CES-485 Approximating the Set of Pareto Optimal Solutions in Both the Decision and Objective Spaces by an Estimation of Distribution Algorithm

Most existing multiobjective evolutionary algorithms aim at approximating the PF, the distribution of the Pareto optimal solutions in the objective space. In many real-life applications, however, a good approximation to the PS, the distribution of the Pareto optimal solutions in the decision space, is also required by a decision maker. This paper considers a class of MOPs, in which the dimensionalities of the PS and PF are different so that a good approximation to the PF might not approximate the PS very well. It proposes a probabilistic model based multiobjective evolutionary algorithm, called MMEA, for approximating the PS and the PF simultaneously for a MOP in this class. In the modelling phase of MMEA, the population is clustered into a number of subpopulations based on their distribution in the objective space, the PCA technique is used to detect the dimensionality of the centroid of each subpopulation, and then a probabilistic model is built for modelling the distribution of the Pareto optimal solutions in the decision space. Such modelling procedure could promote the population diversity in both the decision and objective spaces. To ease the burden of setting the number of subpopulations, a dynamic strategy for periodically adjusting it has been adopted in MMEA. The experimental comparison between MMEA and the two other methods, KP1 and Omni-Optimizer on a set of test instances, some of which are proposed in this paper, have been made in this paper. It is clear from the experiments that MMEA has a big advantage over the two other methods in approximating both the PS and the PF of a MOP when the PS is a nonlinear manifold, although it might not be able to perform significantly better in the case when the PS is a linear manifold

The Association of Elevated 2′,5′-Oligoadenylate-Dependent RNase L with Lung Cancer Correlated with Deficient Enzymatic Activity and Decreased Capacity of RNase L Dimerization

RNase L mediates critical cellular functions including antiviral, proapoptotic, antiproliferative and tumor suppressive activities. In this study, the expression and function of RNase L in lung cancer cells were examined. Interestingly we have found that the expression of RNase L in lung cancer cells was 3- and 9-fold higher in its mRNA and protein levels, but a significant decrease of its enzymatic activity when compared to that in corresponding normal lung cells. Further investigation revealed that 2-5A-induced dimerization of the RNase L protein, a necessary prerequisite for activation of RNase L, was inhibited, as a result of that RLI, a specific inhibitor of RNase L, was remarkably up-regulated in the cancer cells. Our findings provide new insight into how cancer cells escape normal growth-regulating mechanisms to form a tumor and the information may be useful for the design of novel strategies for treating lung cancer through regulating RNase L activity

Enhancing SAEAs with Unevaluated Solutions: A Case Study of Relation Model for Expensive Optimization

Surrogate-assisted evolutionary algorithms (SAEAs) hold significant importance in resolving expensive optimization problems~(EOPs). Extensive efforts have been devoted to improving the efficacy of SAEAs through the development of proficient model-assisted selection methods. However, generating high-quality solutions is a prerequisite for selection. The fundamental paradigm of evaluating a limited number of solutions in each generation within SAEAs reduces the variance of adjacent populations, thus impacting the quality of offspring solutions. This is a frequently encountered issue, yet it has not gained widespread attention. This paper presents a framework using unevaluated solutions to enhance the efficiency of SAEAs. The surrogate model is employed to identify high-quality solutions for direct generation of new solutions without evaluation. To ensure dependable selection, we have introduced two tailored relation models for the selection of the optimal solution and the unevaluated population. A comprehensive experimental analysis is performed on two test suites, which showcases the superiority of the relation model over regression and classification models in the selection phase. Furthermore, the surrogate-selected unevaluated solutions with high potential have been shown to significantly enhance the efficiency of the algorithm.Comment: 18 pages, 9 figure

RNase L: Its Biological Roles and Regulation

2\u27-5\u27oligoadenylate-dependent ribonuclease L (RNase L) is one of the key enzymes involved in the function of interferons (IFNs), a family of cytokines participating in innate immunity against viruses and other microbial pathogens. Upon binding with its activator, 5\u27-phosphorylated, 2\u27-5\u27 linked oligoadenylates (2-5A), RNase L degrades single-stranded viral and cellular RNAs and thus plays an important role in the antiviral and antiproliferative functions of IFNs. In recent years, evidence has revealed that RNase L displays a broad range of biological roles which are summarized in this review

RNase L: Its Biological Roles and Regulation

2\u27-5\u27oligoadenylate-dependent ribonuclease L (RNase L) is one of the key enzymes involved in the function of interferons (IFNs), a family of cytokines participating in innate immunity against viruses and other microbial pathogens. Upon binding with its activator, 5\u27-phosphorylated, 2\u27-5\u27 linked oligoadenylates (2-5A), RNase L degrades single-stranded viral and cellular RNAs and thus plays an important role in the antiviral and antiproliferative functions of IFNs. In recent years, evidence has revealed that RNase L displays a broad range of biological roles which are summarized in this review

A Facile and Efficient Synthesis of Some (6E)-Hydroximino-4-En-3-One Steroids, Steroidal Oximes From Cinachyrella spp. Sponges

Using β-sitosterol as a starting material, (6E)-hydroximino-24-ethylcholest-4-en-3-one (1), a natural steroidal oxime from Cinachyrella alloclada and C. apion, was synthesized in four steps with a high overall yield. First, β-sitosterol (5a) is transformed into the corresponding 24-ethylcholest-4-en-3,6-dione (6a) via oxidation with pyridinium chlorochromate (PCC). Selective reduction of 6a by NaBH4 in the presence of CoCl2 gives 24-ethylcholest- 4-en-3β-ol-6-one (7a). The reaction of 7a with hydroxylamine hydrochloride offers the oxime 8a and the oxidation of 8a by Jones reagent gives the target steroid 1. (6E)-Hydroximinocholest-4-en-3-one (2) and (6E)-hydroximino-24-ethylcholest-4,22-dien-3-one (4) were synthesized by a similar method. The cytotoxicity of the synthesized compounds against sk-Hep-1 (human liver carcinoma cell line), H-292 (human lung carcinoma cell line), PC-3 (human prostate carcinoma cell line) and Hey-1B (human ovarian carcinoma cell line) cells were investigated. The presence of a cholesterol-type side chain appears to be necessary for the biological activity

RNase L contributes to lipid metabolism

Macrophage-derived foam cell formation is a milestone of the atherosclerotic lesion initiation and progression, leading to cardiovascular diseases and stroke. Foam cells are formed from the disruption of a homeostatic mechanism that manipulates the uptake, intracellular metabolism and efflux of cholesterol within macrophages. Although studies have yielded much information about the homeostatic mechanism, the molecular basis of foam cell formation remains to be fully understood. We recently found that deficiency of RNase L attenuated macrophage functions including macrophage migration and its endocytic activity. Furthermore, RNase L markedly impacted the expression of certain pro- and anti-foam cell genes in macrophages. Most interestingly we have revealed that lack of RNase L significantly increased the formation of foam cells from bone marrow derived macrophages (BMMs). The increase of foam cell formation was associated with up-regulation of the expression of scavenger receptors such as CD36, SR-A, and PPAR-g. These studies provide new insights into foam cell formation and novel therapeutic strategies for atherosclerosis may be designed through activation/up-regulation of RNase L.https://engagedscholarship.csuohio.edu/u_poster_2014/1001/thumbnail.jp

Synthesis and Cytotoxic Analysis of Some Disodium 3β,6β-Dihydroxysterol Disulfates

Disodium 3β,6β-dihydroxy-5α-cholestane disulfate (1) was synthesized in 4 steps with a high overall yield from cholesterol. First, cholesterol (4a) was converted to cholest-4-en-3,6-dione (5a) via oxidation with pyridinium chlorochromate (PCC) and then 5a was reduced by NaBH4 in the presence of NiCl2 to produce cholest-3β,6β-diol (6a). The reaction of 6a with the triethylamine-sulfur trioxide complex generated diammonium 3β,6β-dihydroxy-5α-cholestane disulfate (7a) and the treatment of 7a by cation exchange resin 732 (sodium form)(Na+) yielded the target steroid 1. Disodium 24-ethyl-3β,6β-dihydroxycholest-22-ene disulfate (2) and disodium 24-ethyl-3β,6β-dihydroxycholestane disulfate (3) were synthesized using a similar method. The cytotoxicity of these compounds against Sk-Hep-1 (human liver carcinoma cell line), H-292 (human lung carcinoma cell line), PC-3 (human prostate carcinoma cell line) and Hey-1B (human ovarian carcinoma cell line) cells was investigated. Our results indicate that presence of a cholesterol-type side chain at position 17 is necessary for their biological activity