Optimally solving real-world expensive Black-Box Optimization (BBO) problems w.r.t. real-world constraints, such as wall-clock time and computational costs, is extremely difficult and tedious.

Constraint multi-objective optimization with a limited budget for function evaluations is challenging. This thesis tackles this problem by proposing new optimization algorithms. These algorithms are applied on holistic ship design problems. This helps naval architects balance objectives like cost, efficiency,…

Microneedle-based vaccination has several advantages over vaccination by using conventional hypodermic needles.

A modern ship design process is subject to a wide variety of constraints such as safety constraints, regulations, and physical constraints.

It is a common technique in global optimization with expensive black-box functions to learn a surrogate-model of the response function from past evaluations and use it to decide on the location of future evaluations.

Over several decades, a variety of computational methods for drug discovery have been proposed and applied in practice. With the accumulation of data and the development of machine learning methods, computational drug design methods have gradually shifted to a new paradigm, i.e. deep learning methods…

Promotores: A.P. IJzerman, H.W.T. van Vlijmen

Optimality in plant properties and processing.

The goal of hit and lead optimization is to optimize suitable chemical starting points that can modulate a drug target. The methods and technologies used are similar to those in Hit Discovery, but once the compound has shown activity in an animal model, it moves from 'hit' to 'lead.'

Optimization tasks in practice have multifaceted challenges as they are often black box, subject to multiple equality and inequality constraints and expensive to evaluate.

Promotores: Prof.dr. T.H.W. Bäck, Prof.dr. M.R.V. Chaudron, Co-Promotor: M.T.M. Emmerich

The increasing competition in the automotive industry requires the tailored, swift development of technologically sophisticated vehicles. Therefore, the computationally expensive state-of-the-art simulation technologies are combined with optimization algorithms. An example of a real-world optimization…

On a structural level, the properties featured by a majority of mechanical metamaterials can be ascribed to the finite number of soft internal degrees-of freedom allowing for low-energy deformations.

In design optimization problems, engineers typically handcraft design representations based on personal expertise, which leaves a fingerprint of the user experience in the optimization data. Thus, learning this notion of experience as transferrable design features has potential to improve the performance…

The currently available in vitro generated human skin equivalents resemble the human skin in many aspects. However, some essential barrier characteristics do not fully mimic the native barrier. Consequently, the human skin equivalents cannot be used for screening of drugs for skin penetration.

The drug discovery pipeline is used to describe the stages in drug discovery. The earliest stage concerns with the identification of potential targets and molecules ('hits') that can modulate their function, while more advanced stages are about developing these hits into viable experimental drugs and…

In the research programme Drug Discovery & Safety, we are interested in the efficacy and safety of new drugs and novel means to decipher these aspects. Hence, we employ advanced imaging and high-throughput screening techniques next to computational approaches such as chem- and bioinformatics.

This thesis seeks to combine two different research topics; Multi-Objective Optimization and Complex Network Analysis.

DSE 2.0 concerns research on DSE techniques for complex dCPS

This thesis covers several aspects of quantum algorithms for near-term quantum computers and its applications to quantum chemistry and material science.

Promotor: Prof.dr. H.A.G. Wijshoff

Drug-related homicide (DRH) has the potential to act as a valuable indicator of wider drug-related crime. Yet DRH remains a knowledge gap within this broader field of study.

Supervisor: Indira Nederpelt

Research in the Natural Computing and Optimization cluster covers theoretical foundations, the development of new algorithms, and interdisciplinary applications of natural computing methods.

To get a feeling of how we operate at LED3 when it comes to Early Drug Discovery, please browse through our case studies. When you select a case study you’ll find relevant contacts.

Sepsis is a life-threatening condition caused by a dysregulated host response to infection, it is associated with significant morbidity, mortality, and with a high financial burden on global healthcare systems. Bacterial infections are the primary cause of sepsis, but the growing prevalence of antimicrobial…

The Leiden Academic Centre for Drug Research (LACDR) is a centre of excellence for multidisciplinary research on drug discovery and development.

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.

The research within the Division of Cell Systems and Drug Safety, headed by Prof. Bob van de Water, is focused on novel therapeutic modalities and novel concepts in early drug discovery, in order to develop more effective and safer therapeutic strategies. We generate advanced cell and computational…

In this thesis, topics relating to the optimization of high-throughput pipelines used for imaging are discussed. In particular, different levels of implementation, i.e., conceptual, software, and hardware, are discussed and the thesis outlines how advances on each level need to be made to make gains…

This thesis involves three topics: benchmarking discrete optimization algorithms, empirical analyses of evolutionary computation, and automatic algorithm configuration.

Continuous optimization is never easy: the exact solution is always a luxury demand and the theory of it is not always analytical and elegant.

The focus of the Multicriteria Optimization and Decision Analysis (MODA) group is to develop foundations of methods in multi-objective optimization.

A common method to solve expensive function evaluation problem is using Bayesian Global Optimization, instead of Evolutionary Algorithms.

Carbon dioxide capture and utilization technologies are necessary to create a truly circular economy. The electrochemical reduction of carbon dioxide to formate is an appealing carbon utilization method as it can be performed at room temperature and pressure, it only requires two electrons, and it has…

The better teaching is for pupils and students, the more solid the basis will be that we give them for their future careers. This type of teaching requires strong instructors and insight into the best ways in which pupils can be supported, and research at Leiden University is making a contribution in…

Fungal infections pose a significant threat to individuals with compromised immune systems and despite advancements in diagnosis and treatment, they continue to jeopardize patient’s health.

In the Drug Research theme, we primarily work with rodents. Rodents, such as mice, are one of the most common laboratory animals. These small mammals are easily housed and exhibit a rapid rate of reproduction.

Previous research has found important inter-individual differences in the pharmacokinetics (PK) of morphine in special populations such as children, the morbidly obese or the critically ill.

Promotores: Prof.dr. T.H.W. Bäck, Prof.dr. M. Bongards (Cologne University)

Uncertainty and noise are frequently-encountered obstacles in real-world applications of numerical optimization. The practice of optimization that deals with uncertainties and noise is commonly referred to as robust optimization.

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

Drug-target binding kinetics determine the time course of the central event in pharmacotherapy: Drug-target interaction.

In previous studies at our laboratory it was demonstrated that drug exposure of HepG2 cells can lead to an altered TNFα-induced NF-κB oscillatory phenotype, concurrent with a synergistically increased sensitivity for TNFα-induced apoptosis.

How are new drugs developed? This question is central to the Minor Modern Drug Discovery (MDD), which covers the entire trajectory from disease to drug molecule and vice versa. The various research groups involved offer a complementary and interdisciplinary perspective by connecting the diverse subjects…

The Data-Driven Drug Discovery Network (D4N) is an initiative by researchers from Leiden University and collaborators to join efforts in applying and developing novel techniques from data science to drug discovery and related topics from bioinformatics.

Citizens in multiple crime-ridden countries strongly support the militarization of security—that is, placing the military in charge of traditional policing duties. Yet, we know little about the determinants of such support. Do people approve of militarization even in the face of human fatalities? Political…

We focus on a better understanding of the mechanisms of cancer drug resistance and metastasis.

Our research in the area of safety sciences aims to increase the mechanistic understanding of cellular toxicity of drugs and, in a broader sense, chemicals.