A Review of Trimming in Isogeometric Analysis: Challenges, Data Exchange and Simulation Aspects.
ABSTRACT: We review the treatment of trimmed geometries in the context of design, data exchange, and computational simulation. Such models are omnipresent in current engineering modeling and play a key role for the integration of design and analysis. The problems induced by trimming are often underestimated due to the conceptional simplicity of the procedure. In this work, several challenges and pitfalls are described.
Project description:Propensity score weighting is sensitive to model misspecification and outlying weights that can unduly influence results. The authors investigated whether trimming large weights downward can improve the performance of propensity score weighting and whether the benefits of trimming differ by propensity score estimation method. In a simulation study, the authors examined the performance of weight trimming following logistic regression, classification and regression trees (CART), boosted CART, and random forests to estimate propensity score weights. Results indicate that although misspecified logistic regression propensity score models yield increased bias and standard errors, weight trimming following logistic regression can improve the accuracy and precision of final parameter estimates. In contrast, weight trimming did not improve the performance of boosted CART and random forests. The performance of boosted CART and random forests without weight trimming was similar to the best performance obtainable by weight trimmed logistic regression estimated propensity scores. While trimming may be used to optimize propensity score weights estimated using logistic regression, the optimal level of trimming is difficult to determine. These results indicate that although trimming can improve inferences in some settings, in order to consistently improve the performance of propensity score weighting, analysts should focus on the procedures leading to the generation of weights (i.e., proper specification of the propensity score model) rather than relying on ad-hoc methods such as weight trimming.
Project description:Carbon fiber reinforced polymers (CFRPs) have found wide-ranging applications in numerous industrial fields such as aerospace, automotive, and shipping industries due to their excellent mechanical properties that lead to enhanced functional performance. In this paper, an experimental study on edge trimming of CFRP was done with various cutting conditions and different geometry of tools such as helical-, fluted-, and burr-type tools. The investigation involves the measurement of cutting forces for the different machining conditions and its effect on the surface quality of the trimmed edges. The modern cutting tools (router tools or burr tools) selected for machining CFRPs, have complex geometries in cutting edges and surfaces, and therefore a traditional method of direct tool wear evaluation is not applicable. An acoustic emission (AE) sensing was employed for on-line monitoring of the performance of router tools to determine the relationship between AE signal and length of machining for different kinds of geometry of tools. The investigation showed that the router tool with a flat cutting edge has better performance by generating lower cutting force and better surface finish with no delamination on trimmed edges. The mathematical modeling for the prediction of cutting forces was also done using Artificial Neural Network and Regression Analysis.
Project description:A series of N-glycans, each sequentially trimmed from biantennary sialoglycans, were homo- or heterogeneously clustered efficiently on fluorescent albumin using a method that combined strain-promoted alkyne-azide cyclization and 6?-azaelectrocyclization. Noninvasive in vivo kinetics and dissection analysis revealed, for the first time, a glycan-dependent shift from urinary to gall bladder excretion mediated by sequential trimming of non-reducing end sialic acids. N-glycoalbumins that were trimmed further, in particular, GlcNAc- and hybrid biantennary-terminated congeners, were selectively taken up by sinusoidal endothelial and stellate cells in the liver, which are critical for diagnosis and treatment of liver fibrillation. Our glycocluster strategy can not only reveal the previously unexplored extracellular functions of N-glycan trimming, but will be classified as the newly emerging glycoprobes for diagnostic and therapeutic applications.
Project description:BACKGROUND: Nucleotides are trimmed from the ends of variable (V), diversity (D) and joining (J) genes during immunoglobulin (IG) and T cell receptor (TR) rearrangements in B cells and T cells of the immune system. This trimming is followed by addition of nucleotides at random, forming the N regions (N for nucleotides) of the V-J and V-D-J junctions. These processes are crucial for creating diversity in the immune response since the number of trimmed nucleotides and the number of added nucleotides vary in each B or T cell. IMGT sequence analysis tools, IMGT/V-QUEST and IMGT/JunctionAnalysis, are able to provide detailed and accurate analysis of the final observed junction nucleotide sequences (tool "output"). However, as trimmed nucleotides can potentially be replaced by identical N region nucleotides during the process, the observed "output" represents a biased estimate of the "true trimming process." RESULTS: A probabilistic approach based on an analysis of the standardized tool "output" is proposed to infer the probability distribution of the "true trimmming process" and to provide plausible biological hypotheses explaining this process. We collated a benchmark dataset of TR alpha (TRA) and TR gamma (TRG) V-J rearranged sequences and junctions analysed with IMGT/V-QUEST and IMGT/JunctionAnalysis, the nucleotide sequence analysis tools from IMGT, the international ImMunoGeneTics information system, http://imgt.cines.fr. The standardized description of the tool output is based on the IMGT-ONTOLOGY axioms and concepts. We propose a simple first-order model that attempts to transform the observed "output" probability distribution into an estimate closer to the "true trimming process" probability distribution. We use this estimate to test the hypothesis that Poisson processes are involved in trimming. This hypothesis was not rejected at standard confidence levels for three of the four trimming processes: TRAV, TRAJ and TRGV. CONCLUSION: By using trimming of rearranged TR genes as a benchmark, we show that a probabilistic approach, applied to IMGT standardized tool "outputs" opens the way to plausible hypotheses on the events involved in the "true trimming process" and eventually to an exact quantification of trimming itself. With increasing high-throughput of standardized immunogenetics data, similar probabilistic approaches will improve understanding of processes so far only characterized by the "output" of standardized tools.
Project description:Degradation of mRNAs is usually initiated by deadenylation, the shortening of long poly(A) tails to oligo(A) tails of 12-15 As. Deadenylation leads to decapping and to subsequent 5' to 3' degradation by XRN proteins, or alternatively 3' to 5' degradation by the exosome. Decapping can also be induced by uridylation as shown for the non-polyadenylated histone mRNAs in humans and for several mRNAs in Schizosaccharomyces pombe and Aspergillus nidulans. Here we report a novel role for uridylation in preventing 3' trimming of oligoadenylated mRNAs in Arabidopsis. We show that oligo(A)-tailed mRNAs are uridylated by the cytosolic UTP:RNA uridylyltransferase URT1 and that URT1 has no major impact on mRNA degradation rates. However, in absence of uridylation, oligo(A) tails are trimmed, indicating that uridylation protects oligoadenylated mRNAs from 3' ribonucleolytic attacks. This conclusion is further supported by an increase in 3' truncated transcripts detected in urt1 mutants. We propose that preventing 3' trimming of oligo(A)-tailed mRNAs by uridylation participates in establishing the 5' to 3' directionality of mRNA degradation. Importantly, uridylation prevents 3' shortening of mRNAs associated with polysomes, suggesting that a key biological function of uridylation is to confer 5' to 3' polarity in case of co-translational mRNA decay.
Project description:MicroRNAs (miRNAs) are typically generated as ~22-nucleotide double-stranded RNAs via the processing of precursor hairpins by the ribonuclease III enzyme Dicer, after which they are loaded into Argonaute (Ago) proteins to form an RNA-induced silencing complex (RISC). However, the biogenesis of miR-451, an erythropoietic miRNA conserved in vertebrates, occurs independently of Dicer and instead requires cleavage of the 3' arm of the pre-miR-451 precursor hairpin by Ago2. The 3' end of the Ago2-cleaved pre-miR-451 intermediate is then trimmed to the mature length by an unknown nuclease. Here, using a classical chromatographic approach, we identified poly(A)-specific ribonuclease (PARN) as the enzyme responsible for the 3'-5' exonucleolytic trimming of Ago2-cleaved pre-miR-451. Surprisingly, our data show that trimming of Ago2-cleaved precursor miRNAs is not essential for target silencing, indicating that RISC is functional with miRNAs longer than the mature length. Our findings define the maturation step in the miRNA biogenesis pathway that depends on Ago2-mediated cleavage.
Project description:BACKGROUND:Quality control is a necessary step of any Next Generation Sequencing analysis. Although customary, this step still requires manual interventions to empirically choose tuning parameters according to various quality statistics. Moreover, current quality control procedures that provide a "good quality" data set, are not optimal and discard many informative nucleotides. To address these drawbacks, we present a new quality control method, implemented in UrQt software, for Unsupervised Quality trimming of Next Generation Sequencing reads. RESULTS:Our trimming procedure relies on a well-defined probabilistic framework to detect the best segmentation between two segments of unreliable nucleotides, framing a segment of informative nucleotides. Our software only requires one user-friendly parameter to define the minimal quality threshold (phred score) to consider a nucleotide to be informative, which is independent of both the experiment and the quality of the data. This procedure is implemented in C++ in an efficient and parallelized software with a low memory footprint. We tested the performances of UrQt compared to the best-known trimming programs, on seven RNA and DNA sequencing experiments and demonstrated its optimality in the resulting tradeoff between the number of trimmed nucleotides and the quality objective. CONCLUSIONS:By finding the best segmentation to delimit a segment of good quality nucleotides, UrQt greatly increases the number of reads and of nucleotides that can be retained for a given quality objective. UrQt source files, binary executables for different operating systems and documentation are freely available (under the GPLv3) at the following address: https://lbbe.univ-lyon1.fr/-UrQt-.html .
Project description:In Drosophila, microRNAs (miRNAs) typically guide Argonaute1 to repress messenger RNA (mRNA), whereas small interfering RNAs (siRNAs) guide Argonaute2 to destroy viral and transposon RNA. Unlike siRNAs, miRNAs rarely form extensive numbers of base pairs to the mRNAs they regulate. We find that extensive complementarity between a target RNA and an Argonaute1-bound miRNA triggers miRNA tailing and 3'-to-5' trimming. In flies, Argonaute2-bound small RNAs--but not those bound to Argonaute1--bear a 2'-O-methyl group at their 3' ends. This modification blocks target-directed small RNA remodeling: In flies lacking Hen1, the enzyme that adds the 2'-O-methyl group, Argonaute2-associated siRNAs are tailed and trimmed. Target complementarity also affects small RNA stability in human cells. These results provide an explanation for the partial complementarity between animal miRNAs and their targets.
Project description:Previous work showed that, in the presence of DNA-dependent protein kinase (DNA-PK), Artemis slowly trims 3'-phosphoglycolate-terminated blunt ends. To examine the trimming reaction in more detail, long internally labeled DNA substrates were treated with Artemis. In the absence of DNA-PK, Artemis catalyzed extensive 5'-->3' exonucleolytic resection of double-stranded DNA. This resection required a 5'-phosphate, but did not require ATP, and was accompanied by endonucleolytic cleavage of the resulting 3' overhang. In the presence of DNA-PK, Artemis-mediated trimming was more limited, was ATP-dependent and did not require a 5'-phosphate. For a blunt end with either a 3'-phosphoglycolate or 3'-hydroxyl terminus, endonucleolytic trimming of 2-4 nucleotides from the 3'-terminal strand was accompanied by trimming of 6 nt from the 5'-terminal strand. The results suggest that autophosphorylated DNA-PK suppresses the exonuclease activity of Artemis toward blunt-ended DNA, and promotes slow and limited endonucleolytic trimming of the 5'-terminal strand, resulting in short 3' overhangs that are trimmed endonucleolytically. Thus, Artemis and DNA-PK can convert terminally blocked DNA ends of diverse geometry and chemical structure to a form suitable for polymerase-mediated patching and ligation, with minimal loss of terminal sequence. Such processing could account for the very small deletions often found at DNA double-strand break repair sites.
Project description:Trimming low quality bases from sequencing reads is considered as routine procedure for genome assembly; however, we know little about its pros and cons. Here, we used empirical data to examine how read trimming affects assembled genome quality and computational time for a widespread East Asian passerine, the rufous-capped babbler (Cyanoderma ruficeps Blyth). We found that scaffolds assembled from raw reads were always longer than those from trimmed ones, whereas computational times for the former were sometimes much longer than the latter. Nevertheless, assembly completeness showed little difference among the trimming strategies. One should determine the optimal trimming strategy based on what the assembled genome will be used for. For example, to identify single nucleotide polymorphisms (SNPs) associated with phenotypic evolution, applying PLATANUS to gently trim reads would yield a reference genome with a slightly shorter scaffold length (N50 = 15.64 vs. 16.89 Mb) than the raw reads, but would save 75% of computational time. We also found that chromosomes Z, W, and 4A of the rufous-capped babbler were poorly assembled, likely due to a recently fused, neo-sex chromosome. The rufous-capped babbler genome with long scaffolds and quality gene annotation can provide a good system to study avian ecological adaptation in East Asia.