Deletion Of Element Research Articles

Finite element modelling of traction-free cracks: Benchmarking the augmented finite element method (AFEM)

This paper investigates the accuracy and the convergence properties of the augmented finite element method (AFEM). The AFEM is here used to model strong discontinuities independently of the underlying mesh. One noticeable advantage of the AFEM over other partition of unity methods is that it does not introduce additional global unknowns to represent cracks. Numerical 2D experiments illustrate the performance of the method and draw comparisons with the element deletion method (EDM), the phantom node method (PNM), the finite element method (FEM) and the embedded finite element method (EFEM). The h-convergence in the energy norm of the AFEM is studied for the first time and it is shown to outperform the aforementioned numerical methods when cracks are loaded in Mode I.

Abstract LB247: A forward genetic screen to identify drivers of neuroendocrine prostate cancer

Abstract Neuroendocrine prostate cancer (NEPC) is a deadly variant of prostate cancer for which no cure is yet available. Up to 20 percent of the patients with castration resistant prostate cancer (CRPC), will progress to NEPC after treatment with standard-of-care therapies, such as abiraterone and enzalutamide, that target the androgen receptor (AR) pathway. However, the molecular mechanisms that drive the emergence of NEPC are largely unknown, contributing to a lack of treatment options for patients with NEPC. We implemented a forward genetic approach to identify novel drivers of NEPC, by using the Sleeping Beauty (SB) transposon-based forward genetic mutagenesis screening system in our Pten-, Trp53-deficient mouse model that is primed to develop NEPC at a low frequency. We generated a mouse strain (NPp53SBT2Onc) in which the Nkx3.1 promoter regulates the expression of tamoxifen-inducible Cre specifically in the mouse prostate epithelium, resulting in transposition of the T2Onc2 transposable element and conditional deletion of Pten and Trp53 in mouse prostate epithelium. We observed an increased NEPC incidence in our NPp53SBT2Onc mouse model compared to control mice without the transposon T2Onc2, suggesting that the SB-mediated insertional mutagenesis events are driving the development of NEPC. To elucidate the genetic events that are driving the observed NEPC phenotype, we identified the common insertion sites (CISs) of the transposon insertions, which revealed a total of 330 CIS-associated genes. We further performed an integrative analysis using RNA-seq data from our SB cohort, a second mouse dataset and a metastatic CRPC patient cohort, which allowed us to identify the Master Regulator (MR) proteins that are associated with NEPC, as well as the upstream genomic events that modulate these MRs and the emergence of NEPC. Altogether, our approach resulted in the identification of CIS-associated genes that are upstream of these MRs associated to NEPC and that are likely to drive this lethal subtype of prostate cancer. We will further validate and elucidate the role of these candidate genes in prostate cancer progression to NEPC, in both mouse and human using CRISPR technology. In summary, we have developed a Sleeping Beauty forward genetic screen in our mouse model of CRPC, which not only accelerates disease progression, but also increases the incidence of NEPC. Our integrative analysis identified a panel of CIS-associated genes that are likely to be functionally involved in progression to NEPC. Validation of candidate drivers resulting from our analysis will shed light on mechanisms that this aggressive disease uses to evade treatments and may inform the development of novel therapies. Citation Format: Francisca Nunes de Almeida, Alessandro Vasciaveo, Min Zou, Matteo Di Bernardo, Andrea Califano, Cory Abate-Shen. A forward genetic screen to identify drivers of neuroendocrine prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB247.

3D finite element modelling of drilling: The effect of modelling method

A comprehensive benchmarking study has been carried out to determine the influence of the mesh formulation and chip separation methods on the reliability and accuracy of finite element modelling of large diameter drilling operations. The Coupled Eulerian–Lagrangian and the updated-Lagrangian (with element deletion) formulations available in ABAQUS/Explicit, together with the updated-Lagrangian (with re-meshing) formulation in DEFORM 3D are compared by simulating through-coolant drilling of AISI 1045. The Johnson–Cook damage model was implemented by a sub-routine in DEFORM 3D to ensure a consistent damage model is implemented across the formulations. Experimentally measured drilling thrust force, torque, and chip thickness values were used to compare the models performance and assess the accuracy of the predictions. The updated-Lagrangian with dynamic re-meshing was found to be the best performing methodology concerning the accuracy of predictions, whilst the Coupled Eulerian–Lagrangian methodology significantly under-predicted the drilling thrust force and torque. Due to numerical instabilities and computational cost, the updated-Lagrangian with element deletion method is not recommended to model large diameter drilling.

A Comparison between Finite Element Model (FEM) Simulation and an Integrated Artificial Neural Network (ANN)-Particle Swarm Optimization (PSO) Approach to Forecast Performances of Micro Electro Discharge Machining (Micro-EDM) Drilling.

Artificial Neural Network (ANN), together with a Particle Swarm Optimization (PSO) and Finite Element Model (FEM), was used to forecast the process performances for the Micro Electrical Discharge Machining (micro-EDM) drilling process. The integrated ANN-PSO methodology has a double direction functionality, responding to different industrial needs. It allows to optimize the process parameters as a function of the required performances and, at the same time, it allows to forecast the process performances fixing the process parameters. The functionality is strictly related to the input and/or output fixed in the model. The FEM model was based on the capacity of modeling the removal process through the mesh element deletion, simulating electrical discharges through a proper heat-flux. This paper compares these prevision models, relating the expected results with the experimental data. In general, the results show that the integrated ANN-PSO methodology is more accurate in the performance previsions. Furthermore, the ANN-PSO model is faster and easier to apply, but it requires a large amount of historical data for the ANN training. On the contrary, the FEM is more complex to set up, since many physical and thermal characteristics of the materials are necessary, and a great deal of time is required for a single simulation.

Expression of Mug14 is regulated by the transcription factor Rst2 through the cAMP-dependent protein kinase pathway in Schizosaccharomyces pombe.

The cAMP-dependent protein kinase (Pka1) regulates many cellular events, including sexual development and glycogenesis, and response to the limitation of glucose, in Schizosaccharomyces pombe. Despite its importance in many cellular events, the targets of the cAMP/PKA pathway have not been fully investigated. Here, we demonstrate that the expression of mug14 is induced by downregulation of the cAMP/PKA pathway and limitation of glucose. This regulation is dependent on the function of Rst2, a transcription factor that regulates transition from mitosis to meiosis. The loss of the C2H2-type zinc finger domain in Rst2, termed Rst2 (C2H2∆), abolished the induction of Mug14 expression. Upon deletion of the stress starvation response element of the S. pombe (STREP: CCCCTC) sequence, which is a potential binding site of Rst2 on mug14, in the pka1∆ strain, its induction was abolished. The expression of Mug14 was significantly reduced and delayed by the limitation of glucose and also by nitrogen starvation in the rst2∆ strain. Mug14 is known to share a common function with Mde1 and Mta3 in the methionine salvage pathway, but the expression of mde1 and mta3 mRNAs was not enhanced by pka1 deletion and limitation of glucose. We conclude that the expression of Mug14 is upregulated by Rst2 under the control of the cAMP/PKA signaling pathway, which senses the limitation of glucose.

Finite Element Modeling for Orthogonal Machining of AA2024-T351 Alloy With an Advanced Fracture Criterion

Abstract Numerical modeling of the plastic deformation and fracture during the high-speed machining is highly challengeable. Consequently, there is a need for an advanced constitutive model and fracture criterion to make the numerical models more reliable. The aim of the present study is to extend the recent advanced static Lou-Yoon-Huh (LYH) ductile fracture creation to high strain rate and temperature applications such as machining. In the present work, the LYH static fracture creation was extended to machining conditions by introducing strain rate and temperature dependency terms. This extended LYH fracture criterion was calibrated over the wide range of stress triaxialities and different temperatures. Modified Khan- Huang-Liang (KHL) constitutive model along with the variable friction model was employed to predict the flow behavior of work material during the machining simulation. Damage evolution method was coupled to identify the element deletion point during the machining simulation. Orthogonal machining experiments were carried out for an aerospace-grade AA2024-T351 at cutting speeds varying between 100 and 400 m/min with the feed rates varying between 0.1 and 0.3 mm/rev. To assess the prediction capabilities of extended LYH fracture criterion, numerical simulations were also carried out using Johnson-Cook (JC) fracture criterion under all experimental conditions. Specific cutting energy, chip morphology, and compression ratio predictions were compared with the experimental data. Numerical predictions with coupled extended LYH criterion showed good agreement with experimental results compared to coupled JC fracture criterion.

Genetic interaction network has a very limited impact on the evolutionary trajectories in continuous culture-grown populations of yeast

BackgroundThe impact of genetic interaction networks on evolution is a fundamental issue. Previous studies have demonstrated that the topology of the network is determined by the properties of the cellular machinery. Functionally related genes frequently interact with one another, and they establish modules, e.g., modules of protein complexes and biochemical pathways. In this study, we experimentally tested the hypothesis that compensatory evolutionary modifications, such as mutations and transcriptional changes, occur frequently in genes from perturbed modules of interacting genes.ResultsUsing Saccharomyces cerevisiae haploid deletion mutants as a model, we investigated two modules lacking COG7 or NUP133, which are evolutionarily conserved genes with many interactions. We performed laboratory evolution experiments with these strains in two genetic backgrounds (with or without additional deletion of MSH2), subjecting them to continuous culture in a non-limiting minimal medium. Next, the evolved yeast populations were characterized through whole-genome sequencing and transcriptome analyses. No obvious compensatory changes resulting from inactivation of genes already included in modules were identified. The supposedly compensatory inactivation of genes in the evolved strains was only rarely observed to be in accordance with the established fitness effect of the genetic interaction network. In fact, a substantial majority of the gene inactivations were predicted to be neutral in the experimental conditions used to determine the interaction network. Similarly, transcriptome changes during continuous culture mostly signified adaptation to growth conditions rather than compensation of the absence of the COG7, NUP133 or MSH2 genes. However, we noticed that for genes whose inactivation was deleterious an upregulation of transcription was more common than downregulation.ConclusionsOur findings demonstrate that the genetic interactions and the modular structure of the network described by others have very limited effects on the evolutionary trajectory following gene deletion of module elements in our experimental conditions and has no significant impact on short-term compensatory evolution. However, we observed likely compensatory evolution in functionally related (albeit non-interacting) genes.

A computational framework for energy absorption and damage assessment of laminated composites under ballistic impact and new insights into target parameters

In this research, by means of advanced methods within the framework of the FE method, an effective modeling approach is proposed to simulate the ballistic perforation behaviors of multi-directional woven composite panels. Within that scope, constitutive models for intraply and interfacial or interply damage mechanisms are formulated and implemented into ABAQUS/Explicit FE code. The constitutive law of ply-level damage model incorporates the nonlinear material response, degradation of material properties, progressive failure and the element deletion scheme. The interfaces between the individual plies are modeled using a cohesive surface method, and the behaviors of interply degradation and failure are described using a traction-separation law. Besides, the material responses with large nonlinearity due to fiber rupture, matrix cracking, plasticity effects due to micro-matrix cracking under shear loading, and interface delamination are accounted for by appropriate material degradation models. The proposed developments are first validated against the available experimental and analytical results. Next, the ballistic impact simulations of woven composite targets are carried out in a two-phase research. The first phase analyzes the ballistic impact behavior and ballistic performance of the composite laminates in terms of residual velocity and energy absorbing capacity. The second phase involves the investigation of the impact characteristics and failure mechanisms of the composite materials. More specifically, the key perforation mechanisms and associated impact damage extents and patterns with respect to projectile velocity are investigated for the composite panels. We further perform parametric analysis in order to understand the influence of a certain number of parameters on the laminate ballistic impact response. These parameters are categorized based on materials such as fiber type material, interface systems, and geometry such as stacking sequences and support conditions. Numerical results reveal that the ballistic impact performance depends significantly on the cohesive material properties, the stacking sequence, and the woven fabric material, whereas less contribution of support conditions to the ballistic perforation characteristic is noticed.

Study on the JH-2 Model Parameters for Metro Shield Cutting Reinforced Concrete Pile

In order to investigate the application of JH-2 (Johnson-Holmquist-2) constitutive model in concrete, a series of parameters study have been conducted to evaluate the JH-2 model in C30 concrete. The finite element analysis software ABAQUS is utilized to simulate the compression test of the three-dimensional standard concrete test based on the ALE adaptive mesh and the damage failure criterion of element deletion function. The numerical analysis of 3D concrete pile foundation and simplified shield machine cutter head to simulate shield cutting pile is established. Analyzing the numerical simulation and construction data, the key points of the shield machine cutting pile are illustrated. Research shows that: (1) JH-2 constitutive model can be used to simulate the concrete cutting. (2) The better damage parameters have been represented and verified against the results of experiments, which are D1 = 0.6 and D2 = 0.1 in the JH-2 model of C30 concrete. (3) In the simulation example of concrete compression and cutting pile, the failure form of concrete is brittle failure, and the non-linear characteristics of concrete has been observed. (4) The simulated torque vibration of the cutter head is relatively large than actual pile cutting, and the actual shield machine cutting pile construction should have a low rotation speed and low propulsion speed.

Activation-dependent post-transcriptional regulation of CD40L mediates B cell development and survival in germinal centers

Abstract We have described a posttranscriptional pathway of induced mRNA stability that occurs at late times of T cell activation and is engaged by the binding of a polypyrimidine tract-binding protein (PTBP1) complex to the 3′UTR of the CD40L transcript. We explored the in vivo role of this pathway by generating a mouse bearing a deletion of the CD40L stability element (termed CD40LΔ5) and found that Tfh cells harboring the stability defect expressed approximately 60% of WT CD40L. Importantly, this decrease in CD40L corresponded to a poorly elaborated germinal center (GC) response which included significantly decreased levels of switched antibodies, antibody-secreting cells, GL7+ B cells and differentiated GC B cell subsets. In contrast, there was little difference in either somatic hypermutation or affinity maturation between B cells from WT compared to CD40LD5 mice. Notably, both the number and percentage of early memory B cells and plasmablasts were significantly decreased indicating that CD40L expression linked to mRNA stability was critical for B cell differentiation. To understand the impact of this stability pathway on gene expression, CD19+ B cells from CD40LD5 immunized mice were transcriptionally profiled using RNAseq and pathways associated with cell survival and proliferation were downregulated and apoptotic pathways upregulated compared to WT B cells. Importantly, the level of AID mRNA was unchanged whereas c-myc expression was significantly reduced in GL7+ B cells. Together these findings reveal that the CD40L stability element plays a critical role in regulating CD40L expression in Tfh cells, which in turn supports the optimal proliferation and cell survival of high affinity GC B cells and the differentiation of B cell subsets.

Deletion of putative xenobiotic response elements (XREs) in hpol κ alters the replication stress response and overall genomic instability in glioblastoma cells

Aberrant activation of human DNA polymerase kappa (hpol κ) via the kynurenine pathway-aryl hydrocarbon receptor (KP-AhR) pathway contributes to replication stress and genome instability in glioblastoma. Our previous studies relied solely on a small-molecule inhibitor of tryptophan 2-3-deoxygenase and an AhR antagonist. Xenobiotic response elements (XREs) are short DNA sequences present in gene promoter regions that act as binding sites for the ligand complexed AhR. To elucidate hpol κ regulation by KP-AhR, we generated POLK-ΔXRE cell lines using CRISPR/Cas9 editing. XRE ablation in glioblastoma cells led to decreased hpol κ expression. Disconnecting hpol κ transcriptional regulation from AhR signaling resulted in a diminished capacity for fork restart and a slight increase in degradation of forks stalled by hydroxyurea (HU). In spite of the reduced ability to resolve replication stress, the POLK-ΔXRE T98G cell lines had fewer micronuclei and ultra-fine bridges (UFBs), indicative of less chromosomal instability. These results further support the idea that hpol κ regulation by the AhR may influence the replication stress response and overall genomic instability in glioblastoma cells.

Elevated Expression of Toxin TisB Protects Persister Cells against Ciprofloxacin but Enhances Susceptibility to Mitomycin C.

Bacterial chromosomes harbor toxin-antitoxin (TA) systems, some of which are implicated in the formation of multidrug-tolerant persister cells. In Escherichia coli, toxin TisB from the tisB/istR-1 TA system depolarizes the inner membrane and causes ATP depletion, which presumably favors persister formation. Transcription of tisB is induced upon DNA damage due to activation of the SOS response by LexA degradation. Transcriptional activation of tisB is counteracted on the post-transcriptional level by structural features of tisB mRNA and RNA antitoxin IstR-1. Deletion of the regulatory RNA elements (mutant Δ1-41 ΔistR) uncouples TisB expression from LexA-dependent SOS induction and causes a ‘high persistence’ (hip) phenotype upon treatment with different antibiotics. Here, we demonstrate by the use of fluorescent reporters that TisB overexpression in mutant Δ1-41 ΔistR inhibits cellular processes, including the expression of SOS genes. The failure in SOS gene expression does not affect the hip phenotype upon treatment with the fluoroquinolone ciprofloxacin, likely because ATP depletion avoids strong DNA damage. By contrast, Δ1-41 ΔistR cells are highly susceptible to the DNA cross-linker mitomycin C, likely because the expression of SOS-dependent repair systems is impeded. Hence, the hip phenotype of the mutant is conditional and strongly depends on the DNA-damaging agent.

C/EBPα is indispensable for PML/RARα-mediated suppression of long non-coding RNA NEAT1 in acute promyelocytic leukemia cells.

Better understanding of the transcriptional regulatory network in acute promyelocytic leukemia (APL) cells is critical to illustrate the pathogenesis of other types of acute myeloid leukemia. Previous studies have primarily focused on the retinoic acid signaling pathway and how it is interfered with by promyelocytic leukemia/retinoic acid receptor-α (PML/RARα) fusion protein. However, this hardly explains how APL cells are blocked at the promyelocytic stage. Here, we demonstrated that C/EBPα bound and transactivated the promoter of long non-coding RNA NEAT1, an essential element for terminal differentiation of APL cells, through C/EBP binding sites. More importantly, PML/RARα repressed C/EBPα-mediated transactivation of NEAT1 through binding to NEAT1 promoter. Consistently, mutation of the C/EBP sites or deletion of retinoic acid responsive elements (RAREs) and RARE half motifs abrogated the PML/RARα-mediated repression. Moreover, silencing of C/EBPα attenuated ATRA-induced NEAT1 upregulation and APL cell differentiation. Finally, simultaneous knockdown of C/EBPα and C/EBPβ reduces ATRA-induced upregulation of C/EBPε and dramatically impaired NEAT1 activation and APL cell differentiation. In sum, C/EBPα binds and transactivates NEAT1 whereas PML/RARα represses this process. This study describes an essential role for C/EBPα in PML/RARα-mediated repression of NEAT1 and suggests that PML/RARα could contribute to the pathogenesis of APL through suppressing C/EBPα targets.

A finite element assessment of chip formation mechanisms in the machining of CFRP laminates with different fibre orientations

The virtual assessment of a composite machining process using finite element (FE) models constitutes a cost-effective solution to study the surface quality of machined parts. Thus, the correct simulation of the chip fracture becomes essential to obtain consistent numerical results. This work develops an original FE approach to emulate the chip formation in the machining of carbon fibre reinforced polymer (CFRP) laminates. Composite damage initiation modes are evaluated via hybrid Puck-Hashin composite failure criteria. Subsequently, mechanical properties of the damaged elements are linearly degraded. Finally, a novel strain-based element deletion criterion is applied to reliably simulate the chip release process. Five different cutting configurations are successfully modelled. The influence of relevant fibre orientations and cutter rake angles on chip formation are analysed in detail. The shape of the simulated chips reaches a high similarity with the chips obtained in relevant experimental trials presented in the literature. Useful insights about the modelling of sub-surface damage in composite machining are also produced in this investigation. For instance, the modelling of the fibre bending damage which take place in the machining of 90° laminates is modelled with great precision.

Validation of the ductile fracture modeling of CGI at quasi-static loading conditions

Fracture modeling and experimental validation of Compacted Graphite Iron (CGI) specimens loaded under quasi-static conditions at room temperature are considered. Continuum damage mechanics coupled to plasticity is adopted to describe the evolution of damage. The damage production is based on a recently developed rate dependent damage evolution law, where the damage–plasticity coupling is modeled based on a damage driving energy that involves both stored energy and plasticity contributions. To describe ductile fracture accounting for stress triaxiality on the damage initiation, the inelastic contribution to the damage driving energy is controlled by the Johnson-Cook failure criterion. Three different damage models are defined based on elastic/inelastic damage driving energies. The damage models are validated against experiments on a set of notched specimens made of CGI with different notch geometries, where the global force-displacement curves and corresponding strain fields are obtained using digital image correlation technology. It is shown from the testing and the simulations that plastic strains generally need to be accounted for in order to properly describe the different failure processes of the CGI specimens. In addition, the ductile damage model is shown to more accurately predict the experimental force-displacement response as compared to the more simplistic stress drop, element deletion technique.

Element activation method and non-conformal dynamic remeshing strategy to model additive manufacturing

Modeling of Additive Manufacturing (AM) at the part scale involves non-linear thermo-mechanical simulations. Such a process also imposes a very fine discretization and requires altering the geometry of the models during the simulations to model the addition of matter, which is a computational challenge by itself. The first focus of this work is the addition of an additive manufacturing module in the fully implicit in-house Finite Element code Metafor [1] which is developed at the University of Liège. The implemented method to activate elements and to activate and deactivate boundary conditions during a simulation is adapted from the element deletion algorithm implemented in Metafor in the scope of crack propagation [2]. This algorithm is modified to allow the activation of elements based on a user-specified criterion (e.g. geometrical criterion, thermal criterion, etc.). The second objective of this work is to improve the efficiency of the AM simulations, in particular by using a dynamic remeshing strategy to reduce the computational cost of the simulations. This remeshing is done using non-conformal meshes, where hanging nodes are handled via the use of Lagrange multiplier constraints. The mesh data transfer used after remeshing is based on projection methods involving finite volumes [3]. The presented model is then compared against a 2D numerical simulation of Direct Energy Deposition of a High-Speed Steel thick deposit from the literature [4].

Driven Pile Effects on Nearby Cylindrical and Semi-Tapered Pile in Sandy Clay

A pile foundation is commonly adopted for transferring superstructure loads into the ground in weaker soil. They diminish the settlement of the infrastructure and augment the soil-bearing capacity. This paper emphases the pile-driving effect on an existing adjacent cylindrical and semi-tapered pile. Driving a three-dimensional pile into the ground is fruitfully accomplished by combining the arbitrary Lagrangian–Eulerian (ALE) adaptive mesh and element deletion methods without adopting any assumptions that would simplify the simulation. Axial forces, bending moment, and lateral displacement were studied in the neighboring already-installed pile. An investigation was made into some factors affecting the forces and bending moment, such as pile spacing and the shape of the already-installed pile (cylindrical, tapered, or semi-tapered). An important response was observed in the impact of the driven pile on the nearby existing one, the bending moment and axial forces were not negligible, and when the pile was loaded, it was recommended to consider the coupling effect. Moreover, the adjacent semi-tapered pile was subjected to less axial and lateral movement than the cylindrical one with the same length and volume for taper angles smaller than 1.0°, and vice versa for taper angles greater than 1.4°.

Overexpression of Nrf2 in Renal Proximal Tubular Cells Stimulates Sodium-Glucose Cotransporter 2 Expression and Exacerbates Dysglycemia and Kidney Injury in Diabetic Mice.

We investigated the impact of nuclear factor erythroid 2-related factor 2 (Nrf2) overexpression in renal proximal tubular cells (RPTCs) on blood glucose, kidney injury, and sodium-glucose cotransporter 2 (Sglt2) expression in diabetic Akita Nrf2 -/-/Nrf2RPTC transgenic (Tg) mice. Immortalized human RPTCs (HK2) stably transfected with plasmid containing the SGLT2 promoter and human kidneys from patients with diabetes were also studied. Nrf2 overexpression was associated with increased blood glucose, glomerular filtration rate, urinary albumin-to-creatinine ratio, tubulointerstitial fibrosis, and Sglt2 expression in Akita Nrf2 -/-/Nrf2RPTC Tg mice compared with their Akita Nrf2 -/- littermates. In vitro, oltipraz or transfection of NRF2 cDNA stimulated SGLT2 expression and SGLT2 promoter activity in HK2, and these effects were inhibited by trigonelline or NRF2 siRNA. The deletion of the NRF2-responsive element (NRF2-RE) in the SGLT2 promoter abolished the stimulatory effect of oltipraz on SGLT2 promoter activity. NRF2 binding to the NRF2-RE of the SGLT2 promoter was confirmed by gel mobility shift assay and chromatin immunoprecipitation assays. Kidneys from patients with diabetes exhibited higher levels of NRF2 and SGLT2 in the RPTCs than kidneys from patients without diabetes. These results suggest a link by which NRF2 mediates hyperglycemia stimulation of SGLT2 expression and exacerbates blood glucose and kidney injury in diabetes.

Bloom Filter With a False Positive Free Zone

Bloom filters and their variants are widely used as space-efficient probabilistic data structures for representing sets and are very popular in networking applications. They support fast element insertion and deletion, along with membership queries with the drawback of false positives. Bloom filters can be designed to match the false positive rates that are acceptable for the application domain. However, in many applications, a common engineering solution is to set the false positive rate very small and ignore the existence of the very unlikely false positive answers. This article is devoted to close the gap between the two design concepts of <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">unlikely</i> and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">not having</i> false positives. We propose a data structure called EGH filter that supports the Bloom filter operations, and besides, it can guarantee false positive free operations for a finite universe and a restricted number of elements stored in the filter. We refer to the limited universe and filter size as the false positive free zone of the filter. We describe necessary conditions for the false-positive free zone of a filter. We then generalize the filter to support the listing of the elements through the use of counters rather than bits. We detail networking applications of the filter and discuss potential generalizations. We evaluate the performance of the filter in comparison with the traditional Bloom filters. We also evaluate the price in terms of memory that needs to be paid to guarantee real false positive-free operations for having a deterministic Bloom filter-like behavior. Our data structure is based on recently developed combinatorial group testing techniques.

Prestressed bridge deck responses to blast loads

Bridges are critical to most transportation systems, especially in times of crisis; however, as highly visible and accessible structures, they are also potential targets for terrorist attacks. An understanding of the performance of bridges subjected to blast loads is of critical importance to prevent progressive collapse of such structures that could lead to a catastrophic loss of life. The current research focuses on investigating the behaviour of bridge decks under blast loads from various explosions. The bridge in this investigation is the Sheikh Saad Bridge in Wassit Province, Iraq, whose deck is made of simply supported spans with two types of prestressed concrete girders. Both spans were accurately modelled using the finite element software Abaqus/Explicit, and both concrete and steel mechanical material properties were modified to match the properties under high strain rate conditions of the blast analysis. The latest element deletion technique of the built-in Concrete Damaged Plasticity (CDP) model (available since Abaqus 2019) was used to provide a realistic simulation of concrete damage and spalling. The model was separately subjected to various explosive charges placed at different locations above or below the bridge deck in order to determine the influence of size and location of blast on the bridge superstructure, detailed results and the relevant conclusions are thus presented. Overall, the modelling managed to successfully simulate the blast load response and the cracking propagation within the damaged deck components.