Combining filter method and dynamically dimensioned search for constrained global optimization

In this work we present an algorithm that combines the filter technique and the dynamically dimensioned search (DDS) for solving nonlinear and nonconvex constrained global optimization problems. The DDS is a stochastic global algorithm for solving bound constrained problems that in each iteration generates a randomly trial point perturbing some coordinates of the current best point. The filter technique controls the progress related to optimality and feasibility defining a forbidden region of points refused by the algorithm. This region can be given by the flat or slanting filter rule. The proposed algorithm does not compute or approximate any derivatives of the objective and constraint functions. Preliminary experiments show that the proposed algorithm gives competitive results when compared with other methods.The first author thanks a scholarship supported by the International Cooperation Program CAPES/ COFECUB at the University of Minho. The second and third authors thanks the support given by FCT (Funda¸c˜ao para Ciˆencia e Tecnologia, Portugal) in the scope of the projects: UID/MAT/00013/2013 and UID/CEC/00319/2013. The fourth author was partially supported by CNPq-Brazil grants 308957/2014-8 and 401288/2014-5.info:eu-repo/semantics/publishedVersio

Robot life: simulation and participation in the study of evolution and social behavior.

This paper explores the case of using robots to simulate evolution, in particular the case of Hamilton's Law. The uses of robots raises several questions that this paper seeks to address. The first concerns the role of the robots in biological research: do they simulate something (life, evolution, sociality) or do they participate in something? The second question concerns the physicality of the robots: what difference does embodiment make to the role of the robot in these experiments. Thirdly, how do life, embodiment and social behavior relate in contemporary biology and why is it possible for robots to illuminate this relation? These questions are provoked by a strange similarity that has not been noted before: between the problem of simulation in philosophy of science, and Deleuze's reading of Plato on the relationship of ideas, copies and simulacra

The plight of the sense-making ape

This is a selective review of the published literature on object-choice tasks, where participants use directional cues to find hidden objects. This literature comprises the efforts of researchers to make sense of the sense-making capacities of our nearest living relatives. This chapter is written to highlight some nonsensical conclusions that frequently emerge from this research. The data suggest that when apes are given approximately the same sense-making opportunities as we provide our children, then they will easily make sense of our social signals. The ubiquity of nonsensical contemporary scientific claims to the effect that humans are essentially--or inherently--more capable than other great apes in the understanding of simple directional cues is, itself, a testament to the power of preconceived ideas on human perception

Survivability Is More Fundamental Than Evolvability

For a lineage to survive over long time periods, it must sometimes change. This has given rise to the term evolvability, meaning the tendency to produce adaptive variation. One lineage may be superior to another in terms of its current standing variation, or it may tend to produce more adaptive variation. However, evolutionary outcomes depend on more than standing variation and produced adaptive variation: deleterious variation also matters. Evolvability, as most commonly interpreted, is not predictive of evolutionary outcomes. Here, we define a predictive measure of the evolutionary success of a lineage that we call the k-survivability, defined as the probability that the lineage avoids extinction for k generations. We estimate the k-survivability using multiple experimental replicates. Because we measure evolutionary outcomes, the initial standing variation, the full spectrum of generated variation, and the heritability of that variation are all incorporated. Survivability also accounts for the decreased joint likelihood of extinction of sub-lineages when they 1) disperse in space, or 2) diversify in lifestyle. We illustrate measurement of survivability with in silico models, and suggest that it may also be measured in vivo using multiple longitudinal replicates. The k-survivability is a metric that enables the quantitative study of, for example, the evolution of 1) mutation rates, 2) dispersal mechanisms, 3) the genotype-phenotype map, and 4) sexual reproduction, in temporally and spatially fluctuating environments. Although these disparate phenomena evolve by well-understood microevolutionary rules, they are also subject to the macroevolutionary constraint of long-term survivability

Filter-based DIRECT method for constrained global optimization

This paper presents a DIRECT-type method that uses a filter methodology to assure convergence to a feasible and optimal solution of nonsmooth and nonconvex constrained global optimization problems. The filter methodology aims to give priority to the selection of hyperrectangles with feasible center points, followed by those with infeasible and non-dominated center points and finally by those that have infeasible and dominated center points. The convergence properties of the algorithm are analyzed. Preliminary numerical experiments show that the proposed filter-based DIRECT algorithm gives competitive results when compared with other DIRECT-type methods.The authors would like to thank two anonymous referees and the Associate Editor for their valuable comments and suggestions to improve the paper. This work has been supported by COMPETE: POCI-01-0145-FEDER-007043 and FCT - Fundac¸ao para a Ciência e Tecnologia within the projects UID/CEC/00319/2013 and ˆ UID/MAT/00013/2013.info:eu-repo/semantics/publishedVersio

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

In vitro leishmanicidal, antibacterial and antitumour potential of anhydrocochlioquinone A obtained from the fungus Cochliobolus sp

The bioassay-guided fractionation of the ethyl acetate extract of the fungus Cochliobolus sp. highlighted leishmanicidal activity and allowed for anhydrocochlioquinone A (ANDC-A) isolation. MS, 1D and 2D NMR spectra of this compound were in agreement with those published in the literature. ANDC-A exhibited leishmanicidal activity with EC50value of 22.4 \uc2\ub5g/mL (44 \uce\ubcM) and, when submitted to the microdilution assay against Gram-positive and Gram-negative bacteria, showed a minimal inhibitory concentration against Staphylococcus aureus ATCC 25295 of 128 \uce\ubcg/mL (248.7 \uce\ubcM). It was also active against five human cancer cell lines, showing IC50values from 5.4 to 20.3 \uce\ubcM. ANDC-A demonstrated a differential selectivity for HL-60 (SI 5.5) and THP-1 (SI 4.3) cell lines in comparison with Vero cells and was more selective than cisplatin and doxorubicin against MCF-7 cell line in comparison with human peripheral blood mononuclear cells. ANDC-A was able to eradicate clonogenic tumour cells at concentrations of 20 and 50 \uce\ubcM and induced apoptosis in all tumour cell lines at 20 \uce\ubcM. These results suggest that ANDC-A might be used as a biochemical tool in the study of tumour cells biochemistry as well as an anticancer agent with durable effects on tumours

Magnetic Hydroxyapatite Bone Substitutes to Enhance Tissue Regeneration: Evaluation In Vitro Using Osteoblast-Like Cells and In Vivo in a Bone Defect

In case of degenerative disease or lesion, bone tissue replacement and regeneration is an important clinical goal. In particular, nowadays, critical size defects rely on the engineering of scaffolds that are 3D structural supports, allowing cellular infiltration and subsequent integration with the native tissue. Several ceramic hydroxyapatite (HA) scaffolds with high porosity and good osteointegration have been developed in the past few decades but they have not solved completely the problems related to bone defects. In the present study we have developed a novel porous ceramic composite made of HA that incorporates magnetite at three different ratios: HA/Mgn 95/5, HA/Mgn 90/10 and HA/Mgn 50/50. The scaffolds, consolidated by sintering at high temperature in a controlled atmosphere, have been analysed in vitro using human osteoblast-like cells. Results indicate high biocompatibility, similar to a commercially available HA bone graft, with no negative effects arising from the presence of magnetite or by the use of a static magnetic field. HA/Mgn 90/10 was shown to enhance cell proliferation at the early stage. Moreover, it has been implanted in vivo in a critical size lesion of the rabbit condyle and a good level of histocompatibility was observed. Such results identify this scaffold as particularly relevant for bone tissue regeneration and open new perspectives for the application of a magnetic field in a clinical setting of bone replacement, either for magnetic scaffold fixation or magnetic drug delivery

Filter-based stochastic algorithm for global optimization

We propose the general Filter-based Stochastic Algorithm (FbSA) for the global optimization of nonconvex and nonsmooth constrained problems. Under certain conditions on the probability distributions that generate the sample points, almost sure convergence is proved. In order to optimize problems with computationally expensive black-box objective functions, we develop the FbSA-RBF algorithm based on the general FbSA and assisted by Radial Basis Function (RBF) surrogate models to approximate the objective function. At each iteration, the resulting algorithm constructs/updates a surrogate model of the objective function and generates trial points using a dynamic coordinate search strategy similar to the one used in the Dynamically Dimensioned Search method. To identify a promising best trial point, a non-dominance concept based on the values of the surrogate model and the constraint violation at the trial points is used. Theoretical results concerning the sufficient conditions for the almost surely convergence of the algorithm are presented. Preliminary numerical experiments show that the FbSA-RBF is competitive when compared with other known methods in the literature.The authors are grateful to the anonymous referees for their fruitful comments and suggestions.The first and second authors were partially supported by Brazilian Funds through CAPES andCNPq by Grants PDSE 99999.009400/2014-01 and 309303/2017-6. The research of the thirdand fourth authors were partially financed by Portuguese Funds through FCT (Fundação para Ciência e Tecnologia) within the Projects UIDB/00013/2020 and UIDP/00013/2020 of CMAT-UM and UIDB/00319/2020