EAE （Experimental Autoimmune Encephalomyelitis）, Corticotropin-Releasing Factor and the Blood Brain Barrier

EAE （experimental autoimmune encephalomyelitis） is an established, inducible animal model employed in the study of MS （multiple sclerosis） characterized by inflammation, BBB （blood brain barrier） malfunction, demyelination and neuronal disruption. CRF （corticotropin releasing factor） is a neuropeptide critically associated with immune function, BBB permeability, and the hypothalamic-pituitary-adrenal axis. Potential CRF targets in the brain include astrocytes, as well as endothelial cells of cerebral microvessels, since they have been reported to express CRFR （CRF receptors）. Further, both of these cell types function critically in regulating BBB permeability. CRF-BP （CRF binding protein） is also expressed in both neurons and glial cells. Changes in the cortical CRF system could be a contributing factor to the BBB disruption associated with MS/EAE and has been suggested to play a protective role against cytokine-induced inflammation. The current study assessed alterations associated with the C57BL/6 mouse model of EAE in the cortical CRF system and correlated these events with changes to the microvascular unit. Immunohistochemical confocal microscopy was used to analyze the distribution of CRF, CRF-BP, and CRFR in the mouse cerebral cortex. The authors observed a reduction in detectable CRF immunofluorescence in the EAE motor cortex, an increase in CRFBP immunoreactivity in EAE astrocytes and a concurrent reduction in astrocytic CRFR immunofluorescence. Staining techniques were used to visualize astrocytes/microvessels to document alterations in BBB integrity. Changes in the CRF system were associated with a modification of the blood brain barrier as manifested by a poorly defined astrocytic barrier in EAE microvessels. Evidence suggests that manipulation of CRF signaling pathways offers an intriguing target for interventional therapies designed to modify BBB permeability that may be beneficial for treating disease states such as MS.

Fasudil-modified macrophages reduce inflammation and regulate the immune response in experimental autoimmune encephalomyelitis

Multiple sclerosis is characterized by demyelination and neuronal loss caused by inflammatory cell activation and infiltration into the central nervous system.Macrophage polarization plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis,a traditional experimental model of multiple sclerosis.This study investigated the effect of Fasudil on macrophages and examined the therapeutic potential of Fasudil-modified macrophages in experimental autoimmune encephalomyelitis.We found that Fasudil induced the conversion of macrophages from the pro-inflammatory M1 type to the anti-inflammatory M2 type,as shown by reduced expression of inducible nitric oxide synthase/nitric oxide,interleukin-12,and CD16/32 and increased expression of arginase-1,interleukin-10,CD14,and CD206,which was linked to inhibition of Rho kinase activity,decreased expression of toll-like receptors,nuclear factor-κB,and components of the mitogen-activated protein kinase signaling pathway,and generation of the pro-inflammatory cytokines tumor necrosis factor-α,interleukin-1β,and interleukin-6.Crucially,Fasudil-modified macrophages effectively decreased the impact of experimental autoimmune encephalomyelitis,resulting in later onset of disease,lower symptom scores,less weight loss,and reduced demyelination compared with unmodified macrophages.In addition,Fasudil-modified macrophages decreased interleukin-17 expression on CD4^(+)T cells and CD16/32,inducible nitric oxide synthase,and interleukin-12 expression on F4/80^(+)macrophages,as well as increasing interleukin-10 expression on CD4^(+)T cells and arginase-1,CD206,and interleukin-10 expression on F4/80^(+)macrophages,which improved immune regulation and reduced inflammation.These findings suggest that Fasudil-modified macrophages may help treat experimental autoimmune encephalomyelitis by inducing M2 macrophage polarization and inhibiting the inflammatory response,thereby providing new insight into cell immunotherapy for multiple sclerosis.

Recent progresses in the development of tubular segmented-in-series solid oxide fuel cells:Experimental and numerical study

Solid oxide fuel cells(SOFCs)have attracted a great deal of interest because they have the highest efficiency without using any noble metal as catalysts among all the fuel cell technologies.However,traditional SOFCs suffer from having a higher volume,current leakage,complex connections,and difficulty in gas sealing.To solve these problems,Rolls-Royce has fabricated a simple design by stacking cells in series on an insulating porous support,resulting in the tubular segmented-in-series solid oxide fuel cells(SIS-SOFCs),which achieved higher output voltage.This work systematically reviews recent advances in the structures,preparation methods,perform-ances,and stability of tubular SIS-SOFCs in experimental and numerical studies.Finally,the challenges and future development of tubular SIS-SOFCs are also discussed.The findings of this work can help guide the direction and inspire innovation of future development in this field.

Experimental investigation on the permeability of gap-graded soil due to horizontal suffusion considering boundary effect

The boundary condition is a crucial factor affecting the permeability variation due to suffusion.An experimental investigation on the permeability of gap-graded soil due to horizontal suffusion considering the boundary effect is conducted,where the hydraulic head difference(DH)varies,and the boundary includes non-loss and soil-loss conditions.Soil samples are filled into seven soil storerooms connected in turn.After evaluation,the variation in content of fine sand(ΔR_(f))and the hydraulic conductivity of soils in each storeroom(C_(i))are analyzed.In the non-loss test,the soil sample filling area is divided into runoff,transited,and accumulated areas according to the negative or positive ΔR_(f) values.ΔR_(f) increases from negative to positive along the seepage path,and Ci decreases from runoff area to transited area and then rebounds in accumulated area.In the soil-loss test,all soil sample filling areas belong to the runoff area,where the gentle-loss,strengthened-loss,and alleviated-loss parts are further divided.ΔR_(f) decreases from the gentle-loss part to the strengthened-loss part and then rebounds in the alleviated-loss part,and C_(i) increases and then decreases along the seepage path.The relationship between ΔR_(f) and Ci is different with the boundary condition.Ci exponentially decreases with ΔR_(f) in the non-loss test and increases with ΔR_(f) generally in the soil-loss test.

Experimental Investigation on Vertical Hydraulic Transport of Ores in Deepsea Mining

Deepsea mining has been proposed since the 1960s to alleviate the lack of resources on land.Vertical hydraulic transport of collected ores from the seabed to the sea surface is considered the most promising method for industrial applications.In the present study,an indoor model test of the vertical hydraulic transport of particles was conducted.A noncontact optical method has been proposed to measure the local characteristics of the particles inside a vertical pipe,including the local concentration and particle velocity.The hydraulic gradient of ore transport was evaluated with various particle size distributions,particle densities,feeding concentrations and mixture flow velocities.During transport,the local concentration is larger than the feeding concentration,whereas the particle velocity is less than the mixture velocity.The qualitative effects of the local concentration and local fluid velocity on the particle velocity and slip velocity were investigated.The local fluid velocity contributes significantly to particle velocity and slip velocity,whereas the effect of the local concentration is marginal.A higher feeding concentration and mixture flow velocity result in an increased hydraulic gradient.The effect of the particle size gradation is slight,whereas the particle density plays a crucial role in the transport.

Experimental and numerical study of buckling-restrained braces configured with out-of-plane eccentricity under cyclic loading

This study focuses on variations in the hysteretic behavior of buckling-restrained braces(BRBs)configured with or without out-of-plane eccentricity under cyclic loading.Quasi-static experiments and numerical simulations were carried out on concentrically and eccentrically loaded BRB specimens to investigate the mechanical properties,energy dissipation performance,stress distribution,and high-order deformation pattern.The experimental and numerical results showed that compared to the concentrically loaded BRBs,the stiffness,yield force,cumulated plastic ductility(CPD)coefficient,equivalent viscous damping coefficient and energy dissipation decreased,and the yield displacement and compression strength adjustment factor increased for the eccentrically loaded BRBs.With the existence of the out-of-plane eccentricity,the initial yield position changes from the yield segment to the junction between the yield segment and transition segment under a tensile load,while the initial high-order buckling pattern changes from a first-order C-shape to a secondorder S-shape under a compressive load.

Multi-environment BSA-seq using large F3 populations is able to achieve reliable QTL mapping with high power and resolution: An experimental demonstration in rice

Bulked-segregant analysis by deep sequencing(BSA-seq) is a widely used method for mapping QTL(quantitative trait loci) due to its simplicity, speed, cost-effectiveness, and efficiency. However, the ability of BSA-seq to detect QTL is often limited by inappropriate experimental designs, as evidenced by numerous practical studies. Most BSA-seq studies have utilized small to medium-sized populations, with F2populations being the most common choice. Nevertheless, theoretical studies have shown that using a large population with an appropriate pool size can significantly enhance the power and resolution of QTL detection in BSA-seq, with F_(3)populations offering notable advantages over F2populations. To provide an experimental demonstration, we tested the power of BSA-seq to identify QTL controlling days from sowing to heading(DTH) in a 7200-plant rice F_(3)population in two environments, with a pool size of approximately 500. Each experiment identified 34 QTL, an order of magnitude greater than reported in most BSA-seq experiments, of which 23 were detected in both experiments, with 17 of these located near41 previously reported QTL and eight cloned genes known to control DTH in rice. These results indicate that QTL mapping by BSA-seq in large F_(3)populations and multi-environment experiments can achieve high power, resolution, and reliability.

Unexpected Diversity in Ecosystem Nutrient Responses to Experimental Drought in Temperate Grasslands

The responses of ecosystem nitrogen (N) and phosphorus (P) to drought are an important component of globalchange studies. However, previous studies were more often based on site-specific experiments, introducing a significantuncertainty to synthesis and site comparisons. We investigated the responses of vegetation and soil nutrientsto drought using a network experiment of temperate grasslands in Northern China. Drought treatment (66%reduction in growing season precipitation) was imposed by erecting rainout shelters, respectively, at the driest,intermediate, and wettest sites. We found that vegetation nutrient concentrations increased but soil nutrient concentrationsdecreased along the aridity gradient. Differential responses were observed under experimentaldrought among the three grassland sites. Specifically, the experimental drought did not change vegetation andsoil nutrient status at the driest site, while strongly reduced vegetation but increased soil nutrient concentrationsat the site with intermediate precipitation. On the contrary, experimental drought increased vegetation N concentrationsbut did not change vegetation P and soil nutrient concentrations at the wettest site. In general, the differentialeffects of drought on ecosystem nutrients were observed between manipulative and observationalexperiments as well as between sites. Our research findings suggest that conducting large-scale, consistent, andcontrolled network experiments is essential to accurately evaluate the effects of global climate change on terrestrialecosystem bio-geochemistry.

Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.

Experimental Study on the Electrochemical Performance of PEMFC under Different Assembly Forces

Proton exchange membrane fuel cell(PEMFC)is of paramount significance to the development of clean energy.The components of PEMFC are assembled using many pairs of nuts and bolts.The assembly champing bolt torque is critical to the electrochemical performance and mechanical stability of PEMFC.In this paper,a PEMFC with the threechannel serpentine flow field was used and studied.The different assembly clamping bolt torques were applied to the PEMFC in three uniform assembly bolt torque and six non-uniform assembly bolt torque conditions,respectively.And then,the electrochemical performance experiments were performed to study the effect of the assembly bolt torque on the electrochemical performance.The test results show that the assembly bolt torque significantly affected the electrochemical performance of the PEMFC.In uniform assembly bolt torque conditions,the maximal power density increased initially as the assembly bolt torque increased,and then decreased on further increasing the assembly torque.It existed the optimum assembly torque which was found to be 3.0 N·m in this work.In non-uniform assembly clamping bolt torque conditions,the optimum electrochemical performance appeared in the condition where the assembly torque of each bolt was closer to be 3.0 N·m.This could be due to the change of the contact resistance between the gas diffusion layer and bipolar plate and mass transport resistance for the hydrogen and oxygen towards the catalyst layers.This work could optimize the assembly force conditions and provide useful information for the practical PEMFC stack assembly.

Theoretical and Experimental Study on the Performance of Hermetic Diaphragm Squeeze Film Dampers for Gas-Lubricated Bearings

Low damping characteristics have always been a key sticking points in the development of gas bearings.The application of squeeze film dampers can significantly improve the damping performance of gas lubricated bearings.This paper proposed a novel hermetic diaphragm squeeze film damper(HDSFD)for oil-free turbomachinery supported by gas lubricated bearings.Several types of HDSFDs with symmetrical structure were proposed for good damping performance.By considering the compressibility of the damper fluid,based on hydraulic fluid mechanics theory,a dynamic model of HDSFDs under medium is proposed,which successfully reflects the frequency dependence of force coefficients.Based on the dynamic model,the effects of damper fluid viscosity,bulk modulus of damper fluid,thickness of damper fluid film and plunger thickness on the dynamic stiffness and damping of HDSFDs were analyzed.An experimental test rig was assembled and series of experimental studies on HDSFDs were conducted.The damper fluid transverse flow is added to the existing HDSFD concept,which aims to make the dynamic force coefficients independent of frequency.Although the force coefficient is still frequency dependent,the damping coefficient at high frequency excitation with damper fluid supply twice as that without damper fluid supply.The results serve as a benchmark for the calibration of analytical tools under development.

Dynamic Modeling and Experimental Verification of an RPR Type Compliant Paralle Mechanism with Low Orders

Efficiency of calculating a dynamic response is an important point of the compliant mechanism for posture adjustment.Dynamic modeling with low orders of a 2R1T compliant parallel mechanism is studied in the paper.The mechanism with two out-of-plane rotational and one lifting degrees of freedom(DoFs)plays an important role in posture adjustment.Based on elastic beam theory,the stiffness matrix and mass matrix of the beam element are established where the moment of inertia is considered.To improve solving efficiency,a dynamic model with low orders of the mechanism is established based on a modified modal synthesis method.Firstly,each branch of the RPR type mechanism is divided into a substructure.Subsequently,a set of hypothetical modes of each substructure is obtained based on the C-B method.Finally,dynamic equation of the whole mechanism is established by the substructure assembly.A dynamic experiment is conducted to verify the dynamic characteristics of the compliant mechanism.

Experimental investigation on coal pore-fracture variation and fractal characteristics synergistically affected by solvents for improving clean gas extraction

Chemical solvents instead of pure water being as hydraulic fracturing fluid could effectively increase permeability and improve clean methane extraction efficiency.However,pore-fracture variation features of lean coal synergistically affected by solvents have not been fully understood.Ultrasonic testing,nuclear magnetic resonance analysis,liquid phase mass spectrometry was adopted to comprehensively analyze pore-fracture change characteristics of lean coal treated by combined solvent(NMP and CS_(2)).Meanwhile,quantitative characterization of above changing properties was conducted using geometric fractal theory.Relationship model between permeability,fractal dimension and porosity were established.Results indicate that the end face fractures of coal are well developed after CS2and combined solvent treatments,of which,end face box-counting fractal dimensions range from 1.1227 to 1.4767.Maximum decreases in ultrasonic longitudinal wave velocity of coal affected by NMP,CS_(2)and combined solvent are 2.700%,20.521%,22.454%,respectively.Solvent treatments could lead to increasing amount of both mesopores and macropores.Decrease ratio of fractal dimension Dsis 0.259%–2.159%,while permeability increases ratio of NMR ranges from 0.1904 to 6.4486.Meanwhile,combined solvent could dissolve coal polar and non-polar small molecules and expand flow space.Results could provide reference for solvent selection and parameter optimization of permeability-enhancement technology.

Analysis and experimental study on resistance-increasing behavior of composite high efficiency autonomous inflow control device

Bottom water coning is the main reason to reduce the recovery of horizontal bottom water reservoir. By water coning, we mean the oil-water interface changes from a horizontal state to a mound-shaped cone and breaks through to the wellbore. Autonomous inflow control device(AICD) is an important instrument maintain normal production after bottom water coning, however, the resistance increasing ability of the swirl type AICD is insufficient at present, which seriously affects the water control effect. Aiming this problem, this paper designs a multi-stage resistance-increasing and composite type AICD. The separation mechanism of oil-water two phases in this structure, the resistance form of oil-water single phase and the resistance-increasing principle of water phase are analyzed. Establishing the dual-phase multi-stage separation and resistance-increasing model, and verified by measuring the throttling pressure drop and oil-water volume fraction of the AICD, it is found that the composite type AICD has the effect of ICD and AICD at the same time, which can balance the production rate of each well section at the initial stage of production, delay the occurrence of bottom water coning. In the middle and later stages of production, water-blocking can be effectively increased to achieve water control and stable production.After structural sensitivity analysis, the influence law of various structural parameters on the water control performance of composite AICD was obtained. The simulation calculation results show that,compared with the existing swirl type AICD, composite AICD has higher sensitivity to moisture content,the water phase throttling pressure drop is increased by 4.5 times on average. The composite AICD is suitable for the entire stage of horizontal well production.

Analysis of the Erosion-Corrosion Mechanism of the Air Cooler in a Hydrocracking Unit:A Numerical and Experimental Study

Corrosion leakages often occur in the air cooler of a hydrocracking unit,with the failure sites mainly located in the entrance area of the tubes.An analysis of the macroscopic morphology and corrosion products confirmed that the damage was caused by erosion-corrosion(E-C).Numerical and experimental methods were applied to investigate the E-C mechanism in the air cooler.Computational fluid dynamics(CFD)was used to calculate the hydrodynamic parameters of the air cooler.The results showed that there was a biased flow in the air cooler,which led to a significant increase in velocity,turbulent kinetic energy and wall shear within 0.2 m of the tube entrance.A visualization experiment was then performed to determine the principles of migration and transformation of multiphase flow in the air cooler tubes.Various flow patterns(pure droplet flow,mist flow,and annular flow)and their evolutionary processes were clearly depicted experimentally.The initiation mechanism and processes leading to the development of E-C in the air cooler were also determined.This study provided a comprehensive explanation for the E-C failures that occur in air coolers during operation.

Visualization and characterization of experimental hydraulic fractures interacting with karst fracture-cavity distributions

Karst fracture-cavity carbonate reservoirs,in which natural cavities are connected by natural fractures to form cavity clusters in many circumstances,have become significant fields of oil and gas exploration and exploitation.Proppant fracturing is considered as the best method for exploiting carbonate reservoirs;however,previous studies primarily focused on the effects of individual types of geological formations,such as natural fractures or cavities,on fracture propagation.In this study,true-triaxial physical simulation experiments were systematically performed under four types of stress difference conditions after the accurate prefabrication of four types of different fracture-cavity distributions in artificial samples.Subsequently,the interaction mechanism between the hydraulic fractures and fracture-cavity structures was systematically analyzed in combination with the stress distribution,cross-sectional morphology of the main propagation path,and three-dimensional visualization of the overall fracture network.It was found that the propagation of hydraulic fractures near the cavity was inhibited by the stress concentration surrounding the cavity.In contrast,a natural fracture with a smaller approach angle(0°and 30°)around the cavity can alleviate the stress concentration and significantly facilitate the connection with the cavity.In addition,the hydraulic fracture crossed the natural fracture at the 45°approach angle and bypassed the cavity under higher stress difference conditions.A new stimulation effectiveness evaluation index was established based on the stimulated reservoir area(SRA),tortuosity of the hydraulic fractures(T),and connectivity index(CI)of the cavities.These findings provide new insights into the fracturing design of carbonate reservoirs.

Theoretical and experimental investigations on an X-shaped vibration isolator with active controlled variable stiffness

A novel X-shaped variable stiffness vibration isolator(X-VSVI)is proposed.The Runge-Kutta method,harmonic balance method,and wavelet transform spectra are introduced to evaluate the performance of the X-VSVI under various excitations.The layer number,the installation angle of the X-shaped structure,the stiffness,and the active control parameters are systematically analyzed.In addition,a prototype of the X-VSVI is manufactured,and vibration tests are carried out.The results show that the proposed X-VSVI has a superior adaptability to that of a traditional X-shaped mechanism,and shows excellent vibration isolation performance in response to different amplitudes and forms of excitations.Moreover,the vibration isolation efficiency of the device can be improved by appropriate adjustment of parameters.

An internal ballistic model of electromagnetic railgun based on PFN coupled with multi-physical field and experimental validation

To accelerate the practicality of electromagnetic railguns,it is necessary to use a combination of threedimensional numerical simulation and experiments to study the mechanism of bore damage.In this paper,a three-dimensional numerical model of the augmented railgun with four parallel unconventional rails is introduced to simulate the internal ballistic process and realize the multi-physics field coupling calculation of the rail gun,and a test experiment of a medium-caliber electromagnetic launcher powered by pulse formation network(PFN)is carried out.Various test methods such as spectrometer,fiber grating and high-speed camera are used to test several parameters such as muzzle initial velocity,transient magnetic field strength and stress-strain of rail.Combining the simulation results and experimental data,the damage condition of the contact surface is analyzed.

Experimental Analysis of Radial Centrifugal Pump Shutdown

Centrifugal pumps are widely used in the metallurgy,coal,and building sectors.In order to study the hydraulic characteristics of a closed impeller centrifugal pump during its shutdown in the so-called power frequency and frequency conversion modes,experiments were carried to determine the characteristic evolution of parameters such as speed,inlet and outlet pressure,head,flow rate and shaft power.A quasi-steady-state method was also used to further investigate these transient behaviors.The results show that,compared to the power frequency input,the performance parameter curves for the frequency conversion input are less volatile and smoother.The characteristic time is longer and the response to shutdown is slower.The quasi-steady-state theoretical head-flow curves match the experimental head-flow curves more closely at low flow rates when the frequency conversion input is considered.Moreover,in this case,the similarity law predicts the hydraulic performance more accurately.

Theoretical and experimental investigation of the resonance responses and chaotic dynamics of a bistable laminated composite shell in the dynamic snap-through mode

The dynamic model of a bistable laminated composite shell simply supported by four corners is further developed to investigate the resonance responses and chaotic behaviors.The existence of the 1:1 resonance relationship between two order vibration modes of the system is verified.The resonance response of this class of bistable structures in the dynamic snap-through mode is investigated,and the four-dimensional(4D)nonlinear modulation equations are derived based on the 1:1 internal resonance relationship by means of the multiple scales method.The Hopf bifurcation and instability interval of the amplitude frequency and force amplitude curves are analyzed.The discussion focuses on investigating the effects of key parameters,e.g.,excitation amplitude,damping coefficient,and detuning parameters,on the resonance responses.The numerical simulations show that the foundation excitation and the degree of coupling between the vibration modes exert a substantial effect on the chaotic dynamics of the system.Furthermore,the significant motions under particular excitation conditions are visualized by bifurcation diagrams,time histories,phase portraits,three-dimensional(3D)phase portraits,and Poincare maps.Finally,the vibration experiment is carried out to study the amplitude frequency responses and bifurcation characteristics for the bistable laminated composite shell,yielding results that are qualitatively consistent with the theoretical results.