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MOOCs, as a new educational mode and form, has been widely welcomed around the world and also flourished in China for nearly ten years. Under the background that China has the largest total amount of MOOCs in the world, it is of great significance to explore the characteristics of high-quality MOOCs presentation mode for the future development. At present, although many studies have proved that the presentation mode of MOOCs’ teaching video has an impact on the teaching effect of MOOCs, there are few answers to questions such as “how to present” and “why to present in this way”. Based on this, from the perspective of qualitative research, this study selects the “national high-quality online open course”, which represents the highest level of online video in China, and analyzes the current online teaching video mode. The study found that in different types of teaching videos, the frequency and location of teacher images are different, and the key points and auxiliary teaching methods of making videos are also different. At the same time, the research also talks with a large number of existing researches in order to provide the construction ideas of high-quality resources for the builders of follow-up MOOCs courses.

The formation and development of professional identity are affected by many factors. Clarifying the influencing factors of Educational Technology graduates’ professional identity plays an important role in improving the quality of talent training. Based on the basic principles of grounded theory, this study takes the undergraduates of educational technology in a Chinese university as an example, and analyzes the main factors affecting the establishment of professional identity. It includes “whether students’ expectations of the major are consistent with the reality” and “whether they are satisfied with the status quo”. And then this study constructs the cause model of professional identity. It is suggested to improve the professional identity of educational technology graduates from four aspects: 1) Establishing objective professional cognition; 2) Rationalizing curriculum; 3) Strengthening career planning and guidance; 4) Cultivating students’ independent ideas and improving self-confidence.

In the rapidly growing area of high-frequency communications, polyimide films with ultralow dielectric constant and dielectric loss, adequate insulating strength, and recyclability are in high demand. Using a synthesized soluble fluorinated polyimide, a series of recyclable porous dielectric films with varying porosities were fabricated in this study through nonsolvent-induced phase separation. By manipulating the mass ratio of the binary solvent used to dissolve the polyimide, the shape, size, and size distribution of the pores generated throughout the polyimide matrix can be accurately regulated. The porosity and average pore size of the as-prepared porous films were adjustable between 71% and 33% and between 9.31 and 1.00 μm, respectively, which resulted in a variable dielectric constant of 1.51–2.42 (100 kHz) and electrical breakdown strength of 30.3–119.7 kV/mm. The porous sPI film with a porosity rate of 48% displayed a low dielectric constant of 2.48 at 10 GHz. Coupled with their superior thermal stability, mechanical characteristics, and recyclability, these porous polyimide films are highly promising for constructing high-frequency microelectronic devices.

The numerical simulations of the dynamics of high Reynolds number ($$Re>100{,}000$$) swirling flows in pipes with varying geometries of engineering applications continues to be a challenging computational problem, specifically when vortex-breakdown zones or wall-separation regions naturally evolve in the flows. To tackle this challenge, the present paper describes a simulation scheme of the evolution of inviscid, axisymmetric and incompressible swirling flows in expanding or contracting pipes. The integration in time of the circulation together with azimuthal vorticity uses an explicit, first-order accurate finite-difference scheme with a second-order accurate upwind difference formulation in the axial and radial directions. The Poisson solver for advancing in time the spatial distribution of the stream function as a function of azimuthal vorticity uses a second-order accurate over-relaxation difference scheme. No additional numerical steps are needed for computing the natural evolution of flows including the dynamics to states with slow-speed recirculation zones along the pipe centerline or attached to pipe wall. This numerical method shows convergence of the computed results with mesh refinement for various swirl levels and pipe geometry variations. The computed results of time-asymptotic states also present agreement with available theoretical predictions of steady vortex flows in diverging or contracting pipes. In addition, comparison with available experimental data demonstrates that the present algorithm accurately predicts instability processes and long-term mean-flow dynamics of vortex flows in pipes at high Re. The inviscid-flow simulation results support the theoretical predictions and clarify the nature of high-Re flow evolution.

A viscous extension of Arnold’s inviscid theory for planar parallel non-inflectional shear flows is developed and a viscous Arnold’s identity is obtained. Special forms of the viscous Arnold’s identity have been revealed that are closely related to the perturbation’s enstrophy identity derived by Synge (Proceedings of the Fifth International Congress for Applied Mechanics, 1938, pp. 326–332, John Wiley) (see also Fraternale et al., Phys. Rev. E, vol. 97, 2018, 063102). Firstly, an alternative derivation of the perturbation’s enstrophy identity for strictly parallel shear flows is acquired based on the viscous Arnold’s identity. The alternative derivation induces a weight function. Thereby, a novel weighted perturbation’s enstrophy identity is established, which extends the previously known enstrophy identity to include general streamwise translation-invariant shear flows. Finally, the validity of the enstrophy identity for parallel shear flows is rigorously examined and established under global nonlinear dynamics imposed with two classes of wall boundary conditions. As an application of the enstrophy identity, we quantitatively investigate the mechanism of linear instability/stability within the normal modal framework. The investigation reveals a subtle interaction between a critical layer and its adjacent boundary layer, which determines the stability nature of the disturbance. As an implementation of the relaxed wall boundary conditions imposed for the enstrophy identity, a control scheme is proposed that transitions the wall settings from the no-slip condition to the free-slip condition, through which a flow is stabilized quickly in an early stage of the transition.

Steady states of inviscid, compressible and axisymmetric swirling flows of a single-phase, inert, thermodynamically supercritical fluid in a rotating, finite-length, straight, long circular pipe are studied. The fluid thermodynamic behaviour is modelled by the van der Waals equation of state. A nonlinear partial differential equation for the solution of the flow streamfunction is derived from the fluid equations of motion in terms of the inlet flow specific total enthalpy, specific entropy and circulation functions. This equation reflects the complicated, nonlinear thermo-physical interactions in the flows, specifically when the inlet state temperature and density profiles vary around the critical thermodynamic point, flow compressibility is significant and the inlet swirl ratio is high. Several types of solutions of the resulting nonlinear ordinary differential equation for the axially independent case describe the flow outlet state when the pipe is sufficiently long. The approach is applied to an inlet flow described by a solid-body rotation with uniform profiles of the axial velocity and temperature. The solutions are used to form the bifurcation diagrams of steady compressible flows of real fluids as the inlet swirl level and the centreline inlet density are increased at a fixed inlet Mach number and temperature. Focus is on heavy-molecule fluids with low values of $R/C_{v}$. Computed results provide theoretical predictions of the critical swirl levels for the exchange of stability of the columnar state and for the appearance of non-columnar states and of vortex breakdown states as a function of inlet centreline density. The difference in the dynamical behaviour between that of a calorically perfect gas and of a real gas is explored. The analysis sheds new fundamental light on the complex dynamics of high-Reynolds-number, compressible, subsonic swirling flows of real gases.

Direct numerical simulations are used to study the three-dimensional, incompressible and viscous flow dynamics of a base solid-body rotation flow with a uniform axial velocity entering a rotating, finite-length, straight circular pipe. Steady in time profiles of the axial, radial and circumferential velocities are prescribed along the pipe inlet. The convective boundary conditions for each velocity flux component is set at the pipe outlet. The simulation results describe the neutral stability line in response to either axisymmetric or three-dimensional perturbations in a diagram of Reynolds number ($Re$, based on inlet axial velocity and pipe radius) versus the incoming flow swirl ratio ($\unicode[STIX]{x1D714}$). This line is in good agreement with the neutral stability line recently predicted by the linear stability theory of Wang et al. (J. Fluid Mech., vol. 797, 2016, pp. 284–321). The computed time history of the velocity components at a certain point in the flow is used to describe three-dimensional phase portraits of the flow global dynamics and its long-term behaviour. They show three types of flow evolution scenarios. First, the Wang & Rusak (Phys. Fluids, vol. 8 (4), 1996, pp. 1007–1016) axisymmetric instability mechanism and evolution to a stable axisymmetric breakdown state is recovered at certain operational conditions in terms of $Re$ and $\unicode[STIX]{x1D714}$. However, at other operational conditions with same $\unicode[STIX]{x1D714}$ but with a higher $Re$, a second scenario is found. The axisymmetric breakdown state continues to evolve and a spiral instability mode appears on it and grows to a rotating spiral breakdown state. Moreover, at higher levels of $\unicode[STIX]{x1D714}$ a third scenario is found where there exists a dominant three-dimensional spiral type of instability mode that agrees with the linear stability theory of Wang et al. (J. Fluid Mech., vol. 797, 2016, pp. 284–321). The growth of this mode leads directly to a spiral type of flow roll-up and nonlinearly saturates on a rotating spiral type of vortex breakdown. The Reynolds–Orr equation is used to reveal the mechanism that drives all the instabilities as well as the nonlinear global flow evolution. At high swirl ratios, the confined kinetic energy in the swirling flow can be triggered to be released through various physical agents, such as the asymmetric inlet–outlet conditions, that eliminate axial homogeneity along the pipe and induce flow instabilities and evolution to breakdown states. It is also shown that local instability analysis or its extension using the assumption of a weakly non-parallel flow to conduct convective instability–absolute instability analyses is definitely not related to any of the instability modes found in the present study. Moreover, a stability study based on the strongly non-parallel flow character, including axial inhomogeneity due to a finite-domain boundary conditions, must be conducted to reveal instabilities in such flows.

Rationale Pimavanserin, a selective serotonin 2A receptor inverse agonist, is a promising candidate for treating Parkinson's disease psychosis. Our previous study exhibited that there might be an existence of extensive metabolites of pimavanserin in rats. However, the metabolic fate of pimavanserin in vivo remains unknown. Thus, it is essential to develop an efficient method to investigate metabolic profile of pimavanserin in rats. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) to date has the highest mass measurement accuracy and resolution of any mass spectrometry platforms. Methods After a single intragastric administration of pimavanserin at a dose of 50 mg/kg, plasma, bile, urine and feces were collected from rats. A novel and efficient strategy was developed to analyze the metabolic profile of pimavanserin in vivo based on ultra high performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry (UHPLC/FT-ICR-MS). Results A total of 23 metabolites were detected and tentatively identified through comparing their mass spectrometry profiles with those of pimavanserin. Among these metabolites, feces (22), bile (21), rat urine (16) and plasma (15) were obtained. Results demonstrated that metabolic pathways of pimavanserin in rats included dehydrogenation, demethylation, deethylation, depropylation, debutylation, hydroxylation, dihydroxylation, and trihydroxylation reaction. Conclusions A total of 22 phase I metabolites of pimavanserin were detected and tentatively identified. This study presents the first report of screening and identifying the metabolites of pimavanserin. UHPLC/FT-ICR-MS method was a powerful tool to explore and identify metabolites in complex biological samples.

Ethylene tetrafluoroethylene (ETFE) cushion roofs are used for improving indoor natural lighting. However, their poor thermal insulation compromises the indoor thermal environment. Water spraying offers promising potential in roof cooling, but its cooling and shading effects on ETFE cushion roofs have not been examined. This paper on roof-mount spraying systems aimed to address this gap with numerical simulation and a full-scale field experiment. Our findings indicated that exterior surface temperatures of ETFE cushion roofs should be kept below 33.7°C to establish a thermally tolerable indoor environment. Secondly, under limitations of field conditions, decreases in exterior and interior surface temperatures yielded by the spraying system respectively ranged from 4.8°C to 19.5°C and from 0.2°C to 4.9°C. Thirdly, the shading effects generated by spraying have been insignificant, with the average solar radiation shading rate being only 0.23. Lastly, decreases in temperatures for both exterior and interior roof surfaces could be expressed as a function of only four parameters with good accuracy (R2 = 0.93 and 0.87, respectively). Decreases in exterior surface temperatures were most affected by exterior surface temperatures, followed by solar radiation, wind speed, and lastly the wet-bulb temperature, whereas decreases in interior surface temperatures were most affected by solar radiation.

A simple, rapid and sensitive method based on an ultra-performance liquid chromatographyâtandem mass spectrometry (UPLCâMS/MS) has been developed and validated for the determination of pimavanserin in rat plasma. The analyte was extracted by protein precipitation with methanol and separated on an ACQUITY BEH C18 column (100 à 2.1 mm, 1.7 µm; Waters, USA), with an isocratic elution of acetonitrile-water containing 10 mM ammonium acetate (70:30, v/v), at a flow rate of 0.2 mL/min for 2.5 min. The analyte and clarithromycin (the internal standard) were detected and quantified in positive ion mode using multiple reaction monitoring transitions at m/z 428.2 â 223.0 for pimavanserin and m/z 748.5 â 589.5 for clarithromycin. Relative coefficient (r) for the calibration curve was more than 0.9980. The intra-day and inter-day precisions (relative standard deviation, RSD%) were less than 13.3% and 10.5%, respectively, and the accuracy (relative error, RE%) was within ± 11.5%. The analytical method was successfully applied to a routine pharmacokinetic study of pimavanserin in rats after oral administration at the dose of 10 mg/kg. Keywords: UPLCâMS/MS, Pimavanserin, Pharmacokinetics, Rat plasma

The dynamics of inviscid-limit, incompressible and axisymmetric swirling flows in finite-length, diverging or contracting, long circular pipes is studied through global analysis techniques and numerical simulations. The inlet flow is described by the profiles of the circumferential and axial velocity together with a fixed azimuthal vorticity while the outlet flow is characterized by a state with zero radial velocity. A mathematical model that is based on the Squire–Long equation (SLE) is formulated to identify steady-state solutions of the problem with special conditions to describe states with separation zones. The problem is then reduced to the columnar (axially-independent) SLE, with centreline and wall conditions for the solution of the outlet flow streamfunction. The solution of the columnar SLE problem gives rise to the existence of four types of solutions. The SLE problem is then solved numerically using a special procedure to capture states with vortex-breakdown or wall-separation zones. Numerical simulations based on the unsteady vorticity circulation equations are also conducted and show correlation between time-asymptotic states and steady states according to the SLE and the columnar SLE problems. The simulations also shed light on the stability of the various steady states. The uniqueness of steady-state solutions in a certain range of swirl is proven analytically and demonstrated numerically. The computed results provide the bifurcation diagrams of steady states in terms of the incoming swirl ratio and size of pipe divergence or contraction. Critical swirls for the first appearance of the various types of states are identified. The results show that pipe divergence promotes the appearance of vortex-breakdown states at lower levels of the incoming swirl while pipe contraction delays the appearance of vortex breakdown to higher levels of swirl and promotes the formation of wall-separation states.

Three-dimensional direct numerical simulations of a solid-body rotation superposed on a uniform axial flow entering a rotating constant-area pipe of finite length are presented. Steady in time profiles of the radial, axial, and circumferential velocities are imposed at the pipe inlet. Convective boundary conditions are imposed at the pipe outlet. The Wang and Rusak (Phys. Fluids 8:1007–1016, 1996. doi: 10.1063/1.86882 ) axisymmetric instability mechanism is retrieved at certain operational conditions in terms of incoming flow swirl levels and the Reynolds number. However, at other operational conditions there exists a dominant, three-dimensional spiral type of instability mode that is consistent with the linear stability theory of Wang et al. (J. Fluid Mech. 797: 284–321, 2016). The growth of this mode leads to a spiral type of flow roll-up that subsequently nonlinearly saturates on a large amplitude rotating spiral wave. The energy transfer mechanism between the bulk of the flow and the perturbations is studied by the Reynolds-Orr equation. The production or loss of the perturbation kinetic energy is combined of three components: the viscous loss, the convective loss at the pipe outlet, and the gain of energy at the outlet through the work done by the pressure perturbation. The energy transfer in the nonlinear stage is shown to be a natural extension of the linear stage with a nonlinear saturated process.

Graphical Abstract A HPLC-MS method had been developed and applied to investigate the influence of pretreatment of piperazine ferulate on pharmacokinetic parameters of methotrexate. The changes in the pharmacokinetic behavior indicated that the pretreatment of piperazine ferulate might exert the protective effect on methotrexate-induced renal injury. Unlabelled image, The present study was designed to investigate the influence of the pretreatment of piperazine ferulate on pharmacokinetic parameters of methotrexate in methotrexate-induced renal injury rats. A simple and efficient high performance liquid chromatography coupled with mass spectrometry (HPLC-MS) method was developed to determine methotrexate in rat plasma. Methotrexate and syringic acid (internal standard) were extracted from rat plasma samples by protein precipitation with acetonitrile. The analysis was performed on a CAPCELL PAK C18 column (150 mm × 4.6 mm, 5 µm) with acetonitrile and 5 mmol/l ammonium acetate aqueous (10:90, v/v). The linear range was 5.0 × 10−2 to 100.0 µg/ml for methotrexate. Other parameters were all within the acceptance criteria. The validated method was successfully applied the pharmacokinetic study of methotrexate between two methotrexate treated groups (with and without the pretreatment of piperazine ferulate). Compared with the methotrexate treated alone group, the pharmacokinetic parameters in the methotrexate with the pretreatment of piperazine ferulate group showed significantly lower MRT(0-t), MRT(0-∞) and T1/2. Results suggested that methotrexate can be rapidly eliminated, cleared or metabolized in rat blood, which might be related to the pretreatment of piperazine ferulate. The method provided deeper insights into rational clinical use of methotrexate with the pretreatment of piperazine ferulate on cancer patients with renal dysfunction.

The interaction between flow inertia and elasticity in high-Reynolds-number, axisymmetric and near-critical swirling flows of an incompressible and viscoelastic fluid in an open finite-length straight circular pipe is studied at the limit of low elasticity. The stresses of the viscoelastic fluid are described by the generalized Giesekus constitutive model. This model helps to focus the analysis on low fluid elastic effects with shear thinning of the viscosity. The application of the Giesekus model to columnar streamwise vortices is first investigated. Then, a nonlinear small-disturbance analysis is developed from the governing equations of motion. It reveals the complicated interactions between flow inertia, swirl and fluid rheology. An effective Reynolds number that links between steady states of swirling flows of a viscoelastic fluid and those of a Newtonian fluid is revealed. The effects of the fluid viscosity, relaxation time, retardation time and mobility parameter on the flow development in the pipe and on the critical swirl for the appearance of vortex breakdown are explored. It is found that in vortex flows with either an axial jet or an axial wake profile, increasing the shear thinning by decreasing the ratio of the viscoelastic characteristic times from one (with fixed values of the Weissenberg number and the mobility parameter) increases the critical swirl ratio for breakdown. Increasing the fluid elasticity by increasing the Weissenberg number from zero (with a fixed ratio of the viscoelastic characteristic times and a fixed value of the mobility parameter) or increasing the fluid mobility parameter from zero (with fixed values of the Weissenberg number and the ratio of viscoelastic times) causes a similar effect. The results may explain the trend of changes in the appearance of breakdown zones as a function of swirl level that were observed in the experiments by Stokes et al. (J. Fluid Mech., vol. 429, 2001, pp. 67–115), where Boger fluids were used. This work extends for the first time the theory of vortex breakdown to include effects of non-Newtonian fluids.

The three-dimensional, inviscid and viscous flow instability modes that appear on a solid-body rotation flow in a finite-length straight, circular pipe are analysed. This study is a direct extension of the Wang & Rusak (Phys. Fluids, vol. 8 (4), 1996a, pp. 1007–1016) analysis of axisymmetric instabilities on inviscid swirling flows in a pipe. The linear stability equations are the same as those derived by Kelvin (Phil. Mag., vol. 10, 1880, pp. 155–168). However, we study a general mode of perturbation that satisfies the inlet, outlet and wall conditions of a flow in a finite-length pipe with a fixed in time and in space vortex generator ahead of it. This mode is different from the classical normal mode of perturbations. The eigenvalue problem for the growth rate and the shape of the perturbations for any azimuthal wavenumber $m$ consists of a linear system of partial differential equations in terms of the axial and radial coordinates ($x,r$). The stability problem is solved numerically for all azimuthal wavenumbers $m$. The computed growth rates and the related shapes of the various perturbation modes that appear in sequence as a function of the base flow swirl ratio (${\it\omega}$) and pipe length ($L$) are presented. In the inviscid flow case, the $m=1$ modes are the first to become unstable as the swirl ratio is increased and dominate the perturbation’s growth in a certain range of swirl levels. The $m=1$ instability modes compete with the axisymmetric ($m=0$) instability modes as the swirl ratio is further increased. In the viscous flow case, the viscous damping effects reduce the modes’ growth rates. The neutral stability line is presented in a Reynolds number ($Re$) versus swirl ratio (${\it\omega}$) diagram and can be used to predict the first appearance of axisymmetric or spiral instabilities as a function of $Re$ and $L$. We use the Reynolds–Orr equation to analyse the various production terms of the perturbation’s kinetic energy and establish the elimination of the flow axial homogeneity at high swirl levels as the underlying physical mechanism that leads to flow exchange of stability and to the appearance of both spiral and axisymmetric instabilities. The viscous effects in the bulk have only a passive influence on the modes’ shapes and growth rates. These effects decrease with the increase of $Re$. We show that the inviscid flow stability results are the inviscid-limit stability results of high-$Re$ rotating flows.

A nonlinear stability analysis of the viscous circular Couette flow to axisymmetric finite-amplitude perturbations under axial periodic boundary conditions is developed. The analysis is based on investigating the properties of a reduced Arnol’d energy-Casimir function $\mathscr{A}_{rd}$ of Wang (Phys. Fluids, vol. 2, 2009, 084104). A weighted kinetic energy of the perturbation, which has a form of ${\rm\Delta}\mathscr{A}_{rd}$, the difference between the reduced Arnol’d function and its base flow value, is used as a Lyapunov function. We show that all the inviscid flow effects as well as all the viscous-dependent terms that are related to the flow boundaries vanish. The evolution of ${\rm\Delta}\mathscr{A}_{rd}$ depends only on the viscous effects of the perturbation’s dynamics inside the flow domain. The requirement for the temporal decay of ${\rm\Delta}\mathscr{A}_{rd}$ leads to two novel sufficient conditions for the nonlinear stability of the circular Couette flow in response to axisymmetric perturbations. The linearized version of these conditions for infinitesimally small perturbations recovers the recent linear stability results by Kloosterziel (J. Fluid Mech., vol. 652, 2010, pp. 171–193). By examining the nonlinear stability conditions, we establish a definite operational region of the viscous circular Couette flow that is independent of the fluid viscosity. In this region of operation, the flow is nonlinearly stable in response to perturbations of any size, provided that the initial total circulation function is above a minimum level determined by the operational conditions of the base flow. Comparisons with historical studies show that our results shed light on the experimental measurements of Wendt (Ing.-Arch., vol. 4, 1933, pp. 577–595) and extend the classical nonlinear stability results of Serrin (Arch. Rat. Mech. Anal., vol. 3, 1959, pp. 1–13) and Joseph & Hung (Arch. Rat. Mech. Anal., vol. 44, 1971, pp. 1–22). When the flow is nonlinearly stable and evolves axisymmetrically for all time, then it always decays asymptotically in time to the circular Couette flow determined uniquely by the set-up of the rotating cylinders. Finally, we derive upper-bound estimates on the decay rate of finite-amplitude perturbations for the solid-body rotation flow between two coaxial rotating cylinders and for the circular Couette flow. We demonstrate via numerical simulations that the theoretical upper bound is relevant to the dynamics of various axisymmetric perturbations tested, where it is strictly obeyed. This present study provides new physical insights into a classical flow problem that was studied for many decades.

A global analysis of steady states of low Mach number inviscid premixed reacting swirling flows in a straight circular finite-length open pipe is developed. We focus on modelling the basic interaction between the swirl and heat release of the reaction. For analytic simplicity, a one-step first-order Arrhenious reaction kinetics is considered in the limit of high activation energy and infinite Peclet number. Assuming a complete reaction with chemical equilibrium upstream and downstream of the reaction zone, a nonlinear partial differential equation is derived for the solution of the flow stream function downstream of the reaction zone in terms of the specific total enthalpy, specific entropy and circulation functions prescribed at the inlet. Several types of solutions of the nonlinear ordinary differential equation for the columnar flow case describe the outlet states of the flow in a long pipe. These solutions are used to form the bifurcation diagram of steady reacting flows with swirl as the inlet swirl level is increased at a fixed heat release from the reaction. The approach is applied to two profiles of inlet flows, the solid-body rotation and the Lamb–Oseen vortex, both with constant profiles of the axial velocity, temperature and mixture reactant mass fraction. The computed results provide theoretical predictions of the critical inlet swirl levels for the appearance of vortex breakdown states and for the size of the breakdown zone as a function of the inlet flow swirl level, Mach number and heat release of the reaction. For the inlet solid-body rotation, flow is decelerated to breakdown as the inlet swirl is increased above the critical swirl level, and there is a delay in the appearance of breakdown with the increase of the heat release of the reaction. For the inlet Lamb–Oseen vortex at low values of heat release, the critical swirl for breakdown is decreased with the increase of heat release while, at high values of heat release, the appearance of breakdown is delayed to higher incoming flow swirl levels with the increase of heat release. The analysis sheds light on the global dynamics of low Mach number reacting flows with swirl and vortex breakdown and on the interaction between vortex breakdown and heat release that affects the shape of the reaction zone in the domain.

Chinese herbal drugs are often combined with chemotherapy drugs for the treatment of cancers. However, the combination administrations often do not have scientifically sound bases established on full preclinical and clinical investigations. A commonly used anti-colon-cancer herb-drug pair, irinotecan (CPT-11) hydrochloride injection and Kang'ai (KA) injection was taken as an example to investigate the possible pharmacokinetic interactions between Chinese herbal drugs and chemotherapy injections to determine the potential adverse drug reactions (ADRs). Rats were randomly divided into three groups and received 20 mg/kg CPT-11 injection 15 min after administration of 4 mL/kg saline for the CPT-11 single administration group and 4 mL/kg KA injection for the separated co-administration group, respectively. In the pre-mixed co-administration group, rats received a mixture of 20 mg/kg CPT-11 injection and 4 mL/kg KA injection. Blood samples were collected at 10 pre-determined time points between 0 and 24 h. The tissue samples were collected at 5 and 8 min after the injections, respectively. A reliable LC-MS/MS method was established for the simultaneous determination of CPT-11 and its metabolites, SN-38, SN-38 G and APC in the rat plasma and tissue samples, after full confirmation of two injections chemical and stability compatibilities. Compared to the C0 (5129 ± 757 ng/mL) and AUC0-t (7858 ± 1307 ng h/mL) of CPT-11 in the CPT-11 single administration group, the C0 (4574 ± 371 ng/mL) and AUC0-t (8779 ± 601 ng h/mL) after the separated co-administration remained unchanged, but the pre-mixed co-administration resulted with a significant increased C0 (29,454 ± 12,080 ng/mL) and AUC0-t (15,539 ± 5165 ng h/mL) (p < 0.05). Since the exposures of CPT-11 in most tissues in the pre-mixed co-administration group were dramatically lower than the separated co-administration group, the increased CPT-11 plasma concentration may be produced by the delayed tissue distribution because of the encapsulation by the components contained in KA injection, such as polysaccharides. Similar differences were also found in its metabolite, SN-38 G. There are obvious herb-drug interactions between CPT-11 injection and KA injection after the pre-mixed co-administration. The resulting excessive CPT-11 in the plasma may lead to many serious ADRs. Therefore, the full evaluation of herb-drug interactions is necessary and inappropriate combinations should be avoided.

The influence of various inlet swirling flow profiles on the manifold of steady axisymmetric states of flows, their domain of attraction, and on flow dynamics in a straight, long circular pipe is investigated.

A model problem of low-Mach number lean premixed reacting swirling flows with wall-separation zones in a contracting open chamber is studied. A theoretical feasibility for a technology of swirl-assisted combustion where the reaction zone is supported by a wall-separation zone is established.

A global analysis of steady states of inviscid compressible subsonic swirling flows in a finite-length straight circular pipe is developed. A nonlinear partial differential equation for the solution of the flow stream function is derived in terms of the inlet flow specific total enthalpy, specific entropy and circulation functions. The equation reflects the complicated thermo–physical interactions in the flows. Several types of solutions of the resulting nonlinear ordinary differential equation for the columnar case together with a flow force condition describe the outlet state of the flow in the pipe. These solutions are used to form the bifurcation diagram of steady compressible flows with swirl as the inlet swirl level is increased at a fixed inlet Mach number. The approach is applied to two profiles of inlet flows, solid-body rotation and the Lamb–Oseen vortex, both with a uniform axial velocity and temperature. The computed results provide for each inlet flow profile theoretical predictions of the critical swirl levels for the appearance of vortex breakdown states as a function of the inlet Mach number, suggesting that the results are robust for a variety of inlet swirling flows. The analysis sheds light on the dynamics of compressible flows with swirl and vortex breakdown, and shows the delay in the appearance of breakdown with increase of the inlet axial flow Mach number in the subsonic range of operation. The present theory is limited to axisymmetric dynamics of swirling flows in pipes where the wall boundary layer is thin and attached and does not interact with the flow in the bulk.

An active feedback flow control theory of the axisymmetric vortex breakdown process in incompressible swirling flows in a finite-length straight circular pipe is developed. Flow injection distributed along the pipe wall is used as the controller. The flow is subjected to non-periodic inlet and outlet conditions where the inlet profiles of the axial velocity, circumferential velocity and azimuthal vorticity are prescribed, along with no radial velocity at the outlet. A long-wave asymptotic analysis at near-critical swirl ratios, which involves a rescaling of the axial distance and time, results in a model problem for the dynamics and the nonlinear control of both inviscid and high-Reynolds-number ($\mathit{Re}$) flows. The approach provides the bifurcation diagram of steady states and the stability characteristics of these states. In addition, an energy analysis of the controlled flow dynamics suggests a feedback control law that relates the flow injection to the evolving maximum radial velocity at the inlet. Computed examples of the flow dynamics based on the full Euler and Navier–Stokes formulations at various swirl levels demonstrate the evolution to near-steady breakdown states when swirl is above a critical level that depends on $\mathit{Re}$. Moreover, applying the proposed feedback control law during flow evolution shows for the first time the successful and robust elimination of the breakdown states and flow stabilization on an almost columnar state for a wide range of swirl (up to at least 30 %) above critical. The feedback control cuts the natural feed-forward mechanism of the breakdown process. Specifically, in the case of high-$\mathit{Re}$ flows, the control approach establishes a branch of columnar states for all swirl levels studied, where in the natural flow dynamics no such states exist. The present theory is limited to the control of axisymmetric flows in pipes where the wall boundary layer is thin and attached and does not interact with the flow in the bulk.

Myocardial oxidative stress injury plays a crucial role in the pathogenesis of diabetic cardiomyopathy (DCM). Wnt/β-catenin signaling has been reported to involve in various heart diseases. However, the underlying mechanism associated with β-catenin in DCM remains elusive. This study intended to explore the effect of β-catenin on oxidative damage of DCM by establishing streptozotocin (STZ)-induced diabetic mouse model and hydrogen peroxide (H2O2)-treated myocardial cell model. Cardiac oxidative stress in DCM was detected by measurements of lipid peroxidation and anti-oxidative enzyme activities as well as DHE staining. Nuclear β-catenin activity and oxidative damage degree were measured by western blotting, qPCR, MTT assay and TUNEL staining. Cardiac function and morphology were evaluated by echocardiography and histopathology. Under diabetic oxidative stress or H2O2 stimulation, nuclear β-catenin accumulation upregulated downstream c-Myc and further facilitated DNA damage and p53-mediated apoptosis as well as cell viability reduction, followed by phenotypic changes of cardiac dysfunction, interstitial fibrosis deposition and myocardial atrophy. Conversely, through directly inhibiting nuclear β-catenin/c-Myc axis, not only did siRNA knockdown of β-catenin or c-Myc attenuate cell injury in H2O2-stimulated cardiomyocytes, but also diabetic cardiac-specific β-catenin-knockout mice displayed the same prevention of heart injury as insulin-treated diabetic mice. The present study demonstrated that activated nuclear β-catenin/c-Myc axis was responsible for oxidative cardiac impairment of DCM. Therefore, repressing functional nuclear β-catenin may provide a hopeful therapeutic strategy for DCM.

1. There are numerous investigations demonstrating that the cyclooxygenase-2 (COX-2) inhibitors might enhance the efficiency of anastrozole in breast cancer. Hence, this study was conducted to investigate the comparative pharmacokinetics of anastrozole after single administration and combination with celecoxib. 2. A simple protein precipitation procedure was adopted for the sample preparation with satisfactory extraction recovery for both anastrozole and the internal standard, and then anastrozole was separated and analysed on an ACQUITY BEH UPLC C

1. (S)-MP3950 is the (S)-enantiomer of active metabolite of mosapride, which exhibits higher 5-HT4 receptor agonistic effect than mosapride. It shows promise to become a novel drug candidate for the treatment of gastrointestinal motility disorders (GMDs). However, the pharmacokinetic behavior of (S)-MP3950 in the pathological state of GMDs remains unclear. Herein, we investigated the comparative pharmacokinetics of (S)-MP3950 in normal and GMDs rats. 2. The comparative pharmacokinetics of (S)-MP3950 in normal and atropine-induced GMD rats were studied by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The validated UPLC-MS/MS method was successfully applied to investigate the pharmacokinetic profiles of (S)-MP3950 in normal and atropine-induced GMDs rats. Results showed that comparing to normal rats, Cmax reduced by 73.8%, AUC0-t decreased by 57.6% and AUC0-∞ declined by 56.8% in model rats. Additionally, the elimination half-life (t1/2) and Tmax were prolonged slightly. 3. The pharmacokinetic results demonstrated that the atropine-induced GMDs reduced the absorption of (S)-MP3950. The pharmacokinetics research in the pathological state might provide more useful information for further study of novel gastric motility candidates.

Annealing furnaces are used to heat steel in order to change its chemical structure. In this paper we model an electric radiant furnace. One of the major defects in steel strips processed in such furnaces is a wave-like pattern near the edges of the strip, apparently due to extra heating near the edges. The aim of the paper is to model this effect and provide a way to calculate the elevated temperatures near the edges. We analyse two processes that are suspected to contribute to uneven heating. The modelling involves an asymptotic analysis of the effect of heat flux at the edges and a detailed analysis of the integral equations associated with radiant heat transfer in the furnace.

The incompressible, inviscid and axisymmetric dynamics of perturbations on a solid-body rotation flow with a uniform axial velocity in a rotating, finite-length, straight, circular pipe are studied via global analysis techniques and numerical simulations. The investigation establishes the coexistence of both axisymmetric wall-separation and vortex-breakdown zones above a critical swirl level, ${\it\omega}_{1}$. We first describe the bifurcation diagram of steady-state solutions of the flow problem as a function of the swirl ratio ${\it\omega}$. We prove that the base columnar flow is a unique steady-state solution when ${\it\omega}$ is below ${\it\omega}_{1}$. This state is asymptotically stable and a global attractor of the flow dynamics. However, when ${\it\omega}>{\it\omega}_{1}$, we reveal, in addition to the base columnar flow, the coexistence of states that describe swirling flows around either centreline stagnant breakdown zones or wall quasi-stagnant zones, where both the axial and radial velocities vanish. We demonstrate that when ${\it\omega}>{\it\omega}_{1}$, the base columnar flow is a min–max point of an energy functional that governs the problem, while the swirling flows around the quasi-stagnant and stagnant zones are global and local minimizer states and become attractors of the flow dynamics. We also find additional min–max states that are transient attractors of the flow dynamics. Numerical simulations describe the evolution of perturbations on above-critical columnar states to either the breakdown or the wall-separation states. The growth of perturbations in both cases is composed of a linear stage of the evolution, with growth rates accurately predicted by the analysis of Wang & Rusak (Phys. Fluids, vol. 8, 1996a, pp. 1007–1016), followed by a stage of saturation to either one of the separation zone states. The wall-separation states have the same chance of appearing as that of vortex-breakdown states and there is no hysteresis loop between them. This is strikingly different from the dynamics of vortices with medium or narrow vortical core size in a pipe.

We develop a novel and general approach to the discretization of partial differential equations. This approach overcomes the rigid restriction of the traditional method of lines (MOL) and provides flexibility in the treatment of spatial discretization. This method is essential for developing efficient numerical schemes for PDEs based on two-derivative Runge–Kutta (TDRK) methods, where the first and second derivatives must be discretized in an efficient way. This is unlikely to be achieved by using MOL. We then apply the explicit TDRK methods to the advection equations and analyze the numerical stability in the linear advection equation case. We conduct numerical experiments on the Burgers' equation using the TDRK methods developed. We also apply a two-stage semi-implicit TDRK method of order-4 and stage-order-4 to the heat equation. A very significant improvement in the efficiency of this TDRK method is observed when compared to the popular Crank-Nicolson method. This paper is partially based on the work in Tsai's PhD thesis (2011) [10].

The physical properties of a recently proposed feedback-stabilization method of a vortex flow in a finite-length straight pipe are studied for the case of a solid-body rotation flow. In the natural case, when the swirl ratio is beyond a certain critical level, linearly unstable modes appear in sequence as the swirl level is increased. Based on an asymptotic long-wave (long-pipe) approach, the global feedback control method is shown to enforce the decay in time of the perturbation’s kinetic energy and thereby quench all of the instability modes for a swirl range above the critical swirl level. The effectiveness of an extended version of this feedback flow control approach is further analysed through a detailed mode analysis of the full linear control problem for a solid-body rotation flow in a finite-length pipe that is not necessarily long. We first rigourously prove the asymptotic decay in time of all modes with real growth rates. We then compute the growth rate and shape of all modes according to the full linearized control problem for swirl levels up to 50 % above the critical level. We demonstrate that the flow is stabilized in the whole swirl range and can be even further stabilized for higher swirl levels. However, the control effectiveness is sensitive to the choice of the feedback control gain. A potentially best range of the gain is identified. An inadequate level of gain, either insufficient or excessive, could lead to a marginal control or failure of the control method at high swirl levels. The robustness of the proposed control law to stabilize both initial waves and continuous inlet flow perturbations and the elimination of the vortex breakdown process are demonstrated through numerical computations.

Vascular smooth muscle cells (VSMCs) exhibit a notably increased rate of migration, which is one of the most common pathological changes in atherosclerosis. Investigations into the role of micro (mi)RNAs in the regulation of VSMC migration are beginning to emerge and additional miRNAs involved in VSMC migration modulation require identification. In the current study, VSMCs were primarily cultured from rat thoracic aortas, transfected with miR‑92a mimics and induced by hydrogen peroxide (H2O2) for 24 h. Total mRNA and protein were collected for quantitative polymerase chain reaction and western blot analysis. In addition, the sirtuin 1 (SIRT1) gene was detected by luciferase reporter assay and VSMC migration was detected by Transwell migration assay. The current results demonstrated that reduced expression of miR‑92a and overexpression of SIRT1 at the mRNA level were observed in H2O2‑induced VSMCs. Furthermore, luciferase reporter assay demonstrated that the activity of the SIRT1 3'‑untranslated region was reduced by miR‑92a mimics. The upregulation of MMP9 and the downregulation of TIMP3 in H2O2‑induced VSMCs were observed to be reversed by miR‑92a mimics in addition to SIRT1 siRNA. Finally, Transwell migration assay revealed that miR‑92a overexpression and silencing SIRT1 mitigated VSMC migration following H2O2 treatment. The present study indicated that miR‑92a prevented the migration of H2O2‑induced VSMCs by repressing the expression of SIRT1, and also provided a novel therapy to protect against the phenotypic change of VSMCs in atherosclerosis.

Current simulations of swirling flows in pipes are limited to relatively low Reynolds number flows (Re 20,000) in most of engineering applications. To address this difficulty, this paper presents a numerical simulation algorithm of the dynamics of incompressible, inviscid-limit, axisymmetric swirling flows in a pipe, including the vortex breakdown process. It is based on an explicit, first-order difference scheme in time and an upwind, second-order difference scheme in space for the time integration of the circulation and azimuthal vorticity. A second-order Poisson equation solver for the spatial integration of the stream function in terms of azimuthal vorticity is used. In addition, when reversed flow zones appear, an averaging step of properties is applied at designated time steps. This adds slight artificial viscosity to the algorithm and prevents growth of localized high-frequency numerical noise inside the breakdown zone that is related to the expected singularity that must appear in any flow simulation based on the Euler equations. Mesh refinement studies show agreement of computations for various mesh sizes. Computed examples of flow dynamics demonstrate agreement with linear and nonlinear stability theories of vortex flows in a finite-length pipe. Agreement is also found with theoretically predicted steady axisymmetric breakdown states in a pipe as flow evolves to a time-asymptotic state. These findings indicate that the present algorithm provides an accurate prediction of the inviscid-limit, axisymmetric breakdown process. Also, the numerical results support the theoretical predictions and shed light on vortex dynamics at high Re.

The dynamics of a perturbed incompressible, inviscid, axisymmetric, near-critical swirling flow in a long, finite-length, straight, circular pipe is studied through a weakly nonlinear analysis. The flow is subjected to non-periodic inlet and outlet conditions. The long-wave approach involves a rescaling of the axial distance and time. It results in a separation of the perturbation’s structure into a critical standing wave in the radial direction and an evolving wave in the axial direction, that is described by a nonlinear model problem. The approach is first validated by establishing the bifurcation of non-columnar states from the critical swirl and the linear stability modes of these states. Examples of the flow dynamics at various near-critical swirl levels in response to different initial perturbations demonstrate the important role of the nonlinear steepening terms in perturbation dynamics. The computed dynamics shows quantitative agreement with results from numerical simulations that are based on the axisymmetric Euler equations for various swirl levels and as long as perturbations are small, thereby verifying the accuracy of each computation and capturing the essence of flow dynamics. Results demonstrate the various stages of the flow dynamics, specifically during the transition to vortex breakdown states. They reveal the evolution of faster-than-exponential and shape-changing modes as perturbations grow into the vortex breakdown process. These explosive modes provide the sudden and abrupt nature of the vortex breakdown phenomenon. Further analysis of the model problem shows the important role of the nonlinear evolution of perturbations and its relevance to the transfer of the perturbation’s kinetic energy between the boundaries and flow bulk, the evolution of perturbations in practical concentrated vortex flows, and the design of control methods of vortex flows. A robust feedback control method to stabilize a solid-body rotation flow in a pipe at a wide range of swirl levels above critical is developed. The applicability of this method to stabilizing medium and small core-size vortices is also discussed.

Temperature in a continuous steel annealing furnace is studied using a 3D finite element model with minimal simplification of the furnace design and heat transfer physics. This allows investigation of the temperature distribution of the furnace and steel strip and provides understanding of important operational factors such as increased heating of the strip edges and cooling of thermocouple probes due to radiative heat transfer. This information enables the use of simpler models in production situations and can help optimize furnace operating methods and improve product quality.

The rate of change of the perturbation's kinetic energy E of a perturbed inviscid, incompressible, axisymmetric, columnar and near-critical swirling flow in a finite-length, straight, circular pipe with periodic and non-periodic inlet–outlet conditions is studied using the Reynolds–Orr equation. The perturbation's mode shape and growth rate are computed from the linear-stability eigenvalue problem using a novel asymptotic solution in the case of a flow in a long pipe. This solution technique is general and can be applied to any vortex flow profile, in a range of swirl levels around the critical level, and for various boundary conditions. The solutions are used to analytically estimate the production (or loss) of E at the pipe boundaries and inside the domain and to shed new light on the Wang–Rusak mechanism of exchange of global stability around the critical swirl, that is leading to the vortex breakdown process. It is shown that the production of E inside the domain is modulated by the base flow strain-rate tensor. For the special case of a solid-body rotating flow, this term vanishes and the stability is determined only by the asymmetric transfer of E at the boundaries. For a general base flow, the dominant perturbation's mode shape develops deviations in response to the non-periodic inlet–outlet conditions. These deviations couple with the base flow strain-rate tensor to generate production or loss of E in the bulk. Together with the asymmetric transfer of E at the boundaries, they form a critical balance of production of E and determine the flow stability around the critical state. This behaviour is demonstrated for the Lamb–Oseen and Q vortex models. This analysis reveals a more complicated, as well more realistic, interaction between the perturbed flow in the domain and at the boundaries that dominates vortex flow dynamics.

Some new star-shaped polydentate ligands were synthesized using 2,4,6-tris(p-formylphenoxy)-1,3,5-triazine as a template and were characterized by infrared, 1H NMR, and 13C NMR spectra and elemental analysis. These products may form polynuclear complexes with metal ions, and the complexes may possess potential applications in the area of electromaterials, optomaterials, magnetic materials, and bio-organic materials.

Temperature in a continuous annealing furnace is studied by furnace modelling using two methods. A 3D model is used to investigate the temperature distribution of the steel strip that is being annealed and the furnace thermocouple probes, and information from the 3D model enables the construction of a highly simplified 1D/2D model, which predicts furnace and strip temperatures with very good agreement to the 3D model. The simple model has a very short solution time and is suitable for rapid simulation of alternative furnace operating conditions in order to optimise heat treatment quality, plant throughput and energy consumption.

This paper studies the summer natural wind environments inside an airport terminal building under two cases by the method of computational fluid dynamics (CFD). The two cases have different opening...

Feedback stabilization of inviscid and high Reynolds number, axisymmetric, swirling flows in a long finite-length circular pipe using active variations of pipe geometry as a function of the evolving inlet radial velocity is studied. The complicated dynamics of the natural flow requires that any theoretical model that attempts to control vortex stability must include the essential nonlinear dynamics of the perturbation modes. In addition, the control methodology must establish a stable desired state with a wide basin of attraction. The present approach is built on a weakly nonlinear model problem for the analysis of perturbation dynamics on near-critical swirling flows in a slightly area-varying, long, circular pipe with unsteady changes of wall geometry. In the natural case with no control, flows with incoming swirl ratio above a critical level are unstable and rapidly evolve to either vortex breakdown states or accelerated flow states. Following an integration of the model equation, a perturbation kinetic-energy identity is derived, and an active feedback control methodology to suppress perturbations from a desired columnar state is proposed. The stabilization of both inviscid and high-Re flows is demonstrated for a wide range of swirl ratios above the critical swirl for vortex breakdown and for large-amplitude initial perturbations. The control gain for the fastest decay of perturbations is found to be a function of the swirl level. Large gain values are required at near-critical swirl ratios while lower gains provide a successful control at swirl levels away from critical. This feedback control technique cuts the feed-forward mechanism between the inlet radial velocity and the growth of perturbation's kinetic energy in the bulk and thereby enforces the decay of perturbations and eliminates the natural explosive evolution of the vortex breakdown process. The application of this proposed robust active feedback control method establishes a branch of columnar states with a wide basin of attraction for swirl ratios up to at least 50% above the critical swirl. This study provides guidelines for future flow control simulations and experiments. However, the present methodology is limited to the control of high-Reynolds number (nearly inviscid), axisymmetric, weakly nonparallel flows in long pipes.