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Finite element analyses of the propagation of damage such as fiber compressive failure and delamination have greatly contributed to the understanding of failure mechanisms of fiber-reinforced plastics owing to extensive studies on methodologies using Continuum Damage Mechanics and Fracture Mechanics. Problems without the need for consideration of inertia, such as Double-Cantilever Beam tests, are usually solved by implicit FE solvers, and explicit FE solvers are appropriate for phenomena that progress with very high velocity such as impact problems. However, quasi-static problems with unstable damage propagation observed in experiments such as Open-Hole Compression tests are still not easy to solve for both types of solvers. We propose a method to enable the static FE solver to solve problems with unstable propagation of damage. In the present method, an additional process of convergence checks on the averaged energy release rate of damaged elements is incorporated in a conventional Newton–Raphson scheme. The feasibility of the present method was validated by two numerical examples consisting of analyses of Open-Hole Compression tests and Double-Cantilever Beam tests. The results of the analyses of OHC tests showed that the present method was applicable to problems with unstable damage propagation. In addition, the results from the analyses of DCB tests with the present method indicated that mesh density and loading history are not significantly influential to the solution. [ABSTRACT FROM AUTHOR]

An applied electrochemical method in the form of a chronocoulometry technique is proposed for measuring Fick's diffusion constant of a thin protective coating layer over the conductive base materials. Using this method, the capacitance is monitored for a capacitor formed using the base material, an electrolyte such as aqueous NaCl, and an insulating coating layer in between. The capacitance increases when the distance between the base material and the electrolyte decreases in the diffusion of the electrolyte through the insulating coating layer. Therefore, the change in the capacitance provides a diffusion rate related to Fick's diffusion constant. Conventional gravimetric methods require a long measurement time to reach saturation, and thin coating layers of minimal weight increment through water diffusion were demonstrated to be inadequate for the methods. However, the new electrochemical method is appropriate for thin coating layers and requires a limited duration after the onset of diffusion. Experimental for 1-mm thick PA6 films provided Fick's diffusion constants of safer side with the new method of 15h by reflecting the heterogeneous properties of the surface, while the conventional gravimetric method in 360h provided smaller or danger-side values. [ABSTRACT FROM AUTHOR]

Abstract Background Human hepatocellular carcinoma (HCC) cells express WT1 and/or carcinoembryonic antigen (CEA) as potential targets for the induction of antitumor immunity. In this study, generation of cytotoxic T lymphocytes (CTL) and regulatory T cells (Treg) by fusions of dendritic cells (DCs) and HCC cells was examined. Methods HCC cells were fused to DCs either from healthy donors or the HCC patient and investigated whether supernatants derived from the HCC cell culture (HCCsp) influenced on the function of DCs/HCC fusion cells (FCs) and generation of CTL and Treg. Results FCs coexpressed the HCC cells-derived WT1 and CEA antigens and DCs-derived MHC class II and costimulatory molecules. In addition, FCs were effective in activating CD4+ and CD8+ T cells able to produce IFN-γ and inducing cytolysis of autologous tumor or semiallogeneic targets by a MHC class I-restricted mechanism. However, HCCsp induced functional impairment of DCs as demonstrated by the down-regulation of MHC class I and II, CD80, CD86, and CD83 molecules. Moreover, the HCCsp-exposed DCs failed to undergo full maturation upon stimulation with the Toll-like receptor 4 agonist penicillin-inactivated Streptococcus pyogenes. Interestingly, fusions of immature DCs generated in the presence of HCCsp and allogeneic HCC cells promoted the generation of CD4+ CD25high Foxp3+ Treg and inhibited CTL induction in the presence of HCCsp. Importantly, up-regulation of MHC class II, CD80, and CD83 on DCs was observed in the patient with advanced HCC after vaccination with autologous FCs. In addition, the FCs induced WT1- and CEA-specific CTL that were able to produce high levels of IFN-γ. Conclusion The current study is one of the first demonstrating the induction of antigen-specific CTL and the generation of Treg by fusions of DCs and HCC cells. The local tumor-related factors may favor the generation of Treg through the inhibition of DCs maturation; however, fusion cell vaccination results in recovery of the DCs function and induction of antigen-specific CTL responses in vitro. The present study may shed new light about the mechanisms responsible for the generation of CTL and Treg by FCs.

The effects of specimen geometry on the Poisson's ratio of a quasi-isotropic carbon-fiber-reinforced polymer laminate were examined using compression tests. In particular, the divergence of the apparent Poisson's ratio from the theoretical value was experimentally determined for a decreasing specimen width/thickness ratio (b/t). The observed tendency was then confirmed by simulations using a finite element analysis (FEA). The FEA was performed using a 3D model of the specimens to investigate the strain and stress distribution. In the evaluation of the apparent Poisson's ratio, the strain in the width direction was shown to vary under the condition of low b/t. The FEA results revealed that changes to the width strain were caused by cross-sectional deformation under compressive loading, resulting from differences in layer angles and stiffness between the outermost and inner layers. [ABSTRACT FROM AUTHOR]

To propose a test method for the out-of-plane tensile modulus of laminated carbon fiber-reinforced plastics, 3-point bending tests using a laminated CFRP with the span direction coinciding with out-of-plane (through-the-thickness) direction were performed. It was demonstrated that the apparent bending modulus depends on the length of span to thickness ratio (L/t) and the tensile modulusEto shear modulusGratio (E/G). Sensitivity analyses were performed to select the length of span to thickness ratio in order to evaluate the bending modulus near material modulus. Consequently, it is predicted that the bending modulus performed with theL/t > 25 bending specimen is equivalent to tensile modulus, if the apparent bending modulus were evaluated from 1 to 15 GPa, while modified equations for the out-of-plane modulus of QI-CFRP laminates obtained by three-dimensional laminate theory were also derived. This modification took stress condition in consideration of the small in-plane size like bending specimens into account. Moreover, it is demonstrated that apparent bending moduli were evaluated between upper and lower bound solutions. The upper bound solution is an out-of-plane modulus based on existing three-dimensional laminate theory, and the other is modified out-of-plane modulus. [ABSTRACT FROM PUBLISHER]

Abstract: Fetal calf serum (FCS)-independent pancreatic cancer cells were established in plasma protein fraction (PPF)-supplemented medium that is an agent of good manufacturing practice (GMP) grade. Dendritic cells (DCs) were activated with the Toll-like receptor agonist, penicillin-inactivated Streptococcus pyogenes (OK-432) that is also a GMP grade agent. Therefore, sufficient amounts of FCS-independent fusions were successfully generated with decreased potential hazards of FCS. The FCS-independent fusions expressed tumor-associated antigens, HLA-DR, costimulatory molecules, IL-12, and IL-10. Stimulation of T cells with fusions from healthy donors resulted in proliferation of T cells with high expression levels of perforin/granzyme B and IFN-γ and efficient induction of antigen-specific cytotoxic T lymphocytes (CTLs). Selection and expansion of T-cell clones were confirmed by TCR Vβ analysis. However, fusions from patients with metastatic pancreatic cancer induced increased expression levels of TGF-β1 in CD4+ CD25high T cells and low levels of CTLs with decreased IFN-γ production. [Copyright &y& Elsevier]

The goal of cancer vaccines is to induce antitumor immunity that ultimately will reduce tumor burden in tumor environment. Several strategies involving dendritic cells- (DCs)- based vaccine incorporating different tumor-associated antigens to induce antitumor immune responses against tumors have been tested in clinical trials worldwide. Although DCs-based vaccine such as fusions of whole tumor cells and DCs has been proven to be clinically safe and is efficient to enhance antitumor immune responses for inducing effective immune response and for breaking T-cell tolerance to tumor-associated antigens (TAAs), only a limited success has occurred in clinical trials. This paper reviews tumor immune escape and current strategies employed in the field of tumor/DC fusions vaccine aimed at enhancing activation of TAAs-specific cytotoxic T cells in tumor microenvironment. [ABSTRACT FROM AUTHOR]

The aim of cancer vaccines is induction of tumor-specific cytotoxic T lymphocytes (CTLs) that can reduce the tumor mass. Dendritic cells (DCs) are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Thus, DCs-based vaccination represents a potentially powerful strategy for induction of antigen-specific CTLs. Fusions of DCs and whole tumor cells represent an alternative approach to deliver, process, and subsequently present a broad spectrum of antigens, including those known and unidentified, in the context of costimulatory molecules. Once DCs/tumor fusions have been infused back into patient, they migrate to secondary lymphoid organs, where the generation of antigen-specific polyclonal CTL responses occurs. We will discuss perspectives for future development of DCs/tumor fusions for CTL induction. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Therefore, their use for the active immunotherapy against cancers has been studied with considerable interest. The fusion of DCs with whole tumor cells represents in many ways an ideal approach to deliver, process, and subsequently present a broad array of tumor-associated antigens, including those yet to be unidentified, in the context of DCs-derived costimulatory molecules. DCs/tumor fusion vaccine stimulates potent antitumor immunity in the animal tumor models. In the human studies, T cells stimulated by DC/tumor fusion cells are effective in lysis of tumor cells that are used as the fusion partner. In the clinical trials, clinical and immunological responses were observed in patients with advanced stage of malignant tumors after being vaccinated with DC/tumor fusion cells, although the antitumor effect is not as vigorous as in the animal tumor models. This review summarizes recent advances in concepts and techniques that are providing new impulses to DCs/tumor fusions-based cancer vaccination. [ABSTRACT FROM AUTHOR]

Background: Human hepatocellular carcinoma (HCC) cells express WT1 and/or carcinoembryonic antigen (CEA) as potential targets for the induction of antitumor immunity. In this study, generation of cytotoxic T lymphocytes (CTL) and regulatory T cells (Treg) by fusions of dendritic cells (DCs) and HCC cells was examined. Methods: HCC cells were fused to DCs either from healthy donors or the HCC patient and investigated whether supernatants derived from the HCC cell culture (HCCsp) influenced on the function of DCs/HCC fusion cells (FCs) and generation of CTL and Treg. Results: FCs coexpressed the HCC cells-derived WT1 and CEA antigens and DCs-derived MHC class II and costimulatory molecules. In addition, FCs were effective in activating CD4+ and CD8+ T cells able to produce IFN-γ and inducing cytolysis of autologous tumor or semiallogeneic targets by a MHC class I-restricted mechanism. However, HCCsp induced functional impairment of DCs as demonstrated by the down-regulation of MHC class I and II, CD80, CD86, and CD83 molecules. Moreover, the HCCsp-exposed DCs failed to undergo full maturation upon stimulation with the Toll-like receptor 4 agonist penicillin-inactivated Streptococcus pyogenes. Interestingly, fusions of immature DCs generated in the presence of HCCsp and allogeneic HCC cells promoted the generation of CD4+ CD25high Foxp3+ Treg and inhibited CTL induction in the presence of HCCsp. Importantly, up-regulation of MHC class II, CD80, and CD83 on DCs was observed in the patient with advanced HCC after vaccination with autologous FCs. In addition, the FCs induced WT1- and CEA-specific CTL that were able to produce high levels of IFN-γ. Conclusion: The current study is one of the first demonstrating the induction of antigen-specific CTL and the generation of Treg by fusions of DCs and HCC cells. The local tumor-related factors may favor the generation of Treg through the inhibition of DCs maturation; however, fusion cell vaccination results in recovery of the DCs function and induction of antigen-specific CTL responses in vitro. The present study may shed new light about the mechanisms responsible for the generation of CTL and Treg by FCs. [ABSTRACT FROM AUTHOR]