Solid Model Research Articles

Therapeutic Efficacy of IL7/CCL19-Expressing CAR-T Cells in Intractable Solid Tumor Models of Glioblastoma and Pancreatic Cancer.

Despite the clinical development of CAR T-cell therapy, its efficacy in solid cancers has yet to be established. This study explored the therapeutic potential and immunologic mechanisms of IL7/CCL19-producing CAR-T therapy in preclinical solid cancer models of glioblastoma and pancreatic cancer. We found that IL7/CCL19-producing CAR-T cells generated from the patient's PBMC showed potent therapeutic effects against the solid cancer model established by inoculating organoids from the autologous tumor tissue.

Effective Strategies For Small Startups To Attract Venture Capital

In essence, for small startups, securing VC is a major breakthrough for growing and scaling up their business. The paper now zeroes in on the tactics that small startups can employ to capture, to a larger extent, the potential attention of VCs. The most critical strategies in order to engage VCs will be what this discussion will be based on as we turn into a collection of previous literature, case studies, and expert insights. Forge a Convincing Business Model: One solid business model is what lies at the core of how to attract VC investment. How a startup can sketch out its value proposition, revenue streams, and path to scaling. This business model does not only bring out the potential for high returns that the startup might have; it also aligns with the risk appetite of these venture capitalists. Network Building: Networking forms one of the core functions of the entire venture capital business. This paper looks into just how a network of one's own can be built and leveraged via industrial connections, along with mentors and advisors. Proper networking will result in more visibility and credibility, thus increasing the opportunity for start-ups to reach out to potential investors. Demonstrating Market Potential: For venture capitalists, the ability to demonstrate a clear market potential is very much desirable from startups. We will see how startups can present information on market size, customer segments, and competitive landscape to secure an investment interest. Making a Strong Pitch: Preparing a convincing pitch is a sure way of attracting the interest of VCs. We will look at the main components of the pitch: elevator pitch, articulating the problem and solution, definition of the market opportunity, articulation of the solution itself, business model, traction, team, and financial projections. Preparing a sound pitch can dramatically increase the chance of receiving venture capital. Apart from these, the paper also makes the target to address the critical pitfalls which startup companies often face in the form of indistinct ideas, over-promise on market size, and unrealistic projections for financials. It must help the startups, through practical recommendations and insights, reach an optimization of approaches toward venture capital and hence secure the necessary funding portions of growth and success

Intermediate statistics: Addressing the thermoelectric properties of solids.

We study the thermodynamics of a crystalline solid by applying intermediate statistics obtained by deforming known solid state models using the mathematics of qanalogs. We apply the resulting qdeformation to both the Einstein and Debye models and study the deformed thermal and electrical conductivities and the deformed Debye specific heat. We find that the qdeformation acts in two different ways-but not necessarily as independent mechanisms. First, it acts as an effective factor of disorder or impurity, modifying the characteristics of a crystalline structure, which are phenomena described by qbosons. Second, it also manifests intermediate statistics, namely, the Banyons (or B-type systems). For the latter case we have identified the Schottky effect, normally associated with high-T_{c} superconductors in the presence of rare-earth-ion impurities. We also find that it increases the specific heat of the solids beyond the Dulong-Petit limit at high temperature. Such an effect is usually related to anharmonicity of interatomic interactions. Alternatively, since in the q-boson's case the statistics are in principle maintained, the effect of the deformation acts more slowly due to a small change in the crystal lattice. On the other hand, Banyons that belong to modified statistics are more sensitive to the deformation. The results reported here may be verified experimentally, for instance, in experimental samples by inserting impurities, or changes in pressure or temperature if one assumes these tuning quantities are related with the q-deformation parameter.

Test and simulation of corroded high strength steel wires: From scanned morphology feature to mechanical degradation

This paper presents a coupled experimental-numerical study aimed at understanding the mechanical behavior of corroded high-strength steel wires. Accelerated corrosion tests were conducted on steel wires to achieve varying corrosion levels, and the mechanical properties of the corroded wires were characterized by tensile test. The surface morphology of the corroded wires was derived by 3D optical scanning and point cloud models was generated that precisely captured the surface pits. These models were then converted into solid models by surface reconstruction and finite element discretization. Numerical simulations, based on reconstructed surface morphology, effectively predict key mechanical characteristics and align closely with experimental data. The research establishes relationships between statistical pit parameters and macro-mechanical properties, providing valuable insights for predicting the mechanical performance of corroded wires and evaluating the integrity of structures compromised by corrosion.

CatchyCFDEM: Open-source microkinetic modeling of heterogeneous catalysis in Eulerian-Lagrangian CFD applied to oxidative coupling of methane

This work introduces catchyCFDEM, an OpenFOAM-based open-source CFD-DEM framework designed for simulating reactive gas–solid fluidized beds with both gas-phase chemistry and heterogeneous catalytic chemistry. A convective gas–solid heat transfer model is implemented and validated using experimental data gathered in a non-reactive pseudo-2D fluidized bed. Catalytic chemistry including different levels of complexity are included: pseudo-homogeneous, heterogeneous without mass transfer, and heterogeneous with diffusive mass transfer. Verification studies are performed by simulating a packed bed reactor using catchyCFDEM and comparing mass fraction profiles to a 1D plug flow simulation in Cantera. To enhance the computational efficiency of the resource-intensive reactive CFD-DEM simulations, speed-up algorithms such as Particle Agglomeration (PA) and in-situ adaptive tabulation (ISAT) are integrated in catchyCFDEM. As a case study, a gas–solid vortex reactor (GSVR) is simulated using the validated framework. The applicability of the GSVR for the oxidative coupling of methane (OCM) is evaluated based on an isothermal analysis evaluating the influence of several operational and geometrical parameters on the process. Finally, a proof-of-concept adiabatic simulation of the GSVR is presented. The catchyCFDEM framework is made publicly available on GitHub.

Controllable synthesize of ZnS/PbS nanostructure and their structural and morphological properties

ZnS is an appealing material with wide potential applications in optoelectronics, sensors, and photocatalysis due to its fascinating properties, low cost, and eco-friendly. In this paper, we report the synthesis of ZnS nanowires and nanorods via a simple thermal-evaporation method using different concentrations of PbS as a dopant. The prepared nanostrutures were investigated in detalis using a scanning electron microscopy (SEM), X-ray diffraction (XRD), and high resolution transmission electron microscopy (HRTEM). The results show that the fabricated ZnS nanowire/nanorod has a wurtzite (hcp) structure. In addition, based on the experimental results, the growth mechanism of the prepared nanostructures is reported. X-ray photoelectron spectroscopy (XPS) and energy-dispersive X-ray (EDX) mapping analyses confirmed that the ZnS nanorods were stoichiometric without impurities or defects, whereas PbS quantum dots were formed inside the high-quality nanowires. The formation mechanism of ZnS nanowires is discussed based on the vapor–liquid–solid (VLS) growth model. Results demonstrated that thermal evaporation is a simple and effective techniques for producing high-quality heterostructured ZnS nanowires with potential applications in different fields.

Numerical modelling strategy and load resisting mechanism of palace-type traditional wooden frame

This paper is aimed at proposing the numerical modeling strategy of the palace-style traditional wooden frame in Chinese Song dynasty and revealing its load resisting mechanism. Firstly, the restoring moments of the column foot (CF) and column head (CH) of free-standing column are formulated, the proposed model of the frame with CF and CH is validated by the corresponding solid element models. Then, the mechanical behavior of the dowel at the CH is formulated based its deformation characteristics, and the proposed model of the frame with CF, CH and dowel is also validated by its solid element model. Finally, the effectiveness of the proposed model of the whole frame with CF, CH, dowel and dovetail mortise-tenon (DMT) joint is confirmed by the corresponding experimental and solid element models. The results show that difference of mechanical performance of the CF with compressive deformation parallel-to-grain and CH with compressive deformation perpendicular-to-grain is minor, the bending behavior of the dowel in the frame without lower beam has been changed into the shearing behavior of the dowel in the frame with lower beam. The rotational behaviors of the DMT at the two ends of the beam are different when the frame is lateral deformed, and the proportion of the lateral resistance provided by the column and DMT is more and less than 60 % and 30 %. And the upper beam of the wooden frame significantly increases its lateral resistance.

Origins of complexity in the rheology of Soft Earth suspensions

When wet soil becomes fully saturated by intense rainfall, or is shaken by an earthquake, it may fluidize catastrophically. Sand-rich slurries are treated as granular suspensions, where the failure is related to an unjamming transition, and friction is controlled by particle concentration and pore pressure. Mud flows are modeled as gels, where yielding and shear-thinning behaviors arise from inter-particle attraction and clustering. Here we show that the full range of complex flow behaviors previously reported for natural debris flows can be reproduced with three ingredients: water, silica sand, and kaolin clay. Going from sand-rich to clay-rich suspensions, we observe continuous transition from brittle (Coulomb-like) to ductile (plastic) yielding. We propose a general constitutive relation for soil suspensions, with a particle rearrangement time that is controlled by yield stress and jamming distance. Our experimental results are supported by models for amorphous solids, suggesting that the paradigm of non-equilibrium phase transitions can help us understand and predict the complex behaviors of Soft Earth suspensions.

Abnormal low-magnitude seismicity preceding large-magnitude earthquakes

Unraveling the precursory signals of potentially destructive earthquakes is crucial to understand the Earth’s crust dynamics and to provide reliable seismic warnings. Earthquake precursors are ambiguous, but recent experimental studies suggest that robust warning signs may precede large seismic events in the short (day-to-months) term. Here, we show that the M6.4-M7.1 2019 Ridgecrest sequence (California) and the M7.1 2018 Anchorage earthquake (Alaska) were preceded by up to ~3 months of tectonic unrest on regional scales, as evidenced by abnormal low-magnitude seismicity spreading over the ~15-25% of Southern California and Southcentral Alaska. This precursory unrest has been discovered with an algorithm that integrates an innovative random forest machine learning approach and statistical features built from earthquake catalogs. Supported by a novel suite of finite element solid mechanics models, we propose that precursory, abnormal, low-magnitude seismicity arises if the pore fluid pressure within large fault segments escalates significantly as they approach failure, which leads to major uneven changes in the regional stress field. Our findings and method may open up new perspectives for surveillance agencies to anticipate when a region approaches an earthquake of great magnitude weeks to months before it occurs.

Generation of Customized Bone Implants from CT Scans Using FEA and AM.

Additive manufacturing (AM) allows the creation of customized designs for various medical devices, such as implants, casts, and splints. Amongst other AM technologies, fused filament fabrication (FFF) facilitates the production of intricate geometries that are often unattainable through conventional methods like subtractive manufacturing. This study aimed to develop a methodology for substituting a pathological talus bone with a personalized one created using additive manufacturing. The process involved generating a numerical parametric solid model of the specific anatomical region using computed tomography (CT) scans of the corresponding healthy organ from the patient. The healthy talus served as a mirrored template to replace the defective one. Structural simulation of the model through finite element analysis (FEA) helped compare and select different materials to identify the most suitable one for the replacement bone. The implant was then produced using FFF technology. The developed procedure yielded commendable results. The models maintained high geometric accuracy, while significantly reducing the computational time. PEEK emerged as the optimal material for bone replacement among the considered options and several specimens of talus were successfully printed.

BRD-810 is a highly selective MCL1 inhibitor with optimized in vivo clearance and robust efficacy in solid and hematological tumor models

The MCL1 gene is frequently amplified in cancer and codes for the antiapoptotic protein myeloid cell leukemia 1 (MCL1), which confers resistance to the current standard of care. Therefore, MCL1 is an attractive anticancer target. Here we describe BRD-810 as a potent and selective MCL1 inhibitor and its key design principle of rapid systemic clearance to potentially minimize area under the curve-driven toxicities associated with MCL1 inhibition. BRD-810 induced rapid cell killing within 4 h in vitro but, in the same 4-h window, had no impact on cell viability or troponin I release in human induced pluripotent stem cell-derived cardiomyocytes, even at suprapharmacologic concentrations. In vivo BRD-810 induced efficacy in xenograft hematological and solid tumor models despite the short residence time of BRD-810 in plasma. In totality, our data support the hypothesis that short-term inhibition of MCL1 with BRD-810 can induce apoptosis in tumor cells while maintaining an acceptable safety profile. We, therefore, intend to advance BRD-810 to clinical trials.

Progressive failure analysis of laminar composites under compression using smeared crack-band damage model and full layerwise theory

This paper presents an original finite element (FE) model that integrates the smeared crack band (SCB) approach and full layerwise plate theory (FLWT). The model enhances the computational efficiency of progressive failure analysis (PFA) of laminar composites in compression, by utilizing the layerwise approach which reduces a 3D model to a 2D one. The model distributes damage throughout the FE domain, with fracture mechanisms represented by material stiffness degradation controlled by damage variables (based on equivalent strains specifically defined for each failure mode). Mesh dependency issues are addressed by scaling fracture energy using a characteristic element length, and failure initiation and modes are determined using the 3D Hashin failure criterion.Accurately describing lamina response in fiber direction under compression requires linear-brittle softening with a stress plateau. The study showed that a model considering 30 % of residual stress accurately predicts maximum stress regardless of mesh refinement, demonstrating results’ minor dependence from the selected element size.The model accuracy has been confirmed by comparing the obtained results against experimental and benchmark data from the literature. The size effect study demonstrated a decrease in maximum stress of the open-hole laminates in compression with increasing specimen in-plane size. This trend is consistent with experimental and reference numerical observations, confirming the model accuracy and applicability even for relatively coarse meshes. Therefore, computational efficiency is improved, with preserved accuracy of conventional solid finite element models.

Investigating perforated egg crates as dynamic shading systems for open-plan offices in tropical climates

This study explores the use of perforated egg crates as a dynamic shading system to improve daylight quality by achieving better uniformity in open-plan offices. Glazed curtain walls, although a popular choice in modern open-plan offices, can cause problems especially in tropical climates, such as glare and heat particularly near the windows. As egg crates (EC) generally perform better as shading devices than plain horizontal or vertical systems, this study simulated three different combinations of perforated, solid, overlapping and non-overlapping egg crate models for an existing open-plan office building in Indonesia. Daylight measurements of the existing horizontal shading device without any egg crate (NO-EC) were first recorded. Subsequent simulations of non-overlapping perforated (EC-NP) egg crate models with different blade widths and blade rotation angles in accordance with the sun elevation angles on specified working hours were performed. Similar simulations were then performed for two combinations: other combinations of overlapping solid (EC-OS) and overlapping perforated (EC-OP) egg crate models. Finally, a full-scale site mock-up of the EC-NP and NO-EC were tested under real-life climatic conditions. Results show that EC-NP provides better uniformity than the other two combinations, which is within the range of 0.59–0.99. This is due to the deeper penetration of daylight achieved by the overlapping placement of the horizontal blades in front of vertical blades, while keeping the building envelope shaded.

A sub-grid gas–solid interaction model for coarse-grained CFD–DEM simulations

Computational fluid dynamics has been coupled with coarse-grained discrete element method (CFD–CGDEM) to study industrial-scale gas–solid fluidized beds. However, solving the fluid flow at a grid size of several coarse-grained particles (CGPs) cannot accurately predict the gas–solid interaction, and thus reasonable correction model is required. This study develops a sub-grid model to correct the gas–solid interaction and thereby improve the accuracy of coarse-grid CFD–CGDEM simulation. First, the fluid grids with the size of several CGPs are divided into the auxiliary three-dimensional sub-grids. Then, the CGPs are mapped onto the sub-grids by the weight function to reconstruct the local solid velocities and solid fractions of the sub-grids. After that, the simplified mass and momentum conservation equations are solved to resolve the local gas velocities of sub-grids. Finally, the drag on each CGP is corrected based on the local gas-phase hydrodynamics of sub-grids. Results show that the sub-grid model resolving the local gas velocity in all the three directions works better than that just in the main stream direction. The coarse-grid CFD–CGDEM simulations with this sub-grid model agree well with the experiment for the bubbling, turbulent and rapid fluidized beds. Besides, by solving the simplified conservation equations with graphics processing units, the coarse-grid CFD–CGDEM coupled with the sub-grid model achieves 674 times speedup compared to the fine-grid simulation, demonstrating a much more efficient method to study industrial-scale gas–solid fluidized beds.

Simplified soil–structure interaction modeling techniques for the dynamic assessment of end shield bridges

In this paper, the dynamic behavior of four railway bridges with integrated retaining walls, considering the effect of soil–structure interaction (SSI), is investigated both numerically and experimentally. Among these bridges, two are single-span, and the remaining two are three-span. Each bridge is equipped with numerous accelerometers and is excited by a hydraulic actuator across various frequencies. Full 3D solid Finite Element (FE) models incorporating the railway bridges and surrounding soils are developed and calibrated using the Frequency Response Functions (FRFs) from each accelerometer. Furthermore, simplified 3D solid and 2D beam models are created for each railway bridge, incorporating springs and dashpots to account for the effect of surrounding soils. The values for these springs and dashpots are obtained from simple equations, except for the impact of the backfill soil in the simplified 2D beam models, which are derived from the impedance functions of the soil medium. The performance of these simplified models is then compared to the calibrated 3D models in terms of modal properties of the first bending mode and the maximum acceleration response during high-speed train passages. The results indicate that the simplified models closely align with the calibrated models in terms of modal properties and high-speed train passage response and can be used as simple and efficient alternatives for practical usage in bridge design.

The study of solid flame model of diffusion jet flame for the ammonia and propane mixed gas under the inclined ceiling

In order to solve the environmental pollution and energy dilemma, the ammonia has been considered as a new fuel and a carbon-free hydrogen carrier, which can be blended into the traditional hydrocarbon fuels. In this study, the evolution of flame emissivity, view factor and radiative heat flux have been investigated under different mass flow rates of ammonia and propane, and inclined angle of ceiling. A radiation prediction model of ammonia-propane mixed gas jet flame under inclined ceiling with different inclined angles has been developed. This prediction model can accurately describe the flame morphology and simplify the calculations, and consider the influence of mixing ratio on combustion reaction. The experimental results indicated that the flame emissivity, view factor, and radiative heat flux decrease with the increase of ammonia concentration. The prediction error of the traditional model will be enlarged with the increase in the inclined angle of ceiling. The modified model added the undersurface of ceiling jet flame, which reduces the prediction error from 25 % to 14 %. These prediction models are helpful in predicting the thermal radiation of jet flame under inclined ceiling.

Modified C-type natriuretic peptide normalizes tumor vasculature, reinvigorates antitumor immunity, and improves solid tumor therapies.

Deficit of oxygen and nutrients in the tumor microenvironment (TME) triggers abnormal angiogenesis that produces dysfunctional and leaky blood vessels, which fail to adequately perfuse tumor tissues. Resulting hypoxia, exacerbation of metabolic disturbances, and generation of an immunosuppressive TME undermine the efficacy of anticancer therapies. Use of carefully scheduled angiogenesis inhibitors has been suggested to overcome these problems and normalize the TME. Here, we propose an alternative agonist-based normalization approach using a derivative of the C-type natriuretic peptide (dCNP). Multiple gene expression signatures in tumor tissues were affected in mice treated with dCNP. In several mouse orthotopic and subcutaneous solid tumor models including colon and pancreatic adenocarcinomas, this well-tolerated agent stimulated formation of highly functional tumor blood vessels to reduce hypoxia. Administration of dCNP also inhibited stromagenesis and remodeling of the extracellular matrix and decreased tumor interstitial fluid pressure. In addition, treatment with dCNP reinvigorated the antitumor immune responses. Administration of dCNP decelerated growth of primary mouse tumors and suppressed their metastases. Moreover, inclusion of dCNP into the chemo-, radio-, or immune-therapeutic regimens increased their efficacy against solid tumors in immunocompetent mice. These results demonstrate the proof of principle for using vasculature normalizing agonists to improve therapies against solid tumors and characterize dCNP as the first in class among such agents.

The Design and Analysis of the Helical Gear in the Car Gear Box for the Slag Port Transfer

The design and analysis of helical gears with involutes profiles is the primary focus of this study. The most widely utilized gearing system in use today is the involutes gear profile. Power and torque are typically transmitted through them. When compared to other forms of transmission, the efficiency of power transmission via gears is extremely high. Bending and contact stress are the main causes of gear tooth failure. The current study examines helical gear, which has to do with slag transfer in the steel production sector. The most affected stress concentrated location of any set of gears in the slag port transfer car (SPTC) gear box is identified by examining the contact stresses for the current design set of gears. The high stress concentration gear set was redesigned with a constant (45mm) face width at various Helix angles (14, 15, 16, 17, 19^, 20 ̊, 25^, and 30 ̊) and a constant pressure angle (20). To calculate the contact stresses between two gears that are mating. The robust and cutting-edge solid modeling program AUTODESK FUSION 360 creates a three-dimensional solid model. The ANSYS Workbench module was utilized to do the numerical analysis. The outcomes of the workbench module for ANSYS. The current study is helpful in quantifying the previously mentioned factors, which aids in the safe and effective design of the helical gear in the SPTC Gearbox.

Simplifying bidisperse pore diffusion model for adsorbent felt

Mass transfer resistance within the adsorbent felt, governed by pore diffusion, limits adsorption efficiency. Current gas and solid side resistance models, which cover both micro- and macro-pore diffusion, are complex due to their numerous parameters. Sometimes, adsorbate transfer in the felt is predominantly controlled by macro-pore diffusion. This paper uses two key assumptions to introduce a simplified macro-pore diffusion model, distilled from a detailed macro–micro pore diffusion model. The model’s accuracy was confirmed by simulating two desiccant wheels, demonstrating its effectiveness in streamlining adsorbent felt analysis and predicting mass transfer dynamics.

BP1003 Decreases STAT3 Expression and Its Pro-Tumorigenic Functions in Solid Tumors and the Tumor Microenvironment.

Overexpression and aberrant activation of signal transducer and activator of transcription 3 (STAT3) contribute to tumorigenesis, drug resistance, and tumor-immune evasion, making it a potential cancer therapeutic target. BP1003 is a neutral liposome incorporated with a nuclease-resistant P-ethoxy antisense oligodeoxynucleotide (ASO) targeting the STAT3 mRNA. Its unique design enhances BP1003 stability, cellular uptake, and target affinity. BP1003 efficiently reduces STAT3 expression and enhances the sensitivity of breast cancer cells (HER2+, triple negative) and ovarian cancer cells (late stage, invasive ovarian cancer) to paclitaxel and 5-fluorouracil (5-FU) in both 2D and 3D cell cultures. Similarly, ex vivo and in vivo patient-derived models of pancreatic ductal adenocarcinoma (PDAC) show reduced tissue viability and tumor volume with BP1003 and gemcitabine combination treatments. In addition to directly affecting tumor cells, BP1003 can modulate the tumor microenvironment. Unlike M1 differentiation, monocyte differentiation into anti-inflammatory M2 macrophages is suppressed by BP1003, indicating its potential contribution to immunotherapy. The broad anti-tumor effect of BP1003 in numerous preclinical solid tumor models, such as breast, ovarian, and pancreatic cancer models shown in this work, makes it a promising cancer therapeutic.