An analysis of the XOR dynamic problem generator based on the dynamical system

This is the post-print version of the article - Copyright @ 2010 Springer-VerlagIn this paper, we use the exact model (or dynamical system approach) to describe the standard evolutionary algorithm (EA) as a discrete dynamical system for dynamic optimization problems (DOPs). Based on this dynamical system model, we analyse the properties of the XOR DOP Generator, which has been widely used by researchers to create DOPs from any binary encoded problem. DOPs generated by this generator are described as DOPs with permutation, where the fitness vector is changed according to a permutation matrix. Some properties of DOPs with permutation are analyzed, which allows explaining some behaviors observed in experimental results. The analysis of the properties of problems created by the XOR DOP Generator is important to understand the results obtained in experiments with this generator and to analyze the similarity of such problems to real world DOPs.This work was supported by Brazil FAPESP under Grant 04/04289-6 and by UK EPSRC under Grant EP/E060722/2

On Non-Elitist Evolutionary Algorithms Optimizing Fitness Functions with a Plateau

We consider the expected runtime of non-elitist evolutionary algorithms (EAs), when they are applied to a family of fitness functions with a plateau of second-best fitness in a Hamming ball of radius r around a unique global optimum. On one hand, using the level-based theorems, we obtain polynomial upper bounds on the expected runtime for some modes of non-elitist EA based on unbiased mutation and the bitwise mutation in particular. On the other hand, we show that the EA with fitness proportionate selection is inefficient if the bitwise mutation is used with the standard settings of mutation probability.Comment: 14 pages, accepted for proceedings of Mathematical Optimization Theory and Operations Research (MOTOR 2020). arXiv admin note: text overlap with arXiv:1908.0868

COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function

Background: Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature cells that accumulates in tumour-bearing hosts. These cells are induced by tumour-derived factors (e.g. prostaglandins) and have a critical role in immune suppression. MDSC suppress T and NK cell function via increased expression of arginase I and production of reactive oxygen species (ROS) and nitric oxide (NO). Immune suppression by MDSC was found to be one of the main factors for immunotherapy insufficiency. Here we investigate if the in vivo immunoregulatory function of MDSC can be reversed by inhibiting prostaglandin synthesis by specific COX-2 inhibition focussing on ROS production by MDSC subtypes. In addition, we determined if dietary celecoxib treatment leads to refinement of immunotherapeutic strategies.Methods: MDSC numbers and function were analysed during tumour progression in a murine model for mesothelioma. Mice were inoculated with mesothelioma tumour cells and treated with cyclooxygenase-2 (COX-2) inhibitor celecoxib, either as single agent or in combination with dendritic cell-based immunotherapy.Results: We found that large numbers of infiltrating MDSC co-localise with COX-2 expression in those areas where tumour growth takes place. Celecoxib reduced prostaglandin E2 levels in vitro and in vivo. Treatment of tumour-bearing mice with dietary celecoxib prevented the local and systemic expansion of all MDSC subtypes. T

Clinical determinants of vaginal dryness in patients with primary Sjögren's syndrome

Objective. The majority of women with primary Sjogren's syndrome (pSS) suffer from vaginal dryness, which negatively impacts daily and sexual activities. As little is known about the aetiology and clinical context of this complaint, this study investigated the relationship between vaginal dryness and other clinical parameters associated with pSS. Methods. Female participants of the REgistry of Sjogren syndrome at UMCG - LongiTudinal (RESULT) cohort who fulfilled ACR-EULAR and/or AECG classification criteria for pSS were included, using baseline data for analyses. Patient-reported vaginal dryness (range 0-10) was correlated with demographic characteristics, systemic disease activity (i.e. ESSDAI), Sjogren's Syndrome Disease Damage Index, salivary and lacrimal gland function, patient-reported outcomes (ESSPRI, MFI), serology and quality of life (SF-36, EQ-5D). Significantly associated parameters (p Results. This cross-sectional study included 199 women with pSS; mean age was 52 +/- 14 years, 53% were postmenopausal, and median vaginal dryness score was 5 (IQR 2-7). Vaginal dryness was significantly associated with older age, postmenopausal status, peripheral neuropathy, oral and ocular dryness, ESSPRI and SF-36 mental and general health. After correction for age, menopausal status and medication use, peripheral neuropathy (B=1.632), oral dryness (B=0.302), and ocular dryness (B=0.230) were independently associated with vaginal dryness. Conclusion. The independent association of vaginal dryness with oral and ocular dryness might imply that the aetiology of these symptoms is partly shared. Of all extraglandular features, only peripheral neuropathy was independently associated with vaginal dryness, suggesting that peripheral neuropathy plays a significant role in the pathology of vaginal dryness in pSS

Selective pressures on genomes in molecular evolution

We describe the evolution of macromolecules as an information transmission process and apply tools from Shannon information theory to it. This allows us to isolate three independent, competing selective pressures that we term compression, transmission, and neutrality selection. The first two affect genome length: the pressure to conserve resources by compressing the code, and the pressure to acquire additional information that improves the channel, increasing the rate of information transmission into each offspring. Noisy transmission channels (replication with mutations) gives rise to a third pressure that acts on the actual encoding of information; it maximizes the fraction of mutations that are neutral with respect to the phenotype. This neutrality selection has important implications for the evolution of evolvability. We demonstrate each selective pressure in experiments with digital organisms.Comment: 16 pages, 3 figures, to be published in J. theor. Biolog

Does the Red Queen reign in the kingdom of digital organisms?

In competition experiments between two RNA viruses of equal or almost equal fitness, often both strains gain in fitness before one eventually excludes the other. This observation has been linked to the Red Queen effect, which describes a situation in which organisms have to constantly adapt just to keep their status quo. I carried out experiments with digital organisms (self-replicating computer programs) in order to clarify how the competing strains' location in fitness space influences the Red-Queen effect. I found that gains in fitness during competition were prevalent for organisms that were taken from the base of a fitness peak, but absent or rare for organisms that were taken from the top of a peak or from a considerable distance away from the nearest peak. In the latter two cases, either neutral drift and loss of the fittest mutants or the waiting time to the first beneficial mutation were more important factors. Moreover, I found that the Red-Queen dynamic in general led to faster exclusion than the other two mechanisms.Comment: 10 pages, 5 eps figure