Automated Design of Metaheuristics Using Reinforcement Learning within a Novel General Search Framework

Metaheuristic algorithms have been investigated intensively to address highly complex combinatorial optimisation problems. However, most metaheuristic algorithms have been designed manually by researchers of different expertise without a consistent framework to support effective algorithm design. This paper proposes a general search framework to formulate in a unified way a range of different metaheuristics. This framework defines generic algorithmic components, including selection heuristics and evolution operators. The unified general search framework aims to serve as the basis of analysing algorithmic components for automated algorithm design. With the established new general search framework, two reinforcement learning based methods, deep Q-network based and proximal policy optimisation based methods, have been developed to automatically design a new general population-based algorithm. The proposed reinforcement learning based methods are able to intelligently select and combine appropriate algorithmic components during different stages of the optimisation process. The effectiveness and generalization of the proposed reinforcement learning based methods are validated comprehensively across different benchmark instances of the capacitated vehicle routing problem with time windows. This study contributes to making a key step towards automated algorithm design with a general framework supporting fundamental analysis by effective machine learning

Mixed Jacobi-Fourier spectral method for Fisher equation

In this paper, we propose a mixed Jacobi-Fourier spectral method for solving the Fisher equation in a disc. Some mixed Jacobi-Fourier approximation results are established, which play important roles in numerical simulation of various problems defined in a disc. We use the generalized Jacobi approximation to simulate the singularity of solution at the regional center. This also simplifies the theoretical analysis and provides a sparse system. The stability and convergence of the proposed scheme are proved. Numerical results demonstrate the efficiency of this new algorithm and coincide well with the theoretical analysis

Immunogenicity in mice and rhesus monkeys vaccinated with recombinant vaccinia virus expressing bivalent E7E6 fusion proteins from human papillomavirus types 16 and 18

<p>Abstract</p> <p>Background</p> <p>Persistent infection with high-risk human papillomavirus (HPV) is a predominant cause of cervical cancer, and HPV16 and HPV18 occur in 50% and 20% of cervical cancer cases, respectively. The viral oncogenes E6 and E7 are constitutively expressed by HPV-associated tumour cells and can therefore be used as target antigens for immunotherapy. In this study, we constructed a recombinant vaccinia virus co-expressing the HPV16/18 E7E6 fusion proteins (rVVJ16/18E7E6) for use as a therapeutic vaccine for the treatment of HPV16⁺and HPV18⁺cancers.</p> <p>Methods</p> <p>We constructed a bivalent recombinant vaccinia virus expressing modified E7E6 fusion proteins of HPV type 16 and 18 (rVVJ16/18E7E6) based on the vaccinia virus Tiantan strain. We then defined the cellular immune responses to the virus in mice and rhesus monkeys and assessed antitumour efficacy of these responses in mice using the TC-1 tumour challenge model.</p> <p>Results</p> <p>Our data demonstrated that rVVJ16/18E7E6 was able to elicit varying levels of CD8⁺T cell immune responses and lysis of target cells in mice in response to peptides HPV16E7_49-57and HPV18E6_67-75. Furthermore, the virus was also able to induce anti-tumour responses in the HPV16⁺TC-1 tumour challenge model, including partial protection (30-40%) and delayed tumour appearance. In addition, the virus was able to induce immune responses in rhesus monkeys.</p> <p>Conclusions</p> <p>The recombinant vaccinia virus rVVJ16/18E7E6 can generate clear and significant cellular immunity in both mice and rhesus monkeys. These data provide a basis for the use of this recombinant virus as a potential vaccine candidate for further study.</p

Scattered differentiation of unlinked loci across the genome underlines ecological divergence of the selfing grass Brachypodium stacei

Ecological divergence without geographic isolation, as an early speciation process that may lead finally to reproductive isolation through natural selection, remains a captivating topic in evolutionary biology. However, the pattern of genetic divergence underlying this process across the genome may vary between species and mating systems. Here, we present evidence that Brachypodium stacei, an annual and highly selfing grass model species, has undergone sympatric ecological divergence without geographic isolation. Genomic, transcriptomic, and metabolomic analyses together with lab experiments mimicking the two opposite environmental conditions suggest that diploid B. stacei populations have diverged sympatrically in two slopes characterized by distinct biomes at Evolution Canyon I (ECI), Mount Carmel, Israel. Despite ongoing gene flow, primarily facilitated by seed dispersal, the level of gene flow has progressively decreased over time. This local adaptation involves the scattered divergence of many unlinked loci across the total genome that include both coding genes and noncoding regions. Additionally, we have identified significant differential expressions of genes related to the ABA signaling pathway and contrasting metabolome composition between the arid- vs. forest-adapted B. stacei populations in ECI. These results suggest that multiple small loci involved in environmental responses act additively to account for ecological adaptations by this selfing species in contrasting environments

Subgenomic Stability of Progenitor Genomes During Repeated Allotetraploid Origins of the Same Grass Brachypodium hybridum

Both homeologous exchanges and homeologous expression bias are generally found in most allopolyploid species. Whether homeologous exchanges and homeologous expression bias differ between repeated allopolyploid speciation events from the same progenitor species remains unknown. Here, we detected a third independent and recent allotetraploid origin for the model grass Brachypodium hybridum. Our homeologous exchange with replacement analyses indicated the absence of significant homeologous exchanges in any of the three types of wild allotetraploids, supporting the integrity of their progenitor subgenomes and the immediate creation of the amphidiploids. Further homeologous expression bias tests did not uncover significant subgenomic dominance in different tissues and conditions of the allotetraploids. This suggests a balanced expression of homeologs under similar or dissimilar ecological conditions in their natural habitats. We observed that the density of transposons around genes was not associated with the initial establishment of subgenome dominance; rather, this feature is inherited from the progenitor genome. We found that drought response genes were highly induced in the two subgenomes, likely contributing to the local adaptation of this species to arid habitats in the third allotetraploid event. These findings provide evidence for the consistency of subgenomic stability of parental genomes across multiple allopolyploidization events that led to the same species at different periods. Our study emphasizes the importance of selecting closely related progenitor species genomes to accurately assess homeologous exchange with replacement in allopolyploids, thereby avoiding the detection of false homeologous exchanges when using less related progenitor species genomes

circFBXW7 attenuates malignant progression in lung adenocarcinoma by sponging miR-942-5p

Background: As a type of non-coding RNA, circular RNAs (circRNAs) are considered to be functional molecules associated with human cancers. An increasing number of circRNAs have been verified in malignant progression in a number of cancers. The circRNA, circFBXW7, has been proven to play an important role in tumor proliferation and metastasis. However, whether circFBXW7 influences progression in lung adenocarcinoma (LUAD) remains unclear. Methods: Quantitative real-time reverse transcriptase PCR (qRT-PCR) was used to verify circFBXW7 in LUAD cell lines and LUAD tissues. Kaplan-Meier analysis was then used to compare the disease-free survival (DFS) and overall survival (OS) of these LUAD patients. The biological function of circFBXW7 was examined by overexpression and knockdown of circFBXW7 using MTT assay, EdU assay, wound-healing assay, and Transwell in vitro assays. To explore the mechanism of the circFBXW7, RNA pull-down assay, dual luciferase reporter assay, and RNA immunoprecipitation (RIP) assay were employed to examine the interaction between circFBXW7 and miR-942-5p. Western blot was used to study the fundamental proteins associated with the epithelial-mesenchymal transition (EMT) pathway. In vivo studies with BALB/c nude mice subcutaneously injected with cells stably overexpressing circFBXW7 were performed to further validate the in vitro results. Results: circFBXW7 was downregulated in LUAD cell lines and tissues, and LUAD patients with lower levels had shorter DFS and OS. The in vitro study showed that circFBXW7 overexpression inhibited proliferation and migration of A549 and HCC2279 cell lines. These results were confirmed by circFBXW7 knockdown, which showed the reverse effect. The in vivo model showed that the circRNA levels influenced the tumor growth. Finally, we determined that circFBXW7 target miRNA-942-5p which regulates the EMT gene BARX2. The modulation of circFBXW7 levels produced significant changes in EMT genes in vitro and in vivo. Conclusions: Our findings showed that circFBXW7 inhibits proliferation and migration by controlling the miR-942-5p/BARX2 axis in LUAD cell lines and its levels correlates with patient survival suggesting that regulating circFBXW7 could have therapeutic value in treating LUAD patients