982 zoekresultaten voor “lacdr amber terrorism” in de Publieke website
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Targeted Therapy for Triple-Negative Breast Cancer
The research described in this thesis focused on identifying novel drug targets and synergistic combinations for triple-negative breast cancer (TNBC), a virulent subtype of breast cancer with a dismal prognosis and limited therapeutic options.
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Targeting the adenosinergic system
Adenosine is an endogenous ligand which exerts its action by activating adenosine receptors (ARs), while its circulating levels are controlled via a variety of mechanism and proteins, amongst others the equilibrative nucleoside transporters (ENTs).
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A novel formulation for skin barrier repair : from ex vivo assessment towards clinical studies
The stratum corneum is the outermost skin layer and consists of dead cells embedded in a lipid matrix.
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Investigating lipid formulations for efficient RNA delivery using zebrafish models
Lipid formulations have demonstrated strong potential for nucleic acid delivery,particularly with the success of COVID-19 vaccines. Despite these advances, manyaspects of lipid formulations remain unclear.
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Optimizing antifungal treatment through pharmacometrics: dosing considerations to enhance outcome
Fungal infections pose a significant threat to individuals with compromised immune systems and despite advancements in diagnosis and treatment, they continue to jeopardize patient’s health.
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Towards a system-based pharmacology approach to predict developmental changes in renal drug clearance in children
Promotores: Prof.dr. C.A.J. Knibbe, Prof.dr. M. Danhof, Prof.dr. K. Allegaert (Leuven)
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The quantification of growth hormone secretion : application of model-informed drug development in acromegaly
Growth hormone profiles are pulsatile and highly variable between individuals, limiting the implementation of mathemathical models to quantify an individual's secretion.
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Human skin equivalents for atopic dermatitis: investigating the role of filaggrin in the skin barrier
Promotor: Prof.dr. J.A. Bouwstra, Co-promotor: A. El Ghalbzouri
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B cell modulation in atherosclerosis
Cardiovascular disease is a major global burden and atherosclerosis is the main underlying pathological process.
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Microengineered Human Blood Vessels For Next Generation Drug Discovery
Heart failure is a major health care problem with high mortality.
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Shaping the pharmacokinetic landscape for renally cleared antibiotics in obesity
The prevalence of obesity (BMI >40 kg/m2) has increased rapidly over the recent years, not only in adults, but also in children and adolescents.
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CD8+ T-cells in atherosclerosis: mechanistic studies revealing a protective role in the plaque microenvironment
Atherosclerosis is the most important underlying process that drives cardiovascular disease, and is characterized by an accumulation of cholesterol which triggers an inflammatory response in the vessel wall.
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Quantitative pharmacology of antimicrobials
Antimicrobial drugs constitute a fundamental part of modern medicine. The global rise in antimicrobial resistance poses a major threat to global health.
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Development of human skin equivalents to unravel the impaired skin barrier in atopic dermatitis skin
Promotor: J.A. Bouwstra Co-promotor: A. El Ghalbzouri
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Phenotypic plasticity and genetic adaptation of plant functional traits on global scales
In light of climate change, it is crucial to determine whether plant species can adapt to future climates to avoid extinction. Plants adapt to various conditions by altering their functional traits, such as leaf size or photosynthetic rate. Some traits appear linked and vary together between species,…
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Precision modeling of breast cancer in the CRISPR era
The molecular mechanisms that instigate a healthy cell to become malignant are fueled by (epi)genetic alterations in so-called driver genes.
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Individualized dosing of serotherapy in allogeneic hematopoietic cell transplantation - a delicate balance
Promotor: C.A.J. Knibbe, Co-promotor: J.J. Boelens, R.G.M. Bredius
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Automated de novo metabolite identification with mass spectrometry and cheminformatics
Promotor: T. Hankemeier, Co-Promotores: T. Reijmers, L. Coulier
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Quantification in untargeted mass spectrometry-based metabolomics
Promotor: T. Hankemeier, Co-promotor: T.H. Reijmers
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Development of automatic image analysis methods for high-throughput and high-content screening
Promotor: Prof.dr. B. van de Water
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Microfluidic 3D cell culture for high throughput screening
There is an urgent need for more physiologically relevant cell culture methods to guide compound selection in pre-clinical stages of the drug development pipeline.
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Protein arginine methyltransferases as modulators of lipid metabolism and inflammation and the relevance for atherosclerosis
Acute cardiovascular clinical events such as myocardial infarction and cerebral stroke represent the major cause of death in Western societies. These pathologies are primarily resulting from atherosclerosis, a progressive condition characterized by the accumulation of lipids, immune cells, and fibrous…
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Omics data integration with genome-scale modelling of dopaminergic neuronal metabolism
Parkinson's disease is the second most common neurodegenerative disease in the world. One of its symptoms is the loss of dopaminergic neurons in the substantia nigra pars compacta.
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Triblock polypept(o)ides for siRNA delivery: unique polymeric designs for versatile carrier systems
Utilizing the polymeric platform of polypept(o)ides, this thesis describes synthesis and investigation of novel triblock copolymers to obtain carrier systems with multiple compartments for efficient siRNA delivery. Although the individual microstructure of nanoparticles differs depending on the polymeric…
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Systematic investigations into the role of ceramide subclass composition on lipid organization and skin barrier
The lipids in the uppermost layer of the skin, the stratum corneum (SC), play an important role in the skin barrier function. The three main SC lipid classes are ceramides (CER), cholesterol and free fatty acids.
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Pulling the strings on anti-cancer immunity
Promotores: J. Jonkers, K.E. de Visser
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Intradermal delivery of nanoparticulate vaccines using coated and hollow microneedles
In summary, the collective results described in this thesis show that nanoparticulate vaccines can be delivered intradermally by coated and hollow microneedles and evoke antigen-specific immune responses.
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Novel Immune Cell-Based Therapies for Atherosclerosis
Promotor: Prof.dr. J. Kuiper
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Characterization of age-associated immunity in atherosclerosis
Healthy aging is one of the prime goals in today's society and atherosclerosis is among the greatest causes of morbidity in elderly. Cardiovascular disease patients receiving treatment are often of advanced aged and have an aged immune system, which limits translating experimental findings to the pa…
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Dyslipidemia at the crossroad of the skin barrier and the arterial wall
The research described in this thesis shows that hypercholesterolemia, a well-established risk factor for atherosclerosis, can impact skin lipid pool and barrier function already at young age. In the field of atherosclerosis, we showed that the small peptide Lyp-1 can be used as a targeting molecule…
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High throughput microscopy of mechanism-based reporters in druginduced liver injury
Promotor: B. van de Water
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Dosing considerations for preterm neonates: from pharmacometrics to clinical practice
Prematurely born neonates require, amongst others, pharmaceutical therapy. Dosing guidelines for these therapies are often based on data from term born neonates or older infants, while these are not necessarily similar to prematurely born neonates.
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Towards controlled microneedle-mediated intradermal immunization
Traditionally, vaccines are administered intramuscularly using conventional hypodermic needles, which cause pain and distress. Microneedles are very short needles (smaller than 1 mm) that are practically invisible to the naked eye.
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Metabolomics approaches for unravelling host-gut microbiota changes in different stages of cognitive impairment
The investigation into the bidirectional communication between the gut and its host is a rapidly growing area of research, attracting considerable attention for its potential to provide crucial insights into health and disease.
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Diagnosis and treatment of obese children with insulin resistance
Promotors: C.A.J. Knibbe, Anthonius de Boer, Co-promotor: M.M.J. van der Vorst
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Lost in translation: The toll-like receptor 7 induced pharmacological challenge model of the skin
This thesis investigates a pharmacological challenge model induced by Toll-like receptor 7 (TLR7) activation, focusing on skin inflammation and its implications for early drug development.
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The impact of obesity on the pharmacokinetics of drugs in adolescents and adults
Promotores: C.A.J. Knibbe; J.N. van den Anker, Co-promotores: H.P.A. van Dongen; B. van Ramshorst
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Non-invasive biomarkers for inflammatory skin diseases: towards systems dermatology
Inflammatory skin diseases such as psoriasis and atopic dermatitis can severely impact both the physical and social aspect of a patient’s life. Aberrant inflammatory responses are thought to be a major causative factor in these disorders, but an abundance of different factors contribute to the development…
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Systems vaccinology: molecular signatures of immunity to Bordetella pertussis
Promotor: G.F.A. Kersten, W. Jiskoot, Co-promotor: B. Metz
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Concepts and applications for evidence-based dosing in morbidly obese patients before and after weight loss surgery
Promotor: C.A.J. Knibbe, Co-promotores: H.P.A. van Dongen, B. van Ramshorst
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Gene networks-based mechanistic assessment of drug-induced organ toxicity: a focus on liver and kidney
Drug induced organ toxicity is the main problem of the drug development and drug usage in the clinic. The liver and kidneys are the most sensitive organs towards drug induced toxicity.
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Miniaturized metabolomics methods for enabling the study of biomass- restricted samples
This thesis investigated miniaturized mass spectrometry (MS)-based analytical methods to address challenges in analyzing biomass-restricted biological samples.
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Advancing the LeiCNS-PK3.0 model for prediction of CNS Pharmacokinetics Nonlinear BBB Transport, Inter-species Scaling, and Machine Learning
This thesis focuses on enhancing predictions of central nervous system drug exposure using the LeiCNS-PK3.0, a physiologically based pharmacokinetic model.
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Novel analytical approaches to characterize particles in biopharmaceuticals
Particles are omnipresent in biopharmaceutical products. In protein-based therapeutics such particles are generally associated with impurities, either derived from the drug product itself (e.g. protein aggregates), or from extrinsic contaminations (e.g. cellulose fibers).
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CD8+ T-cells in atherosclerosis, recognizing their contribution
Atherosclerosis is the most prominent underlying pathology of cardiovascular disease and an important cause of major adverse cardiovascular events.
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Vaccination and Targeted Therapy Using Liposomes; Opportunities for Treatment of Atherosclerosis and Cancer
This thesis focuses on using liposomes in two different treatment strategies; vaccination (or immunotherapy) and delivery of a small molecule, and in two different disease models; cancer and atherosclerosis.
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Systems pharmacology of the amyloid cascade
According to the amyloid cascade hypothesis, accumulation of beta-amyloid (Aβ) peptides initiates the pathological cascade in Alzheimer's disease (AD).
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Optimisation of first clinical studies in special populations: towards semi-physiological pharmacokinetic models
M. Danhof, Co-promotores: J. Freijer, A. Yassen
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Disrupting the transcriptional machinery to combat triple-negative breast cancer
Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by limited treatment options and unfavorable clinical outcomes. Therefore, the research described in this thesis focused on the exploration of novel targeted therapies for TNBC.
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Sensing Transport
Solute carrier (SLC) transporters are a large and diverse class of relatively understudied transmembrane proteins.