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.

Mouse models are commonly used to assess the immunogenicity of therapeutic proteins and to investigate the immunological processes leading to antidrug antibodies. The aim of this work was to develop a transgenic (TG) Balb/c mouse model for evaluating the immunogenicity of recombinant human insulin (insulin)…

Cardiovascular disease is the leading cause of death worldwide.

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

Invasive lobular carcinoma (ILC) is the second most common type of breast cancer.

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…

Promotor: H.J.M. de Groot, Co-Promotor: A. Alia

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.

Inactivating mutations in BRCA1 or BRCA2 genes predispose to several types of cancer.

In this thesis, we used genetically engineered mouse models to identify genes and pathways that are involved in ILC formation and in the development of resistance to FGFR-targeted therapy.

Promotores: J. Jonkers, K.E. de Visser

In this thesis, we used genetically engineered mouse models and a variety of cell-culture based assays to identify genes and pathways that are involved in the development and treatment of invasive lobular carcinoma (ILC).

The clinical potential of applying synthetic lethality to cancer treatment is famously demonstrated by the BRCA1/PARP1 paradigm: a tumor specific defect in BRCA1 – a component of the DNA double-strand break (DSB) repair pathway homologous recombination (HR) – results in a remarkable sensitivity to PARP1…

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

PhD defence

In the theme Drug research we generally work with rodents.

Can the (industrial) herbal extraction process be mathematically described and can this model be used to optimize the extraction in terms of quality and economical parameters?

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

PhD defence

Existing work in probabilistic language modeling can be mostly divided into two categories:

This thesis describes the use of an activity-based proteomics method to study the endocannabinoid system.

Mathematical models of software systems enable characterizations, abstractions, simulations, and analysis of complex software during its development.

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)

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

Main challenges in skin vaccination are overcoming the stratum corneum (SC) barrier and targeting the antigen presenting cells (APC) in the epidermis and the dermis.

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

Arts and leisure, Arts and leisure

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

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.

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

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.

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

Arts and leisure, Arts and leisure

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

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.

Can zebrafish provide a fast, sensitive in vivo vertebrate model for identifying novel mechanisms of Ewing sarcoma progression and for development of new anticancer compounds in a time- and cost-effective manner?

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

Systems pharmacology aims to apply techniques from systems biology to pharmacological models.

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

Peter Grunwald

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

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

An integrated approach of physiological concepts, advanced statistical approaches and large clinical datasets.

ASLU 14

In this project, we aim to develop mathematical models to mechanistically and quantitatively predict the dynamics of cellular stress pathway activation and its relation with toxic effects when cells are exposed to various toxicants.

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

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.