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.

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

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

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

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.

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.

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: A.W. van der Vaart

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

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

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.

This dissertation is organised into three parts, each addressing a distinct research area related to Gibbs measures.

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: 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

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

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…

Promotor: Prof.dr. E. Deprettere

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

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…

Promotor: S.M. Verduyn Lunel

Kunst en vrije tijd, Kunst en vrije tijd

Endothelial dysfunction and microvascular diseases are key drivers of cardiovascular disease, the world's leading cause of death.

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.

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.

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

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

In this thesis, we study systems of electrons in which strong correlations give rise to emergent exotic physics.

In this thesis,

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

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

To improve treatment of breast cancer patients it is important to understand all stages of breast cancer from initiation to in situ disease and progression to invasive disease. In this thesis we use intraductal injections of patient derived tissue to model ductal carcinoma in situ and invasive breast…

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

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.

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).

SDN (Software-Defined Networking) represents a revolutionary approach to network architecture that enables the dynamic and flexible management of network resources through software-based control. This dissertation introduces the idea of SDN and its southbound protocol OpenFlow, then presents the formal…

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.

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

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

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.

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…