Optimal control of impulsive switched systems with minimum subsystem durations

This paper presents a new computational approach for solving optimal control problems governed by impulsive switched systems. Such systems consist of multiple subsystems operating in succession, with possible instantaneous state jumps occurring when the system switches from one subsystem to another. The control variables are the subsystem durations and a set of system parameters influencing the state jumps. In contrast with most other papers on the control of impulsive switched systems, we do not require every potential subsystem to be active during the time horizon (it may be optimal to delete certain subsystems, especially when the optimal number of switches is unknown). However, any active subsystem must be active for a minimum non-negligible duration of time. This restriction leads to a disjoint feasible region for the subsystem durations. The problem of choosing the subsystem durations and the system parameters to minimize a given cost function is a non-standard optimal control problem that cannot be solved using conventional techniques. By combining a time-scaling transformation and an exact penalty method, we develop a computational algorithm for solving this problem. We then demonstrate the effectiveness of this algorithm by considering a numerical example on the optimization of shrimp harvesting operations

Optimal Control of Nonlinear Switched Systems: Computational Methods and Applications

A switched system is a dynamic system that operates by switching between different subsystems or modes. Such systems exhibit both continuous and discrete characteristics—a dual nature that makes designing effective control policies a challenging task. The purpose of this paper is to review some of the latest computational techniques for generating optimal control laws for switched systems with nonlinear dynamics and continuous inequality constraints. We discuss computational strategiesfor optimizing both the times at which a switched system switches from one mode to another (the so-called switching times) and the sequence in which a switched system operates its various possible modes (the so-called switching sequence). These strategies involve novel combinations of the control parameterization method, the timescaling transformation, and bilevel programming and binary relaxation techniques. We conclude the paper by discussing a number of switched system optimal control models arising in practical applications

A framework for automated enrichment of functionally significant inverted repeats in whole genomes

<p>Abstract</p> <p>Background</p> <p>RNA transcripts from genomic sequences showing dyad symmetry typically adopt hairpin-like, cloverleaf, or similar structures that act as recognition sites for proteins. Such structures often are the precursors of non-coding RNA (ncRNA) sequences like microRNA (miRNA) and small-interfering RNA (siRNA) that have recently garnered more functional significance than in the past. Genomic DNA contains hundreds of thousands of such inverted repeats (IRs) with varying degrees of symmetry. But by collecting statistically significant information from a known set of ncRNA, we can sort these IRs into those that are likely to be functional.</p> <p>Results</p> <p>A novel method was developed to scan genomic DNA for partially symmetric inverted repeats and the resulting set was further refined to match miRNA precursors (pre-miRNA) with respect to their density of symmetry, statistical probability of the symmetry, length of stems in the predicted hairpin secondary structure, and the GC content of the stems. This method was applied on the <it>Arabidopsis thaliana</it> genome and validated against the set of 190 known Arabidopsis pre-miRNA in the miRBase database. A preliminary scan for IRs identified 186 of the known pre-miRNA but with 714700 pre-miRNA candidates. This large number of IRs was further refined to 483908 candidates with 183 pre-miRNA identified and further still to 165371 candidates with 171 pre-miRNA identified (i.e. with 90% of the known pre-miRNA retained).</p> <p>Conclusions</p> <p>165371 candidates for potentially functional miRNA is still too large a set to warrant wet lab analyses, such as northern blotting, on all of them. Hence additional filters are needed to further refine the number of candidates while still retaining most of the known miRNA. These include detection of promoters and terminators, homology analyses, location of candidate relative to coding regions, and better secondary structure prediction algorithms. The software developed is designed to easily accommodate such additional filters with a minimal experience in Perl.</p

PI3K(p110 alpha) Protects Against Myocardial Infarction-Induced Heart Failure Identification of PI3K-Regulated miRNA and mRNA

Objective: Myocardial infarction (MI) is a serious complication of atherosclerosis associated with increasing mortality attributable to heart failure. Activation of phosphoinositide 3-kinase [PI3K(p110α)] is considered a new strategy for the treatment o

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

The control parameterization method for nonlinear optimal control: A survey

The control parameterization method is a popular numerical technique for solving optimal control problems. The main idea of control parameterization is to discretize the control space by approximating the control function by a linear combination of basis functions. Under this approximation scheme, the optimal control problem is reduced to an approximate nonlinear optimization problem with a finite number of decision variables. This approximate problem can then be solved using nonlinear programming techniques. The aim of this paper is to introduce the fundamentals of the control parameterization method and survey its various applications to non-standard optimal control problems. Topics discussed include gradient computation, numerical convergence, variable switching times, and methods for handling state constraints. We conclude the paper with some suggestions for future research

The mir-51 Family of microRNAs Functions in Diverse Regulatory Pathways in Caenorhabditis elegans

The mir-51 family of microRNAs (miRNAs) in C. elegans are part of the deeply conserved miR-99/100 family. While loss of all six family members (mir-51-56) in C. elegans results in embryonic lethality, loss of individual mir-51 family members results in a suppression of retarded developmental timing defects associated with the loss of alg-1. The mechanism of this suppression of developmental timing defects is unknown. To address this, we characterized the function of the mir-51 family in the developmental timing pathway. We performed genetic analysis and determined that mir-51 family members regulate the developmental timing pathway in the L2 stage upstream of hbl-1. Loss of the mir-51 family member, mir-52, suppressed retarded developmental timing defects associated with the loss of let-7 family members and lin-46. Enhancement of precocious defects was observed for mutations in lin-14, hbl-1, and mir-48(ve33), but not later acting developmental timing genes. Interestingly, mir-51 family members showed genetic interactions with additional miRNA-regulated pathways, which are regulated by the let-7 and mir-35 family miRNAs, lsy-6, miR-240/786, and miR-1. Loss of mir-52 likely does not suppress miRNA-regulated pathways through an increase in miRNA biogenesis or miRNA activity. We found no increase in the levels of four mature miRNAs, let-7, miR-58, miR-62 or miR-244, in mir-52 or mir-52/53/54/55/56 mutant worms. In addition, we observed no increase in the activity of ectopic lsy-6 in the repression of a downstream target in uterine cells in worms that lack mir-52. We propose that the mir-51 family functions broadly through the regulation of multiple targets, which have not yet been identified, in diverse regulatory pathways in C. elegans

A Role for Phosphatidic Acid in the Formation of “Supersized” Lipid Droplets

Lipid droplets (LDs) are important cellular organelles that govern the storage and turnover of lipids. Little is known about how the size of LDs is controlled, although LDs of diverse sizes have been observed in different tissues and under different (patho)physiological conditions. Recent studies have indicated that the size of LDs may influence adipogenesis, the rate of lipolysis and the oxidation of fatty acids. Here, a genome-wide screen identifies ten yeast mutants producing “supersized” LDs that are up to 50 times the volume of those in wild-type cells. The mutated genes include: FLD1, which encodes a homologue of mammalian seipin; five genes (CDS1, INO2, INO4, CHO2, and OPI3) that are known to regulate phospholipid metabolism; two genes (CKB1 and CKB2) encoding subunits of the casein kinase 2; and two genes (MRPS35 and RTC2) of unknown function. Biochemical and genetic analyses reveal that a common feature of these mutants is an increase in the level of cellular phosphatidic acid (PA). Results from in vivo and in vitro analyses indicate that PA may facilitate the coalescence of contacting LDs, resulting in the formation of “supersized” LDs. In summary, our results provide important insights into how the size of LDs is determined and identify novel gene products that regulate phospholipid metabolism

Overlapping functions of microRNAs in control of apoptosis during Drosophila embryogenesis

Regulation of apoptosis is crucial for tissue homeostasis under normal development and environmental stress. In Drosophila, cell death occurs in different developmental processes including embryogenesis. Here, we report that two members of the miR-2 seed family of microRNAs, miR-6 and miR-11, function together to limit the level of apoptosis during Drosophila embryonic development. Mutants lacking both miR-6 and miR-11 show embryonic lethality and defects in the central nervous system (CNS). We provide evidence that miR-6/11 functions through regulation of the proapoptotic genes, reaper (rpr), head involution defective (hid), grim and sickle (skl). Upregulation of these proapoptotic genes is responsible for the elevated apoptosis and the CNS defects in the mutants. These findings demonstrate that the activity of the proapoptotic genes is kept in check by miR-6/11 to ensure normal development