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OBJECTIVES/GOALS: #NAME? METHODS/STUDY POPULATION: Cell culture & protein identification: human T cells were purified from healthy blood, then activated & cultured for 5d. CAR-T cells were collected from infusion bags of cancer patients undergoing CAR-T. Silver staining of naive & activated healthy T-cell lysates was compared; B-II spectrin was upregulated and confirmed by Western blot. Migration assays: naive & activated T-cells were imaged during migration on ICAM-1 and ICAM-1 + CXCL12 coated plates. T-cells were transfected with BII-spectrin cDNA & the chemokine dependence of migration was compared with controls. In-vivo studies: in a melanoma mouse model, BII-spectrin transfected or control T-cells were injected; tumors were followed with serial imaging. Human patient records were examined to correlate endogenous BII-spectrin levels and CAR-T response. RESULTS/ANTICIPATED RESULTS: Activated T-cells downregulate the cytoskeletal protein B-II spectrin compared to naive cells, leading to chemokine-independent migration in in vitro assays and off-target trafficking when CAR-T cells are given in vivo. Restoration of B-II spectrin levels via transfection restores chemokine-dependence of activated T-cells. In a mouse melanoma model, control mice injected with standard activated T-cells showed fewer cells in the tumor site and more cells in the off-target organs (spleen, lungs) when compared to mice injected with B-II spectrin transfected cells. Furthermore, among 3 human patients undergoing CAR-T therapy, those with higher endogenous B-II spectrin levels experienced fewer side-effects, measured by the neurotoxicity and cytokine release syndrome grades. DISCUSSION/SIGNIFICANCE: A major hurdle to widespread CAR-T therapy for cancer is significant, often fatal side-effects. Our work shows that the protein B-II spectrin is downregulated during CAR-T production, and that restoring B-II spectrin levels decreases side-effects while increasing tumor clearance--hopefully translating to better CAR-T regimens for the future.
The forming limit strains (FLSs) of zircaloy-4 sheets are studied. After having obtained the true stress–strain curve of zircaloy-4 using the weighted-average method, limit dome height (LDH) tests are performed to establish experimental FLSs. We summarize related theoretical forming limit curves (FLC) and discuss their limitations. Two finite element (FE) models are established for determining FLSs; an LDH test FE model for the negative minor strain sector, and a biaxial tensile FE model for the positive minor strain sector. The numerical FLSs are found to agree well with experimental data. Since the numerical FLC gives the strain at the onset of local thinning (whereas the experimental FLC provides the strain between local necking and ductile fracture), resulting FE FLS values are slightly lower than the experimental ones so that results can be regarded as conservative. Our FE approach substitutes the expensive and time-demanding experimental LDH tests.
In this study, a method using dual triangular pyramidal indenters is suggested for material property evaluation. First, we demonstrate that the load–depth curves and the projected contact areas from conical and triangular pyramidal indentations are generally different. Nonequal projected contact areas of two indenters and nonplanar contact line of Berkovich indenter are the main sources of different indentation characteristics of two indenters. For this reason, an independent approach to the triangular pyramidal indentation is needed. With finite element (FE) indentation analyses for various materials, we investigate the relationships between material properties, indentation parameters, and load–depth curves. Based on the FE solutions, we suggest mapping functions for evaluating material properties from indentations by two triangular pyramidal WC indenters, which differ in their centerline-to-face angles. Elastic modulus, yield strength, and strain hardening exponent are obtained with an average error of <3%.
In this study, we obtain true stress–strain (SS) curves for a sheet specimen under consideration of local necking and material anisotropy. We first extract the SS curve up to the diffuse necking point from the tensile test load–displacement data. The curve's part after the onset of diffuse necking is extrapolated by the weighted-average method proposed by Ling [Y. Ling, AMP J. Technol. 5, 37–48 (1996)]. Initiation of local necking is predicted by means of the minor-to-major strain ratio in the specimen's center. We propose a criterion to determine the strain ratio at the onset of local necking and the major strain corresponding to the strain ratio at local necking. We complete the true SS curve by cutting off the SS curve at the major strains corresponding to the local necking or apparent fracture point. Finally, the effects of material anisotropy on SS curves are discussed.
High-chromium heat-resistant steel has been widely used as the key material to improve the condition of steam pressure and temperature in the modern high-efficiency power plants. Despite the use of the steel above 550°C for several decades, its major failure is owing to the creep fracture. In this study, the effect of creep stress on the microstructure in 9–12% Cr steel has been investigated microscopically, and it is clarified that the creep stress enhances precipitation of Laves phase and influences the lath width and dislocation density in lath interior.
The numerical approach of Lee et al. [Trans. Korean Soc. Mech. Eng., A28, 816–825 (2004)] to spherical indentation technique for property evaluation of hyperelastic rubber is enhanced. The Yeoh model is adopted as the constitutive form of rubber material because it can express well large deformation and cover various deformation modes with a simple form. We first determine the friction coefficient between a rubber specimen and a spherical indenter in a practical viewpoint and perform finite element simulations for a deeper indentation depth than that selected by Lee et al. [Trans. Korean Soc. Mech. Eng., A28, 816–825 (2004)]. An optimal data acquisition spot is selected, which features sufficiently large strain energy density and negligible frictional effect. We improve then two normalized functions mapping an indentation load–displacement curve onto a strain energy density–invariant curve, the latter of which gives the Yeoh model constants. The enhanced spherical indentation approach successfully produces the rubber material properties with an average error of less than 5%. The validity of our developed approach is verified by experimental evaluation of material properties with three kinds of rubber materials.
The purpose of the present study was to use a meta-analytic approach to examine the convergent validity of the International Physical Activity Questionnaire (IPAQ).
Systematic review by meta-analysis.
The relevant studies were surveyed from five electronic databases. Primary outcomes of interest were the product-moment correlation coefficients between IPAQ and other instruments. Five separate meta-analyses were performed for each physical activity (PA) category of IPAQ: walking, moderate PA (MPA), total moderate PA (TMPA), vigorous PA (VPA) and total PA (TPA). The corrected mean effect size (ESρ) unaffected by statistical artefacts (i.e. sampling error and reliability) was calculated for each PA category. Selected moderator variables were length of IPAQ (i.e. short and long form), reference period (i.e. last 7 d and usual week), mode of administration (i.e. interviewer and self-reported), language (i.e. English and translated) and instruments (i.e. accelerometer, pedometer and subjective measure).
A total of 152 ESρ across five PA categories were retrieved from twenty-one studies.
The results showed small- to medium-sized ESρ (0·27–0·49). The highest value was observed in VPA while the lowest value was found in MPA. The ESρ were differentiated by some of the moderator variables across PA categories.
The study shows the overall convergent validity of IPAQ within each PA category. Some differences in degree of convergent validity across PA categories and moderator variables imply that different research conditions should be taken into account prior to deciding on use of the appropriate type of IPAQ.
Conical indentation methods to determine residual stress are proposed by examining the finite element solutions based on the incremental plasticity theory. We first note that hardness depends on the magnitude and sign of residual stress and material properties and can change by up to 20% over a specific range of elastic tensile and compressive residual stress, although some prior indentation studies reported that hardness is hardly affected by residual stress. By analyzing the characteristics of conical indentation, we then select some normalized indentation parameters, which are free from the effect of indenter tip rounding. Adopting dimensional analysis, we present practical conical indentation methods for the evaluation of elastic/plastic equi- and nonequi-biaxial residual stresses. The validity of developed approaches is confirmed by applying them to the experimental evaluation of four-point bending stress.
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