Nitrogen heterocycle represents a ubiquitous skeleton in natural products and drugs. Late-stage C(sp
)-H bond functionalization of N-heterocycles with broad substrate scope remains a challenge and of ...particular significance to modern chemical synthesis and pharmaceutical chemistry. Here, we demonstrate copper-catalysed late-stage C(sp
)-H functionalizaion of N-heterocycles using commercially available catalysts under mild reaction conditions. We have investigated 8 types of N-heterocycles which are usually found as medicinally important skeletons. The scope and utility of this approach are demonstrated by late-stage C(sp
)-H modification of these heterocycles including a number of pharmaceuticals with a broad range of nucleophiles, e.g. methylation, arylation, azidination, mono-deuteration and glycoconjugation etc. Preliminary mechanistic studies reveal that the reaction undergoes a C-H fluorination process which is followed by a nucleophilic substitution.
Long-term manganese exposure causes a neurodegenerative disorder referred to as manganese poisoning, but the mechanism remains unclear and no specific treatment is available. Oxidative stress is ...widely recognised as one of the main causes of manganese-induced neurotoxicity. In recent years, the role of histone acetylation in neurodegenerative diseases has been widely concerned. curcumin is a natural polyphenol compound extracted from the rhizome of turmeric and exhibits both antioxidant and neuroprotective properties. Therefore, we aimed to investigate whether and how curcumin protects against manganese-induced neurotoxicity from the perspective of histone acetylation, based on the reversibility of histone acetylation modification. In this study, rats were treated with or without curcumin and subjected to long-term manganese exposure. Results that treatment of manganese decreased the protein expression of H3K18 acetylation and H3K27 acetylation at the promoters of oxidative stress-related genes and inhibited the expression of these genes. Nevertheless, curcumin increased the H3K27 acetylation level at the manganese superoxide dismutase (SOD2) gene promoter and promoted the expression of SOD2 gene. Oxidative damage in the rat striatum as well as learning and memory dysfunction were ameliorated after curcumin treatment. Taken together, our results suggest that the regulation of oxidative stress by histone acetylation may be a key mechanism of manganese-induced neurotoxicity. In addition, curcumin ameliorates Mn-induced neurotoxicity may be due to alleviation of oxidative damage mediated by increased activation of H3K27 acetylation at the SOD2 gene promoter.
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•Down-acetylation levels of H3K27 and H3K18 may inhibit the expression of OSR genes.•Curcumin ameliorates Mn-induced neurotoxicity in rat.•Curcumin increases the expression of SOD2 gene by the up-acetylation level of H3K27.
A modified Newton's gravity is obtained as the weak field approximation of the Einstein's equation in Finsler space. It is found that a specified Finsler structure makes the modified Newton's gravity ...equivalent to the modified Newtonian dynamics (MOND). In the framework of Finsler geometry, the flat rotation curves of spiral galaxies can be deduced naturally without invoking dark matter.
The Bohm-Vigier stochastic model is assumed as a natural generalization of the Black-Scholes model in stock market. The behavioral factor of stock market recognizes as a hidden sector in Bohmian ...mechanics. A Fokker-Planck equation description for the Bohm-Vigier stochastic model is presented. We find the familiar Boltzmann distribution is a stationary solution of the Fokker-Planck equation for the Bohm-Vigier model. The return transition distribution of stock market, which corresponds with a time-dependent solution of the Fokker-Planck equation, is obtained.
In the coming era of multi-messenger astrophysics, pulsars might be one of the most possible electromagnetic counterparts of the gravitational wave. The braking indices, which are related closely to ...the electromagnetic radiation of pulsars, are shown to be larger for the pulsars with companion. It motivates us to set up a modified spin-down equation for accelerated pulsars. In this model, we attempt to figure out whether acceleration of a pulsar can cause a larger braking index.
In order to reveal the dynamic characteristics and achieve rapid time series prediction of ship maneuvering motion, a reduced-order dynamic mode decomposition (DMD) algorithm is applied to ...reconstruct and predict the zig-zag and turning circle maneuvering motions. A case study is conducted for a KVLCC2 tanker using its free-running model test data. First, all DMD modes are extracted from the test data, and the dominant DMD modes are selected according to their contributions to the dynamical systems of ship maneuvering motions. Then, the dynamical systems of ship maneuvering motions are reconstructed and predicted by the reduced-order and full-order DMD algorithms. A comparison between reduced-order, full-order DMD algorithms and Gaussian process regression (GPR) is conducted. The dynamic characteristics of the dynamical systems are revealed according to the growth rates and frequencies of the dominant DMD modes. The effects of the truncation rank and input samples are analyzed by a parametric study, which indicates that the truncation rank and input samples are crucial to the prediction accuracy. Besides, the computational time of the different algorithms is compared and analyzed.
•A reduced-order DMD method is applied to the time series prediction of ship maneuvering motion.•A comparison among the reduced-order, the full-order DMD methods and GPR is conducted.•The dynamic characteristics of ship maneuvering motion are revealed by the DMD method.•The effects of the truncation rank and input samples are analyzed by a parametric study.•The reduced-order DMD method has a higher computational efficiency than the full-order one.
An excellent automated guided vehicle (AGV) scheduling scheme can effectively improve the productivity of automated manufacturing factories and reduce costs, so the AGV dispatching problem (AGVDP) ...has become a research hotspot. This paper studies AGVDP with AGV capacity and the latest delivery time to reduce the cost of the total objective consisting of AGV cost, travel cost, and penalty cost. To this end, a mixed-integer linear programming model and a multi-restart iterated greedy (MRIG) algorithm are proposed. According to the characteristics of the problem, an improved nearest neighbor-based heuristic algorithm (INNH) is proposed to generate an initial solution. INNH includes a balanced two-factor selection strategy and a multiple-try insertion strategy. In the MRIG, the destruction stage has been improved to have an adaptive parameter. To enhance the quality of the initial solution and the depth of the evolution, two improved reference local searches are proposed. Furthermore, a multi-restart strategy with a checking mechanism and five restart methods is designed to avoid MRIG falling into the local optimum. The results of sufficient statistical experiments show that the MRIG is obviously superior to the existing algorithms when solving AGVDP.
It is well known that Markowitz's mean-variance model is the pioneer portfolio selection model. The mean-variance model assumes that the probability density distribution of returns is normal. ...However, empirical observations on financial markets show that the tails of the distribution decay slower than the log-normal distribution. The distribution shows a power law at tail. The variance of a portfolio may also be a random variable. In recent years, the maximum entropy method has been widely used to investigate the distribution of return of portfolios. However, the mean and variance constraints were still used to obtain Lagrangian multipliers. In this paper, we use Conditional Value at Risk constraints instead of the variance constraint to maximize the entropy of portfolios. Value at Risk is a financial metric that estimates the risk of an investment. Value at Risk measures the level of financial risk within a portfolio. The metric is most commonly used by investment bank to determine the extent and occurrence ratio of potential losses in portfolios. Value at Risk is a single number that indicates the extent of risk in a given portfolio. This makes the risk management relatively simple. The Value at Risk is widely used in investment bank and commercial bank. It has already become an accepted standard in buying and selling assets. We show that the maximum entropy distribution with Conditional Value at Risk constraints is a power law. Algebraic relations between the Lagrangian multipliers and Value at Risk constraints are presented explicitly. The Lagrangian multipliers can be fixed exactly by the Conditional Value at Risk constraints.
Hull-engine-propeller matching is one of the key issues of ship design. It plays an important role in improving the economy and safety of ship navigation. The hull-engine-propeller matching is ...generally based on the Factory Acceptance Test of engine and the Sea Acceptance Test of ship. These conventional methods cost money and time. To overcome these defects, this paper proposes a simulation method based on the quasi-steady model of engine and CFD for ship hydrodynamics to study the interaction among the hull, engine and propeller, which provides the basis for ship-engine-propeller matching. Taking the PA6 diesel engine and the ONR tumblehome ship as the study objects, the quasi-steady model of engine is constructed by using simulation software and applied to carry out simulation under the operation conditions; the ship resistance test, propeller open-water test and self-propulsion test are simulated by using CFD method. Based on the simulation results, an integrated simulation platform is established for studying the hull-engine-propeller interaction. Further, the external characteristics of diesel engine under the effects of hull-engine-propeller interaction are predicted for the ship sailing straight ahead at different speeds. This paper provides a new method for studying the characteristics of hull-engine-propeller interaction.
•The interaction among hull, engine and propeller during self-propulsion of a ship is numerically studied.•The PA6 diesel engine and the ONR tumblehome ship are taken as the study objects.•A simulation platform composed of quasi-steady model of engine and predicting model of ship power performance is built.•The numerical study on the hull-engine-propeller interaction is carried out on the simulation platform.•The external characteristics of diesel engine under the effects of hull-engine-propeller interaction are predicted.
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