Deletion Of Element Research Articles

PCGF6 controls neuroectoderm specification of human pluripotent stem cells by activating SOX2 expression

Polycomb group (PcG) proteins are known to repress developmental genes during embryonic development and tissue homeostasis. Here, we report that PCGF6 controls neuroectoderm specification of human pluripotent stem cells (PSCs) by activating SOX2 gene. Human PSCs with PCGF6 depletion display impaired neuroectoderm differentiation coupled with increased mesendoderm outcomes. Transcriptome analysis reveals that de-repression of the WNT/β-catenin signaling pathway is responsible for the differentiation of PSC toward the mesendodermal lineage. Interestingly, PCGF6 and MYC directly interact and co-occupy a distal regulatory element of SOX2 to activate SOX2 expression, which likely accounts for the regulation in neuroectoderm differentiation. Supporting this notion, genomic deletion of the SOX2-regulatory element phenocopies the impaired neuroectoderm differentiation, while overexpressing SOX2 rescues the neuroectoderm phenotype caused by PCGF6-depletion. Together, our study reveals that PCGF6 can function as lineage switcher between mesendoderm and neuroectoderm in human PSCs by both suppression and activation mechanisms.

Comparison of numerical modelling approaches for the residual burst pressure of thick type IV composite overwrapped pressure vessels related to low-velocity impact

Residual burst pressure of thick composite pressure vessels related to low-velocity impacts is investigated numerically. Different modelling approaches from simple shell to complex 3D solid models with multiple delamination interfaces are compared. Burst pressure without impact is used to estimate the quality of the different approaches, whereby the best experimental agreement is observed for the complex 3D solid model. For the low-velocity impact, two locations are investigated, one in the cylindrical and another in the dome region. The influence of additional delamination interfaces is investigated and significantly affects the resulting reaction force and intrusion depth of the impactor. Furthermore, it is shown that the consideration of just one interface gives similar results as the shell model, but both models still result in a too stiff behaviour. Only the consideration of multiple interfaces leads to good results compared to the experiments in terms of impact and residual burst pressure behaviour. For the impact on the dome area as well as the shell model, excessive element deletion is observed, leading to problems for the subsequent pressurising, which requires further investigation.

The Genomic 3' UTR of Flaviviruses Is a Translation Initiation Enhancer.

Viruses rely on the cellular machinery of host cells to synthesize their proteins, and have developed different mechanisms enabling them to compete with cellular mRNAs for access to it. The genus Flavivirus is a large group of positive, single-stranded RNA viruses that includes several important human pathogens, such as West Nile, Dengue and Zika virus. The genome of flaviviruses bears a type 1 cap structure at its 5′ end, needed for the main translation initiation mechanism. Several members of the genus also use a cap-independent translation mechanism. The present work provides evidence that the WNV 5′ end also promotes a cap-independent translation initiation mechanism in mammalian and insect cells, reinforcing the hypothesis that this might be a general strategy of flaviviruses. In agreement with previous reports, we show that this mechanism depends on the presence of the viral genomic 3′ UTR. The results also show that the 3′ UTR of the WNV genome enhances translation of the cap-dependent mechanism. Interestingly, WNV 3′ UTR can be replaced by the 3′ UTR of other flaviviruses and the translation enhancing effect is maintained, suggesting a molecular mechanism that does not involve direct RNA-RNA interactions to be at work. In addition, the deletion of specific structural elements of the WNV 3′ UTR leads to increased cap-dependent and cap-independent translation. These findings suggest the 3′ UTR to be involved in a fine-tuned translation regulation mechanism.

Engineering of ultra-high performance self-compacting mortar with recycled steel fibres extracted from waste tires

The main novelty of this study is producing Ultra High-Performance Self Compacting Mortar (UHPSCM) incorporated Recycled Steel Fibre (RSF) from waste tires. For this purpose, different mix compositions including 0%, 1%, and 3% RSF content in terms of volume were proposed. Self-compacting ability was assessed using mini-cone tests, while nondestructive testing has been used to evaluate the effect of RSF inclusion on the compaction of UHPSCM constituent materials. Mechanical performances were investigated using compression and unnotched flexural tests. Residual flexural strength in both service limit state (SLS), ultimate limit state (ULS), and two equivalent flexural strengths were evaluated under notched flexural tests and analysed using statistical approaches. Concrete Damage Plasticity (CDP) has been employed for the analysis behaviour of developed mortars under different loadings. Additionally, an element deletion approach was used to evaluate the fracture of UHPSCM under compression and flexural loadings. The experimental results showed that adding 1% and 3% of RSF resulted in decreasing workability by 3% and 22%, respectively. Improving compressive strength by 16% and 22% and flexural by 7% and 8% were noticed in the case of samples with 1% and 3% fiber, respectively, in 28 days. In spite of the significant improvement of post-cracking behaviour of samples with 3% of RSF, this behaviour was insignificant for the samples with 1% of RSF. However, with less amount of fibre inclusion, brittle failure can be altered to ductile failure. Moreover, the behaviour of the tested specimens under different loadings was successfully predicted using Finite Element (FE) simulations.Graphical abstract

Balanced gene dosage control rather than parental origin underpins genomic imprinting

Mammalian parental imprinting represents an exquisite form of epigenetic control regulating the parent-specific monoallelic expression of genes in clusters. While imprinting perturbations are widely associated with developmental abnormalities, the intricate regional interplay between imprinted genes makes interpreting the contribution of gene dosage effects to phenotypes a challenging task. Using mouse models with distinct deletions in an intergenic region controlling imprinting across the Dlk1-Dio3 domain, we link changes in genetic and epigenetic states to allelic-expression and phenotypic outcome in vivo. This determined how hierarchical interactions between regulatory elements orchestrate robust parent-specific expression, with implications for non-imprinted gene regulation. Strikingly, flipping imprinting on the parental chromosomes by crossing genotypes of complete and partial intergenic element deletions rescues the lethality of each deletion on its own. Our work indicates that parental origin of an epigenetic state is irrelevant as long as appropriate balanced gene expression is established and maintained at imprinted loci.

The dynamic transcriptome during maturation of biofilms formed by methicillin-resistant Staphylococcus aureus.

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA), a leading cause of chronic infections, forms prolific biofilms which afford an escape route from antibiotic treatment and host immunity. However, MRSA clones are genetically diverse, and mechanisms underlying biofilm formation remain under-studied. Such studies form the basis for developing targeted therapeutics. Here, we studied the temporal changes in the biofilm transcriptome of three pandemic MRSA clones: USA300, HEMRSA-15, and ST239.MethodsBiofilm formation was assessed using a static model with one representative strain per clone. Total RNA was extracted from biofilm and planktonic cultures after 24, 48, and 72 h of growth, followed by rRNA depletion and sequencing (Illumina Inc., San Diego, CA, United States, NextSeq500, v2, 1 × 75 bp). Differentially expressed gene (DEG) analysis between phenotypes and among early (24 h), intermediate (48 h), and late (72 h) stages of biofilms was performed together with in silico co-expression network construction and compared between clones. To understand the influence of SCCmec and ACME on biofilm formation, isogenic mutants containing deletions of the entire elements or of single genes therein were constructed in USA300.ResultsGenes involved in primarily core genome-encoded KEGG pathways (transporters and others) were upregulated in 24-h biofilm culture compared to 24-h planktonic culture. However, the number of affected pathways in the ST239 24 h biofilm (n = 11) was remarkably lower than that in USA300/EMRSA-15 biofilms (USA300: n = 27, HEMRSA-15: n = 58). The clfA gene, which encodes clumping factor A, was the single common DEG identified across the three clones in 24-h biofilm culture (2.2- to 2.66-fold). In intermediate (48 h) and late (72 h) stages of biofilms, decreased expression of central metabolic and fermentative pathways (glycolysis/gluconeogenesis, fatty acid biosynthesis), indicating a shift to anaerobic conditions, was already evident in USA300 and HEMRSA-15 in 48-h biofilm cultures; ST239 showed a similar profile at 72 h. Last, SCCmec+ACME deletion and opp3D disruption negatively affected USA300 biofilm formation.ConclusionOur data show striking differences in gene expression during biofilm formation by three of the most important pandemic MRSA clones, USA300, HEMRSA-15, and ST239. The clfA gene was the only significantly upregulated gene across all three strains in 24-h biofilm cultures and exemplifies an important target to disrupt early biofilms. Furthermore, our data indicate a critical role for arginine catabolism pathways in early biofilm formation.

Titanite Spectroscopy and In Situ LA-ICP-MS U–Pb Geochronology of Mogok, Myanmar

With the development of mineral testing technology and ore deposit geochemistry, titanite has become a hot topic in the study of accessory minerals. Two large-grained titanite crystals from Mogok, Myanmar, were used for a detailed study. In this study, the standard gemmological properties and spectral characteristics of titanite crystals were obtained by Fourier transform in-frared, micro ultraviolet-visible-near-infrared and Raman spectroscopy, respectively, which pro-vide a full set of data. Mineral major and trace elements were analysed using Electron-Probe Mi-croAnalysis (EPMA) and Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS). The purpose of this study is to report spectral characteristics and major and trace elements of Mogok, Myanmar, in order to find new potential titanite standard samples. The two titanite crystals have similar major element compositions, and both grains have relatively low Al content (0.011–0.014 apfu) and Al/Fe ratios (0.157–0.222), but high Fe content (0.063–0.079 apfu). The two titanite crystals have similar chondrite-normalised rare earth element (REE) patterns with significantly Light Rare Earth Element (LREE) (La–Gd) enrichment and deletion of Heavy Rare Earth Element (HREE) (Tb–Lu). The 238U/206Pb ages of the two titanite samples are 43.5 ± 5.8 Ma and 34.0 ± 4.2 Ma, respectively. Generally, magmatic titanite has a low Al/Fe ratio, metamorphic and hydrothermal titanite crystals have extremely low Th/U ratios close to zero, with flat chondrite-normalised REE patterns or depletions in light REEs relative to heavy REEs. Different genetic types of titanite can be distinguished by the characteristics of major and trace elements. Combined chemical features such as REE differentiation, Al/Fe and Th/U ratios with formation temperature, the analysed titanite samples are considered magmatic-hydrothermal titanites. Their 238U/206Pb ages may indicate a potential stage of magmatic hydrothermal conversion.

Numerical analysis for mining-induced stress and plastic evolution involving influencing factors: high in situ stress, excavation rate and multilayered heterogeneity

PurposeThis study aims to analyse the deep resource mining that causes high in situ stress, and the disturbance of tunnelling and mining which may induce large stress concentration, plastic deformation and rock strata compression deformation. The depth of deep resources, excavation rate and multilayered heterogeneity are critical factors of excavation disturbance in deep rock. However, at present, there are few engineering practices used in deep resource mining, and it is difficult to analyse the high in situ stress and dynamic three-dimensional (3D) excavation process in laboratory experiments. As a result, an understanding of the behaviours and mechanisms of the dynamic evolution of the stress field and plastic zone in deep tunnelling and mining surrounding rock is still lacking.Design/methodology/approachThis study introduced a 3D engineering-scale finite element model and analysed the scheme involved the elastoplastic constitutive and element deletion techniques, while considering the influence of the deep rock mass of the roadway excavation, coal seam mining-induced stress, plastic zone in the process of mining disturbance of the in situ stress state, excavation rate and layered rock mass properties at the depths of 500 m, 1,500 m and 2,500 m of several typical coal seams, and the tunnelling and excavation rates of 0.5 m/step, 1 m/step and 2 m/step. An engineering-scale numerical model of the layered rock and soil body in an actual mining area were also established.FindingsThe simulation results of the surrounding rock stress field, dynamic evolution and maximum value change of the plastic zone, large deformation and settlement of the layered rock mass are obtained. The numerical results indicate that the process of mining can be accelerated with the increase in the tunnelling and excavation rate, but the vertical concentrated stress induced by the surrounding rock intensifies with the increase in the excavation rate, which becomes a crucial factor affecting the instability of the surrounding rock. The deep rock mass is in the high in situ stress state, and the stress and plastic strain maxima of the surrounding rock induced by the tunnelling and mining processes increase sharply with the excavation depth. In ultra-deep conditions (depth of 2,500 m), the maximum vertical stress is quickly reached by the conventional tunnelling and mining process. Compared with the deep homogeneous rock mass model, the multilayered heterogeneous rock mass produces higher mining-induced stress and plastic strain in each layer during the entire process of tunnelling and mining, and each layer presents a squeeze and dislocation deformation.Originality/valueThe results of this study can provide a valuable reference for the dynamic evolution of stress and plastic deformation in roadway tunnelling and coal seam mining to investigate the mechanisms of in situ stress at typical depths, excavation rates, stress concentrations, plastic deformations and compression behaviours of multilayered heterogeneity.

A simple implementation of localizing gradient damage model in Abaqus

With the localizing gradient enhancement, a damage model for quasi-brittle materials is able to achieve regularized softening responses, with localized damage profiles corresponding to the development of macroscopic cracks, to resolve the numerical spurious effects induced by the conventional gradient enhancement. The typical implementation strategy for a gradient enhanced model is to solve the system of governing equations simultaneously. Focusing on the finite element (FE) package Abaqus, a user element subroutine is required to define the finite elements with additional degrees of freedom for the nonlocal field. Moreover, with user elements, additional effort is required to visualize the numerical results. To an inexperienced engineer/researcher, these requirements can be challenging. In this paper, a simple implementation of the localizing gradient damage model is elaborated. By utilizing the in-built coupled thermo-mechanical elements in Abaqus, the user only needs to define the material constitutive laws, as well as the sensitivity terms with respect to the field variables. Post-processing of results can be done directly in Abaqus. The applicability and ease of implementation are demonstrated via several examples, including those that utilize the Abaqus features of element deletion, contact between surfaces, as well as the incorporation of cohesive elements. Sample files can be downloaded from https://github.com/leonghien/Localizing-Gradient-Damage-with-UMAT-UMATHT

Ballistic resistance and energy dissipation of woven-fabric composite targets: Insights on the effects of projectile shape and obliquity angle

This study aims at investigating the ballistic resistance and energy absorption in woven E-glass composite panels, considering different projectile nose shapes and oblique incidence angles. To that scope, three-dimensional finite element (FE) models of both projectiles and the laminated target are developed and numerical investigations are carried out using Abaqus Explicit solver. The composite damage model's constitutive law encompasses nonlinear material response, material properties degradation, progressive failure, and an element deletion strategy. The cohesive surface technique is used to represent the interface between two adjacent plies in the laminate, and the traction-separation law is used to characterize the behaviors of interlaminar degradation and failure. Material responses attributable to fiber rupture, matrix cracking, and plasticity caused by micro-matrix cracking due to shear loading are taken into account with suitable damage evolution laws. The computational framework is first validated against the experimental results reported in the literature by performing ballistic impact tests on the target laminate with conical, hemispherical and blunt-ended projectile, and the numerical results showed a good comparison in terms of residual velocity. Subsequently the framework is explored in simulating more complex failure mechanisms, with particular emphasis on the influence of the impact angle of obliquity, a parameter that is not usually analyzed in the literature. In that regard, the effects of normal and oblique impact on the damage morphologies and ballistic behavior of the fabric composite target in terms of energy absorption, impact contact force, and projectile residual velocity are conducted and analyzed, comparatively. The findings showed that the ballistic impact behavior of target composite is substantially influenced by projectile nose shape and incidence angle obliquity.

Experimental and numerical study on the effect of electrohydraulic shock wave on concrete fracturing

In order to apply electrohydraulic shock wave (EHS) technology to oil and gas stimulation or assisted rock fracture, it is necessary to analyze how the crack propagation behavior of the rock subjected to the EHS. For this purpose, experiments and numerical simulations are carried out respectively. In the experiment, the relevant parameters of electrical characteristics and acoustic radiation characteristics were given based on the established discharge platform, and 30 times impacts tests are carried out on cubic concrete. The results show that the corner areas of the upper surface of the concrete are the first to be broken; with the increase of impact time, the shape and number of cracks on the surface of the concrete sample change in two stages. In the first stage, the number of microcracks increased rapidly, the cracks are interconnected, and the existing pores gradually become bigger. In the second stage, the growth rate of the number of microcracks gradually decreases, and the width of the formed cracks gradually increases; the damage variable of the concrete obtained by the acoustic test increases sharply first and then increase slowly throughout the impact test. In the numerical simulation, the history match of the EHS pressure is implemented based on the equivalent explosion method (EEM); a two-dimensional numerical model is established to simulate the interaction process between the EHS and the concrete sample; a three-dimensional TNT-water-concrete numerical model is built to simulate the concrete fracturing. The results show that it is reliable to use the equivalent explosion method to simulate the EHS. The concrete sample subjected to the EHS is affected by four aspects: bubble; transmitted wave and reflected wave; diffraction wave; elastic precursor wave and plastic loading wave. When the element deletion method is used to simulate crack generation, adopting the maximum tensile stress failure criterion can accurately simulate the final distribution of cracks, but it is difficult to simulate the evolution process of cracks under cyclic impact loads.

A novel post-processing method for progressive failure analysis of brittle composite compression

Finite element analysis of brittle materials in axial compression typically uses element deletion to allow continued global deformation post-element-failure. However, element deletion produces cyclic load-displacement curves that underestimate energy absorption and are not representative of a continuum system. Two key observations support the conclusion that results from an appropriately discretized model can be an adequate representation of a continuum system. Specifically, the frequency of the oscillations in the load-displacement curve is directly dependent upon element length in the loading direction, and the peak amplitudes of oscillations are mesh size independent. A method of post-processing the analysis results, by connecting the peak amplitudes of oscillations, is proposed and applied to a series of continuous carbon fiber composite crush tubes. The load-displacement curve, stable crushing load, and specific energy absorption of the post-processed results compare well to an experimental study of crush tubes with similar layups.

PqsE Expands and Differentially Modulates the RhlR Quorum Sensing Regulon in Pseudomonas aeruginosa.

ABSTRACTIn the opportunistic pathogen Pseudomonas aeruginosa, many virulence traits are finely regulated by quorum sensing (QS), an intercellular communication system that allows the cells of a population to coordinate gene expression in response to cell density. The key aspects underlying the functionality of the complex regulatory network governing QS in P. aeruginosa are still poorly understood, including the interplay between the effector protein PqsE and the transcriptional regulator RhlR in controlling the QS regulon. Different studies have focused on the characterization of PqsE- and RhlR-controlled genes in genetic backgrounds in which RhlR activity can be modulated by PqsE and pqsE expression is controlled by RhlR, thus hampering identification of the distinct regulons controlled by PqsE and RhlR. In this study, a P. aeruginosa PAO1 mutant strain with deletion of multiple QS elements and inducible expression of pqsE and/or rhlR was generated and validated. Transcriptomic analyses performed on this genetic background allowed us to unambiguously define the regulons controlled by PqsE and RhlR when produced alone or in combination. Transcriptomic data were validated via reverse transcription-quantitative PCR (RT-qPCR) and transcriptional fusions. Overall, our results showed that PqsE has a negligible effect on the P. aeruginosa transcriptome in the absence of RhlR, and that multiple RhlR subregulons exist with distinct dependency on PqsE. Overall, this study contributes to untangling the regulatory link between the pqs and rhl QS systems mediated by PqsE and RhlR and clarifying the impact of these QS elements on the P. aeruginosa transcriptome.IMPORTANCE The ability of Pseudomonas aeruginosa to cause difficult-to-treat infections relies on its capacity to fine-tune the expression of multiple virulence traits via the las, rhl, and pqs QS systems. Both the pqs effector protein PqsE and the rhl transcriptional regulator RhlR are required for full production of key virulence factors in vitro and pathogenicity in vivo. While it is known that PqsE can stimulate the ability of RhlR to control some virulence factors, no data are available to allow clear discrimination of the PqsE and RhlR regulons. The data produced in this study demonstrate that PqsE mainly impacts the P. aeruginosa transcriptome via an RhlR-dependent pathway and splits the RhlR regulon into PqsE-dependent and PqsE-independent subregulons. Besides contributing to untangling of the complex QS network of P. aeruginosa, our data confirm that both PqsE and RhlR are suitable targets for the development of antivirulence drugs.

Distinct super-enhancer elements differentially control Il2ra gene expression in a cell-type specific fashion

Abstract Expression of the IL-2 receptor a-chain (IL-2Ra, also known as CD25) is tightly regulated during T cell development and in mature lymphoid populations. IL-2Ra is constitutively expressed on double negative DN2/DN3 thymocytes and regulatory T cells, but its expression is inducible on mature T and natural killer (NK) cells. The Il2ra gene is regulated in part by a super-enhancer that is extensively bound by STAT5, but whether the super-enhancer elements are differentially used to control the cell-specific expression of Il2ra in distinct cell populations is unknown. Here, we generated a comprehensive series of mutant mice harboring deletion of individual or multiple elements within this super-enhancer. Strikingly, deletions in the upstream super-enhancer region dominantly affected CD25 expression on DN2/DN3 thymocytes and Treg cells, whereas deleting an intronic region primarily decreased IL-2-induced CD25 expression on peripheral CD4+ and CD8+ T and NK cells. Thus, distinct elements control constitutive versus inducible expression of the Il2ra gene in a cell-type-specific manner rather than behaving as simple enhancers whose activity is additive/cooperative, as has been observed for the a-globin and Wap super-enhancers. Moreover, the intronic super-enhancer region was critical for chromatin looping, and deletion of this region altered super-enhancer structure throughout the locus. These results demonstrate differential functions for distinct super-enhancer elements, thereby indicating ways to manipulate CD25 expression in a cell-type specific fashion, an area of importance in autoimmune and other disease states.

The transcription factor Atf1 lowers the transition barrier for nucleosome-mediated establishment of heterochromatin.

Transcription factors can exert opposite effects depending on the chromosomal context. The fission yeast transcription factor Atf1 both activates numerous genes in response to stresses and mediates heterochromatic gene silencing in the mating-type region. Investigating this context dependency, we report here that the establishment of silent heterochromatin in the mating-type region occurs at a reduced rate in the absence of Atf1 binding. Quantitative modeling accounts for the observed establishment profiles by a combinatorial recruitment of histone-modifying enzymes: locally by Atf1 at two binding sites and over the whole region by dynamically appearing heterochromatic nucleosomes, a source of which is the RNAi-dependent cenH element. In the absence of Atf1 binding, the synergy is lost, resulting in a slow rate of heterochromatin formation. The system shows how DNA-binding proteins can influence local nucleosome states and thereby potentiate long-range positive feedback on histone-modification reactions to enable heterochromatin formation over large regions in a context-dependent manner.

The long β2,3-sheets encoded by redundant sequences play an integral role in the channel function of P2X7 receptors

P2X receptors are a class of nonselective cation channels widely distributed in the immune and nervous systems, and their dysfunction is a significant cause of tumors, inflammation, leukemia, and immune diseases. P2X7 is a unique member of the P2X receptor family with many properties that differ from other subtypes in terms of primary sequence, the architecture of N- and C-terminals, and channel function. Here, we suggest that the observed lengthened β2- and β3-sheets and their linker (loop β2,3), encoded by redundant sequences, play an indispensable role in the activation of the P2X7 receptor. We show that deletion of this longer structural element leads to the loss of P2X7 function. Furthermore, by combining mutagenesis, chimera construction, surface expression, and protein stability analysis, we found that the deletion of the longer β2,3-loop affects P2X7 surface expression but, more importantly, that this loop affects channel gating of P2X7. We propose that the longer β2,3-sheets may have a negative regulatory effect on a loop on the head domain and on the structural element formed by E171 and its surrounding regions. Understanding the role of the unique structure of the P2X7 receptor in the gating process will aid in the development of selective drugs targeting this subtype.

Validation of a new system for measuring material constants representing damage limits

This paper describes a test for the determination of damage function limits. The proposed test consists of skew rolling of conical specimens. The test is carried out under real conditions to determine the crack initiation point, and then it is modelled numerically to determine the limit values of the damage function at the determined crack initiation point. This paper presents a methodology for the determination of limit values of the damage function on the example of C45 steel at three different temperatures, i.e. 950 °C, 1050 °C and 1150 °C. The research was carried out using the Oyane criterion as an example. The limit value of the damage function at 1000 °C was determined by regression using the calculated damage function values. The value of the damage function was adapted to a numerical model of a skew-rolling process of a bar with the deletion of elements, which took place when the limit value of the damage function determined in the test was exceeded. The numerically simulated skew rolling case was also realised in real conditions. Based on the results obtained from the skew rolling of bars, a quantitative and qualitative validation of the new damage function limit test was carried out.

Genome assembly, structural variants, and genetic differentiation between lake whitefish young species pairs (Coregonus sp.) with long and short reads.

Nascent pairs of ecologically differentiated species offer an opportunity to get a better glimpse at the genetic architecture of speciation. Of particular interest is our recent ability to consider a wider range of genomic variants, not only single-nucleotide polymorphisms (SNPs), thanks to long-read sequencing technology. We can now identify structural variants (SVs) such as insertions, deletions and other rearrangements, allowing further insights into the genetic architecture of speciation and how different types of variants are involved in species differentiation. Here, we investigated genomic patterns of differentiation between sympatric species pairs (Dwarf and Normal) belonging to the lake whitefish (Coregonus clupeaformis) species complex. We assembled the first reference genomes for both C. clupeaformis sp. Normal and C. clupeaformis sp. Dwarf, annotated the transposable elements and analysed the genomes in the light of related coregonid species. Next, we used a combination of long- and short-read sequencing to characterize SVs and genotype them at the population scale using genome-graph approaches, showing that SVs cover five times more of the genome than SNPs. We then integrated both SNPs and SVs to investigate the genetic architecture of species differentiation in two different lakes and highlighted an excess of shared outliers of differentiation. In particular, a large fraction of SVs differentiating the two species correspond to insertions or deletions of transposable elements (TEs), suggesting that TE accumulation may represent a key component of genetic divergence between the Dwarf and Normal species. Together, our results suggest that SVs may play an important role in speciation and that, by combining second- and third-generation sequencing, we now have the ability to integrate SVs into speciation genomics.

The Effectiveness of CFRP- and Auxetic Fabric-Strengthened Brick Masonry under Axial Compression: A Numerical Investigation.

Bonded brickwork used for loadbearing walls is widely found in heritage structures worldwide. The evaluation of bonded masonry structures and their strengthening strategies against dynamic actions require appropriate understanding under cyclic loading. Subsequently, a simplified 3D microscale numerical model is developed in this paper to analyse bonded brickwork under cyclic compression. A plasticity-based damage constitutive model to represent damage in masonry bricks under cyclic compression loading was employed, and zero-thickness interfaces were considered with non-linear damage properties to simulate the mechanical behaviour of masonry. A threshold strain level was used to enact the element deletion technique for initiating brittle crack opening in the masonry units. The developed model was validated against the experimental results published by the authors in the past. The models were able to accurately predict the experimental results with an error limit of 10% maximum. Mainly, two types of strengthening materials, possessing (1) high energy absorption characteristics (auxetic fabric) and (2) high strength properties (carbon fibre reinforced polymer composites/CFRP) were employed for damage mitigation under cyclic compression. Results show that the CFRP-strengthened masonry failure was mainly attributed to de-bonding of the CFRP and crushing under compression. However, the auxetic strengthening is shown to significantly minimise the de-bonding phenomenon. Enhanced energy dissipation characteristics with relatively higher ductility (up to ~50%) and reduced damages on the bonded brickwork were observed as compared to the CFRP-strengthened brickwork under cyclic compression loading. Additionally, the auxetic fabric application also increased the compressive resistance of brickwork by 38–60% under monotonic loading, which is comparably higher than with the CFRP strengthening technique.

Incremental Element Deletion-Based Finite Element Analysis of the Effects of Impact Speeds, Fall Postures, and Cortical Thicknesses on Femur Fracture.

The proximal femur’s numerical simulation could give an effective method for predicting the risk of femoral fracture. However, the majority of existing numerical simulations is static, which does not correctly capture the dynamic properties of bone fractures. On the basis of femoral fracture analysis, a dynamic simulation using incremental element deletion (IED)-based finite element analysis (FEA) was developed and compared to XFEM in this study. Mechanical tests were also used to assess it. Different impact speeds, fall postures, and cortical thicknesses were also studied for their implications on fracture types and mechanical responses. The time it took for the crack to shatter was shorter when the speed was higher, and the crack line slid down significantly. The fracture load fell by 27.37% when the angle was altered from 15° to 135°, indicating that falling forward was less likely to cause proximal femoral fracture than falling backward. Furthermore, the model with scant cortical bone was susceptible to fracture. This study established a theoretical foundation and mechanism for forecasting the risk of proximal femoral fracture in the elderly.