Welcome to the Proceedings of the 12th Conference on Evolutionary Multi-Criterion Optimization (EMO), held in Leiden, The Netherlands, March 20–24, 2023 in hybrid format.Why hold EMO conferences?...Show moreWelcome to the Proceedings of the 12th Conference on Evolutionary Multi-Criterion Optimization (EMO), held in Leiden, The Netherlands, March 20–24, 2023 in hybrid format.Why hold EMO conferences? This question was discussed at EMO 2007 by its founders. The doubts regarding the viability of the conferences were fortunately cast away as the importance, need, and ubiquity of multi-criterion optimization keeps growing each year at a tremendous pace, impacting other areas and being influenced itself by them.For millennia optimization (improving things) has played a crucial role for humans. In more recent times, EMO (and optimization in general) has become important in sciencein areas such as physics, biology, economics, social sciences,medical sciences, and mathematics. For instance, Snell’s law was discovered by Willebrord Snellius through experimentation, only later it was realized that it can be derived from Fermat’s principle of least time, stating that light always chooses the path that is traveled in the least time.As such, the laws of nature can often be perceived as a process of optimization and optimal decision-making. Secondly, another use of optimization is the following. Many insights can be gained by looking at extremal objects (for instance, given 2n points in the plane no three of which lie on a line, n of them blue and n of them red, it is always possible to create n line segments by using the given points such that the endpoints have different colors and no two segments intersect – this can be understood by looking at the appropriate extremal object). Thirdly, methodologies and techniques developed in the EMO community have been empowering many practical scenarios: from finding the best taxation system, the best returns on investments while avoiding too high risks,discovering potent drug candidates with few side effects, to designing engineering structures that optimally balance the energy consumption and the environmental impact (e.g., minimizing the CO2 or CH4 emission).In the EMO conferences, we focus mainly on the evolutionary approaches to solving multi-criterion optimization and decision-making problems since the applicability of analytical/deterministic methods is often limited. For the scenarios where both categories of approaches are applicable, the hybridizations of analytical and evolutionary algorithms have appeared over the years, combining the strengths of both categories.Such hybridizations were also covered in the EMO conferences. In recent years, the EMOcommunity has been bridged with theMulti-Criterion Decision-Making (MCDM) community, which focuses more on the decision-making aspects of the same problem. According to the EMO tradition, also in this year’s event, many works are dedicated to designing and studying algorithms, ranging from novel algorithmic operators to thetheoretical analysis of existing ones. Notably, there are some contributions that connect EMO with Machine Learning/Artificial Intelligence, which draws more and more research interests nowadays. Also, appropriate attention – also as a tutorial – is paid tobenchmarking and empirical performance assessment, for instance, new benchmarking vi Preface problem sets. Furthermore, some submissions address real-world problems using EMO methodologies, which nicely complete the scope of the conference.Show less
Zhang, C.; Hu, M.; Meide, M. van der; Di Maio, F.; Yang, X.; Gao, X.; ... ; Li, C. 2023
Antibodies targeting the human malaria parasite Plasmodium falciparum circumsporozoite protein (PfCSP) can prevent infection and disease. PfCSP contains multiple central repeating NANP motifs; some... Show moreAntibodies targeting the human malaria parasite Plasmodium falciparum circumsporozoite protein (PfCSP) can prevent infection and disease. PfCSP contains multiple central repeating NANP motifs; some of the most potent anti-infective antibodies against malaria bind to these repeats. Multiple antibodies can bind the repeating epitopes concurrently by engaging into homotypic Fab-Fab interactions, which results in the ordering of the otherwise largely disordered central repeat into a spiral. Here, we characterize IGHV3-33/IGKV1-5-encoded monoclonal antibody (mAb) 850 elicited by immunization of transgenic mice with human immunoglobulin loci. mAb 850 binds repeating NANP motifs with picomolar affinity, potently inhibits Plasmodium falciparum (Pf) in vitro and, when passively administered in a mouse challenge model, reduces liver burden to a similar extent as some of the most potent anti-PfCSP mAbs yet described. Like other IGHV3-33/IGKV1-5-encoded anti-NANP antibodies, mAb 850 primarily utilizes its HCDR3 and germline-encoded aromatic residues to recognize its core NANP motif. Biophysical and cryo-electron microscopy analyses reveal that up to 19 copies of Fab 850 can bind the PfCSP repeat simultaneously, and extensive homotypic interactions are observed between densely-packed PfCSP-bound Fabs to indirectly improve affinity to the antigen. Together, our study expands on the molecular understanding of repeat-induced homotypic interactions in the B cell response against PfCSP for potently protective mAbs against Pf infection.Author summaryMalaria is a life-threatening disease caused by Pf parasites transmitted by infected mosquitoes. The surface of infectious Pf sporozoites is covered by PfCSP, which contains multiple, short amino-acid repeats in its central domain. Antibodies targeting the repeats have been shown to be capable of neutralizing the infection. Here, we describe monoclonal antibody (mAb) 850, which was isolated following immunization with a PfCSP repeat-containing antigen in a transgenic mouse model modified to express human Ig heavy and light chain variable regions. mAb 850 binds PfCSP repeats with high affinity and inhibits Pf sporozoites in in vitro and in vivo models of infection. Our molecular analyses reveal that similar to 19 copies of mAb 850 can simultaneously bind one molecule of PfCSP and induce a spiral-like conformation of the repeat. Extensive antibody-antibody contacts between mAbs result in formation of one of the highest-density mAb-CSP complexes yet described. Our findings improve our understanding of antibody-PfCSP interactions that mediate parasite inhibition. Show less
