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Neuronal cell death has been well acknowledged as the primary pathological basis underlying developmental neurotoxicity following sevoflurane exposure, whereas the exact mechanism remains elusive. Ferroptosis is a programmed cell death featured by iron-dependent lipid peroxidation that is driven by hydrogen peroxide (H2O2) and ferrous iron through Fenton reaction, and participates in the pathogenesis of multiple neurological diseases. As stress response factor, activating transcription factor 3 (ATF3) can be activated by PERK/ATF4-mediated pathway during endoplasmic reticulum (ER) stress and followed by increased intracellular H2O2, which is involved in regulation of apoptosis, autophagy and ferroptosis. Here, we investigated whether ferroptosis and ATF3 activation are implicated in sevoflurane-triggered neuronal cell death in the developing brain. Results showed that sevoflurane exposure induced neuronal death as a result of iron-dependent lipid peroxidation damage secondary to H2O2 accumulation and ferrous iron increase, which was consistent with the criteria for ferroptosis. Furthermore, we observed that increases of iron and H2O2 induced by sevoflurane exposure were associated with the upregulation and nuclear translocation of ATF3 in response to ER stress. Knockdown of ATF3 expression alleviated iron-dependent lipid peroxidation, which prevented sevoflurane-triggered neuronal ferroptosis. Mechanistically, ATF3 promoted sevoflurane-induced H2O2 accumulation through activating NOX4 and suppressing catalase, GPX4 and SLC7A11. Additionally, we detected that increase of H2O2 was accompanied with upregulation of TFR and TF and downregulation of FPN which linked the iron overload to ferroptosis triggered by sevoflurane. Taken together, our results demonstrated ER stress-mediated ATF3 activation contributes to sevoflurane-induced neuronal ferroptosis via H2O2 accumulation and resultant iron overload.

In this paper, we analytically and geometrically investigate the complexity of Maxwell–Bloch system by giving new insight. In the first place, the existence of homoclinic orbits is rigorously prove...

The elliptic problem with a nonlocal boundary condition is widely applied in the field of science and engineering, such as the chaotic system. Firstly, we construct one high-accuracy difference scheme for a kind of elliptic problem by tactfully introducing an equivalent relation for one nonlocal condition. Then, we obtain the local truncation error equation by the Taylor formula and, initially, prove that the new scheme can reach the asymptotic optimal error estimate O h 2 ln h in the maximum norm through ingeniously transforming a two-dimensional problem to a one-dimensional one through bringing in the discrete Fourier transformation. Numerical experiments demonstrate the correctness of theoretical results.

The safety of volatile anesthetics in infants and young children has been drawing increasing concern due to its potential neurotoxicity in the developing brain. Neuronal death is considered a major factor associated with developmental neurotoxicity after exposure to volatile anesthetics sevoflurane, but its mechanism remains elusive. Parthanatos, a new type of programmed cell death, resulting from poly (ADP-ribose) polymerase 1 (PARP-1) hyperactivation in response to DNA damage, was found to account for the pathogenesis of multiple neurological disorders. However, the role of Parthanatos in sevoflurane-induced neonatal neuronal cell death has not been investigated. To test it, neuronal cells treated with 2, 4, and 8% sevoflurane for 6, 12, and 24 h and postnatal day 7 rats exposed to 2.5% sevoflurane for 6 h were used in the present study. Our results found sevoflurane exposure induced neuronal cell death, which was accompanied by PARP-1 hyperactivation, cytoplasmic polymerized ADP-ribose (PAR) accumulation, mitochondrial depolarization, and apoptosis-inducing factor (AIF) nuclear translocation in the neuronal cells and hippocampi of rats. Pharmacological or genetic inhibition of PAPR-1 significantly alleviated sevoflurane-induced neuronal cell death and accumulation of PAR polymer and AIF nuclear translocation, which were consistent with the features of Parthanatos. We observed in vitro and in vivo that sevoflurane exposure resulted in DNA damage, given that 8-hydroxydeoxyguanosine (8-OHdG) and phosphorylation of histone variant H2AX (γH2AX) were improved. Moreover, we detected that sevoflurane exposure was associated with an overproduction of intracellular reactive oxygen species (ROS). Inhibition of ROS with antioxidant NAC markedly alleviated DNA damage caused by sevoflurane, indicating that ROS participated in the regulation of sevoflurane-induced DNA damage. Additionally, sevoflurane exposure resulted in upregulation of Parthanatos-related proteins and neuronal cell death, which were significantly attenuated by pretreatment with NAC. Therefore, these results suggest that sevoflurane exposure induces neuronal cell Parthanatos initiated by DNA damage in the developing brain via the increase of intracellular ROS.

In this paper, global dynamics of the Maxwell–Bloch system is discussed. First, the complete description of its dynamic behavior on the sphere at infinity is presented by using the Poincaré compactification in R3. Second, the existence of singularly degenerate heteroclinic cycles is investigated. It is proved that for a suitable choice of the parameters, there is an infinite set of singularly degenerate heteroclinic cycles in Maxwell–Bloch system. Specially, the chaotic attractors are found nearby singularly degenerate heteroclinic cycles in Maxwell–Bloch system by combining theoretical and numerical analyses for a special parameter value. It is hoped that these theoretical and numerical value results are given a contribution in an understanding of the physical essence for chaos in the Maxwell–Bloch system.

The disk dynamo system, which is capable of chaotic behaviours, is obtained experimentally from two disk dynamos connected together. It models the geomagnetic field and is used to explain the reversals in its polarity. Actually, the parameters of the chaotic systems exhibit random fluctuation to a greater or lesser extent, which can carefully describe the disturbance made by environmental noise. The global dynamics of the chaotic disk dynamo system with random fluctuating parameters are concerned, and some new results are presented. Based on the generalized Lyapunov function, the globally attractive and positive invariant set is given, including a two-dimensional parabolic ultimate boundary and a four-dimensional ellipsoidal ultimate boundary. Furthermore, a set of sufficient conditions is derived for all solutions of the stochastic disk dynamo system being global convergent to the equilibrium point. Finally, numerical simulations are presented for verification.

In recent years, with the rapid development of energy storage technology and electric vehicle business, lithium-ion batteries have attracted more and more attention because of their high energy density, long cycle life, no memory effect, no pollution, etc. It will bring some safety hazards. Some lithium-ion battery burning and explosion accidents have alarmed the safety of lithium-ion batteries. This article will analyze the causes of safety problems in lithium-ion batteries from multiple angles and give adequate preventive measures.

Numerical simulation based on fine-scale reservoir models helps petroleum engineers in understanding fluid flow in porous media and achieving higher recovery ratio. Fine-scale models give rise to large-scale linear systems, and thus require effective solvers for solving these linear systems to finish simulation in reasonable turn-around time. In this paper, we study convergence, robustness, and efficiency of a class of multi-stage preconditioners accelerated by Krylov subspace methods for solving Jacobian systems from a fully implicit discretization. We compare components of these preconditioners, including decoupling and sub-problem solvers, for fine-scale reservoir simulation. Several benchmark and real-world problems, including a ten-million-cell reservoir problem, were simulated on a desktop computer. Numerical tests show that the combination of the alternating block factorization method and multi-stage subspace correction preconditioner gives a robust and memory-efficient solver for fine-scale reservoir simulation.

Zinc (Zn) is known to play crucial roles in numerous brain functions including learning and memory. Zn deficiency is believed to be widespread throughout the world, particularly in patients with Alzheimer's disease (AD). A number of studies have shown that volatile anesthetics, such as isoflurane, might be potential risk factors for the development of AD. However, whether isoflurane exposure accelerates the process of AD and cognitive impairment in AD patients with Zn deficiency is yet to be documented. The aim of the present study was to explore the effects of 1.4% isoflurane exposure for 2 h on learning and memory function, and neuropathogenesis in 10-month-old Zn-adequate, Zn-deficient, and Zn-treated APP/PS1 mice with the following parameters: behavioral tests, neuronal apoptosis, Aβ, and tau pathology. The results demonstrated that isoflurane exposure showed no impact on learning and memory function, but induced transient elevation of neuroapoptosis in Zn-adequate APP/PS1 mice. Exposure of isoflurane exhibited significant neuroapoptosis, Aβ generation, tau phosphorylation, and learning and memory impairment in APP/PS1 mice in the presence of Zn deficiency. Appropriate Zn treatment improved learning and memory function, and prevented isoflurane-induced neuroapoptosis in APP/PS1 mice. Isoflurane exposure may cause potential neurotoxicity, which is tolerated to some extent in Zn-adequate APP/PS1 mice. When this tolerance is limited, like in AD with Zn deficiency, isoflurane exposure markedly exacerbated learning and memory impairment, and neuropathology, indicating that AD patients with certain conditions such as Zn deficiency may be vulnerable to volatile anesthetic isoflurane.

Aims Epithelial-to-mesenchymal transition (EMT) facilitates cell migration and invasion, and contributes to metastasis in bladder cancer. Within the perioperative period, anesthetic such as isoflurane have been found to affect cancer prognosis. In the study, we reported the tumor-promoting effect of isoflurane in bladder cancer. Materials and Methods Human bladder cancer cell lines T24 and BIU-87 were exposed to isoflurane at different concentrations. The immunofluorescent staining of Ki67, Annexin V-FITC/PI staining, Transwell invasion assays and wound-healing assays were performed to assess cell proliferation, apoptosis, invasion and migration. Expressions of EMT markers (E-cadherin, N-cadherin and Vimentin) and metastatic markers (Snail-1, Slug-1 and MMP-2/9) were determined by immunoblotting. Orthotopic tumor models and mice given tail vein injection of T24 cells were developed with or without 4-h exposure to 2% isoflurane. Key findings We found isoflurane promoted bladder cancer cell proliferation, invasion and migration but reduce apoptosis in a concentration-dependent manner. In addition, isoflurane was shown to increase HIF-1α and its nuclear accumulation in bladder cancer cells. HIF-1α knockdown inhibited bladder cancer cell proliferation and delayed EMT, which was reversed in the presence of 4-h exposure to 2% isoflurane. Likewise, we found isoflurane modulated β-catenin/Notch1 pathways via HIF-1α. In vivo studies showed that isoflurane exposure accelerated formation of orthotopic bladder tumor and promoted hepatic metastases from carcinoma of the bladder. Significance Taken together, our study demonstrates that a frequently used anesthetic can exert a protumorigenic effect on bladder cancer. Isoflurane may serve as an important contributory factor to high recurrence following surgery.

Oxidative stress, which is characterized by excessive production of reactive oxygen species (ROS), is a common pathway that results in neuronal injury or death due to various types of pathological stress. Although lycopene has been identified as a potent antioxidant, its effect on hydrogen peroxide (H2O2)-induced neuronal damage remains unclear. In the present study, pretreatment with lycopene was observed to protect SH-SY5Y neuroblastoma cells against H2O2-induced death via inhibition of apoptosis resulting from activation of caspase-3 and translocation of apoptosis inducing factor (AIF) to the nucleus. Furthermore, the over-produced ROS, as well as the reduced activities of anti-oxidative enzymes, superoxide dismutase and catalase, were demonstrated to be alleviated by lycopene. Additionally, lycopene counteracted H2O2-induced mitochondrial dysfunction, which was evidenced by suppression of mitochondrial permeability transition pore opening, attenuation of the decline of the mitochondrial membrane potential, and inhibition of the increase of Bax and decrease of Bcl-2 levels within the mitochondria. The release of cytochrome c and AIF from the mitochondria was also reduced. These results indicate that lycopene is a potent neuroprotectant against apoptosis, oxidative stress and mitochondrial dysfunction, and could be administered to prevent neuronal injury or death.

Little seems to be known about the study of the chaotic system with only Lyapunov stable equilibria from the perspective of differential geometry. Therefore, this paper presents Jacobi analysis of an unusual three-dimensional (3D) autonomous chaotic system. Under certain parameter conditions, this system has positive Lyapunov exponents and only two linear stable equilibrium points, which means that chaotic attractor and Lyapunov stable equilibria coexist. The dynamical behavior of the deviation vector near the whole trajectories (including all equilibrium points) is analyzed in detail. The results show that the value of the deviation curvature tensor at equilibrium points is only related to parameters; the two equilibrium points of the system are Jacobi stable if the parameters satisfy certain conditions. Particularly, for a specific set of parameters, the linear stable equilibrium points of the system are always Jacobi unstable. A periodic orbit that is Lyapunov stable is also proven to be always Jacobi unstable. Next, Jacobi-stable regions of the Lorenz system, the Chen system and the system under study are compared for specific parameters. It can be found that although these three chaotic systems are very similar, their regions of Jacobi stable parameters are much different. Finally, by comparing Jacobi stability with Lyapunov stability, the obtained results demonstrate that the Jacobi stable parameter region is basically symmetric with the Lyapunov stable parameter region.

Mood disorders have many forms, from anxiety attacks, depression, Obsessive Compulsive Disorder (OCD) to Post Traumatic Disorder (PTSD). Recently, many studies have shown that zinc may act as a crucial neuromodulator in glutamatergic and GABAergic balance. What’s more, growing evidences considered that zinc be a trait marker of mood disorder. It was reported that zinc deficiency induces depression, while supplementing with this mineral improved mood as well as cognitive function. In this present review, the links of zinc in the mood disorder and zinc in the Alzheimer’s disease were systemically reviewed. It may be helpful for zinc applicantion in clinical thus address zinc as a new target of research for therapy.

In this study, parallelization of a Discrete Element Method (DEM) code titled Trubal was carried out based on the CPU–GPU heterogeneous architecture where both two- and three-dimensional cases were assessed. In Trubal, the particle–particle/wall interaction rules are governed by the theoretical contact mechanics which enable the direct use of real physical material properties in the calculation. We reconstructed Trubal in two steps: reconstruction of the static storage structure; essential parallelism on the relative newer version code. Numerical simulations were implemented to present the benefits of this research. Firstly, two simulations of die filling with a moving shoe involving 6000 and 60,000 two-dimensional particles were conducted under (i) NVIDIA Tesla C2050 card together with Intel Core-Duo 2.93 GHz CPU and (ii) NVIDIA Tesla K40c card along with Intel Xeon 3.00 GHz CPU. Average speedups of (i) 4.69 and 12.78 as well as (ii) 6.52 and 18.60 in computational time were obtained, respectively. Then, a simulation of die filling with a stationary shoe containing 20,000 three-dimensional particles was carried out under the same conditions where average speedups of (i) 12.90 and (ii) 19.66 in computational time were obtained, respectively. It is shown that the final version parallel code gave a substantial acceleration on the original Trubal.

A numerical simulation of the emergency brake process in granular material transportation was carried out using the Discrete Element Method (DEM). The interaction laws between the particles were based on the contact mechanics in which the normal force was calculated by the Hertz contact law and the incremental tangential force was evaluated by the Mindlin-Deresiewicz theory. Moreover, the liquid bridge force was considered in the wet particle simulation and the effect was especially discussed. Two strategies including the spatial segmentation and reconstruction of orthogonal grids were introduced to analyze the interaction force on the truck during the braking and backfilling processes. It is found that the particles concentrated in front of the truck in the brake process with a slope forming on the upper surface of the agglomerating particles. The liquid bridge force can significantly influence on the particle and force distribution trends. When the liquid bridge force was considered, the particles moved more slowly, the slope was gentler and the force on both the bottom and front wall of the truck was higher. The findings in this study reveal that the liquid bridge force plays an important role on the instantaneous distribution of the particles and pressure on the truck walls and thus cannot be ignored in the simulation.

As a result of the interplay between advances in computer hardware, software, and algorithm, we are now in a new era of large-scale reservoir simulation, which focuses on accurate flow description, fine reservoir characterization, efficient nonlinear/linear solvers, and parallel implementation. In this paper, we discuss a multilevel preconditioner in a new-generation simulator and its implementation on multicore computers. This preconditioner relies on the method of subspace corrections to solve large-scale linear systems arising from fully implicit methods in reservoir simulations. We investigate the parallel efficiency and robustness of the proposed method by applying it to million-cell benchmark problems.

SummaryAims Endoplasmic reticulum (ER) stress has been demonstrated to regulate neuronal death caused by ischemic insults via activation of apoptosis, but it still remains unclear whether ER stress participates in regulation of parthanatos, a new type of programmed cell death characterized by PARP-1 overactivation and intracellular accumulation of PAR polymer. Methods we used oxygen-glucose deprivation (OGD) and human SH-SY5Y cells to simulate neuronal damage caused by ischemia. Results Oxygen-glucose deprivation induced time-dependent death in SH-SY5Y cells, which was accompanied with upregulation of PARP-1, accumulation of PAR polymer, decline of mitochondrial membrane potentials and nuclear translocation of AIF. Pharmacological inhibition of PARP-1 with its specific inhibitor 3AB rescued OGD-induced cell death, as well as prevented PAR polymer accumulation, mitochondrial depolarization, and AIF translocation into nucleus. Similar results could be found when PARP-1 was genetically knocked down with SiRNA. These indicated that OGD triggered parthanatos in SH-SY5Y cells. Then, we found inhibition of overproduction of ROS with antioxidant NAC attenuated obviously OGD-induced parthanatos in SH-SY5Y cells, suggesting ROS regulated OGD-induced parthanatos. Additionally, OGD also induced upregulation of ER stress-related proteins. Mitigation of ER stress with chemical chaperone 4-PBA or trehalose suppressed significantly OGD-induced overproduction of ROS, PARP-1 upregulation, PAR polymer accumulation, and nuclear accumulation of AIF, and cell death in SH-SY5Y cells. Conclusion Endoplasmic reticulum stress regulates OGD-induced parthanatos in human SH-SY5Y cells via improvement of intracellular ROS.

The geometric multigrid method (GMG) is one of the most efficient solving techniques for discrete algebraic systems arising from elliptic partial differential equations. GMG utilizes a hierarchy of grids or discretizations and reduces the error at a number of frequencies simultaneously. Graphics processing units (GPUs) have recently burst onto the scientific computing scene as a technology that has yielded substantial performance and energy-efficiency improvements. A central challenge in implementing GMG on GPUs, though, is that computational work on coarse levels cannot fully utilize the capacity of a GPU. In this work, we perform numerical studies of GMG on CPU-GPU heterogeneous computers. Furthermore, we compare our implementation with an efficient CPU implementation of GMG and with the most popular fast Poisson solver, Fast Fourier Transform, in the cuFFT library developed by NVIDIA.

In this paper, we firstly introduce two BPX-like preconditioners \(B_J^1\) and \(B_J^3\), and present an equivalent but more robust BPX-like preconditioner \(B_J^2\) for the solution of the linear finite element discretization of Poisson problem. Secondly, we implement these preconditioners and their preconditioned conjugate gradient (PCG) solvers \(B_l^p\)-CG(\(l=1,2,3\)) under Compute Unified Device Architecture (CUDA), where we exploit the hierarchical and the overall storage structure, take advantage of the multicolored Gauss–Seidel smoother. Finally, comparisons are made among these PCG solvers and the state-of-the-art SA-AMG preconditioned CG solver (SA-CG) in CUSP library. Numerical results demonstrate that the iteration numbers of \(B_2^p\)-CG holds the weakest dependence on the grid size, while \(B_3^p\)-CG is the most efficient solver. Furthermore, \(B_3^p\)-CG possesses considerable advantages over SA-CG in computational capability and efficiency. In particular, \(B_3^p\)-CG runs 3.67 times faster than SA-CG when solving a problem with about one-million unknowns.

Incomplete LU (ILU) methods are widely used in petroleum reservoir simulation and many other applications. However high complexity often makes them the hotspot in the whole simulation due to high complexity when problem size is large. ILU’s inherent serial nature also makes them difficult to take full advantage of computing power of multi-core and many-core devices. In this paper, a greedy graph coloring method is applied to the ILU(k) factorization and triangular solution phases. This method increases degree of parallelism and improves load balance. A block-wise storage format is employed in our ILU implementation in order to take advantage of hierarchical memory structures. Moreover, a dual intensive parallel model is proposed to further improve the performance of ILU(k) on GPUs. We test the performance of the proposed parallel ILU(k) with a set of Jacobian systems arising from petroleum reservoir simulation. Numerical results suggest that the proposed parallel ILU(k) method is effective and robust on multi-core and many-core architectures. On an Intel Xeon E5 multi-core CPU, the speedup compared with the serial execution time is \(5.6\times \) and \(5.4\times \) for factorization and triangular solution, respectively; on an Nvidia K40c GPU card, the speedup can reach \(8.6\times \) and \(12.7\times \) for factorization and triangular solution, respectively.

In this paper, the steepest descent algorithm without line search is proposed for p-Laplacian. Its search direction is the weighted preconditioned steepest descent one, and step length is estimated by a formula except the first iteration. Continuation method is applied for solving the p-Laplacian with very large p. Lots of numerical experiments are carried out on these algorithms. All numerical results show the algorithm without line search can cut down some computational time. Fast convergence of these new algorithms is displayed by their step length figures. These figures show that if search direction is the steepest descent one, exact step lengths can be substituted properly with step lengths obtained by the formula.