Force Analysis Research Articles

Probing Dual Covalent Irreversible Inhibition of EGFR/FGFR4 by Electrophilic-Based Natural Compounds to Overcome Resistance and Enhance Combination Therapeutic Potentials and Management of Hepatocellular Carcinoma (HCC).

Hepatocellular carcinoma (HCC) is one of the most prevalent cancer types in the world and accounts for the majority of cases of primary liver cancer. A crucial part of the carcinogenesis of HCC involves aberrant stimulation of the FGF19-FGFR4 signaling pathway. Therefore, FGFR4 inhibition has become a strategic therapeutic approach for the treatment of HCC. However, the clinical treatment procedure is significantly hampered by the prevalence of kinase inhibitors resistance. It was recently established that the activation of EGFR signaling was found to be one of the primary mechanisms mediating the acquired resistance to FGFR4 inhibitors, moreover, sensitivity to FGFR4 inhibitors was effectively restored by inhibiting EGFR. These results provide compelling evidence that dual inhibition of EGFR and FGFR4 could represent a viable therapeutic approach to overcome resistance, hence enhanced management of HCC. To this end, we proposed a dual irreversible inhibition strategy through covalent binding by naturally occurring electrophilic warhead-bearing compounds (curcumin, deoxyelephantopin, eupalmerin acetate, syringolin A and andrographolide) to covalently target both EGFR and FGFR4 through cysteine residues, Cys797 and Cys552, respectively. Covalent docking and covalent molecular dynamics (MM/MDcov) simulations combined with thermodynamic binding free energy calculations were performed, and the results were compared against known potent and selective covalent EGFR and FGFR4 inhibitors with available X-ray crystal structures, Afatinib and BLU9931, respectively. Curcumin, deoxyelephantopin, eupalmerin acetate, syringolin A, and andrographolide showed relative binding free energies of -22.85, -17.14, -12.98, -21.81, and - 19.00kcal/mol against EGFR and - 41.06, -29.45, -24.76, -40.11, and - 37.55kcal/mol against FGFR4, respectively. The mechanisms of binding were emphasized by hydrogen bonding and binding forces analysis as well as active site physicochemical profiling. The findings of this study identified that curcumin, syringolin A and andrographolide-but not eupalmerin acetate or deoxyelephantopin -could be viable dual EGFR and FGFR4 covalent irreversible inhibitors and could be implemented in HCC combination therapy protocols alone or in conjunction with other chemotherapeutic agents. Investigations of this study conclusively indicate dual blockade of EGFR and FGFR4 may be a promising future therapeutic strategy for enhanced management of HCC.

High-Speed Stress Field Measurement In A Soft Substrate During Droplet Impact

In this study, we utilized high-speed photoelastic tomography to quantify dynamic stress fields within a soft substrate during droplet impact. This manuscript details the measurement technique, which employs a high-speed polarization camera and the principles of photoelastic tomography. Our method successfully enabled the quantitative measurement of dynamic stress fields in a soft substrate during droplet impact. Additionally, we conducted an analysis of the impact force derived through the spatial integration of the measured stress field. The discussion explored the interplay between the maximum impact force, droplet viscosity, and substrate elasticity. Our findings indicate that the maximum impact force 𝐹max can be expressed as a function with a self-similar variable of 𝑅𝑒 / 𝐶𝑎^2 , where 𝑅𝑒 is Reynolds number representing the droplet inertial force and droplet viscous force and 𝐶𝑎 is Cauchy number representing the ratio of the droplet inertial force and substrate elastic force. This combination, 𝑅𝑒 / 𝐶𝑎^2 , represents the relationship between the relaxation time of droplet and substrate deformation ( 𝜂/ 𝐸), the contact time of the droplet (𝑅 / 𝑉), and the ratio of substrate elastic force to droplet inertial force. Consequently, the maximum impact force 𝑅𝑒 / 𝐶𝑎^2 is determined by the balance between the relaxation and contact times. We believe that our developed method will significantly enhance the understanding of droplet impact phenomena. Furthermore, it holds potential for broader applications in various engineering processes, such as analyzing stress distribution in materials caused by liquid jet impact and studying cavitation bubbles in viscoelastic materials. This method's ability to provide detailed quantitative measurements of dynamic stress fields offers a valuable tool for future research and technological advancements in related fields.

Development and validation of an interpretable machine learning for mortality prediction in patients with sepsis.

Sepsis is a leading cause of death. However, there is a lack of useful model to predict outcome in sepsis. Herein, the aim of this study was to develop an explainable machine learning (ML) model for predicting 28-day mortality in patients with sepsis based on Sepsis 3.0 criteria. We obtained the data from the Medical Information Mart for Intensive Care (MIMIC)-III database (version 1.4). The overall data was randomly assigned to the training and testing sets at a ratio of 3:1. Following the application of LASSO regression analysis to identify the modeling variables, we proceeded to develop models using Extreme Gradient Boost (XGBoost), Logistic Regression (LR), Support Vector Machine (SVM), and Random Forest (RF) techniques with 5-fold cross-validation. The optimal model was selected based on its area under the curve (AUC). Finally, the Shapley additive explanations (SHAP) method was used to interpret the optimal model. A total of 5,834 septic adults were enrolled, the median age was 66 years (IQR, 54-78 years) and 2,342 (40.1%) were women. After feature selection, 14 variables were included for developing model in the training set. The XGBoost model (AUC: 0.806) showed superior performance with AUC, compared with RF (AUC: 0.794), LR (AUC: 0.782) and SVM model (AUC: 0.687). SHAP summary analysis for XGBoost model showed that urine output on day 1, age, blood urea nitrogen and body mass index were the top four contributors. SHAP dependence analysis demonstrated insightful nonlinear interactive associations between factors and outcome. SHAP force analysis provided three samples for model prediction. In conclusion, our study successfully demonstrated the efficacy of ML models in predicting 28-day mortality in sepsis patients, while highlighting the potential of the SHAP method to enhance model transparency and aid in clinical decision-making.

Free and forced vibration analysis of uniform and stepped conical shell based on Jacobi-Ritz time domain semi-analytical method

Free and forced vibration analysis of uniform and stepped conical shell based on Jacobi-Ritz time domain semi-analytical method

Analysis and verification of electrodynamic force, thermal stress and current sharing for CRAFT converter structure design

In the design realm of fusion power supplies, structural components play a pivotal role in ensuring the safety of fusion devices. To verify the reliability of the converter structure design at the Comprehensive Research Facility for Fusion Technology (CRAFT), meticulous analysis of the converter's dynamic impact is carefully performed based on the worst fault current (400 kA), firstly. Subsequently, the thermal stress analysis based on the maximum allowable steady-state temperature is finished, and the equivalent thermal stress, thermal deformation, maximum shear stress of a single bridge arm and the whole converter are studied. Furthermore, a simple research method involving the current-sharing characteristics of a bridge arm with multi-thyristor parallel connection is proposed using a combination of Simplorer with Q3D in ANSYS. The results show that the current-sharing characteristics are excellent. Finally, the structural design has been meticulously tailored to meet the established requirements.

The petrochemical industry in the energy policy of the Kurdistan Region (A Study in Political Geography)

Petrochemical industries have a special importance in the development of the country, because their products are used as raw materials in most other industries. Therefore, in this study, we focused on the petrochemical industry in the energy policy of the Kurdistan Region. In this study, both force analysis and analytical methods were used, and to reach the scientific responses, we divided the research into three main axes. The first topic analyzes the framework of the research and the second deals with the petrochemical industry and its importance, while the third topic deals with the energy policy and petrochemical industry in the region, as a result we concluded that despite the importance of this type of industry, but so far this type of industry has not been taken care of in the Kurdistan Region.

Effects of surface tension and viscosity on the impact process of droplets onto a rotational surface

In the present study, the impact process of droplets onto a rotational surface was experimentally studied. The influences of the rotational speed, liquid surface tension, and viscosity on the impact phenomena were carefully investigated. The phenomena of asymmetric spreading, splashing with and without liquid filament, finger formation, and secondary droplets were observed. The results showed that, at the same rotational speed, decrease in the surface tension could result in increase in the wetting length in angular direction and the wetting area. In addition, the splashing threshold was discussed based on the analysis of the lift force. In addition, increase in the linear velocity of the surface could promote the splashing behavior and generate more fingers and secondary droplets. Moreover, droplets with higher viscosity could produce more secondary droplets and less fingers. Meanwhile, droplets with higher surface tension could produce more fingers and less secondary droplets. In addition, new correlations for the spreading ratio, the number of fingers formed at the angle of 150° after impact, and the number of secondary droplets were proposed.

Theoretical and numerical analysis of end force of multilayer bellows expansion joint

Multilayer bellows expansion joint is a thin-walled shell widely used in underground pipeline systems for displacement compensation and vibration absorbing. The bellows expansion joint’s end force affects the underground pipeline’s safety. It is urgent to solve the end force of the bellows expansion joint theoretically. However, scholars only obtained the coupling solution of the end force of the bellows expansion joint, which is inconvenient in theoretical analysis and engineering application. This paper proposes a decoupling solution for a bellows expansion joint based on theoretical and numerical methods. The end force is decoupled to the deviation of the bending pressure which is caused by overcoming its own stiffness and internal pressure. In the end force expression, stiffness and internal pressure are independent of each other, which can evaluate the influence of asymmetric pressure difference and external load on end force more accurately. In the end, the accuracy of the decoupling solution is verified by the finite element method and coupling solution. The results show that the decoupling solution agrees with the results obtained by the finite element method and coupling solution. It can provide a theoretical basis for the design of the bellows structure.

Optimization of Technical Calculation of Precast Wall Application for Kawo Secondary Canal Improvement in Sempor Irrigation Area, Kebumen, Central Java

This study aims to perform technical calculations using precast lining in the repair of secondary channels. The planning data used included a concrete grade of fc 18.68 MPa and a reinforcement grade of fy 500 MPa. The service condition analysis was carried out by taking into account the loading during the most critical condition, where the channel is empty and active soil pressure and external water pressure are the main loads. The fixed load calculation was the main focus, where the active earth pressure (PD) was calculated by considering the soil-specific gravity, soil shear angle, and soil coefficient. The calculation results show that the PD reaches 12.24 kN, which gives an idea of the load that the structure has to bear. Furthermore, the internal force analysis provides a deeper understanding of the moments occurring at specific points in the structure. For example, the maximum negative moment at point A was calculated by considering the moments due to fixed load and transient load, which reached 12.73 kNm. This research contributes to improving efficiency and safety in the application of precast lining for secondary channel improvement.

Diversity and distribution of bamboo-feeding true bugs in China.

The Bambusoideae subfamily, originating in the late Cretaceous, has evolved to include over 1500 species globally. Notably, China hosts the richest diversity of Bambusoideae, with 728 species documented. After a long period of coevolution, plenty of animals could feed on these plants rich in cellulose and lignin. As an important group of pests and participants in the ecosystem, bamboo-feeding true bugs (BFTBs, or bamboo-feeding Heteropteran insects) have attracted the attention of researchers. However, the diversity and distribution of BFTBs still lack systematic and generalized research. In this study, we reviewed the BFTBs in China and simulated the diversity pattern and the driving forces of this pattern. A list of 36 genera with 69 species of BFTBs in China was obtained through paper review and field surveys. And their bamboo-feeding habit had multiple independent origins. The spatial diversity pattern showed that the biodiversity hotspots of BFTBs are located in and around the tropics of southern China. Environmental driving force analysis showed that the minimum temperature of coldest month and annual precipitation were the dominant environmental factors shaping the spatial diversity of BFTBs. Our work quantified the diversity and distribution of BFTBs in China, providing fundamental data support for pest control and evolutionary research.

Analysis of 2D Beam Structure Using the Matrix Method Using the PTC Mathcad and SAP2000 Applications Article Sidebar Published: Jun 30, 2024 DOI: https://doi.org/10.37253/jcep.v5i1.9208 Keywords: Struktur Balok, Matriks kekakuan, PTC Mathcad, SAP2000 Main Article Content

Concrete beam structure that functions as an element to support bending loads and shear forces. The PTC Mathcad application software has a built-in matrix method, which makes it very easy to use to create simple structural analysis programs using the stiffness matrix method. The aim of this research is to create a simple analysis program using the PTC Mathcad application to analyze 2D beam structures using the matrix method and compare the analysis results with the SAP2000 application. PTC Mathcad and SAP2000 analysis will produce joint reaction values ​​for force, moment, and joint displacement for each beam model. Based on the results of the comparative analysis of internal force results produced from the PTC Mathcad application and the SAP2000 application, it was found that the

INVESTIGATION ON THE DYNAMICS OF MOVEMENT OF CYLINDRICAL CLEANING PIGS THROUGH THE BENDS OF PIPELINE SYSTEMS FOR FLUID TRANSPORTATION

Development and implementation of methods for cleaning the internal cavity of pipelines in the process of transporting fluids is important to ensure their energy efficiency and safe operation. The dynamics of the movement of one-piece cylindrical cleaning pistons made of various materials (silicone compound, self-destructive elastic polymer composition, polyurethane foam assembly foam) in the pipelines of pipeline systems intended for fluid transportation were studied by modelling and experimentally. The dynamics of movement of solid cylindrical cleaning pigs made from various materials (silicone compound, self-destructive elastic-polymer composition, polyurethane foam) in bends of pipeline systems intended for fluid transportation were studied through modelling and experiments. The analysis of forces acting on the pig during its movement in the pipeline bend was conducted, and the equations of pig motion based on Newton's second law were formulated. Contact forces of normal reaction, arising due to pig bending in the pipeline bend and determining the magnitude of frictional force between the pig and the inner wall of the bend, were determined based on classical bending theory. The impact of the material's modulus of elasticity, from which the pig is made, on the magnitude of contact forces of normal reaction at the pig pressing points against the inner wall of the pipeline bend was established. A method for determining the conditions under which pigs made from different materials will pass through pipeline bends without stopping and getting stuck was proposed. An equation for calculating the minimum allowable pig movement speed at the entrance to the bend to ensure its passage without stopping and getting stuck was derived.

Study on the Shear Behaviors and Capacity of Double-Sided Concrete-Encased Composite Steel Plate Shear Walls by Experiment and Finite Element Analysis

Concrete-encased composite plate shear walls (C-PSW/CEs) can realize the in-plane shear yielding of infill steel plate with the buckling restrained from the concrete panel. Concrete panels also additionally resist portions of lateral loading in C-PSW/CEs, whereby the shear stiffness and strength of the C-PSW/CE are improved. However, research on the in-plane behaviors of concrete panels and the interactions between structural elements is limited. In this paper, the mechanical characteristics and the interactions and the shear resistances of C-PSW/CEs with double-sided concrete encasements were studied. First, the effects of concrete thickness on the damage process, steel plate buckling, and shear resistances of C-PSW/CEs under lateral loading were tested. Then, finite element analyses of the internal forces of the horizontal and inclined cross-sections and the shear force–drift ratio responses of C-PSW/CEs were undertaken with the extended finite element method (XFEM) to simulate the cracking behaviors of concrete panels. A shear force–drift ratio model based on mechanics was developed by considering the lateral load resistances of concrete panels and their effects on steel plates in C-PSW/CEs.

Magnetic porous microspheres altering interfacial thermodynamics of sewage sludge to drive metabolic cooperation for efficient methanogenesis

Controllable and recyclable magnetic porous microspheres (MPMs) have been proposed as a means for enhancing the anaerobic digestion (AD) of sludge, as they do not require continuous replenishment and can serve as carriers for anaerobes. However, the effects of MPMs on the interfacial thermodynamics of sludge and the biological responses triggered by abiotic effects in AD systems remain to be clarified. Herein, the underlying mechanisms by which MPMs alter the solid–liquid interface of sludge to drive methanogenesis were investigated. A significant increase in the contents of 13C and 2H (D) in methane molecules was observed in the presence of MPMs, suggesting that MPMs might enhance the CO2-reduction methanogenesis and participation of water in methane generation. Experimental results demonstrated that the addition of MPMs did not promote the anaerobic bioconversion of soluble organics for methanogenesis, suggesting that the enhanced methanogenesis and water participation were not achieved through promotion of the bioconversion of original liquid-state organics in sludge. Analyses of the capillary force, surface adhesion force, and interfacial proton-coupled electron transfer (PCET) of MPMs revealed that MPMs can enhance mass transfer, effective contact, and electron–proton transfer with sludge. These outcomes were confirmed by the statistical analyses of variations in the interfacial thermodynamics and PCET of sludge with and without MPMs during AD. It was thus proposed that the MPMs enhanced the PCET of sludge and PCET-driven release of protons from water by promoting the interfacial Lewis acid–base interactions of sludge, thereby resulting in the enrichment of free and attached methanogenic consortia and the high energy-conserving metabolic cooperation. This proposition was further confirmed by identifying the predominant syntrophic partners, suggesting that PCET-based efficient methanogenesis was attributable to the enrichment of genomes harbouring CO2-reducing pathway and genes encoding water-mediated proton transfer. These findings offer new insights into how substrate properties can be altered by exogenous materials to enable highly efficient methanogenesis.

Design and Research of Intelligent Fixture for Drawing Machine

Tensile machine is a very sophisticated test equipment, which can test the mechanical properties of some materials. In the drawing machine, the clamping device is to prevent the relative displacement and vibration phenomenon in the process of tensile test. The clamping device is the most important part of the structure of the test machine, and the main task of the clamping device is to control the degree of freedom of the specimen needs to be clamped, so as to further add loads to the various specimens to be held, and finally complete the mechanical property test of the material. But at present, the existing fixture mechanism is mainly hydraulic, pneumatic, mechanical fixture. At present, the existing mechanical fixture still has bending stress during the clamping process, which will affect the accuracy of the experiment. Therefore, a clamping mechanism with adjustable clamping force and flat pushing is designed. An electric control type fixture mechanism is very rare, so in this paper, an electrically controlled fixture is designed on this basis. The main contents are as follows: (1) On the basis of the existing fixture types, the working mode of the fixture is studied, and the working principle related to the fixture is mastered. (2) The main components of the fixture mechanism are analysed, the design scheme is determined, and the selection of the components of the drive part and the selection of the related components within the fixture mechanism is completed. ( 3) The force analysis of the main body of the fixture is carried out by using theoretical mechanics knowledge, and the relevant calculations are completed. The solid modeling of the whole mechanism is completed by using SolidWorks. The force analysis of key parts is carried out by using ANSYS software, and the correctness and safety of material selection and design are verified. The main parts of the fixture mechanism to complete the corresponding force analysis, and the theoretical calculation results are compared and verified, and finally realize the electric control of the fixture mechanism and complete the design of the fixture mechanism.

Exploring Harmful Illocutionary Forces Expressed by Older Adults with and Without Alzheimer’s Disease: A Multimodal Perspective

Abstract This study examines the multimodal pragmatic abilities of older adults experiencing typical aging in contrast to those with Alzheimer’s disease, via the statistical and comparative analysis of harmful illocutionary forces expressed in their discourse. The results indicated that individuals with Alzheimer’s disease showed a noticeable lack of emotional engagement, which hindered the felicity of illocutionary forces. Furthermore, these patients struggled to use appropriate prosodic indicators, alongside a diminished integration of conventional gestures. Highlighting the significance of multimodal illocutionary force indicators in speech acts, this study contributes to a more intricate comprehension of interpersonal communication.

The study on the force analysis model of wave energy devices in heaving and pitching motion

The study on the force analysis model of wave energy devices in heaving and pitching motion

3D DEM investigation of shear behavior and interaction mechanism of woven geotextile-sand interfaces

This paper presents a numerical study on the investigation of microscopic mechanism governing the interaction of woven geotextile and angular sand employing the 3D discrete element method (DEM). The surface texture and tensile properties of the geotextile were simulated using overlapping spherical particles, and the angular sand was simulated using rigid blocks. The DEM models were fully calibrated based on previous experimental data. The shear and dilation zones of sand near the interface were quantitatively determined based on particle displacement gradients. Analysis of contact forces was conducted to explain the microscopic mechanism behind the macroscopic strength evolution. The influence of geotextile surface roughness on the shear strength of the geotextile-sand interface is also discussed. The results show that the failure mode of the woven geotextile-sand interface is a combination of particle sliding failure along the geotextile surface and shear failure of the sand within the shear zone above the interface. There is a rapid redistribution of contact forces prior to reaching peak shear resistance, and the average normal contact force within the shear zone remains relatively constant after the peak shear stress is achieved. A completely developed shear zone stabilizes soil deformation, typically after achieving the peak shear resistance.

Analysis of Diaphragm Force on Reinforced Concrete Building Structures with Horizontal Irregularities of Diaphragm Discontinuity

The diaphragm plays a crucial role in distributing seismic forces within buildings during earthquakes, affecting both regular and irregular structures differently. This study investigates the seismic behavior of diaphragms in various building geometries resembling the letters I, T, L, and O, focusing on their influence on structural performance and reinforcement requirements. Using analytical methods, diaphragm seismic forces, slab shear stresses, and internal forces were calculated for a sample of buildings with different geometrical irregularities. The study reveals significant differences in diaphragm earthquake forces between regular and irregular buildings, with irregular geometries exhibiting distinct patterns of shear stress distribution. Particularly, the building with an L-shaped plan and concentrated stress points showed the highest maximum shear stresses in both orthogonal directions. Analysis of internal forces—axial, shear, and moment—highlighted varying reinforcement needs among the studied buildings. While axial and shear forces necessitated minimal additional reinforcement across all structures, moment forces indicated substantial reinforcement requirements, particularly in the L-shaped building. These findings underscore the importance of tailored diaphragm design strategies for buildings with irregular geometries to mitigate potential structural vulnerabilities during seismic events. The study contributes insights into optimizing diaphragm design practices and emphasizes the need for further research in this critical area of structural engineering.

Experimental and numerical analysis of wave forces on a vertical truncated cylinder with different depths of submergence under focused waves

Accurately determining the extreme wave forces acting on marine structures is crucial for ensuring their safety. This study investigates the maximum values and transfer functions of wave forces on a fixed vertical truncated cylinder under focused waves through experimental analysis and numerical simulations. Firstly, an experiment was conducted to examine the influence of the wave steepness kpAp, structural scale D/Lp and depth of submergence S2/d on both the horizontal and the vertical forces exerted on the cylinder. These factors were found to significantly influence the maximum values and transfer functions of the wave forces, particularly those of the vertical force during wave slamming events. To further understand the interactions between the focused waves and the vertical truncated cylinder, a numerical model based on the Reynolds-Averaged Navier-Stokes (RANS) equations in OpenFOAM was employed considering different heights above the surface of static water S1/d and varying depths of submergence S2/d. The validity of this model was confirmed by comparing its results with those of the experiment. Following this, the effects of S1/d and S2/d on the maximum values as well as the transfer functions of wave forces on the cylinder were discussed, including in scenarios involving wave slamming and wave overtopping events. Finally, an empirical formula for calculating the wave force was proposed, taking into account the influence of kpAp, S1/d, and S2/d on the inertial coefficient CM and the coefficient of pressure correction CP. The results demonstrated that this formula can be used to accurately predict the maximum wave forces exerted on the cylinder.