H9C2 cardiomyocyte cell line following differentiation and Doxorubicin exposure" "H Llewelyn Roderick, Heinrich Huber" "Experimental Cardiology, Department of Cardiovascular Sciences" "Introduction: For some decades, the anthracycline doxorubicin (DOX) has been used in the treatment of solid tumors and leukemia. It is one of the most widely and successfully applied chemotherapeutic drugs and over the last 20 years has increased the 5-year survival rates for pediatric cancer patients from 58% to 80%. However, the clinical utility and dosage regimens of DOX are often limited by severe side effects.The most severe side effect of DOX is chronic dilated cardiomyopathy (DCM). Chronic DCM leads to cardiac dysfunction and eventually congestive heart failure that without heart transplant may result in death. Chronic DCM occurs in about 10-20% of cancer survivors and is often manifest 10-15 years following treatment. The molecular mechanisms of disease progression after this long latency remains to be determined however DOX associated reactive oxygen species (ROS) generation has been considered to play a major role in this late toxicity. While not ruling out a contribution for ROS, antioxidant therapy has not however been successful in reducing the incidence of cardiotoxicity in patients treated with DOX. Some studies have suggested that apoptosis is involved in doxorubicin-induced cardiotoxicity although little evidence of substantial apoptosis was reported in heart biopsies of patients with DCM who had previously been treated with DOX. Given that cardiac toxicity arises only years after treatment, a low level of apoptosis may however be sufficient for the DCM phenotype observed.  With this in mind, we investigated the mechanisms of toxicity of DOX and whether its toxic effect involved apoptosis.Hypothesis and aims: The aim of this study was to understand the mechanisms underlying DOX induced late cardiotoxicity. We hypothesized that, DOX sensitization of cardiomyocytes during chemotherapy leads to their lower resistance to a subsequent apoptotic stimulus. We postulated that this increased sensitivity was due to a DOX-induced dedifferentiation of cardiomyocytes, which are relatively resistant to apoptosis, into a cardiomyoblast phenotype that is more sensitive to death-inducing stimulus. To validate our hypothesis, we first compared the sensitivity to apoptosis of H9C2 cardiomyocytes (H9C2 CM) with that of H9C2 cardiomyoblasts. Secondly, to gain insight into the delayed action of DOX in vivo, we tested the effect of preconditioning cells to DOX upon their sensitivity to subsequent DOX treatment. The degree of differentiation and the mechanisms underlying apoptosis were probed in the contexts of these aims.Findings: H9C2 CM show greater resistance to apoptosis than H9C2, and using a non-biased proteomics approach, RT-qPCR as well as an immunoblotting assay, proteins of the apoptotic machinery that might underlie this resistance were identified. In particular, we found that anti-apoptotic proteins XIAP was increased upon differentiation. However, we surprisingly found that pro-apoptotic proteins caspase-8, caspase-3 and FAS were increased upon differentiation. H9C2 CM preconditioned to DOX exhibit signs of partial dedifferentiation. However, preconditioned H9C2 CM exposed to an apoptotic stimulus exhibited increased resistance to apoptosis. Together, these findings shed new light on the cell biology of DOX-induced toxicity and is consistent with the hypothesis that cardiomyocyte dedifferentiation initially protects against cell death.  "