An Improvement Study of the Decomposition-based Algorithm Global WASF-GA for Evolutionary Multiobjective Optimization

The convergence and the diversity of the decompositionbased evolutionary algorithm Global WASF-GA (GWASF-GA) relies on a set of weight vectors that determine the search directions for new non-dominated solutions in the objective space. Although using weight vectors whose search directions are widely distributed may lead to a well-diversified approximation of the Pareto front (PF), this may not be enough to obtain a good approximation for complicated PFs (discontinuous, non-convex, etc.). Thus, we propose to dynamically adjust the weight vectors once GWASF-GA has been run for a certain number of generations. This adjustment is aimed at re-calculating some of the weight vectors, so that search directions pointing to overcrowded regions of the PF are redirected toward parts with a lack of solutions that may be hard to be approximated. We test different parameters settings of the dynamic adjustment in optimization problems with three, five, and six objectives, concluding that GWASF-GA performs better when adjusting the weight vectors dynamically than without applying the adjustment.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Interrupted orthodontic force results in less root resorption than continuous force in human premolars as measured by microcomputed tomography

Introduction. Root resorption is an undesirable but very frequently occurring sequel of orthodontic treatment. The aim of this study was to compare root resorption caused by either continuous (CF) or interrupted (IF) orthodontic force. Material and methods. The study was performed on human subjects on 30 first upper and lower premolars scheduled for extraction for orthodontic reasons. During four weeks before extraction 12 teeth were subjected to either CF or IF. The force was generated by a segmental titanium-molybdenum alloy cantilever spring that was activated in buccal direction. Initially a force of 60 CentiNewton was used in both CF and IF groups, the force in the former, however, was reactivated every week for 4 weeks. There was no reactivation of force in the IF group after initial application. A morphometric analysis of root resorption was performed by microcomputed tomography and the extent of tooth movement was measured on stone casts. Furthermore, a Tartarate-Resistant Acidic Phosphatase activity (TRAP), the marker enzyme of osteoclasts and cementoclasts, was determined by histochemical method. The Mann-Whitney U test was used to compare the difference in measured parameters between treatment and control tooth groups. Results. The number of resorption craters was significantly higher and their average volume almost twice as large in the CF compared to the IF group (p < 0.05). However, the distance of tooth displacement was similar for both groups. Cementoclasts were detected with the TRAP technique on the surface of two teeth only; both were subjected to continuous force. Conclusions. The use of IF leads to less destruction of root structure as opposed to continuous force while the same tooth movement was achieved

Characterization and Validation of Neisseria gonorrhoeae Proteins GmhAGC and NGO1985 as Molecular Targets for Development of Novel Anti-gonorrhea Therapeutic Interventions

The sexually transmitted disease gonorrhea, caused by the Gram-negative bacterium and obligate human pathogen Neisseria gonorrhoeae, remains a significant health and economic burden worldwide. In the absence of a protective vaccine, antimicrobial agents are the only pharmacological intervention for patients with gonorrhea. However, due to the remarkable ability of gonococcus to develop antibiotic resistance, infections caused by N. gonorrhoeae are believed to become untreatable in the near future. Identification and elucidation of the physiological function of novel N. gonorrhoeae proteins is critical for the formulation of new therapeutic interventions. This work focuses on characterization and validation of two gonococcal proteins, GmhA[subscript GC] and NGO1985, as targets for development of new antibiotics and a vaccine antigen, respectively. The sedoheptulose-7-phosphate isomerase, GmhA[subscript GC], is the first enzyme in the biosynthesis of nucleotide-activated-glycero-manno-heptoses. We demonstrate that N. gonorrhoeae GmhA[subscript GC] is essential for lipooligosaccharide (LOS) synthesis and pivotal for bacterial viability. Our crystallization studies have shown that GmhA[subscript GC] forms a homo-tetramer in the closed conformation with four zinc ions in the active site. Site directed mutagenesis studies showed that active site residues E65 and H183 are important for LOS synthesis but not bacterial viability, suggesting that abolition of LOS synthesis is disconnected from the GmhA[subscript GC] involvement in N. gonorrhoeae viability. NGO1985 was initially described as a hypothetical lipoprotein containing two BON (Bacterial OsmY and Nodulation) domains, hypothesized to be involved in maintaining bacterial cell envelope integrity. In our studies we demonstrate that NGO1985 is a surface exposed lipoprotein, conserved among diverse gonococcal isolates. Deletion of ngo1985 results in bacterial cell envelope defects leading to a pleiotropic phenotype including increased susceptibility to antimicrobial agents, decreased survival during in vitro growth conditions mimicking the human host environment, and high attenuation in the murine model of infection. NGO1985 interactome studies indicated a broad network of interactions including potential association with β-Barrel Assembly Machinery (Bam) complex, antibiotic efflux pump(s), and several lipoproteins. Furthermore, we demonstrate that NGO1985 does not undergo lipoprotein sorting according to the +2 residue of the lipobox motif as characterized for Escherichia coli. We determined that both BON domains, in their native orientation, are essential for NGO1985 functionality and stability. Finally, for the first time we have investigated the importance of the BON domains’ conserved glycine residues and showed that these amino acids play a critical role in protein stability. Based on the importance of both GmhA[subscript GC] and NGO1985 on gonococcal physiology, we conclude that these proteins are promising molecular targets for development of new anti-gonorrhea interventions

Functional and Structural Studies on the \u3cem\u3eNeisseria gonorrhoeae\u3c/em\u3e GmhA, the First Enzyme in the \u3cem\u3eglycero-manno\u3c/em\u3e-heptose Biosynthesis Pathways, Demonstrate a Critical Role in Lipooligosaccharide Synthesis and Gonococcal Viability

Sedoheptulose-7-phosphate isomerase, GmhA, is the first enzyme in the biosynthesis of nucleotide-activated-glycero-manno-heptoses and an attractive, yet underexploited, target for development of broad-spectrum antibiotics. We demonstrated that GmhA homologs in Neisseria gonorrhoeae and N. meningitidis (hereafter called GmhAGC and GmhANM, respectively) were interchangeable proteins essential for lipooligosaccharide (LOS) synthesis, and their depletion had adverse effects on neisserial viability. In contrast, the Escherichia coli ortholog failed to complement GmhAGC depletion. Furthermore, we showed that GmhAGC is a cytoplasmic enzyme with induced expression at mid-logarithmic phase, upon iron deprivation and anaerobiosis, and conserved in contemporary gonococcal clinical isolates including the 2016 WHO reference strains. The untagged GmhAGCcrystallized as a tetramer in the closed conformation with four zinc ions in the active site, supporting that this is most likely the catalytically active conformation of the enzyme. Finally, site-directed mutagenesis studies showed that the active site residues E65 and H183 were important for LOS synthesis but not for GmhAGC function in bacterial viability. Our studies bring insights into the importance and mechanism of action of GmhA and may ultimately facilitate targeting the enzyme with small molecule inhibitors

Group A Streptococcal S Protein Utilizes Red Blood Cells as Immune Camouflage and Is a Critical Determinant for Immune Evasion.

Group A Streptococcus (GAS) is a human-specific pathogen that evades the host immune response through the elaboration of multiple virulence factors. Although many of these factors have been studied, numerous proteins encoded by the GAS genome are of unknown function. Herein, we characterize a biomimetic red blood cell (RBC)-captured protein of unknown function-annotated subsequently as S protein-in GAS pathophysiology. S protein maintains the hydrophobic properties of GAS, and its absence reduces survival in human blood. S protein facilitates GAS coating with lysed RBCs to promote molecular mimicry, which increases virulence in vitro and in vivo. Proteomic profiling reveals that the removal of S protein from GAS alters cellular and extracellular protein landscapes and is accompanied by a decrease in the abundance of several key GAS virulence determinants. In vivo, the absence of S protein results in a striking attenuation of virulence and promotes a robust immune response and immunological memory

Mean-risk models using two risk measures: A multi-objective approach

This paper proposes a model for portfolio optimisation, in which distributions are characterised and compared on the basis of three statistics: the expected value, the variance and the CVaR at a specified confidence level. The problem is multi-objective and transformed into a single objective problem in which variance is minimised while constraints are imposed on the expected value and CVaR. In the case of discrete random variables, the problem is a quadratic program. The mean-variance (mean-CVaR) efficient solutions that are not dominated with respect to CVaR (variance) are particular efficient solutions of the proposed model. In addition, the model has efficient solutions that are discarded by both mean-variance and mean-CVaR models, although they may improve the return distribution. The model is tested on real data drawn from the FTSE 100 index. An analysis of the return distribution of the chosen portfolios is presented

Association of GH Gene Polymorphism with Semen Parameters of Boars

Relations between polymorphism of the Growth Hormone gene and semen characters were analyzed. The DNA for the purpose of examination was isolated from the peripheral blood of 173 boars. In the boar herd under study the frequency of allele occurrence for the GH/MspI was as follows: allele GHA - 0.79 and allele GHB - 0.21. As far as the GH/HaeII polymorphism is concerned, the relevant frequency was as follows: allele GHA - 0.53 and allele GHB - 0.47, respectively. The relationship between the GH genotypes and semen characteristic traits were analyzed. The study showed that boars with GHBGHB genotype of both polymorphous loci of the GH gene produced ejaculates of larger volume, higher percentage, number of normozosperms in the ejaculate and number of insemination as compared to GHA GHA and GHAGHB boars. Our current findings suggested that polymorphism of the GH/MspI and GH/HaeII might have potential effect for reproductive performance traits of boars

Structural and Functional Insights Into the Role of BamD and BamE Within the \u3cem\u3eβ\u3c/em\u3e-Barrel Assembly Machinery in \u3cem\u3eNeisseria gonorrhoeae\u3c/em\u3e

The β-barrel assembly machinery (BAM) is a conserved multicomponent protein complex responsible for the biogenesis of β-barrel outer membrane proteins (OMPs) in Gram-negative bacteria. Given its role in the production of OMPs for survival and pathogenesis, BAM represents an attractive target for the development of therapeutic interventions, including drugs and vaccines against multidrug-resistant bacteria such as Neisseria gonorrhoeae. The first structure of BamA, the central component of BAM, was from N. gonorrhoeae, the etiological agent of the sexually transmitted disease gonorrhea. To aid in pharmaceutical targeting of BAM, we expanded our studies to BamD and BamE within BAM of this clinically relevant human pathogen. We found that the presence of BamD, but not BamE, is essential for gonococcal viability. However, BamE, but not BamD, was cell-surface–displayed under native conditions; however, in the absence of BamE, BamD indeed becomes surface-exposed. Loss of BamE altered cell envelope composition, leading to slower growth and an increase in both antibiotic susceptibility and formation of membrane vesicles containing greater amounts of vaccine antigens. Both BamD and BamE are expressed in diverse gonococcal isolates, under host-relevant conditions, and throughout different phases of growth. The solved structures of Neisseria BamD and BamE share overall folds with Escherichia coli proteins but contain differences that may be important for function. Together, these studies highlight that, although BAM is conserved across Gram-negative bacteria, structural and functional differences do exist across species, which may be leveraged in the development of species-specific therapeutics in the effort to combat multidrug resistance

Effect of zinc nanoparticles on embryo and chicken growth, and the content of zinc in tissues and faeces

The hypothesis was that owing to their high bioavailability, zinc oxide nanoparticles (NanoZnO) can effectively replace (Zn) salts and reduce Zn excretion with faeces. The objective of this study was to investigate the effects of NanoZnO on the development of chicken embryos, the growth of broiler chickens, and Zn excretion with faeces. At day 1 of incubation, 120 eggs were randomly divided between a control group (not injected) and groups injected with a hydrocolloid of NanoZnO in increasing concentrations (50, 100, 500 mg/L). At day 19 of incubation, no differences were observed in the bodyweight, but 100 and 500 mg/L affected liver and heart weights, indicating that high levels of NanoZnO may induce differential organ development. In the subsequent experiment, 308 chickens were randomly divided into six groups. The control diet was supplemented with 55 mg Zn/kg (standard level), the 0 group received no Zn supplement, and groups fed NanoZnO received 25%, 50%, 75%, and 100% of the standard level. The 100% replacement of ZnO with NanoZnO increased the chickens’ bodyweight compared with the standard level of ZnO, but to the same level as the diet without ZnO supplementation. Furthermore, NanoZnO did not reduce the content of Zn in faeces, which was only significantly lower in the group without ZnO supplementation in comparison with other groups. The results indicate that the replacement of ZnO with NanoZnO had no negative effects on chicken growth. Compared with ZnO, NanoZnO did not reduce Zn excretion with faeces. Keywords: broiler, development, excretion, mineral, nanonutritio