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.

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.

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.

Promotor: A.W. van der Vaart

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.

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

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

Promotor: R.D. Gill, F. Taroni

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 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).

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

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.

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.

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

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

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. E. Deprettere

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.

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

Promotor: P.D. Grünwald

Promotor: Prof. dr. A.G.G.M. Tielens

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…

In this thesis,

There is a need for alternative methods to replace, reduce and refine (3R) animal experimentation. Combining experimental data from high-throughput in vitro studies with in silico modeling is a promising approach to unravel the effect of chemicals on living cells and to gain a better understanding of…

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…

In surface science there is great effort to move from studying simple, flat model surfaces in vacuum to investigating more complex model catalysts in gas environments (in situ). This thesis gives three examples of such studies using microscopy and spectroscopy.

The main objective of this thesis was to develop clinically relevant survival models for patients with high-grade soft tissue sarcoma of the extremities, in particular the development and validation of prediction models for use in clinical practice.

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.

Promotor: Prof.dr. F. den Hollander, G.Maillard

Promotor: Prof.dr. J.N. Kok

In this thesis we study quantum transport phenomena on the nanometer scale, in two classes of materials: topological insulators with induced superconductivity and graphene superlattices.

To improve cancer treatments, personalized medicine approaches have aimed to identify exactly which mutations are driving tumor development in a given patient and specifically target these mutations using precision therapies.

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)

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…

Promotores: J. Kok, M. Chaudron (Chalmers University)

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

Cholesterol influences many pathways, including serving as precursor for adrenal steroidogenesis. Imbalance of cholesterol levels has been implicated in several diseases including cardiovascular diseases and its underlying pathology, atherosclerosis.

This thesis focuses on two processes involved in fighting infections: metabolism and immune cell motility and navigation.

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…

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

The emergence of complex diseases resulting from abnormal cell-cell signaling and the spread of infectious diseases caused by pathogens are significant threats to humanity. Unraveling the dynamic mechanisms underlying cell-cell signaling and infectious disease spreading is crucial for effective disease…

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.

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.

Pharmaceutical companies, governments and the general public have become increasingly aware that animal models used in drug testing lack vital aspects to serve as an accurate representation of human biology. As models of the human body should become more physiologically relevant, animal models no longer…