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PURPOSE: Inflammation plays a crucial role in the development of atherosclerotic plaques. Pentraxin 3 (PTX3) is produced at the site of inflammation and has been identified as a specific marker of atherosclerosis, vascular inflammation, and progression of the coronary artery disease (CAD). The aim of the study was to establish if PTX3 has potential relations with classical markers of cardiovascular risk, and if PTX3 may act as an independent risk factor of CAD occurrence and advancement. MATERIALS AND METHODS: The study included 98 patients with stable CAD confirmed in coronary angiography (CAD group) (median age 65 interquartile range [IQR] 61-72 years; 72% men). The control group consisted of 40 patients without CAD. RESULTS: The CAD group had significantly higher PTX3 concentration compared to the control group. There was a correlation with age, male gender, lipid profile and intima-media thickness. There was no correlation between PTX3 concentration and the number of coronary vessels with significant atherosclerotic lesions and the advancement of atherosclerotic lesions on the Gensini scoring scale. The cut-off point was determined for 0.89 ng/ml for the exclusion of angiographically significant atherosclerotic lesions. CONCLUSIONS: Patients with CAD have significantly higher concentration of PTX3. There was no correlation between PTX3 and the advancement of angiographically significant atherosclerotic lesions in coronary arteries. Low PTX3 concentration may serve as an indicator for the absence of atherosclerosis.
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Cellular materials are fundamental elements in civil engineering, known for their porous nature and lightweight composition. However, the complexity of its microstructure and the mechanisms that control its behavior presents ongoing challenges. This comprehensive review aims to confront these uncertainties head-on, delving into the multifaceted field of cellular materials. It highlights the key role played by numerical and mathematical analysis in revealing the mysterious elasticity of these structures. Furthermore, the review covers a range of topics, from the simulation of manufacturing processes to the complex relationships between microstructure and mechanical properties. This review provides a panoramic view of the field by traversing various numerical and mathematical analysis methods. Furthermore, it reveals cutting-edge theoretical frameworks that promise to redefine our understanding of cellular solids. By providing these contemporary insights, this study not only points the way for future research but also illuminates pathways to practical applications in civil and materials engineering.
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The main issue in this work is to study the limit functions necessary for the reliability assessment of structural steel with the use of the relative entropy apparatus. This will be done using a few different mathematical theories relevant to this relative entropy, namely those proposed by Bhattacharyya, Kullback-Leibler, Jeffreys, and Hellinger. Probabilistic analysis in the presence of uncertainty in material characteristics will be delivered using three different numerical strategies-Monte Carlo simulation, the stochastic perturbation method, as well as the semi-analytical approach. All of these methods are based on the weighted least squares method approximations of the structural response functions versus the given uncertainty source, and they allow efficient determination of the first two probabilistic moments of the structural responses including stresses, displacements, and strains. The entire computational implementation will be delivered using the finite element method system ABAQUS and computer algebra program MAPLE, where relative entropies, as well as polynomial response functions, will be determined. This study demonstrates that the relative entropies may be efficiently used in reliability assessment close to the widely engaged first-order reliability method (FORM). The relative entropy concept enables us to study the probabilistic distance of any two distributions, so that structural resistance and extreme effort in elastoplastic behavior need not be restricted to Gaussian distributions.
Subject(s)
Archaea , Prostatic Neoplasms , Humans , Male , Archaea/metabolism , Glucokinase/metabolism , ProstateABSTRACT
The present work's main objective is to investigate the natural vibrations of the thin (Kirchhoff-Love) plate resting on time-fractional viscoelastic supports in terms of the Stochastic Finite Element Method (SFEM). The behavior of the supports is described by the fractional order derivatives of the Riemann-Liouville type. The subspace iteration method, in conjunction with the continuation method, is used as a tool to solve the non-linear eigenproblem. A deterministic core for solving structural eigenvibrations is the Finite Element Method. The probabilistic analysis includes the Monte-Carlo simulation and the semi-analytical approach, as well as the iterative generalized stochastic perturbation method. Probabilistic structural response in the form of up to the second-order characteristics is investigated numerically in addition to the input uncertainty level. Finally, the probabilistic relative entropy and the safety measure are estimated. The presented investigations can be applied to the dynamics of foundation plates resting on viscoelastic soil.
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The endoplasmic reticulum is a subcellular organelle key in the control of synthesis, folding, and sorting of proteins. Under endoplasmic reticulum stress, an adaptative unfolded protein response is activated; however, if this activation is prolonged, cells can undergo cell death, in part due to oxidative stress and mitochondrial fragmentation. Here, we report that endoplasmic reticulum stress activates c-Abl tyrosine kinase, inducing its translocation to mitochondria. We found that endoplasmic reticulum stress-activated c-Abl interacts with and phosphorylates the mitochondrial fusion protein MFN2, resulting in mitochondrial fragmentation and apoptosis. Moreover, the pharmacological or genetic inhibition of c-Abl prevents MFN2 phosphorylation, mitochondrial fragmentation, and apoptosis in cells under endoplasmic reticulum stress. Finally, in the amyotrophic lateral sclerosis mouse model, where endoplasmic reticulum and oxidative stress has been linked to neuronal cell death, we demonstrated that the administration of c-Abl inhibitor neurotinib delays the onset of symptoms. Our results uncovered a function of c-Abl in the crosstalk between endoplasmic reticulum stress and mitochondrial dynamics via MFN2 phosphorylation.
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The main aim of this work is to deliver uncertainty propagation analysis for the homogenization process of fibrous metal matrix composites (MMCs). The homogenization method applied here is based on the comparison of the deformation energy of the Representative Volume Element (RVE) for the original and for the homogenized material. This part is completed with the use of the Finite Element Method (FEM) plane strain analysis delivered in the ABAQUS system. The probabilistic goal is achieved by using the response function method, where computer recovery with a few FEM tests enables approximations of polynomial bases for the RVE displacements, and further-algebraic determination of all necessary uncertainty measures. Expected values, standard deviations, and relative entropies are derived in the symbolic algebra system MAPLE; a few different entropy models have been also contrasted including the most popular Kullback-Leibler measure. These characteristics are used to discuss the influence of the uncertainty propagation in the MMCs' effective material tensor components, but may serve in the reliability assessment by quantification of the distance between extreme responses and the corresponding admissible values.
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Arginase 1 (Arg1), the enzyme catalyzing the conversion of arginine to ornithine, is a hallmark of IL-10-producing immunoregulatory M2 macrophages. However, its expression in T cells is disputed. Here, we demonstrate that induction of Arg1 expression is a key feature of lung CD4+ T cells during mouse in vivo influenza infection. Conditional ablation of Arg1 in CD4+ T cells accelerated both virus-specific T helper 1 (Th1) effector responses and its resolution, resulting in efficient viral clearance and reduced lung pathology. Using unbiased transcriptomics and metabolomics, we found that Arg1-deficiency was distinct from Arg2-deficiency and caused altered glutamine metabolism. Rebalancing this perturbed glutamine flux normalized the cellular Th1 response. CD4+ T cells from rare ARG1-deficient patients or CRISPR-Cas9-mediated ARG1-deletion in healthy donor cells phenocopied the murine cellular phenotype. Collectively, CD4+ T cell-intrinsic Arg1 functions as an unexpected rheostat regulating the kinetics of the mammalian Th1 lifecycle with implications for Th1-associated tissue pathologies.
Subject(s)
Arginase , Influenza, Human , Animals , Humans , Mice , Arginase/genetics , Arginase/metabolism , CD4-Positive T-Lymphocytes/metabolism , Glutamine , Kinetics , Lung/metabolism , MammalsABSTRACT
The main objective of this work is to investigate the natural vibrations of a system of two thin (Kirchhoff-Love) plates surrounded by liquid in terms of the coupled Stochastic Boundary Element Method (SBEM), Stochastic Finite Element Method (SFEM), and Stochastic Finite Difference Method (SFDM) implemented using three different probabilistic approaches. The BEM, FEM, and FDM were used equally to describe plate deformation, and the BEM was applied to describe the dynamic interaction of water on a plate surface. The plate's inertial forces were expressed using a diagonal or consistent mass matrix. The inertial forces of water were described using the mass matrix, which was fully populated and derived using the theory of double-layer potential. The main aspect of this work is the simultaneous application of the BEM, FEM, and FDM to describe and model the problem of natural vibrations in a coupled problem in solid-liquid mechanics. The second very important novelty of this work is the application of the Bhattacharyya relative entropy apparatus to test the safety of such a system in terms of potential resonance. The presented concept is part of a solution to engineering problems in the field of structure and fluid dynamics and can also be successfully applied to the analysis of the dynamics of the control surfaces of ships or aircraft.
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The genus Phylacastus Fairmaire (Tenebrionidae, Blaptinae, Platynotini, Eurynotina) is revised. Two new species and one new synonymy are presented along with new diagnoses, descriptions, a distribution map, and key to species. The resulting species of Phylacastus are: P.ancoralium sp. nov., P.crypticoides Koch (= P.pretoriensis Koch syn. nov.), P.makskacymirowi sp. nov., P.rhodesianus Koch, and P.striolatus Fairmaire. Lectotypes are designated for the type species, P.striolatus, to fix the taxonomic status of the species and genus. As a result of examination and subsequent description of P.ancoralium sp. nov., a brief review and treatment of aedeagal morphology is presented. The nomenclature ("clavae" versus "laciniae") and phylogenetic occurrence of accessory structures of the paramere-median lobe area within Blaptinae Leach and Adelinina LeConte (Diaperinae, Diaperini) are discussed. New descriptive terminology (i.e., ancora [singular] and ancorae [plural]) is proposed for these aedeagal structures in Blaptinae to clarify their function and resolve past ambiguities. The morphology within representatives of Adelina Dejean, Alphitophagus Stephens, Gnatocerus Thunberg, and Sitophagus Mulsant is also briefly contrasted and outlined.
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This work is a comprehensive literature overview in the area of probabilistic methods related to composite materials with components exhibiting hyper-elastic constitutive behavior. A practical area of potential applications is seen to be rubber, rubber-like, or even rubber-based heterogeneous media, which have a huge importance in civil, mechanical, environmental, and aerospace engineering. The overview proposed and related discussion starts with some general introductory remarks and a general overview of the theories and methods of hyper-elastic material with a special emphasis on the recent progress. Further, a detailed review of the current trends in probabilistic methods is provided, which is followed by a literature perspective on the theoretical, experimental, and numerical treatments of interphase composites. The most important part of this work is a discussion of the up-to-date methods and works that used the homogenization method and effective medium analysis. There is a specific focus on random composites with and without any interface defects, but the approaches recalled here may also serve as well in sensitivity analysis and optimization studies. This discussion may be especially helpful in all engineering analyses and models related to the reliability of elastomers, whose applicability range, which includes energy absorbers, automotive details, sportswear, and the elements of water supply networks, is still increasing, as well as areas where a stochastic response is the basis of some limit functions that are fundamental for such composites in structural health monitoring.
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The article describes the problem of geometric synthesis of the inspection robot suspension system, designed for operation in difficult conditions with the presence of scattered obstacles. The exemplary application of a mine infrastructure inspection robot is developed and supported by the ideas. The brief introduction presents current trends, requirements and known design approaches of platforms enabled to cross the obstacles. The idea of a nature-inspired wheel-legged robot is given, and the general outline of its characteristics is provided. Then the general idea of kinematic system elements selection is discussed. The main subject of geometrical synthesis of the chosen four-bar mechanism is described in detail. The mathematical model of the suspension and connections between the parts of the structure is clarified. The well-known analytical approach of brute force search is analyzed and validated. Then the method inspired by the branch and bound algorithm is developed. Finally, a novel application of the nature-inspired algorithm (the Chameleon Swarm Algorithm) to synthesis is proposed. The obtained results are analyzed, and a brief comparison of methods is given. The successful implementation of the algorithm is presented. The obtained results are effectively tested with simulations and experimental tests. The designed structure developed with the CSA is assembled and attached to the prototype of a 14-DOF wheel-legged robot. Furthermore, the principles of walking and the elements forming the control structure were also discussed. The paper is summarized with the description of the developed wheel-legged robot LegVan 1v2.
Subject(s)
Robotics , Robotics/methods , Algorithms , Models, Theoretical , WalkingABSTRACT
The main motivation of this work was to present a semi-analytical extension of the correspondence principle in stochastic dynamics. It is demonstrated for the stochastic structural free vibrations of Kirchhoff-Love elastic, isotropic and rectangular plates supported by viscoelastic generalized Maxwell dampers. The ambient temperature of the plate affects the dampers only and is included in a mathematical model using the frequency-temperature correspondence principle. The free vibration problem of the plate-viscoelastic damper system is solved using the continuation method and also the Finite Element Method (FEM). The stochastic approach begins with an initial deterministic sensitivity analysis to detect the most influential parameters and numerical FEM recovery of the polynomial representation for lower eigenfrequencies versus these parameters. A final symbolic integration leads to the first four basic probabilistic characteristics, all delivered as functions of the input uncertainties.
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This paper proposes the framework for reliability-based design optimization (RBDO) of structural elements with an example based on the corrugated web I-girder. It tackles the problem of topological optimization of corroding structures with uncertainties. Engineering restrictions follow a concept of the limit states (LS) and extend it for stability and eigenfrequency assessment. The reliability constraints include all the LS; they are computed according to first- and second-order reliability methods. The RBDO example minimizes the bridge girder cross-section while satisfying the structural reliability level for the ultimate and the serviceability limit states, stability, and eigenfrequency. It takes into consideration two uncorrelated random effects, i.e., manufacturing imperfection and corrosion. They are both Gaussian; the first of them is applied at assembly time, while the second is applied according to the time series. The example confronts three independent FEM models with an increasing level of detailing, and compares RBDO results for three concurrent probabilistic methods, i.e., the iterative stochastic perturbation technique (ISPT), the semi-analytical method, and the Monte Carlo simulation. This study proves that the RBDO analysis is feasible even for computationally demanding structures, can support automation of structural design, and that the level of detailing in the FEM models influences its results. Finally, it exemplifies that reliability restrictions for LS are much more rigorous than for their deterministic counterparts, and that the fastest ISPT method is sufficiently accurate for probabilistic calculations in this RBDO.
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In many extreme arid ecosystems, insects constitute major faunal components and are key contributors in nutrient cycling. Previous research on xerophily in insects has focused on adult forms. This study investigates skeletomuscular and behavioural adaptations of the Kalahari sandworm beetle larvae (Gonopus tibialis Fabricius) for dwelling in the sand. Microcomputed tomography enabled cuticle thickness distribution analysis, revealing structural reinforcements of the mandibular edge, the middle part of the head, and the ventral side of the front legs. Laboratory observations and the analysis of muscular system allowed for the definition and functional description of the elements of the digging apparatus of the sandworm larvae. Obtained results point to the crucial role of the head and mandibles in the digging process. These observations are important for understanding desert ecology and pose a challenge to develop newer excavation techniques.
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Coleoptera , Acclimatization , Animals , Ecosystem , Larva , X-Ray MicrotomographyABSTRACT
Tok-tokkies are one of the most iconic lineages within Tenebrionidae. In addition to containing some of the largest darkling beetles, this tribe is recognized for its remarkable form of sexual communication known as substrate tapping. Nevertheless, the phylogenetic relationships within the group remain poorly understood. This study investigates the usefulness of female terminalia morphology for delimiting Sepidiini and reconstructing relationships among it. Data on the structure of the ovipositors, genital tubes and spicula ventrali have been generated for >200 species representing 28 Pimeliinae tribes. This dataset was used in a comparative analysis at the subfamilial level, which resulted in recognition of several unique features of tok-tokkie terminalia. Additionally, new features linking phenotypically challenging tribes also were recovered (Cryptochilini + Idisiini + Pimeliini). Secondly, 23 characters linked to the structure of female terminalia were defined for tok-tok beetles. Cladistic analysis demonstrates the nonmonophyletic nature of most of the recognized subtribes. The morphological dataset was analysed separately and in combination with available molecular data (CAD, Wg, cox1, cox2, 28S). All obtained topologies were largely congruent, supporting the following changes: Palpomodina Kaminski & Gearner subtr.n. is erected to accommodate the genera Namibomodes and Palpomodes; Argenticrinis and Bombocnodulus are transferred from Hypomelina to Molurina; 153 species and subspecies previously classified within Psammodes are distributed over three separate genera (Mariazofia Kaminski nom.n., Piesomera stat.r., Psammodes sens.n.). Psammodes sklodowskae Kaminski & Gearner sp.n. is described. Preliminary investigation of the ovipositor of Mariazofia basuto (Koch) comb.n. was carried out with the application of microcomputed tomography, illuminating the muscular system as a reliable reference point for recognizing homologous elements in highly modified ovipositors.
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Coleoptera , Animals , Female , Phylogeny , X-Ray Microtomography , Serogroup , GenitaliaABSTRACT
T-cell acute lymphoblastic leukemia (T-ALL) is commonly driven by activating mutations in NOTCH1 that facilitate glutamine oxidation. Here we identify oxidative phosphorylation (OxPhos) as a critical pathway for leukemia cell survival and demonstrate a direct relationship between NOTCH1, elevated OxPhos gene expression, and acquired chemoresistance in pre-leukemic and leukemic models. Disrupting OxPhos with IACS-010759, an inhibitor of mitochondrial complex I, causes potent growth inhibition through induction of metabolic shut-down and redox imbalance in NOTCH1-mutated and less so in NOTCH1-wt T-ALL cells. Mechanistically, inhibition of OxPhos induces a metabolic reprogramming into glutaminolysis. We show that pharmacological blockade of OxPhos combined with inducible knock-down of glutaminase, the key glutamine enzyme, confers synthetic lethality in mice harboring NOTCH1-mutated T-ALL. We leverage on this synthetic lethal interaction to demonstrate that IACS-010759 in combination with chemotherapy containing L-asparaginase, an enzyme that uncovers the glutamine dependency of leukemic cells, causes reduced glutaminolysis and profound tumor reduction in pre-clinical models of human T-ALL. In summary, this metabolic dependency of T-ALL on OxPhos provides a rational therapeutic target.
Subject(s)
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Animals , Electron Transport Complex I/genetics , Electron Transport Complex I/metabolism , Glutamine/metabolism , Mice , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Receptor, Notch1/metabolism , T-Lymphocytes/metabolismABSTRACT
This work aimed to analyze the reliability of a steel hall that was recently erected in central Poland subjected to dynamic wind excitation using the stochastic finite element method. Reliability analysis was completed using the relative entropy concept delivered by Bhattacharyya and contrasted with the first-order reliability method recommended by the engineering design codes. Bhattacharyya probabilistic relative entropy was additionally rescaled in this study to fit the demands and recommended admissibility intervals given in Eurocode 0. The finite element method study was carried out thanks to a discrete model created in the system ABAQUS 2019, while all further statistical and probabilistic computations were programmed and completed in the symbolic environment of MAPLE 2019. Contrary to most engineering analyses in steel structure areas, this study included the important warping effect while designing the hall ridges and the purlins. Dynamic structural responses were determined via the Hilber-Hughes-Taylor algorithm and their series were numerically obtained for a series of input uncertainty parameters representing several mechanical and environmental quantities. The generalized 10th order iterative stochastic perturbation technique was contrasted in this context with statistical estimators from the Monte Carlo simulations and numerical integration resulting from the semi-analytical approach. The key research finding of this study was an extremely good coincidence between the FORM indices and the rescaled relative probabilistic entropies for the given stochastic excitations, which additionally did not depend on a choice of one of the three proposed numerical approaches.
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The main aim of this study is determination of the basic probabilistic characteristics of the effective stiffness for inelastic particulate composites with spherical reinforcement and an uncertain Gaussian volume fraction of the interphase defects. This is determined using a homogenization method with a cubic single-particle representative volume element (RVE) of such a composite and the finite element method solution. A reinforcing particle is spherical, located centrally in the RVE, surrounded by the thin interphase of constant thickness, and remains in an elastic reversible regime opposite to the matrix, which is hyper-elastic. The interphase defects are represented as semi-spherical voids, which are placed on the outer surface of this particle. The interphase is modeled as hyper-elastic and isotropic, whose effective stiffness is calculated by the spatial averaging of hyper-elastic parameters of the matrix and of the defects. A constitutive relation of the matrix is recovered experimentally by its uniaxial stretch. The 3D homogenization problem solution is based upon a numerical determination of strain energy density in the given RVE under specific uniaxial and biaxial stretches as well as under shear deformations. The analytical relation of the effective composite stiffness to the input uncertain parameter is recovered via the response function method, using a polynomial basis and an optimized order. Probabilistic calculations are completed using three concurrent approaches, namely the iterative stochastic finite element method (SFEM), Monte Carlo simulation and by the semi-analytical method. Previous papers consider the composite fully elastic, which limits the applicability of the resulting effective stiffness tensor computed therein. The current study voids this assumption and defines the composite as fully hyper-elastic, thus extending applicability of this tensor to strains up to 0.25. The most important research finding is that (1) the effective stiffness tensor is sensitive to random interface defects in its hyper-elastic range, (2) its resulting randomness is not close to Gaussian, (3) the semi-analytical method is not perfectly suited to stochastic calculations in this region of strains, as opposed to the linear elastic region, and (4) that the increase in random dispersion of defects volume fraction has a much higher effect on the stochastic characteristics of this stiffness tensor than fluctuation of the strain.
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Polyamine synthesis represents one of the most profound metabolic changes during T cell activation, but the biological implications of this are scarcely known. Here, we show that polyamine metabolism is a fundamental process governing the ability of CD4+ helper T cells (TH) to polarize into different functional fates. Deficiency in ornithine decarboxylase, a crucial enzyme for polyamine synthesis, results in a severe failure of CD4+ T cells to adopt correct subset specification, underscored by ectopic expression of multiple cytokines and lineage-defining transcription factors across TH cell subsets. Polyamines control TH differentiation by providing substrates for deoxyhypusine synthase, which synthesizes the amino acid hypusine, and mice in which T cells are deficient for hypusine develop severe intestinal inflammatory disease. Polyamine-hypusine deficiency caused widespread epigenetic remodeling driven by alterations in histone acetylation and a re-wired tricarboxylic acid (TCA) cycle. Thus, polyamine metabolism is critical for maintaining the epigenome to focus TH cell subset fidelity.