Targeted mechanical forces enhance the effects of tumor immunotherapy by regulating immune cells in the tumor microenvironment

Mechanical forces in the tumor microenvironment(TME)are associated with tumor growth,proliferation,and drug resistance.Strong mechanical forces in tumors alter the metabolism and behavior of cancer cells,thus promoting tumor progression and metastasis.Mechanical signals are transformed into biochemical signals,which activate tumorigenic signaling pathways through mechanical transduction.Cancer immunotherapy has recently made exciting progress,ushering in a new era of“chemo-free”treatments.However,immunotherapy has not achieved satisfactory results in a variety of tumors,because of the complex tumor microenvironment.Herein,we discuss the effects of mechanical forces on the tumor immune microenvironment and highlight emerging therapeutic strategies for targeting mechanical forces in immunotherapy.

Nanoscale domain switching mechanism of Bi_(3.15)Eu_(0.85)Ti_3O_(12) thin film under the different mechanical forces

The switching process of ferroelectric thin films in electronic devices is one of the most important requirements for their application. Especially for the different external fields acting on the film surface, the mechanism of domain switching is more complicated. Here we observe the nanoscale domain switchings of Bi3.15Eu0.85Ti3O12 thin film under different mechanical forces at a fast scan rate. As the force increases from initial state to 247.5 n N, the original bright or grey contrasts within the selected grains are all changed into dark contrasts corresponding to the polarization vectors reversed from the up state to the down state, except for the clusters. As the mechanical force increases to 495 n N, the color contrasts in all of the selected grains further turn into grey contrasts and some are even changed into grey contrasts completely showing the typical 90° domain switching. When another stronger loading force 742.5 n N is applied, the phase image becomes unclear and it indicates that the piezoelectric signal can be suppressed under a sufficiently high force, which is coincident with previous experimental results. Furthermore, we adopt the domain switching criterion from the perspective of equilibrium state free energy of ferroelectric nanodomain to explain the mechanisms of force-generated domain switchings.

A Simplified Method for the Stress Analysis of Underground Transfer Structures Crossing Multiple Subway Tunnels

According to the design specifications,the construction of extended piles involves traversing the tunnel’s upper region and extending to the underlying rock layer.To address this challenge,a subterranean transfer structure spanning multiple subway tunnels was proposed.Deliberating on the function of piles in the transfer structure as springs with axial and bending stiffness,and taking into account the force balance and deformation coordination conditions of beams and plates within the transfer structure,we established a simplified mechanical model that incorporates soil stratification by combining it with the Winkler elastic foundation beam model.The resolved established simplifiedmechanicalmodel employed finite difference technology and the Newton-Simpsonmethod,elucidating the mechanical mechanism of the transfer structure.The research findings suggest that the load carried by the upper structural columns can be transferred to the pile foundation beneath the beams through the transfer structure,subsequently reaching the deep soil layer and ensuring minimal impact on adjacent tunnels.The established simplified analysis method can be used for stress analysis of the transfer structure,concurrently considering soil stratification,pile foundation behavior,and plate action.The pile length,pile section size,and beam section size within the transfer structure should account for the characteristics of the upper load,ensuring an even distribution of the beam bending moment.

Holocene Dune Mobility and Forcing Mechanisms at the Northern Margin of the East Asian Monsoon

Dune fields at the northern margin of the East Asian monsoon （EAM）, are mosaics of mobile and vegetation-stabilized aeolian dunes. These sand dunes are highly sensitive to environmental change, thus the distribution and the timing of their development may provide important clues to past environmental dynamics. Due to the strong wind erosion and dune migration, long and continuous stratigraphic records are seldom preserved. Synthesizing a large body of events, ultimately producing a relatively complete and high-resolution record, may be a proper method to investigate the dune development history and climate change. In this study, we synthesized a large body of luminescence ages for aeolian deposits from the Mu Us, Otindag, Horqin dune fields at the northern margin of the EAM. The results show that these dune fields, as a whole experienced a most extensive mobility during the early Holocene, followed by a widespread shift toward limited mobility and soil development in the mid-Holocene, and widespread reactivation occurred during late Holocene. The dune developments are directly linked to the effective moisture change controlled by the EAM changes, which respond to the low latitude summer insolation variation. The increased subsidence at the margin contrary to the core EAM, the delay from the feedback of the soil-vegetation-air coupled system, the increased evaporation due to the high temperature all play partial role in the lag of the margin EAM effective moisture change to the low latitude summer insolation. The asynchronous end of the wetter mid-Holocene mainly responds to the southeastwardly shift of the precipitation belt, while the regional sensitivity, response speed and internal feedback also contributed. The correspondence between dune records and North Atlantic drift-ice records of the rapid climate changes implies a close relationship between North Atlantic climate and the frequent dune activity at the northern margin of EAM.

Method for Six-Legged Robot Stepping on Obstacles by Indirect Force Estimation

Adaptive gaits for legged robots often requires force sensors installed on foot-tips,however impact,temperature or humidity can affect or even damage those sensors.Efforts have been made to realize indirect force estimation on the legged robots using leg structures based on planar mechanisms.Robot Octopus III is a six-legged robot using spatial parallel mechanism（UP-2UPS） legs.This paper proposed a novel method to realize indirect force estimation on walking robot based on a spatial parallel mechanism.The direct kinematics model and the inverse kinematics model are established.The force Jacobian matrix is derived based on the kinematics model.Thus,the indirect force estimation model is established.Then,the relation between the output torques of the three motors installed on one leg to the external force exerted on the foot tip is described.Furthermore,an adaptive tripod static gait is designed.The robot alters its leg trajectory to step on obstacles by using the proposed adaptive gait.Both the indirect force estimation model and the adaptive gait are implemented and optimized in a real time control system.An experiment is carried out to validate the indirect force estimation model.The adaptive gait is tested in another experiment.Experiment results show that the robot can successfully step on a 0.2 m-high obstacle.This paper proposes a novel method to overcome obstacles for the six-legged robot using spatial parallel mechanism legs and to avoid installing the electric force sensors in harsh environment of the robot＇s foot tips.

Type Synthesis of Two-Degrees-of-Freedom Rotational Parallel Mechanism with Two Continuous Rotational Axes

The two-rotational-degrees-of-freedom（2R） parallel mechanism（PM） with two continuous rotational axes（CRAs） has a simple kinematic model.It is therefore easy to implement trajectory planning,parameter calibration,and motion control,which allows for a variety of application prospects.However,no systematic analysis on structural constraints of the 2R-PM with two CRAs has been performed,and there are only a few types of 2R-PM with two CRAs.Thus,a theory regarding the type synthesis of the 2R-PM with two CRAs is systematically established.First,combining the theories of reciprocal screw and space geometry,the spatial arrangement relationships of the constraint forces applied to the moving platform by the branches are explored,which give the 2R-PM two CRAs.The different distributions of the constraint forces in each branch are also studied.On the basis of the obtained structural constraints of branches,and considering the geometric relationships of constraint forces in each branch,the appropriate kinematic chains are constructed.Through the reasonable configuration of branch kinematic chains corresponding to every structural constraint,a series of new 2R-PMs with two CRAs are finally obtained.

A review of research on China's carbon emission peak and its forcing mechanism

In order to make further steps in dealing with climate change, China proposed to peak carbon dioxide emissions by about 2030 and to make best efforts for the peaking early. The carbon emission peak target(CEPT) must result in a forcing mechanism on China's economic transition. This paper, by following the logical order from "research on carbon emission history" to "carbon emission trend prediction," from "research on paths of realizing peak" to "peak restraint research," provides a general review of current status and development trend of researches on China's carbon emission and its peak value. Furthermore,this paper also reviews the basic theories and specific cases of the forcing mechanism.Based on the existing achievements and development trends in this field, the following research directions that can be further expanded are put forward. First, from the perspective of long-term strategy of sustainable development, we should analyze and construct the forcing mechanism of CEPT in a reverse thinking way. Second, economic transition paths under the forcing mechanism should be systematically studied. Third, by constructing a large-scale policy evaluation model, the emission reduction performance and economic impact of a series of policy measures adopted during the transition process should be quantitatively evaluated.

An overview of Antarctic polynyas: sea ice production, forcing mechanisms, temporal variability and water mass formation

Polynyas are irregular open water bodies within the sea ice cover in polar regions under freezing weather conditions.In this study,we reviewed the progress of research work on dynamical forcing,sea ice production(SIP),and water mass formation for both coastal polynyas and open-ocean polynyas in the Southern Ocean,as well as the variability and controlling mechanisms of polynya processes on different time scales.Polynyas play an irreplaceable role in the regulation of global ocean circulation and biological processes in regional ocean ecosystems.The coastal polynyas(latent heat polynyas)are mainly located in the Weddell Sea,the Ross Sea and on the west side of protruding topographic features in East Antarctica.During the formation of coastal polynyas,which are mainly forced by offshore winds or ocean currents,brine rejection triggered by high SIP results in the formation of high salinity shelf water,which is the predecessor of the Antarctic bottom water-the lower limb of the global thermohaline circulation.The open-ocean polynyas(sensible heat polynyas)are mainly found in the Indian sector of the Southern Ocean,which are formed by ocean convection processes generated by topography and negative wind stress curl.The convection processes bring nutrients into the upper ocean,which supports biological production and makes the polynya regions an important sink for atmospheric carbon dioxide.The limitations and challenges in polynya research are also discussed.

Mechanical force enhanced bony formation in defect implanted with calcium sulphate cement

To improve the osteogenic property of bone repairing materials and to accelerate bone healing are major tasks in bone biomaterials research. The objective of this study was to investigate if the mechanical force could be used to accelerate bone formation in a bony defect in vivo. The calcium sulfate cement was implanted into the left distal femoral epiphyses surgically in 16 rats. The half of rats were subjected to external mechanical force via treadmill exercise, the exercise started at day 7 postoperatively for 30 consecutive days and at a constant speed 8 m·min-1 for 45 min·day-1, while the rest served as a control. The rats were scanned four times longitudinally after surgery using microcomputed tomography and newly formed bone was evaluated. After sacrificing, the femurs had biomechanical test of three-point bending and histological analysis. The results showed that bone healing under mechanical force were better than the control with residual defect areas of 0.64±0.19 mm2 and 1.78±0.39 mm2（P〈0.001）, and the ultimate loads to failure under mechanical force were 69.56±4.74 N, stronger than the control with ultimate loads to failure of 59.17±7.48 N（P=0.039）. This suggests that the mechanical force might be used to improve new bone formation and potentially offer a clinical strategy to accelerate bone healing.

Constraint Force Analysis of Metamorphic Joints Based on the Augmented Assur Groups

In order to obtain a simple way for the force analysis of metamorphic mechanisms, the systematic method to unify the force analysis approach of metamorphic mechanisms as that of conventional planar mechanisms is proposed. A force analysis method of metamorphic mechanisms is developed by transforming the augmented Assur groups into Assur groups, so that the force analysis problem of metamorphic mechanisms is converted into the force analysis problems of conventional planar mechanisms. The constraint force change rules and values of metamorphic joints are obtained by the proposed method, and the constraint force analysis equations of revolute metamorphic joints in augmented Assur group RRRR and prismatic metamorphic joints in augmented Assur group RRPR are deduced. The constraint force analysis is illustrated by the constrained spring force design of paper folding metamorphic mechanism, and its metamorphic working process is controlled by the spring force and geometric constraints of metamorphic joints. The results of spring force show that developped design method and approach are feasible and practical. By transforming augmented Assur groups into Assur groups, a new method for the constraint force analysis of metamorphic joints is proposed firstly to provide the basis for dynamic analysis of metamorphic mechanism.

MICRO/NANO-MACHINING ON SILICON SURFACE WITH A MODIFIED ATOMIC FORCE MICROSCOPE

To understand the deformation and removal mechanism of material on nano-scale at ultralow loads,a systemic study on AFM micro/nano-machining on single crystal ailicon is conducted. The results indicate that AFM nano- machining has a precisely dimensional controllability and a good surface quality on nanometer scale.A SEM is adopted to observe nano-machined region and chips,the results indicate that the material removal mechanisms change with the applied normal load. An XPS is used to analyze the changes of chemical composition inside and outside the nano-machined region respectively.The nano-indentation which is conducted with the same AFM diamond tip on the machined region shows a big discrepancy compared with that on the macro-scale. The calculated results show higher nano-hardness and elastic modulus than normal values .This phenomenon on be regarded as the indentation size effect(ISE).

Identification of Forcing Mechanisms of Convective Initiation over Mountains through High-Resolution Numerical Simulations

Convection and its ensuing severe weather, such as heavy rainfall, hail, tornado, and high wind, have significant im- pacts on our society and economy （e.g., Cao et al., 2004; Fritsch and Carbone, 2004; Verbout et al., 2006; Ashley and Black, 2008; Cao, 2008; Cao and Ma, 2009; Zhang et al., 2014）. Due to its localized and transient nature, the initiation of convection or convective initiation remains one of the least understood aspects of convection in the scientific communi- ties, and it is a significant challenge to accurately predict the exact timing and location of convective initiation （e.g., Cai et al., 2006; Wilson and Roberts, 2006; Xue and Martin, 2006; Cao and Zhang, 2016）.

Mechanical force and cytoplasmic Ca^(2+) activate mechanosensitive BK channel in parallel

BK channels are widely expressed in both excitable and non-excitable cells and known to be involved in many physiological processes,such as vascular smooth tone regulation,neuronal firing and endocrine cell secretion[1].Recently, the BK channels have

Dehydration Mechanism of Secondary Cross-linked Gels

In this paper, microscopic characteristics of preformed gels （PGs） and secondary cross-linked gels （SCG） with the same concentration were analyzed by atomic force microscopy （AFM）. Experimental results indicate that the microstructure of secondary cross-linked gels is a thick 3-D network, in which micro-holes and irregular macro-holes are embedded. The maximum width of the irregular macro-holes is 200 nm. In the SCG two different chemical bonds were formed, which leads to the structural inhomogeneity and the asymmetry of the crosslinking density. The structural inhomogeneity of SCG results in the formation of irregular macro-holes. The excessive cross-linking density is the primary reason for dehydration of SCG and the presence of irregular macro-holes in SCG can facilitate dehydration.

ATOMIC FORCE MICROSCOPY OBSERVATION OF MAGNETRON SPUTTERED ALUMINUM－SILICON ALLOY FILMS

wo different surface morphology characteristics of magnetron sputtered aluminumsilicon(Al-Si)alloy films deposited at 0 and 200℃ were observed by atomic force microscopy(AFM).One is irregularly shaped grains put togther on a plane.The other is irregularly shaped grains Piled up in space. Nanometer-sized particles with heights from 1.6 to 2.9 nm were first observed. On the basis of these observations the growth mechanism of magnetron sputtered films is discussed.

REGULARITY OF VIBRATION RESPONSE OF MECHANICAL SYSTEM UNDER AFFECT OF VARI-FREQUENCY EXCITING FORCE

The vibration response formulas of the mechanical system under the affect of thevari-frequency exciting force are deduced. It is proved by the theoretical analysis and experimentalresults that the vibration response amplitude of the mechanical system under the affect of thevari-frequency exciting force is far smaller than that under the affect of the constant frequency exciting force on condition that the exciting force amplitudes are just the same;while the vari-fre-quency rate a increases to 5 Hz per second the vibration amplitude will decrease to 10% only as lowas that under the affect of the constant frequency exciting force. All these conclusions will be of significance for revealing the mechanism of suppressing chatter in van-speed cutting and analyzing theexperimental results of sine-wave scanning exciting test.

Evidence of earthquakes triggered by the tidal force of the sun and the moon——On the temporal characteristics of the earthquakes in Xingtai,Hejian and Tangshan

Studies by many scientists show that Hebei, China is an area with strong correlation between the tidal force and the occurrences of major earthquakes, the Xingtai earthquake of 1966, the Hejian earthquake of 1967 and the Tangshan earthquake of 1976 were triggered by the tidal force, in this paper the study on the common characteristics of their occurrence times confirms these facts. The computed times of maximum horizontal of the semi diurnal solid tide tidal force show that the occurrence times of the above mentioned earthquakes were close to the times of maximum horizontal tidal force of the semi diurnal solid tide at new moon or full moon. The Longyao earthquake of M =6.8, the Ningjin earthquake of M =7.2 and the Hejian earthquake of M =6.3 occurred tens of minutes after the maximum horizontal tidal force of the semi diurnal solid tides, and the Tangshan earthquake of M =7.8 occurred 16 minutes before the maximum horizontal tidal force. The tidal forces were directed to the west. This is their temporal characteristic. It is generally accepted that the 1969 Bohai earthquake of M =7.4 and the 1975 Haicheng earthquake were not triggered by the tidal force. These events did not show such characteristics. The temporal characteristics of the earthquakes indicate that the occurrences of these events were not random, but were controlled by the tidal force from the sun and the moon, and triggered by the tidal force. These facts agree with the triggering mechanism of the tidal force, are evidences of earthquakes triggered by tidal force.

Effects of connection types and elevated temperature on the impact behaviour of restrained beam in portal steel frame

Based on the background of structural protection and Disaster Reduction Engineering, the dynamic behaviour and failure mechanism of restrained beams in portal steel frames in localised fire are investigated via experimental measurement and numerical simulation techniques. Comprehensive parametric studies are carried out to discuss the influence of end connection types, temperature, impact velocity,impact mass and span-to-depth ratio(SDR) on the dynamic response of the beams. The characteristics of deformation, internal force and energy distribution about the restrained beams and its joints are investigated. A temperature dependent criterion for evaluating the frame joint performance is proposed to measure the degree of performance degradation and impact resistance of the joint. The dynamic displacement amplification factor in different temperature environments are proposed for the different beam end constraint types and SDRs. Results of the experimental and numerical analysis show that the welded connection(WC) of three typical joint types is the strongest, and the extended endplate connection(EEC) is the weakest in terms of the impact resistance performance. With regard to the failure mode of the joint, the failure positions of the WC and the welded-bolted connection are located in the inner web of the column. Meanwhile, the EEC is located in the connection position between the beam and the endplate. Three different internal force stages and two obvious critical temperature boundaries of the restrained beams emerge with the increase in temperature, and they have significant characteristics in terms of deformation trend, internal force transfer and energy distribution. During the impact, a phenomenon known as “compression arch action” develops into “catenary action” with the increase in deflection in the frame beam mechanism.

Understanding cell-extracellular matrix interactions for topology-guided tissue regeneration

Tissues are made up of cells and the extracellular matrix(ECM)which surrounds them.These cells and tissues are actively adaptable to enduring significant stress that occurs in daily life.This astonishing mechanical stress develops due to the interaction between the live cells and the non-living ECM.Cells in the matrix microenvironment can sense the signals and forces produced and initiate a signaling cascade that plays a crucial role in the body’s normal functioning and influences various properties of the native cells,including growth,proliferation,and differentiation.However,the matrix’s characteristic features also impact the repair and regeneration of the damaged tissues.The current study reviewed how the cell-ECM interaction regulates cellular behavior and physicochemical properties.Herein,we have described the response of cells to mechanical stresses,the importance of substrate stiffness and geometry in tissue regeneration,and the development of scaffolds to mimic the nature of native ECM in 3D for tissue engineering applications has also been discussed.Finally,the study summarizes the conclusions and promising prospects based on the cell-ECM interplay.

Vibration of a Two-Layer“Metal+PZT”Plate Contacting with Viscous Fluid

The present work investigates the mechanically forced vibration of the hydro-elasto-piezoelectric system consisting of a two-layer plate“elastic+PZT”,a compressible viscous fluid,and a rigid wall.It is assumed that the PZT(piezoelectric)layer of the plate is in contact with the fluid and time-harmonic linear forces act on the free surface of the elastic-metallic layer.This study is valuable because it considers for the first time the mechanical vibration of the metal+piezoelectric bilayer plate in contact with a fluid.It is also the first time that the influence of the volumetric concentration of the constituents on the vibration of the hydro-elasto-piezoelectric system is studied.Another value of the present work is the use of the exact equations and relations of elasto-electrodynamics for elastic and piezoelectric materials to describe the motion of the plate layers within the framework of the piecewise homogeneous body model and the use of the linearized Navier-Stokes equations to describe the flow of the compressible viscous fluid.The plane-strain state in the plate and the plane flow in the fluid take place.For the solution of the corresponding boundary-value problem,the Fourier transform is used with respect to the spatial coordinate on the axis along the laying direction of the plate.The analytical expressions of the Fourier transform of all the sought values of each component of the system are determined.The origins of the searched values are determined numerically,after which numerical results on the stress on the fluid and plate interface planes are presented and discussed.These results are obtained for the case where PZT-2 is chosen as the piezoelectric material,steel and aluminum as the elastic metal materials,and Glycerin as the fluid.Analysis of these results allows conclusions to be drawn about the character of the problem parameters on the frequency response of the interfacial stress.In particular,it was found that after a certain value of the vibration frequency,the presence of the metal layer in the two-layer plate led to an increase in the absolute values of the above interfacial stress.