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.

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.

Systems with local constraints is a new finding in recent researches on complex systems. The heterogeneous spatial interactions and the temporal dependencies among those numerous units make it difficult to describe by traditional statistical physics.

Het onderzoeksprogramma Statistical Science houdt zich bezig met de analyse en interpretatie van grote hoeveelheden data, de kwantificering van onzekerheid met behulp van kansmodellen en de ontwikkeling en benchmarking van algoritmen en methoden gericht op dataonderzoek.

Promotores: J.C. van Houwelingen, S.A. van de Geer

Despite being the object of intense study, embryonic development has been difficult to model due to a number of reasons. First, complex tissues can be comprised of many cell types, of which we probably only know a subset.

Promotor: R.D. Gill, F. Taroni

During embryonic growth, cells proliferate, differentiate, and collectively migrate to form different tissues at the right position and time in the body.

Promotor: A.W. van der Vaart

Explaining treatment response variability between and within patients can support treatment and dosing optimization, to improve treatment of individual patients.

In this thesis, we examine various systems through the lens of several numerical methods.

A complex community of microbes develops in the infant gut shortly after birth. We call this community the infant gut microbiota. The microbiota influences the health of the infant, which makes the composition and function of the infant gut microbiota an important topic to study.

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

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.

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

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

This thesis develops statistical methods for the analysis of high dimensional data: high dimensional networks reconstruction (Chapters 1-4), incorporation of prior information in networks reconstruction (Chapters 2-4), incorporation of prior knowledge in genetic association studies (Chapter 3).

Promotor: P.D. Grünwald

Promotor: F.H.J. Redig, Co-Promotor: W.T.F. den Hollander

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

The parabolic Anderson model (PAM), which is the Cauchy problem for the heat equation with random potential. The PAM is a mathematical model that describes how mass (i.e. matter or energy) flows in a medium in the presence of a field of sources and sinks.

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: S.M. Verduyn Lunel

In 2016 hebben Universitaire Medische Centra (UMC's) van Nederland de zelfevaluatie-tool ontwikkeld gebaseerd op het PhD Competence Model. Onze partners van de Universiteit Utrecht stellen een digitale versie van de tool kosteloos beschikbaar voor onze promovendi binnen de Universiteit Leiden, ook voor…

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

The aim of this thesis was to develop novel treatment strategies for different types of eye melanoma utilizing zebrafish models. We first establish orthotopic and ectopic xenograft models for uveal and conjunctival melanoma by engraftment of the immortalized cells derived from these tumors into zebrafish…

Kunst en vrije tijd, Kunst en vrije tijd

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

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.

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.

Statistical considerations guide the design and implementation of the experiments that scientists perform. For instance, in a clinical trial about a the efficacy of a treatment, its effect in a certain minimum amount of patients has to be observed in order to make confident assertions about the efficacy…

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

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

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

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

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

Promotor: Prof.dr. S.F. Portegies Zwart

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

Promotor: Prof.dr. W.J.G.M. Peijnenburg

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

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.

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

Peter Grunwald

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

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.

Decarbonizing the building stock is critical for realizing the climate-neutral target for the Netherlands.

Accurate prediction of the unbound drug concentration-time profile at the CNS target site is crucial for the assessment of the right drug concentration-effect relationship. PBPK models have supported the PK prediction of the CNS target sites and the translation of PK data between species and between…

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