Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

Design and high-power testing of offline conditioning cavity for CiADS RFQ high-power coupler

To validate the design rationality of the power coupler for the RFQ cavity and minimize cavity contamination,we designed a low-loss offline conditioning cavity and conducted high-power testing.This offline cavity features two coupling ports and two tuners,operating at a frequency of 162.5 MHz with a tuning range of 3.2 MHz.Adjusting the installation angle of the coupling ring and the insertion depth of the tuner helps minimize cavity losses.We performed electromagnetic structural and multiphysics simulations,revealing a minimal theoretical power loss of 4.3%.However,when the cavity frequency varied by110 kHz,theoretical power losses increased to10%,necessitating constant tuner adjustments during conditioning.Multiphysics simulations indicated that increased cavity temperature did not affect frequency variation.Upon completion of the offline high-power conditioning platform,we measured the transmission performance,revealing a power loss of 6.3%,exceeding the theoretical calculation.Conditioning utilized efficient automatic range scanning and standing wave resonant methods.To fully condition the power coupler,a 15°phase difference between two standing wave points in the condition-ing system was necessary.Notably,the maximum continuous wave power surpassed 20 kW,exceeding the expected target.

Tip Clearance Flows in Turbine Cascades

This article describes the effects of some factors on the tip clearance flow in axial linear turbine cascades. The measurements of the total pressure loss coefficient are made at the cascade outlets by using a five-hole probe at exit Mach numbers of 0.10, 0.14 and 0.19. At each exit Mach number, experiments are performed at the tip clearance heights of 1.0%, 1.5%, 2.0%, 2.5% and 3.0% of the blade height. The effects of the non-uniform tip clearance height of each blade in the pitchwise direction are also studied. The results show that at a given tip clearance height, generally, total pressure loss rises with exit Mach numbers proportionally. At a fixed exit Mach number, the total pressure loss augments nearly proportionally as the tip clearance height increases. The increased tip clearance heights in the tip regions of two adjacent blades are to be blame for the larger clearance loss of the center blade. Compared to the effects of the tip clearance height, the effects of the exit Mach number and the pitchwise variation of the tip clearance height on the cascade total pressure loss are so less significant to be omitted.

Disease clearance in ulcerative colitis:A new therapeutic target for the future

Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression.This has fueled the identification of molecular targets,resulting in a rapidly expanding therapeutic armamentarium.Subsequently,management strategies have evolved from symptomatic resolution to well-defined objective endpoints,including clinical remission,endoscopic remission and mucosal healing.While the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications,studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic measures.Current recommendations lack consideration of histological healing.The simultaneous achievement of clinical,endoscopic,and histologic remission has not been fully investigated.This has laid the groundwork for a novel therapeutic outcome termed disease clearance(DC).This article summarizes the concept of DC and its current evidence.

An Error Equivalent Model of Revolute Joints with Clearances for Antenna Pointing Mechanisms

Joint clearances in antenna pointing mechanisms lead to uncertainty in function deviation. Current studies mainly focus on radial clearance of revolute joints, while axial clearance has rarely been taken into consideration. In fact, own?ing to errors from machining and assembly, thermal deformation and so forth, practically, axial clearance is inevitable in the joint. In this study, an error equivalent model(EEM) of revolute joints is proposed with considering both radial and axial clearances. Compared to the planar model of revolute joints only considering radial clearance, the journal motion inside the bearing is more abundant and matches the reality better in the EEM. The model is also extended for analyzing the error distribution of a spatial dual?axis("X–Y" type) antenna pointing mechanism of Spot?beam antennas which especially demand a high pointing accuracy. Three case studies are performed which illustrates the internal relation between radial clearance and axial clearance. It is found that when the axial clearance is big enough, the physical journal can freely realize both translational motion and rotational motion. While if the axial clearance is limited, the motion of the physical journal will be restricted. Analysis results indicate that the consideration of both radial and axial clearances in the revolute joint describes the journal motion inside the bearing more precise. To further validate the proposed model, a model of the EEM is designed and fabricated. Some suggestions on the design of revolute joints are also provided.

Minimum Clearance Offsets for Providing Desired Stopping Sight Distances at Simple Curves with Variable Operating Speeds

Lateral clearance on the inside of horizontal curves is required by all geometric design guidelines in order to provide at least stopping sight distance. There already exist graphical models, analytical models, and design charts for determining minimum clearance offsets to meet the requirement. Some of these models determine the offsets based on constant design sight distance values on the assumption that drivers negotiate horizontal curves at constant speed. Therefore, those models are suitable for sites where there is no difference in speeds between tangent and curved sections. Past studies have reported that there are sites where drivers decelerate on entering horizontal curves and accelerate on departing from the curves. At those sites stopping sight distance for a given driver varies with driver location due to variable speed. This paper presents an analytical model and a chart for determining minimum offsets needed to provide desired sight distances at horizontal curves with variable operating speeds. At those sites the offsets yield roadside clearance boundaries that have transition arcs with performances that are similar to those of elliptical arcs. Therefore, practitioners may choose to use elliptical equations or equations and the chart developed herein. Results of this study will be of value to practitioners in the area of roadside design.

Stabilizing Mechanism and Running Behavior of Couplers on Heavy Haul Trains

Published studies in regard to coupler systems have been mainly focused on the manufacturing process or coupler strength issues. With the ever increasing of tonnage and length of heavy haul trains, lateral in-train forces generated by longitudinal in-train forces and coupler rotations have become a more and more significant safety issue for heavy haul train operations. Derailments caused by excessive lateral in-train forces are frequently reported. This article studies two typical coupler systems used on heavy haul locomotives. Their structures and stabilizing mechanism are analyzed before the corresponding models are developed. Coupler systems models are featured by two distinct stabilizing mechanism models and draft gear models with hysteresis considered. A model set which consists of four locomotives and three coupler systems is developed to study the rotational behavior of different coupler systems and their implications for locomotive dynamics. Simulated results indicate that when the locomotives are equipped with the type B coupler system, locomotives can meet the dynamics standard on tangent tracks; while the dynamics performance on curved tracks is very poor. The maximum longitudinal in-train force for locomotives equipped with the type B coupler system is 2000 kN. Simulations revealed a distinct trend for the type A coupler system. Locomotive dynamics are poorer for the type A case when locomotives are running on tangent tracks, while the dynamics are better for the type A case when locomotives are running on curved tracks. Theoretical studies and simulations carried out in this article suggest that a combination of the two types of stabilizing mechanism can result in a good design which can significantly decrease the relevant derailments.

Design and Fabrication of Ultracompact 3-dB MMI Coupler in Silicon-on-Insulator

An ultracompact 3 dB coupler is designed and fabricated in silicon on insulator,based on 1×2 line tapered multimode interference (MMI) coupler.Comparing with the conventional straight MMI coupler,the device is ～40% shorter in length.The device exhibits uniformity of 1 3dB and excess loss of 2 5dB.

Passively Mode Locked Diode-End-Pumped Nd∶YAG Laser with In_(0.25)Ga_(0.75)As as Output Coupler

A novel InGaAs(LT-In 0.25Ga 0.75As) absorber grown by metal organic chemical vapor deposition at low temperature is presented.Using it as well as an output coupler,passive mode locking,which produces pulses as short as several hundred picoseconds for diode-end-pumped Nd∶YAG laser at 1.06μm,is realized.The pulse frequency is 150MHz.

Full Wave Analysis of a Broad Wall Waveguide Slot Coupler

A rigorous analysis of a broad wall slot coupler composed of two crossed rectangular waveguides by using FDTD method is presented. Two types of slots, a longitudinal/transverse slot and a centered-inclined slot, are analyzed. Coupling slot characteristics are obtained, including scattering parameters and the resonant length for different waveguide dimensions and frequencies. The numerical results are all in good agreement with those by the method of moments. A coupler system with a short circuit port is also analyzed to help designing the slot array.

The influence of AAR coupler features on estimation of in-train forces

Inadequate management of large in-train forces transferred through coupler systems of a railway train leads to running and structural failures of vehicles.Understanding these phenomena and their mitigation requires accurate estimation of relative motions and in-train forces between vehicle bodies.Previous numerical studies have ignored inertia of coupling elements and the impacts between couplers.Thus,existing models underestimate the additional dynamic variations in in-train forces.Detailed multi-body dynamic models of two AAR(Association of American Railroads)coupler systems used in passenger and freight trains are developed,incorporating coupler inertia and various slacks.Due to the modeling and simulation com-plexities involved in a full train model,with such details of coupler system,actual longitudinal train dynamics is not studied.A system comprising only two coupling units,inter-connecting two consecutive vehicles,is modeled.Considered system has been fixed at one end and an excitation force is applied at the other end,to mimic a relative force transmission through combined coupler system.Simulation results obtained from this representative system show that,noticeable influence in in-train forces are expected due to the combined effect of inertia of couplers and intermittent impacts between couplers in the slack regime.Maximum amplitude of longitudinal reaction force,transferred from draft gear housing to vehicle body,is expected to be significantly higher than that predicted using existing models of coupler system.It is also observed that the couplers and knuckles are subjected to significant longitudinal and lateral contact forces,due to the intermittent impacts between couplers.Thus,accurate estimation of draft gear reaction force and impact forces between couplers are essential to design vehicle and coupler components,respectively.

The Tip Leakage Flow Structure of an Axial Fan with Tip Clearance

Experiment and numerical simulation technique are used to investigate the tip leakage flow in an axial fan with tip clearance at the design condition. The flow field in the tip region of fan is measured using a PDA (Particle Dynamics Analysis) system. The flow is surveyed across the whole passage at fifteen axial locations (from the 100% axial chord in front of the leading edge to the 100% axial chord behind the trailing edge), mainly focusing on the outer 90% blade span. Both experiment measurement and numerical simulation indicates the leakage flow originated from the tip clearance along the chord rolls up into three dimensional spiral structure to form leakage flow vortex. The interaction of leakage flow and main flow will produce the low velocity zone, and block the flow. The leakage flow almost occupies the most part of flow passage behind the trailing edge.

IEC711 coupler频响仿真

仿真耳(IEC711 coupler)广泛地应用于手提电话、耳机等的电声性能测量;介绍了利用有限元方法来获得IEC711 coupler的频响仿真,从而可以给出比等效线路图方法(LPM)更为真实的分析。

Analysis of longitudinal forces of coupler devices in emergency braking process for heavy haul trains

To reduce the longitudinal coupler forces of heavy haul trains and improve the running safety, the velocity method and New-mark method were used for the coupler simulation and numerical integration, and a numerical model on the longitudinal dynamics of heavy haul trains was established. Validation was performed against the experimental data. Using this model, the emergency braking process for a combined marshalling heavy haul train was investigated to obtain the distributions of the longitudinal compressive forces and strokes of coupler devices. Then, the influences of the initial braking velocity, the synchronization time of master and slave locomotives, the coupler stiffness and the vibrator mass on the longitudinal forces and strokes were analyzed. The results show that it should be avoided that the emergency braking starts at a low initial speed. Keeping synchronism between master locomotive and slave locomotives effectively helps to reduce the longitudinal forces. Reducing the coupler stiffness appropriately and adding rigid arm connections, the longitudinal vibration frequency can be brought down and the longitudinal forces will be decreased, which improves the running safety of heavy haul trains. All of these research results can provide a reference for the operation and development of heavy haul trains.

Clearance Influence on Dynamic Response of Intermittent Roller Chain Drive

The clearances appear in chain link hinges induced by manufacturing tolerance or wear of components are the most important factor that influences the dynamic performance of the intermittent roller chain drives. Due to the existence of the clearances in chain link hinges, the serious impact vibration phenomenon which influences the stability and the position accuracy of the chain drive system would be caused in the intermittent motion. But, the problem may be that a reasonable modeling on the chain with clearances is difficult due to the large clearance＇s number in chain system and the fact that the clearance＇ size are different. Currently, the studies on the dynamics of the intermittent roller chain considering the multi-clearance＇ joints are rare. Most research works have only focused on the constant moving chains. Taking the intermittent roller chain system as an object, this paper designs and builds the experimental device of this kind of mechanical system. The Longitudinal vibration response of the intermittent chain under the different motion laws was tested. The experimental study shows that the clearances presented in chain link hinges can cause severe impact vibration in the intermittent motion of chain. In subsequent work, the dynamic model of the intermittent roller chain system with the multi-clearance＇ joints was established. By calculating the dynamic response of this kind of mechanical system under the different motion laws, the effect of the clearances on the dynamic response of the intermittent chain drive system was analyzed. The theoretical simulation shows that the serious impact vibration phenomenon of the chain system can be caused by the clearances at the start accelerating period, and the chain drive system is often accompanied by the severe shock and vibration at the moment that the chain moves from the acceleration period to deceleration period. The research conclusions made by the experimental and theoretical studies indicate that the use of motion laws with small and continuous jerk at conversion point can effectively suppress the impact vibration at this point caused by clearances＇ effect. Additionally, the use of nonsymmetrical motion laws with small jerk approaching the end of the indexing period can obtain a smaller residual vibration. The presented motion law can provide an important reference for the improvement of the dynamic performance of the intermittent chain drive systems.

Effects of Semi-floating Ring Bearing Outer Clearance on the Subsynchronous Oscillation of Turbocharger Rotor

Semi-floating ring bearing（SFRB） is developed to control the vibration of turbocharger rotor. The outer clearance of SFRB affects the magnitude and frequency of nonlinear whirl motion, which is significant for the design of turbocharger. In order to explore the effects of outer clearance, a transient finite element analysis program for rotor and oil film bearing is built and validated by a published experimental case. The nonlinear dynamic behaviors ofrotor-SFRB system are simulated. According to the simulation results, two representative subsynchronous oscillations excited by the two hearings respectively are discovered. As the outer clearance of SFRB increases from 24 ~tm to 60 pro, the low-frequency subsynchronous oscillation experiences three steps, including a strong start, a gradual recession and a combination with the other one. At the same time, the high-frequency subsynchronous oscillation starts to appear gradually, then strengthens, and finally combines. If gravity and unbalance are neglected, the combination will start starts from high rotor speed and extents to low rotor speed, just like a ＂zipper＂. It is found from the quantitative analysis that when the outer clearance increases, the vibration amplitude experiences large value firstly, then reduction, and suddenly increasing after combination. A useful design principle of SFRB outer clearance for minimum vibration amplitude is proposed： the outer clearance value should be chosen to keep the frequency of two subsynchronous oscillations clearly separated and their amplitudes close.

Effects of Floating Ring Bearing Manufacturing Tolerance Clearances on the Dynamic Characteristics for Turbocharger

The inner and outer oil film dynamic characteristic coefficients of floating ring bearings（FRBs） change due to the manufacturing tolerance of the floating ring, journal and intermediate, which leads to high-speed turbocharger＇s vibration too large and even causes nonlinear vibration accident. However, the investigation of floating ring bearing manufacturing tolerance clearance on the rotordynamic characteristics is less at present. In order to study the influence law of inner and outer clearance on turbocharger vibration, the rotor dynamic motion equations of turbocharger supported in FRBs are derived by analyzing the size relations between floating ring, journal and intermediate for the inner and outer oil film clearances, the time transient response analysis for combination of FRBs clearance are developed. A realistic turbocharger is taken as a research object, the FE model of the turbocharger with FRBs is modeled. Under the conditions of four kinds of limit state bearing clearances for inner and outer oil film, the nonlinear transient analyses are performed based on the established FE dynamic models of the nonlinear rotor-FRBs system applied incentive combinations of gravity and unbalance force, respectively. From the waterfall, the simulation results show that the speed for the appearance of fractional frequency is not identical and the amplitude magnitude is different under the four kinds of bearing manufacturing tolerance limit clearances, and fractional frequency does not appear in the turbocharger and the amplitude is minimum under the ODMin/IDMax bearing manufacturing tolerance clearances. The turbocharger vibration is reduced by controlling the manufacturing tolerance clearance combinations of FRBs, which is helpful for the dynamic design and production-manufacturing of high-speed turbocharger.

Numerical Analysis of Nozzle Clearance's Effect on Turbine Performance

Variable nozzle turbine （VNT） has become a popular variable geometry turbine （VGT） technology for the diesel engine application. Nozzle clearance, which can＇t be avoided on the hub and shroud side of the VNT turbine due to the pivoting stators, can lead to turbine performance deterioration. However, its mechanism is still not clear. In this paper, numerical investigation, which is validated by experiment, is carried out to study the mechanism of the nozzle clearance＇s effect on the turbine performance. Firstly, performance of the mixed flow turbine with fixed nozzle clearances tested on flow bench. Performance of the tested turbine with the same nozzle clearance is numerically simulated. The numerical result agrees well with the test data, which proves correct of the numerical method. Then the turbine performance with different nozzle clearances is numerically analyzed. The research showed that with nozzle clearance, flow loss in the nozzle increases at first and it reaches the maximum value when the clearance ratio is 5%. Flow at the exit of the nozzle becomes less uniform with nozzle clearance. The negative incidence angle of the rotor also increases with nozzle clearance and leads to more incidence angle loss in the rotor. The low energy fluid formed in the nozzle due to the nozzle clearance migrates from hub to shroud side in the rotor, which is another main reason for the rotor＇s performance degradation. The present research exposed the mechanism of the dramatically decrease of the turbine performance with nozzle clearance： （a） The loss associated with the nozzle leakage increases with the nozzle clearance; （b） The flow loss grows up quickly in the rotor due to the incidence angle loss and migration of the low energy fluid from hub to shroud side.

EFFECT OF TIP CLEARANCE ON PERFORMANCE AND FLOW FIELD OF SMALL SIZED HIGH SPEED CENTRIFUGAL FAN

A centrifugal fan with the high speed and compact dimensions is studied numerically and experimentally. The centrifugal fan consists of a shrouded impeller rotating at 34 000 r/min with a small tip clearance 0.7 mm to the fixed outer casing. Computational models with/without the tip clearance are built and the κ-ω shear stress transport （SST） turbulence model and the unstructured mesh are applied to the numerical simulation for unsteady solutions. The overall performance is measured on a standard experimental bench and the major flow feature of each component inside the centrifugal fan is numerically investigated. In the presence of the tip clearance due to the difference of static pressure between leading and trailing edges of the clearance, i. e. , leading and trailing edges of the impeller, a strong return flow exists inside the clearance passage and re-circulates the main stream inside the impeller passage, and produces the strong flow interaction, thus changing the flow field and influencing the overall performance.

Indocyanine green clearance test combined with MELD score in predicting the short-term prognosis of patients with acute liver failure

BACKGROUND: Acute liver failure(ALF) is an acute severe deterioration of liver function with high mortality. Early and accurate prognostic assessment of patients with ALF is critically important. Although the model for end-stage liver disease(MELD) scores and King’s College Hospital(KCH) criteria are well-accepted as predictive tools, their accuracy is unsatisfactory.The indocyanine green(ICG) clearance test(ICGR15, ICG retention rate at the 15 minutes) is a sensitive indicator of liver function. In this study, we investigated the efficacy of the ICGR15 for the short-term prognosis in patients with ALF. We compared the predictive value of ICGR15 with the MELD scores and KCH criteria.METHODS: Sixty-nine patients who had been diagnosed with ALF were recruited retrospectively. ICGR15 had been performed by ICG pulse spectrophotometry and relevant clinical and laboratory indices were analyzed within 24 hours of diagnosis.In addition, the MELD scores and KCH criteria were calculated.RESULTS: The three-month mortality of all patients was 47.83%.Age, serum total bilirubin and creatinine concentrations,international normalized ratio for prothrombin time, ICGR15,MELD scores and KCH criteria differed significantly between surviving and deceased patients. A positive correlation was observed between ICGR15 and MELD scores(r=0.328, P=0.006).The ICGR15-MELD model, Logit(P)=0.096×ICGR15+0.174 ×MELD score–9.346, was constructed by logistic regression analysis. The area under the receiver operating characteristic curve was 0.855. When set the cut-off point to-0.4684, the sensitivity was 87.90% and specificity, 72.20%. The area under the receiver operating characteristic curve of the ICGR15-MELD model(0.855) was significantly higher than that of the ICGR15(0.793), MELD scores(0.776) and KCH criteria(0.659).Based on this cut-off value, the patients were divided into two groups. The mortality was 74.36% in the first group(ICGR15-MELD≥-0.4686) and 13.33% in the second group(ICGR15-MELD<-0.4686), with a significant difference between the two groups(χ2=25.307, P=0.000).CONCLUSION: The ICGR15-MELD model is superior to the ICGR15, MELD scores, and KCH criteria in predicting the shortterm prognosis of patients with ALF.