Search

Background: We have developed a glypican-1 (GPC1) targeted CAR-T cell with strong anti-tumor effects against solid tumors in vivo (Kato et al 2020 eLife). In general, an antibody is used for detection of target protein expression in the tumor to identify appropriate targets for the CAR-T cell therapy in solid tumors. However, the local conjunction between CAR-T cells and the target is not exactly the same in the antibody and the target because CAR-T cell recognizes the target by single-chain variable fragment (scFv). In this study, we evaluated the anti-GPC1 scFv-Fc fusion protein as a detection tool of GPC1 expression in human cancer cell lines. Methods: The sequences encoding the anti-GPC1 scFv are based on the sequence of anti-GPC1 mAb (clone: 1-12) that recognizes human and mouse GPC1 (Harada et al., 2017). The sequences of anti GPC-1 scFv were cloned into pCAG-Neo mIgG2a-Fc plasmid for the generation of anti GPC1_scFv-mIgG2a_Fc fusion proteins. The plasmids were transfected into 293 T cells and the fusion proteins were purified from their culture supernatants using Antibody TCS Purification Kit. LK2-GPC1 (a GPC1 overexpressing lung carcinoma cell line), TE8 (an esophageal carcinoma cell line with endogenous GPC1) and LK2-mock (a GPC1-negative lung carcinoma cell line) were used for the evaluation of the anti-GPC1 scFv-Fc fusion protein. Results: In FACS assays, fluorescence microscopy analysis and immunohistochemistry staining, GPC1 expression was successfully detected by both anti-GPC1 scFv of VL-VH and VH-VL in LK2-GPC1 and TE-8, and not detected in LK2-mock. Localization of GPC1 expression on the cell membrane was confirmed by fluorescence microscopy. Perspective: Further comparative evaluation between anti-GPC1 antibody and anti-GPC1 scFv-Fc fusion proteins are needed especially in human tumor tissues. We plan to evaluate a relationship between GPC1 positivity in various human tumor tissues detected by anti-GPC1 scFv-Fc fusion protein and CAR-T cell cytotoxicity against the tissue. Citation Format: Takeshi Sawada, Tomonori Yaguchi, Yuko Sakai, Chinatsu Suzuki, Kenji Morii, Masahiko Aoki, Masaru Fukahori, Satoshi Serada, Tetsuji Naka, Jun K. Yamashita, Yutaka Kawakami, Takako E. Nakajima. Evaluation of the anti-GPC1 scFv-Fc fusion protein as a detection tool of GPC1 expression in human cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 907.

BackgroundUnderstanding the mechanisms of non-T cell inflamed tumor microenvironment (TME) and their modulation are important to improve cancer immunotherapies such as immune checkpoint inhibitors. The involvement of various immunometabolisms has recently been indicated in the formation of immunosuppressive TME. In this study, we investigated the immunological roles of stearoyl-CoA desaturase 1 (SCD1), which is essential for fatty acid metabolism, in the cancer immune response.MethodsWe investigated the roles of SCD1 by inhibition with the chemical inhibitor or genetic manipulation in antitumor T cell responses and the therapeutic effect of anti-programmed cell death protein 1 (anti-PD-1) antibody using various mouse tumor models, and their cellular and molecular mechanisms. The roles of SCD1 in human cancers were also investigated by gene expression analyses of colon cancer tissues and by evaluating the related free fatty acids in sera obtained from patients with non-small cell lung cancer who were treated with anti-PD-1 antibody.ResultsSystemic administration of a SCD1 inhibitor in mouse tumor models enhanced production of CCL4 by cancer cells through reduction of Wnt/β-catenin signaling and by CD8+ effector T cells through reduction of endoplasmic reticulum stress. It in turn promoted recruitment of dendritic cells (DCs) into the tumors and enhanced the subsequent induction and tumor accumulation of antitumor CD8+ T cells. SCD1 inhibitor was also found to directly stimulate DCs and CD8+ T cells. Administration of SCD1 inhibitor or SCD1 knockout in mice synergized with an anti-PD-1 antibody for its antitumor effects in mouse tumor models. High SCD1 expression was observed in one of the non-T cell-inflamed subtypes in human colon cancer, and serum SCD1 related fatty acids were correlated with response rates and prognosis of patients with non-small lung cancer following anti-PD-1 antibody treatment.ConclusionsSCD1 expressed in cancer cells and immune cells causes immunoresistant conditions, and its inhibition augments antitumor T cells and therapeutic effects of anti-PD-1 antibody. Therefore, SCD1 is an attractive target for the development of new diagnostic and therapeutic strategies to improve current cancer immunotherapies including immune checkpoint inhibitors.

Modulation of the immunosuppressive tumor microenvironment (TME) is essential for enhancing the anti‐tumor effects of immune checkpoint inhibitors (ICIs). Adhesion molecules and enzymes such as vascular adhesion protein‐1 (VAP‐1), which are expressed in some cancers and tumor vascular endothelial cells, may be involved in the generation of an immunosuppressive TME. In this study, the role of VAP‐1 in TME was investigated in 2 murine colon cancer models and human cancer cells. Intraperitoneal administration of the VAP‐1‐specific inhibitor U‐V296 inhibited murine tumor growth by enhancing IFN‐γ‐producing tumor antigen‐specific CD8+ T cells. U‐V296 exhibited significant synergistic anti‐tumor effects with ICIs. In the TME of mice treated with U‐V296, the expression of genes associated with M2‐like macrophages, Th2 cells (Il4, Retnla, and Irf4), angiogenesis (Pecam1), and fibrosis (Acta2, Loxl2) were significantly decreased, and the Th1/Th2 balance was increased. H2O2, an enzymatic product of VAP‐1, which promoted the production of IL‐4 by mouse Th2 and inhibited IFN‐γ by mouse Th1 and human tumor‐infiltrating lymphocytes, was decreased in tumors and CD31+ tumor vascular endothelial cells in the TMEs of mice treated with VAP‐1 inhibitor. TCGA database analysis showed that VAP‐1 expression was a negative prognostic factor in human cancers, exhibiting a significant positive correlation with IL‐4, IL4R, and IL‐13 expression and a negative correlation with IFN‐γ expression. These results indicated that VAP‐1 is involved in the immunosuppressive TMEs through H2O2‐associated Th2/M2 conditions and may be an attractive target for the development of combination cancer immunotherapy with ICIs., In this study, we have identified the involvement of H2O2, an enzymatic product of vascular adhesion protein‐1, as a new mechanism for the generation of an immunosuppressive tumor microenvironment in murine tumor models and some human cancers. Administration of a VAP‐1 inhibitor augmented tumor antigen‐specific CD8+ T cells by reversing this immunosuppressive condition, and showed synergistic anti‐tumor effects with ICIs including anti‐PD‐1 and CTLA‐4 Abs.

Current xenogeneic mouse models cannot evaluate on-target off-tumor adverse effect, hindering the development of chimeric antigen receptor (CAR) T cell therapies for solid tumors, due to limited human/mouse cross-reactivity of antibodies used in CAR and sever graft-versus-host disease induced by administered human T cells. We have evaluated safety and antitumor efficacy of CAR-T cells targeting glypican-1 (GPC1) overexpressed in various solid tumors. GPC1-specific human and murine CAR-T cells generated from our original anti-human/mouse GPC1 antibody showed strong antitumor effects in xenogeneic and syngeneic mouse models, respectively. Importantly, the murine CAR-T cells enhanced endogenous T cell responses against a non-GPC1 tumor antigen through the mechanism of antigen-spreading and showed synergistic antitumor effects with anti-PD-1 antibody without any adverse effects in syngeneic models. Our study shows the potential of GPC1 as a CAR-T cell target for solid tumors and the importance of syngeneic and xenogeneic models for evaluating their safety and efficacy.

Immunodeficient mice engrafted with human peripheral blood cells are promising tools for in vivo analysis of human patient individual immune responses. However, when human peripheral blood mononuclear cells (PBMCs) are transferred into NOG (NOD/Shi-scid, IL-2rg (null)) mice, severe graft versus host disease (GVHD) hinders long term detailed analysis. Administration of human PBMCs into newly developed murine MHC class I- and class II-deficient NOG (NOG-dKO; NOG- Iab, B2m-double-knockout) mice showed sufficient engraftment of human immune cells with little sign of GVHD. Immunization with influenza vaccine resulted in an increase in influenza-specific human IgG Ab, indicating induction of antigen-specific B cells in the NOG-dKO mice. Immunization with human dendritic cells pulsed with HLA-A2 restricted cytomegalovirus peptide induced specific cytotoxic T cells, indicating the induction of antigen-specific T cells in the NOG-dKO mice. Adoptive cell therapies (ACTs) using melanoma antigen recognized by T cells (MART-1)-specific TCR-transduced activated T cells showed strong tumor growth inhibition in NOG-dKO mice without any sign of GVHD accompanied by preferential expansion of the transferred MART-1-specific T cells. ACTs using cultured human melanoma infiltrating T cells also showed anti-tumor effects against autologous melanoma cells in NOG-dKO mice, in which changes in human cancer phenotypes by immune intervention, such as increased CD271 expression, could be evaluated. Therefore, NOG-dKO mice are useful tools for more detailed analysis of both the induction and effector phases of T-cell and B-cell responses for a longer period than regular NOG mice.

Immune checkpoint blockade (ICB) and adoptive cell therapies (ACT) with antigen-receptor gene-engineered T cells have been shown to be successful for a limited number of patients with solid tumors. Responders to ICB therapy typically have T cell-inflamed tumors. Thus, it is important to develop strategies that convert non-T cell-inflamed tumors to T cell-inflamed tumors. Although chimeric antigen receptor transduced T (CAR-T) cell therapy targeting hematological malignancies demonstrated durable clinical responses, the success of gene-engineered T cell therapies in solid tumors is hampered by a lack of unique antigens, antigen loss in cancer cells, and the immune-suppressive tumor microenvironment (TME) of solid tumors. However, gene-engineered T cells possess strong killing activity and cytokine production capacity, which can induce antigen spreading and modulate the TME of non-T cell-inflamed tumors seen in non-responders to ICB therapy. Immune responses against cancer are highly heterogeneous, not only between tumor types, but also within a patient or between different patients with the same type of cancer, indicating that personalized immunotherapy should be employed, based on the immune status of the individual patient. Here, we offer our perspective for personalized combination immunotherapy for solid tumors based on ACT and ICB therapies.

Objective To determine the involvement of homeobox D9 (HOXD9) in the survival, proliferation, and metastasis of cervical cancer cells through regulating the expression of human papillomavirus (HPV) 16 E6/E7 genes using the P97 promoter. Methods One hundred cases of cervical cancer (CC), CC cell lines SKG-I, SKG-II, SKG-IIIa, SKG-IIIb, HeLa, and SiHa, and a human tumor xenograft mouse model were used to examine the roles of HOXD9 in CC. Knockdown experiments employed RNA interference of HOXD9. qPCR, functional assays, western blotting, DNA microarray, and luciferase and ChIP assays were applied for assessments. Results All CC cell lines expressed HOXD9 mRNA and protein. In uterine CC, HOXD9 gene expression was significantly higher than in normal cervical tissues. A positive correlation of lymphovascular space invasion and lymph node metastasis with high levels of HOXD9 expression was found in patient samples. HOXD9-knockdown cells in the mouse xenograft model only formed small or no tumors. Knockdown of HOXD9 markedly reduced CC cell proliferation, migration and invasion, induced apoptosis, increased P53 protein expression, and suppressed HPV E6/E7 expression by directly binding to the P97 promoter of HPV16 E6/E7 genes. A positive correlation between HOXD9 and HPV16 E6 expression was found in CC patients. Conclusions HOXD9 promotes HPV16 E6 and E7 expression by direct binding to the P97 promoter, which enhances proliferation, migration, and metastasis of CCr cells. Our results suggest that HOXD9 could be a prognostic biomarker and potential therapeutic target in CC.

Seebeck coefficient of the structurally one-dimensional material, TlInSe 2 , known as a p-type conductor, has been measured in the temperature range 70 °C to 500 °C in vacuum by using four probe techniques. At temperatures above 200 °C this coefficient is found to be negative. With temperature down to below 200 °C, the coefficient is becoming positive and huge to a cutting-edge value of 10 7 μV/°C. The obtained results are discussed in terms of an incommensurate superlattice phase, which might have taken place in TlInSe 2 at temperatures below 200 °C, and led to the above unique thermoelectric properties of this material. It is expected that thermoelectric devices based on TlInSe 2 will have superior parameters.

[PtMnSb 15 nm /Si 10 nm ] *7 ferromagnet/semiconductor multilayered films were synthesized by solid-state reaction of [(Pt 0.69 nm /Mn 0.44 nm /Sb 0.37 nm ) *10 /Si 10 nm ] *7 elemental multilayers. Two different thermal treatments, i.e . the post-annealing and the simultaneous annealing (substrate heating during deposition) were employed to control the interdiffusion and the compound phase formation. Structural characterizations revealed that these films were composed of the PtMnSb, amorphous Si and interdiffusion layers. Moreover, the films produced by simultaneous annealing had the relatively thick interdiffusion layers rather than the films by the post-annealing. According to the magnetization measurements, we obtained the larger value of saturation magnetization for the simultaneous annealed film rather than that for the post-annealed one. We will discuss the structural and magnetic properties of the samples in conjunction with the extent of the interdiffusion as well as the crystallinity of the magnetic compound.

A novel synthesis method of Ba–Ga–Ge type-I clathrates is proposed. It enables us to use BaCO 3 for one of the starting materials in place of Ba metals, which should be the greatest advantage of handling the materials, from the viewpoint of possible industrial application in the near future. By using this method, we have successfully produced the Ba 8 Ga 16 Ge 30 compounds from the starting materials BaCO 3 , Ge and Ga. The synthesis reaction should occur simultaneously with the reduction reaction of BaCO 3 , which requires rather high reaction temperature beyond 1573 K. However, the resulting reactant still contains additional phases, such as Ge and Ba–Ga–O phases. The samples exhibited a positive value of the Seebeck coefficient from room temperature to 973 K, in spite of the fact that the Ba–Ga–Ge type-I clathrates were usually reported to show negative Seebeck coefficient.

High coercivity barium ferrite (BaFe12O19) powders have been prepared by a coprecipitation method. After removing fine powders, they were incorporated into a natural rubber matrix with different loading levels up to 120 phr (part per hundred rubber). The variations in characteristics of rubber–ferrite composites (RFCs) were evaluated as a function of ferrite loading. The results showed that the coercivity is improved and the saturation magnetization is linearly dependent on the mass fraction of the filler, while the tensile strength, strain at break and modules are highly influenced by the size, shape and volume fraction of ferrite particles. The present RFCs showed a typical characteristic of low density (2.2 g/cm3), high stored energy (BHmax = 1.18 MG Oe) and flexibility (resilience = 0.844) at 120 phr of ferrite, which are relatively high when compared to previous works.

Six kinds of powder samples with a different particle size and its distribution have been prepared from coprecipitated precursors by light grinding followed by sieving, and calcined in air to form the barium ferrite (BaFe 1 2 O 1 9 ) phase. Correlation between the particle morphology and Fe/Ba molar ratio or magnetic properties has been examined. The results indicated that the powders consisting of coarse particles (100-200 μm) exhibit a single phase of BaFe 1 2 O 1 9 , and a higher saturation magnetization and coercivity than the powders having fine particles or a wide size distribution. The optimized powders showed a high coercivity of 5.85 kOe and a saturation magnetization of 71 emu/g that are closed to the theoretical values.

To study dry sliding wear behavior and its relation to microstructure, Ti–50Al alloys and Ti–47Al–3W alloy and its composite with varying reinforcement of Ti2AlC were prepared by reactive arc-melting. Dispersion of fine B2 particles is obtained by the addition of tungsten to TiAl alloy, which improves both the hardness and wear resistance of the matrix. By adding carbon to Ti–47Al–3W alloy, composite can be produced having a random distribution of reacted rod-like Ti2AlC particles and smaller Ti2AlC precipitates with fine B2 particles in the matrix. The Ti–47Al–3W/3.5 vol%Ti2AlC intermetallic composite features excellent wear resistance compared to 10 and 18 vol% composites, and fine dispersion of the Ti2AlC and B2 particles in the matrix has improved the wear resistance properties.

The growth of single crystalline oxides on silicon substrates still remains a subject of significant technological interest, since fruitful achievements can be expected by their use in various silicon device technologies. We have examined the possibility of the epitaxial growth of BaZrO3 films on Si(001) substrates by pulsed laser beam deposition. It was found that the 3-ML-thick Ba-rich Ba–Zr–O layer could act as an excellent buffer layer leading to epitaxial growth of the subsequently deposited stoichiometric BaZrO3 layer. We succeeded in obtaining the heteroepitaxially grown BaZrO3 films on Si(001) substrates.

Ti-B-N cast alloys were prepared by a reactive arc-melting technique using elemental titanium and boron nitride powders. The alloys obtained were composites of titanium matrix containing nitrogen of 3 mol% or less and a small amount of TiB reinforcement. The microstructure of the matrix was a cellular structure consisting of elongated dislocation cells with 1-2 μm in width and 5-10 μm in length, for Ti-1B-1N alloy. The TiB particles were rod-like in shape with size of less than 0.5 μm in diameter and agglomerated to form clusters along the grain boundary. The mechanical properties were mainly dependent on the content of nitrogen and the influence of TiB on the mechanical properties was relatively small. The Ti-B-N cast alloys containing suitable concentration of nitrogen, Ti-0.58-0.5N alloys, had a high strength of 920 MPa with adequate ductility of more than 5%.

TiAl(Cr)/Ti 2 AlC composites have been prepared by a reactive arc-melting technique using elemental powders of Ti, Al, Cr and C. Resulting composites have been reinforced using 3.5, 10 and 18 vol% Ti 2 AlC in a matrix of TiAl with and without addition of Cr. The axial ratio of γ-phase has been lowered through the complete solid solution of chromium. The grain size of the matrix has been found to decrease whereas its distribution converges along the content of Ti 2 AlC. The lamella grains in the matrix have been changed both into TiAl and very fine Ti 2 AlC particles by a homogenizing treatment. Compared to TiAl single-phase alloy, studied composite materials have revealed superior mechanical properties, such as bending strength, compressive strength and fracture toughness. This improvement is caused by the formation of Cr solid-solution for hardening, dispersion of the Ti 2 AlC particles and the fine grain of the TiAl matrix.

Antimony-doped MnPt 3 thin films have been successfully fabricated by solid-state reaction of thin multilayered Mn/Sb/Pt films. It was found that the (100) preferential orientation of the MnPt 3 phase was developed with increasing antimony content. In addition to this, an anomalous crystalline growth with (100) oriented grains was observed, which resulted in a wide distribution of the grain size of the annealed samples. This behavior is considered to be secondary grain growth, which is usually caused by a surface free energy minimization rule. However, the (100) planes of MnPt 3 do not have the lowest surface free energy. We discuss the mechanism of this anomalous grain growth from the view-point of strain energy minimization, in conjunction with the anisotropy in the strain energy density for each crystallographic plane of MnPt 3 .

We have successfully produced LaCoO 3 thin films by ion-beam sputtering and subsequent heat treatment. The compacts of La 2 O 3 and CoO powder mixture were used for the targets. The films were mainly composed of the LaCoO 3 phase, with a very small amount of an unidentified second phase. The resistivity at room temperature for the annealed 50 at.% La sample was determined to be 51 Ω m, whereas at high temperature, the resistivity was found to be same order of that for bulk LaCoO 3 , that is, comparable to the resistivity for metals. The possibility of a metal–insulator transition is described.

TiAl/Ti2AlN composites were prepared by a reactive arc-melting technique using elemental powders of Ti, Al, and AlN . Ti2AlN particles synthesized by the combustion reaction synthesis were dispersed in the lamella grains, with rod-like shapes with sizes of 1–3 \\micron width and 5–15 \\micron length. The grain size of the matrix was decreased and the deviation of the grain size was converged by the distribution of the Ti2AlN . The lamella grains in the matrix were decomposed both into TiAl and very fine Ti2AlN particles by the homogenizing treatment. The bending strength of these composites was larger than that of TiAl single-phase material and it was improved by increasing the Ti2AlN content. Their ductility kept the same level of that of TiAl. Fracture toughness values were enhanced by the dispersion of Ti2AlN, since crack propagation can be deviated by such dispersoids in the composite materials.

We have investigated the structural and electric properties of TiB 2 thin films produced by RF sputtering on glass substrates. The films are composed of the TiB 2 small crystallites as well as the Brich amorphous phase, which is resulting from the Brich composition of the films. The resistivities of the films vary from 239 to 323 μΩ cm depending on the RF power and the sputter time. These values are considerably larger than that of a bulk sample. The temperature dependence of the resisitivities is found to be carrier concentration dependent. However, the very high carrier densities (0.7–1.2×10 22 /cm 3 ) and the relatively small mobilities (2.3–5.7 cm 2 V −1 s −1 ) were obtained, suggesting that the conduction carrier might behave like nearly free electrons. We discuss these features in conjunction with the microstructure of the films.

The Ll 2 -(Al, Cr) 3 Ti/TiB 2 + Ti 2 AlC composites were prepared by reactive arc-melting from the elemental powders of titanium, aluminum, chromium, and B 4 C powder. The resulting composites have reinforcement 3.8, 7.5, and 15 vol% (TiB 2 + Ti 2 AlC) in the matrix of Ll 2 trialuminide Ti-61Al-14Cr alloy. The TiB 2 particles were mass-like with 5-10 μm in diameter, while the Ti 2 AlC particles were rod-like in shape with 1-2 μm in width and 5-15 μm in length and they are homogeneously distributed in the matrix. These composite materials have a high strength at ambient temperature; about 600 MPa with an ambient temperature ductility of 0.3-0.4% (plastic bend strain). The fracture toughness tests have shown that the composites have higher toughness than that of the matrix alloy. The zigzag cracks propagated in the composite, and the reinforcements TiB 2 and Ti 2 AlC particles and the fine grains of matrix were the main obstacles to the crack propagation.

Sintering of elemental powders and conventional arc-melting were used to form temary L1 2 intermetallic compounds in the Al-Ti-Fe system. The L1 2 phase field and phase equilibria surrounding the L1 2 phase in the temperature range of interest were established. Two isothermal sections at 1423 and 1273 K were determined from metallography, X-ray diffraction and electron probe microanalyses. The compositions of L12 phase field, the center compositions of oval-shaped region, were about 28Ti-8Fe-64Al and 27Ti-9Fe-64Al compositions at 1423 and 1273 K, respectively. Thus the L1 2 phases had less ternary and more titanium than those reported in the other Al-Ti-X (X = Mn, Cr) systems. Besides the L1 2 phase, the pertinent second phases were TiAl (L1 0 -type), TiAl 2 (HfGa 2 -type), Ti 2 Al 5 (28 atoms/unit cell-type), Al 3 Ti (D0 22 -type), C14 (Laves phase, MgZn 2 -type), and D8 a (cubic, Mn 23 Th 6 -type). The solubility of iron in TiAl 2 phase was about 2 and 3 mol% at 1423 and 1273 K, respectively. The TiAl 2 phase is more stable at 1273 K and can coexist with L1 2 , TiAl, C14, and D8 a phases in separate phase fields. Thus in the isothermal section at 1273 K, no two-phase equilibrium between the TiAl and L1 2 phases exists. This impedes the development of bonding between TiAl and L1 2 alloys in coating applications.

Gamma titanium aluminides ({gamma}-TiAl alloys), having an L1{sub 0}-type structure, are candidate materials for use in future gas turbine aero-engines and automotive engines because of their low density, high specific strength and high stiffness. In air, however, it is well known that titanium aluminide oxidizes at a more rapid rate at temperatures above 1,123 K; therefore, the oxidation resistance becomes a critical factor for TiAl alloys to be used at high temperatures (perhaps above 1,073 K). Coatings for the TiAl alloy are essential to high temperature oxidation resistance. The Al-Ti-Cr ternary phase diagram at 1,423 K indicates that the L1{sub 2} phase field is in equilibrium with the TiAl(L1{sub 0}) phase field. Furthermore, the L1{sub 0}- and L1{sub 2}-alloys in this ternary system resemble each other very closely in crystal structure and lattice parameter (TiAl(L1{sub 0}); a = 0.4005, c = 0.4070 nm (27), Ti-67Al-8Cr(L1{sub 2}); a = 0.3960nm (25)). Therefore, the L1{sub 2}-(Al,Cr){sub 3}Ti alloy can be considered applicable to L1{sub 0}-TiAl alloys as an optimum material for coatings. The purpose of this study is to apply L1{sub 2} alloy coatings to the TiAl alloys by pack cementation techniques, and to evaluate the oxidation resistance of the coated alloys.

Solid-state phase formation in Mn/Ge thin multilayered films with the composition of 75 at%Mn–25 at%Ge was investigated. The κ-Mn5Ge2(LT) and ζ-Mn5Ge2(HT) phases were identified on annealing at 773 K. Although ζ-Mn5Ge2 is known to be a high-temperature phase above 900 K, the formation of this phase was confirmed on 773 K annealing. This may be due to non-equilibrium thin film reaction process in multilayered films. Whereas on annealing at 973 K, the unknown magnetic phase with a tetragonal cell structure was formed. The lattice constant was determined to be a=0.5174 and c=1.580 nm by micro beam electron diffraction. The saturation magnetization of this phase is 2.4 emu/g at room temperature and 160 emu/g at low temperature (5 K), which is almost equal to the magnetization of ferromagnetic η-Mn5Ge3.

In order to increase the capacity of miniaturized button-type batteries, the thickness of the Cu/18Cr-8Ni-Fe(SUS304)/Ni clad metals which are applied to the anode cases should be reduced. Therefore it is required that the clad metals have higher strength and excellent drawability. We found that the clad metals had good properties (high tensile strength and small planar anisotropy) which the SUS304 single sheet did not have, as a result of examination of the rolling and annealing process. The texture formation of the clad metals was investigated, and the influence of texture on the r-values is discussed in this research. The SUS304 in the clad metals with good properties has lower Goss and higher brass orientation density than the SUS304 single sheet under the 25% finish rolled condition after annealing. The orientation densities on α- and β-fibers of SUS304 and Cu in the clad metals are qualitatively similar to each other, and different from those of the SUS304 single sheet. This suggests that the characteristic texture of SUS304 in the clad metals is formed through the influence of the Cu layer. The planar anisotropy of r-values was calculated from ODF to inquire into the effect of the texture on r-values by using Taylor's full constraints model and relaxed constraints model. This result corresponded well to the measured r-value, especially in the relaxed constraints model.

Intermetallic compound TiAl-base composites have been prepared by the hot isostatic pressing (HIP) reactive sintering technique. These composites have been synthesized from a powder mixture of titanium, aluminum and boron nitride, and contain Ti 2 AlN and TiB 2 strengthening particles. Nearly spherical particles of Ti 3 Al and Ti 2 AlN of about 20 μm in diameter have been embedded in the TiAl phase. The composite has been found with a dual phase matrix structure. The Ti 2 AlN phase is composed of about 300-500 nm grains and includes dispersion of nano scaled TiB 2 particles (about 50-100 nm). Both compression tests and hardness measurements have revealed that this composite material attains higher strength as compared with non-reinforced TiAl. The insufficient bending ductility, however, hinders its bending fracture strength at ambient temperature.

To improve the oxidation resistance of γ-TiAl alloys, Ti-43Al-5Cr(L1 0 ) alloy substrates were coated with the L1 2 -(Al, Cr) 3 Ti layer by pack cementation. Coatings were formed by immersing the substrate in a mixture consisting typically of 90%Ti-61Al-14Cr(L1 2 ) alloy powders and 10%Al 2 O 3 powders, without activators, e.g., NH 4 Cl powders, and then heating in an alumina boat under a vacuum of ∼ 10 -4 Pa for 1 ∼ 96 h at 1423 K. The coating layer for γ-TiAl alloys was effectively formed by surface diffusion and bulk diffusion of aluminum, titanium and chromium from pack alloy powders, and consisted of the two diffusion layers; outer L1 2 -phase layer and inner L1 0 -phase layer. In these layers, the graded alloy composition for the oxidation resistant coating was successfully established. The coated alloy showed a remarkable improvement in the oxidation resistance over the uncoated TiAl alloys.

Diffusion bonding of L10-type and L12-type alloys in the Ti-Al-Cr system was carried out to study graded diffusion layer. The Ti52Cr5Al43(L10) and Ti25Cr14Al61(L12) alloys were bonded at 1473 K for 1 h under 30 MPa, and annealed at 1423 K for 48 h in a vacuum(-10-4Pa). The resulting diffusion layer had Al-rich L10 phase layer of about 50μm and L12/L10 (coherent precipitated) two phase layer of about 50μm. The formation of the L12/L10 two phase layer is caused by the presence of the Ti-rich L12 phase field at higher temperatures. It was found that such diffusion layers have a preferable composition gradient and a graded linear expansion coefficient for functionally graded materials.

Using elemental powders, reactive hot-pressing was carried out to prepare Si3N4/SiC composite ceramics. Silicon and graphite powders with additives (Al2O3 and Y2O3) were reacted at 1873K in gaseous nitrogen (0. 15MPa) and hot-pressed at 2073K for 7.2ks with applied pressure of 70MPa, and finally formed a Si3N4(β-Si3N4)-SiC(β-SiC) composite with a small amount of glassy and crystalline phases from additives. The resulting composites had 12-34vol%SiC, and the SiC grains were granular with sizes of about 0.1-1μm, and homogeneously distributed and well bonded to the matrix Si3N4. On the other hand, the Si3N4 matrix grains were rod-like in shape with sizes of 0.3-3μm. It was found that the composite ceramics had a relatively higher bending strength at both ambient and elevated (at 1423K) temperatures; about 1000 and 700 MPa, respectively. Fracture toughness of 5.3 MPam1/2 was obtained by indentation fracture tests. It was evident that reactive hot-pressing was very effective process for in-situ synthesis of Si3N4/SiC composite ceramics.

To improve low room-and high-temperature strength of titanium alminides, TiAI based composites reinforced with TiB2 and Ti2AIN particles were made by combustion reaction process using Ti-AI-BN powder mixtures, and arc-melted for densification. The powder compositions included Ti47.4Al44.2(BN)8.4, Ti49.0Al42.6(BN)8.4 and Ti50.5Al41.1(BN)8.4 in at%, corresponding to matrix composition of Ti48Al52, Ti50Al50 and Ti52Al48, respectively. The volume fraction of reinforced particles was about 18%. The as cast specimens had a matrix of TiAl(γ) with a lamellar structure of Ti3Al(α2). In the annealed specimens, such lamellar structures were completely or partially disappeared, while smaller particles (about 100-200nm) were observed in the matrix of all specimens. These particles were found to be MAIN and mainly formed in place of disappeared Ti3Al in the lamellae. The formation of these particles was attributed to different solubility limit for nitrogen in yand α2 and solutionizing α2 phase by heat treatment. It was found that the composite materials had a high strength at both room and elevated(1173K) temperatures; 800-1100MPa and about 600MPa, respectively. The bending and fracture toughness tests also proved that the composite annealed is better than the as cast, and values were about 0.4% in ductility and 13-15 MPam in fracture toughness.

To enhance the negligible low-temperature strength and ductility and low high-temperature strength of titanium aluminides, TiAl-(TiB2+Ti2A1C) composites were made by the combustion reaction processing using Ti, Al, and B4C powders, and homogenized by arc melting. The alloy composition included Ti52.2A145.6(B4C)2, 2 in at.%. The resulting composites had about 14 vol.% (TiB2+Ti2AIC) in the matrix TiAl with a lamellar structure of Ti3Al. In the homogenized specimens, such lamellar structures were not observed, therefore, the matrix after the homogenizing treatment consisted predominantly of the TiAl phase which is expected from the Ti-Al equilibrium phase diagram. On the other hand, smaller particles were visible in the matrix, and appeared to form in place of solutionizing lamellae. These particles have also identified as a Ti2A1C phase with an average particle size of about 100-200 run. This suggested that carbon atoms in the matrix, probably in the Ti3Al phase, formed carbide Ti2Al particles when the lamellar Ti3Al phase was disappeared during the homogenization treatment. It was found that the composite material has a high strength at both ambient and elevated (at 1173 K) temperatures ; about 900 and 500 MEN, respectively, and ambient-temperature ductility as large as 0.8% was obtained in bending.

Sintering of elemental powders was carried out to form ternary L1 2 intermetallic compounds in Al-Ti-Cr alloys. The L1 2 phase field and equilibrium phases surrounding the L1 2 phase at 1423 K have been established. Besides the L1 2 phase, the pertinent second phase fields have been also estimated; TiAl, TiAl 2 , Ti 2 Al 5 , Al 3 Ti, Al 17 Cr 9 , AlCr 2 , and TiAlCr phase fields. The vertical section of the Al-25 mol%Ti-Cr alloys has been experimentally determined, and the presence of the L1 2 + Liquid phase field in the present composition and temperature ranges was confirmed. Button ingots of some ternary L1 2 compounds in the Al-Ti-Cr alloys were prepared by arc-melting to investigate their microstructure (especially second phases and porosity), microhardness, and bend ductility. In general, homogenization of as arc-melted alloys substantially reduced the amount of second phases but introduced extensive porosity. Therefore, the formation of porosity is closely associated with the second phase solutionized during homogenization treatment. However, no residual porosity was observed in higher Cr alloys. The porosity after homogenization was observed when Al 17 Cr 9 phase is formed and not when the TiAlCr or AlCr 2 phase is formed. The ternary L1 2 compounds in the Al-Ti-Cr alloys had some bend ductility at ambient temperature, which can be increased to about 0.9% (plastic bend strain) by increasing the Cr content when porosity is reduced.

BaTiO3 thin films having a fine grain size

In this work, the effects of deposition and annealing conditions on the dielectric properties and dc conductivity were investigated on the thin amorphous SrTiO3 films prepared by a sputtering method using neutralized argon-ion beams. It was demonstrated that the dielectric constant and dc conductivity increased markedly by vacuum annealing and by increasing the target-substrate distance during deposition. The amorphous SrTiO3 films have the optical band gap of about 2.5eV, accompanying with rather wide band tails. This suggests the existence of structural defects which may be caused by oxygen deficiency in the amorphous structure. The amounts of the oxygen deficiency were considered to be dependent on the annealing atmosphere as well as the target-substrate spacing. It is supposed that the ionization of oxygen vacancies, Vo→Vo¨+2e', plays an important role for the dielectric properties and dc conductivity of the amorphous SrTiO3 thin flms. The relative dielectric constants obtained ranged from 20 to 550.

The ceramic composites were prepared from elemental powders, i.e., titanium powders, aluminum powders and graphite powders. The powder mixtures, with a composition Ti50Al25C25 (in atomic% ) were cold pressed, and combustion reaction was carried out to form ceramic composites in Ti-Al-C system. However, the reaction products had extensive pores. Then the products densified by hot pressing for 1.8ks at 1473K under 70MPa in Ar gas atmosphere. It was found that the matrix phase (Ti2AlC) had good properties, e.g., microhardness and thermal expansion coefficient, as a composite phase for TiAl alloys. The processing technique in the present investigation is of interest as a new combustion reaction process to synthesize in-situ ceramics and ceramic composites.