Improved gradient descent algorithms for time-delay rational state-space systems: Intelligent search method and momentum method

This study proposes two improved gradient descent parameter estimation algorithms for rational state-space models with time-delay. These two algorithms, based on intelligent search method and momentum method, can simultaneously estimate the time-delay and parameters without the matrix eigenvalue calculation in each iteration. Compared with the traditional gradient descent algorithm, the improved algorithms come with two advantages: having quicker convergence rates and less computational efforts, particularly meaningful for those large scale systems. A simulated example is selected to illustrate the efficiency of the proposed algorithms

Adaptive Copy Number Evolution in Malaria Parasites

Copy number polymorphism (CNP) is ubiquitous in eukaryotic genomes, but the degree to which this reflects the action of positive selection is poorly understood. The first gene in the Plasmodium folate biosynthesis pathway, GTP-cyclohydrolase I (gch1), shows extensive CNP. We provide compelling evidence that gch1 CNP is an adaptive consequence of selection by antifolate drugs, which target enzymes downstream in this pathway. (1) We compared gch1 CNP in parasites from Thailand (strong historical antifolate selection) with those from neighboring Laos (weak antifolate selection). Two percent of chromosomes had amplified copy number in Laos, while 72% carried multiple (2–11) copies in Thailand, and differentiation exceeded that observed at 73 synonymous SNPs. (2) We found five amplicon types containing one to greater than six genes and spanning 1 to >11 kb, consistent with parallel evolution and strong selection for this gene amplification. gch1 was the only gene occurring in all amplicons suggesting that this locus is the target of selection. (3) We observed reduced microsatellite variation and increased linkage disequilibrium (LD) in a 900-kb region flanking gch1 in parasites from Thailand, consistent with rapid recent spread of chromosomes carrying multiple copies of gch1. (4) We found that parasites bearing dhfr-164L, which causes high-level resistance to antifolate drugs, carry significantly (p = 0.00003) higher copy numbers of gch1 than parasites bearing 164I, indicating functional association between genes located on different chromosomes but linked in the same biochemical pathway. These results demonstrate that CNP at gch1 is adaptive and the associations with dhfr-164L strongly suggest a compensatory function. More generally, these data demonstrate how selection affects multiple enzymes in a single biochemical pathway, and suggest that investigation of structural variation may provide a fast-track to locating genes underlying adaptation

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Versatile nanoplatforms with enhanced photodynamic therapy : designs and applications

202009 bcrcVersion of RecordPublishe

Dynamics and stability analysis on stairs climbing of wheel-track mobile robot

A transformable wheel-track robot with the tail rod whose winding will coordinate the center of gravity of the robot is researched, and a theoretical basis for the stable climbing of the robot is provided. After a general introduction of the research, firstly the mechanical hardware and control hardware composition of the wheel-track robot is provided and the principles of its mechanical structure are illustrated. Secondly, through studying the fundamental constrains during the process of the robot climbing the obstacles, a mathematical model based on classical mechanics method is built to help analyze the dynamic principles of a wheel-track mobile robot climbing stairs. Thirdly, the dynamic stability analysis is carried out by analyzing not only the interaction among forces of track, track edge, and stair step but also the different stabilities of the robot when the track and the stairs have different touch points. Finally, an experiment of the modeling track robot climbing the stairs has convinced the effectiveness of the dynamic theories researched, which will be a beneficial reference for the future mobile robots obstacle climbing studies

RBS STUDIES OF THE LATTICE DAMAGE CAUSED BY 1 MEV SI+ IMPLANTATION INTO AL0.3GA0.7AS/GAAS SUPERLATTICES AT ELEVATED-TEMPERATURE

The lattice damage accumulation in GaAs and Al0.3Ga0.7As/GaAs superlattices by 1 MeV Si+ irradiation at room temperature and 350-degrees-C has been studied. For irradiations at 350-degrees-C, at lower doses the samples were almost defect-free after irradiation, while a large density of accumulated defects was induced at a higher dose. The critical dose above which the damage accumulation is more efficient is estimated to be 2 x 10(15) Si/cm2 for GaAs, and is 5 x 10(15) Si/cm2 for Al0.8Ga0.7As/GaAs superlattice for implantation with 1.0 MeV Si ions at 350-degrees-C. The damage accumulation rate for 1 MeV Si ion implantation in Al0.3Ga0.7As/GaAs superlattice is less than that in GaAs