The zebrafish is a promising vertebrate model organism in early drug discovery and development.

Discovery and development of Central Nervous System (CNS) drugs is hampered by high attrition rates.

Growth hormone profiles are pulsatile and highly variable between individuals, limiting the implementation of mathemathical models to quantify an individual's secretion.

The overarching clinical aim of this thesis was to improve pharmacological pain management by characterizing the pharmacodynamics of analgesics. This promotion has been awarded the predicate cum laude.

M. Danhof, Co-promotores: J. Freijer, A. Yassen

Clinical development of drugs for central nervous system (CNS) disorders has been particularly challenging and still suffers from high attrition rates.

In this thesis population pharmacokinetic and physiologically-based pharmacokinetic (PBPK) approaches were applied to investigate the influence of glomerular filtration (GF) and active tubular secretion (ATS) on renal clearance in children.

Model based approaches, integrating physiological parameters or linking exposure with response, are powerful tools to quantify and evaluate the impact of genetic differences that are reflected as variability of drug exposure and/or clinical response(s). This thesis “Pharmacogenomics in Drug Development: …

Promotor: Prof.dr. M. Danhof, Co-Promotor: J. de Jongh

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.

Antimicrobial drugs constitute a fundamental part of modern medicine. The global rise in antimicrobial resistance poses a major threat to global health.

The last decades it is increasingly recognized that acute as well as chronic postoperative pain is an important problem. Treatment and prevention of postoperative pain is a challenge, especially in special patient populations where there is only limited guidance on how to optimally use opioids.

In this thesis, mathematical modeling and simulation was applied as a tool to inform quantitative decision making in oncology drug discovery and development.

Promotor: Prof.dr. M. Danhof, Co-promotor: O.E. Della Pasqua

Promotores: C.A.J. Knibbe; J.N. van den Anker, Co-promotores: H.P.A. van Dongen; B. van Ramshorst

Promotor: Prof.dr. M. Danhof

Promotor: C.A.J. Knibbe, Co-promotor: J.J. Boelens, R.G.M. Bredius

A novel mathematical model describes spatial-temporal drug distribution within one or more brain units, which are cubic representations of a piece of brain tissue with brain capillaries at the edges.

Growth and development affect the metabolism of drugs administered to neonates, infants, and children.

The aim of this thesis is to expedite and ensure the systematic accuracy of clearance scaling from adults to paediatric patients, with a special focus on drugs undergoing hepatic metabolism.

We strive to address the challenge of constructing a modeling language to write software which can take advantage of recent hardware developments (multicore, cloud) without compromising in its abstraction levels.

Promotor: Roeland M.H. Merks

Description of Biotic ligand models: making an inventory of available models & assessment of the variability of the predicted HC5 using the BLMs in different Dutch water types (2005 - 2007)

Promotor: M. Danhof, Co-promotor: E.C.M. de Lange

... which builds on self-regulation and stress-regulation theories and considers the modification of cognitions as a mediator of therapeutic change.

Na 41 jaar neemt Meindert Danhof, hoogleraar Farmacologie, op 31 maart afscheid van het Leiden Academic Centre for Drug Research. Een symposium ter ere van hem, voorafgaand aan het afscheidscollege, laat zien wat er in die periode bereikt is. Danhof kijkt met plezier terug.

Epithelial-mesenchymal plasticity (EMP) and tumor cell migration play an important role in cancer progression, and an improved understanding of the mechanisms underlying these concepts is essential for developing new targeted approaches.

Real-life processes are characterized by dynamics involving time. Examples are walking, sleeping, disease progress in medical treatment, and events in a workflow.

Promotor: Prof.dr. E. Deprettere

Kunst en vrije tijd, Kunst en vrije tijd

Death in all types of melanomas is generally caused by metastasis. Uveal melanoma (UM) is the most common intraocular melanoma, there are currently no (patient-derived) animal models that faithfully recapitulate metastatic dissemination of UM.

This dissertation studies the Asymptotics of Bayesian nonparametric inference for Gaussian linear models.

Promotores: Prof.dr. P.C.W. Hogendoorn & Prof.dr. H.P. Spaink Co-promotor: Dr. B.E. Snaar-Jagalska

Industrial manufacturing processes, such as the production of steel or the stamping of car body parts, are complex semi-batch processes with many process steps, machine parameters and quality indicators.

Promotores: Prof.dr. C.A.J. Knibbe, Prof.dr. M. Danhof, Prof.dr. K. Allegaert (Leuven)

Immunotherapies for cancer are an emerging class of therapeutic strategies which aim to treat cancer via augmentation of the immune system.

Wiskunde en Natuurwetenschappen, Leiden Academic Centre for Drug Research (LACDR)

Making a dynamic substance stock model in order to conduct scenario analyses and make forecasts.

Promotor: Prof.dr. J.N. Kok, Co-promotor: F.J. Verbeek

The molecular mechanisms that instigate a healthy cell to become malignant are fueled by (epi)genetic alterations in so-called driver genes.

This dissertation focuses on developing new mathematical and statistical methods to properly represent time-varying covariates and model them within the context of time-to-event analysis.

From surface science towards industrial practice using high-pressure scanning tunneling microscopy.

Peter Grunwald

In this thesis, we extend the concept of null models as canonical ensembles of multi-graphs with given constraints and present new metrics able to characterize real-world layered systems based on their correlation patterns.

Promotor: Prof.dr. F.S. de Boer, Co-promotor: D. Clarke

Wiskunde en Natuurwetenschappen, Centrum voor Milieuwetenschappen Leiden (CML)

Promotor: B.van de Water, Co-promotor: L.S.Price

Synthetic microswimmers take an important place within the interdisciplinary field of active soft matter.

Promotor: Prof.dr. B. van de Water, Co-promotores: L.T.M. van der Ven, A.S. Kienhuis

Lysosomal storage disorders (LSDs) are a group of orphan diseases characterized by lysosomal dysfunction or impaired lysosomal catabolism and affect collectively about 1 in 5000 live births.