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A precise method is given for measuring the transconductance of an MOS transistor (MOST) and also its value and rate of variation. The measuring setup uses a differential amplifier, in which the output voltage of a sample MOST operated as a common-source amplifier is compared with the reference voltage derived from the attenuators used as a standard, and also a synchronous demodulator, with which the difference signal obtained from the differential amplifier is converted into corresponding dc voltage used in determining the null point. The transconductance from the 0.1 to 100-m? range is measured with an accuracy of less than two percent, over the frequency range of 0.1-10 kHz. The transconductance variation in excess of 1 ?? and also the percentage variation of transconductance in excess of 0.2 percent for an MOST with a transconductance of 1 m? is measured. Measured examples are also given.

F. r a the. retical treatment, f excess ultras, nie abs, rpti, n due t, critica uctuation, lhe reported that, the ftequency dependence of sound absorptien coefficient predicted by Fixman was appropriate to compare it quantitatively with the experimental data.In his study, the frequency dependence of sound absorption coellfieient was determined concerning critical binary mixtures above critical temperature. As the comparison of the relaxationr parameter (arialyzed by the Fixman theory) in critical binary aqueous mixture with that in non-aqueous mixture was of interest, the five systems (acetnitrile-water, triethylaminer water, diethylenglycoldiethylether-water, n-hexane-nitrobenzene and n-octane-nitrobenzene) were prepared.As the experimental results on the above systems supported the Fixman prediction, they were analyzed in terms of the Fixman theory, The results of relaxation parameter (in Table 2)sh, wed that the characteristic frequency due t, the decay rate of ctuati, n in critical binary aqueous mixtures was smaller than that in non-aqueous mixtures. These results were also supperted by the molecular parameter (in Table 4) based on the temperature dependence of sound absorption.

The cathodic polarization characteristics of the electrode consisting of poly (4-vinylpyridine) bromine complex and graphite powder were investigated. The electrolyte was propylene carbonate containing 1 M LiBr. The rest potential of the electrode was approx. 0.5 V (versus SCE). The coulometric efficiency of the continuous discharge was 52–53%.

同期信号発生器のモレクトロン化第一段階の試作を行ない, 約90%の部分をモレクトロンに置き換えることに成功し, 信頼性が向上した.しかし, 今後さらに集積化を進めるにあたって著しい小形化および性能の向上を実現するためには, 素子の高密度化, 実装方式の改良だけでは限界があり, 回路方式の再検討, 規格の統一による単純化, 機器の多機能化などが必要である.

MOSトランジスタは, ゲートとソース間からみたインピーダンスが高く, ミラー効果を利用すればQの高い可変キャパシタンス回路が構成できる. 負荷にLC並列同調回路, 固定抵抗器, およびいまひとつのMOSトランジスタを使用した可変キャパシタンス回路をそれぞれ示して解析し, 変調感度を求めた. MOSトランジスタによる正弦波発振器と組合せ, MOSトランジスタのみでAFC付発振器を構成し, 実用性を確認した. この回路はテレビ同期信号発生器のAFC付主発振回路に有用である.

ブリッジ接続形エミッタホロワのトランジスタ部分を集積化した.このブリッジ接続形エミッタホロワの電圧伝達特性は, DC～50Mcの帯域をもち, 入力アドミッタンス約30kΩ, 10pF, 出力インピーダンス約6Ωである.この回路の動作は直流動作状態の解析, hパラメーター表示, 入力アドミッタンスの周波数特性の解析などによって知られる.なお, ブリッジ接続形エミッタホロワは映像分配器, 映像切換回路などに応用できる.

The dilute solution properties of vinyl acetate–methyl acrylate random copolymers are investigated by the viscometric two-parameter theories in the statistical thermodynamics of homopolymer solution at zero frequency and by the measurement of adiabatic compressibility at 1 MHz. The short-range interaction parameter and “compressibility of mixing unit” for the copolymer are examined in relation with those of the parent homopolymers. It is found that the “compressibility of mixing unit” of polymer depends on the short-range interaction independently of the long-range interaction.

As a molecular model of the longitudinal wave relaxation at MHz range for a polymer solution, Miyahara et al. proposed the crankshaft model with single thermal relaxation. Ludlow et al. reported the model with double motions in polymer chain, regarding it as a double relaxation. Recently, Ikeda et al. reported that the MHz range compressibility of PMA in acetone solution was abnormal and the compressibility of high molecular weight PMA was smaller than that of the low molecular weight PMA when the molecular weight was higher than 1×106. It was suggested that the phenomena were related with the molecular motion during the longitudinal wave relaxation at MHz range for the polymer solution.In this study, the molecular weight dependence of the molecular motion taking place during the longitudinal wave relaxation at MHz range in PMA-acetone solution was determined by the ultrasonic method, Two PMA samples with different molecular weights (B-3, 1×106 and C-3, 56×104) were prepared.The excess absorption of PMA-acetone solution was estimated from the difference between the absorption of polymer solution and that of solvent. The result of C-3 solution was a single relaxation (hypothetical thermal relaxation). The result of B-3 solution was analyzed by the double relaxation theory. The relaxation frequencies obtained were 4MHz and 40MHz. The molecular model of relaxation for C-3 sample was given as the rotational isomer of a head-tail bond in polymer chain (ΔH°=220cal/mol, ΔH_??_=1600cal/mol). The second relaxation at 40MHz for B-3 sample was presumed to be correlated with the spreading of polymer chain, based on the solvent dependence of the relaxation.

The compressibility of polymer solutions was measured by the ultrasonic method (in Mc range). The partial specific compressibility of polymer in the solution was determined, and they yielded information about the polymer in the solution.The information on the polymer were divided into the following two parts: (1) the response of a spherical polymer chain in the solution as a pearl necklace model, (2) the response of a mixing unit of the polymer chain as a pearl in necklace.The response of a spherical polymer chain was proportional to the intrinsic viscosity of each solution, and was related to the chain dimentions as the viscometric expantion parameter was. On the other hand, the compressibility of a mixing unit of the polymer was the specific value of each component.

The release of a water soluble material, carboxyfluorescein (CF), from the interior of liposomes induced by several spermicidal agents, nonionic surfactants (TS-88, INP-90, and NOP-90), has been investigated. The efficiency of the agents for CF-release was significantly correlated with that for the inhibition of fertilizing ability of sea urchin sperm (p

Raman spectra were measured for the system consisting of α-Al 2 O 3 powder and aqueous electrolyte solution of LiNO 3 , NaNO 3 , CH 3 COOLi, and CH 3 COONa, in order to discuss a hetero-phase coexisting effect of the solid phase on the properties of the liquid phase. The Raman bands assigned to the stretching mode of OH 2 at 2800°-4000 cm −1 was distorted by the hetero-phase coexisting effect, and the distortion depended on the dissolved anionic species. The distortion for the system containing acetate anions, which have hydrophobic and hydrophilic groups, was different from those for the other systems, i.e. pure water and aqueous nitrate solutions as the liquid phase. The NO 3 symmetric stretching mode ( v 1 ) of nitrate anion at ca. 1045 cm −1 , the COO stretching mode of ( v 3 ) at ca. 1415 cm −1 , and the C-C stretching mode ( v 4 ) at ca. 925 cm −1 of acetate ion were also measured and the changes of their position are discussed. Each Raman band shifted and broadened with the content and specific surface area of the solid phase from the original position and shift for the bulk of each aqueous solution. It is suggested that the intra-molecular structure of ionic species is influenced by the existance of solid surface. The hetero-phase coexisting effects, caused by the solid phase, mainly depend mainly on the nature of anionic species in the system.

Adoptive cell therapy with lymphocytes transduced with chimeric antigen receptor (CAR) is a promising strategy to treat cancer patients. Recent success in the treatment of patients with B cell malignancy by CD19-CAR encourages the development of successive CAR therapy targeting other tumor-associated antigens. However, the search for the appropriate target molecule for CAR, other than B cell markers, is a serious question. The target of CAR is generally limited to the cellular surface molecules, making difficult to expand CAR therapy for broad range of cancer patients. Inspired by the physiological recognition of epitope peptide and MHC molecule (pMHC) by T cells, we have generated a series of antibodies that recognize the pMHC complexes with peptides derived from tumor antigens expressed intracellularly. We isolated an scFv antibody clone WT#213 that can specifically recognize WT1 p235-243 peptide (CMTWNQMNL) complexed with HLA-A*24:02 molecule by the screening of human antibody scFv phage display library. We have constructed retrovirus that encodes the CAR consists of WT#213 and intracellular signal transduction domains of CD3z and GITR (WT#213 CAR). We confirmed the specific recognition of endogenous WT1-expressing cells by the CAR-T cells with the intracellular cytokine staining and the 51Cr release cytotoxic assay. Utilizing NOG immunodeficient mice, we demonstrated the effectiveness of adoptive cell therapy with WT#213 CAR against the WT1 expressing HLA-A*24:02 positive human leukemia cells. To evaluate the safety of the WT#213 CAR, we predicted the potential property of WT#213 CAR to cross-react to normal tissues in humans. We conducted alanine scan analysis of WT1p235-243 peptide that was recognized by WT#213 CAR as well as the TCR derived from CTL clone TAK-1 which recognizes same epitope peptide in association with HLA-A*24:02 to define the amino acids that were critically important in the recognition by the WT#213 CAR or TAK-1-derived TCR. After BLAST search, we synthesized the normal protein-derived peptides with potential risk of cross-reactivity, and tested the recognition of these peptides by WT#213 CAR or TAK-1-derived TCR. Although the critical peptides, and therefore the peptides with potential risk, were quite different between the WT#213 CAR and TAK-1-derived TCR, none of these peptides showed the stimulation of WT#213 CAR or TAK-1-derived TCR. The results here suggest that the immunotherapy with WT#213 CAR will be effective for the treatment of the leukemia patients without the predicted risk at least in the evaluation we performed. Figure 1. Figure 1. Disclosures Ikeda: Takara Bio Inc.: Research Funding. Akahori:Takara Bio Inc.: Research Funding. Miyahara:Takara Bio Inc.: Research Funding. Amaishi:Takaa Bio Inc.: Employment. Okamoto:Takara Bio Inc.: Employment. Mineno:Takara Bio Inc.: Employment. Takesako:TAKARA BIO INC.: Employment. Fujiwara:Celgene: Honoraria, Other: Travel, Acomodations, Expenses.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for refractory hematologic malignancies such as leukemia and myelodysplastic syndrome. Tumor relapse, graft-vs host disease (GVHD) and infections are, however, major obstacles to successful allo-HSCT. Donor lymphocyte infusion (DLI) is carried out in some cases of tumor relapse and infections after allo-HSCT. DLI potentially induces or aggravates GVHD due to allo-reactivity of the lymphocytes used for infusion and the efficacy of DLI for tumor relapse is actually limited. Therefore, development of the method of DLI with enhanced anti-tumor effects without induction or aggravation of GVHD is expected to improve the results of DLI in the context of tumor relapse. Tumor antigen-specific T cell receptor (TCR)-expressing cell infusion is one of the potentially effective immunotherapies for refractory tumors. We previously reported that tumor antigen-specific TCR-gene-transduced human lymphocytes engineered with a novel retrovirus vector silencing endogenous TCRs showed reduced allo-reactivity (ASH annual meeting 2014). Utilizing this technology, we may be able to enhance anti-tumor effects without induction or aggravation of GVHD. In this study, we conducted a mouse pre-clinical model that mimics tumor-specific TCR-engineered DLI for tumor relapse after MHC-haploidentical HSCT and explored the effect of DLI on tumor growth and GVHD. We performed experimental study utilizing the following model: MHC-haploidentical BALB/c(H-2d)→CB6F1(H-2b/d) HSCT, BALB/c-derived sarcoma CMS5a and T cells from TCR-transgenic mouse DUC18. CMS5a has a unique mutated form of a mitogen-activated kinase ERK2, and a nonamer peptide, called 9m, incorporating the resulting amino acid substitution is presented on H-2Kd and recognized by the CD8+ CTL clone C18. DUC18 is a BALB/c-background TCR transgenic line that expresses the rearranged Vα10.1 and Vβ8.3 genes of the C18. CD8+ T cells of DUC18 mice can suppress CMS5a tumor growth in the syngeneic BALB/c hosts. Allo-reactivity of DUC18 T cells was reduced as compared to that of wild type BALB/c T cells. Based on the results of preliminary experiments, we set standard experimental conditions as follows: X-ray irradiation (10 Gy) for pre-conditioning, 5x106 whole bone marrow and 0.25x106 T cell transplant (BMT) for mild GVHD induction, 1x106 CMS5a inoculation for progressive tumor growth in BMT recipients, and 4x106 CD8+ T cells for observation of the effect of DLI on tumor growth and GVHD. In some experiment, CD4+ T cells were co-infused with CD8+ T cells. DLI was carried out 3 days after CMS5a inoculation at 2, 4 or 8 weeks after BMT. We first used CD8+ T cells from naïve BALB/c or DUC18 mice for DLI at 8 weeks after BMT. No GVHD aggravation was observed in either BALB/c or DUC18 CD8+ T cell recipients and, as expected, suppression of tumor growth was observed only in the DUC18 CD8+ T cell recipients. Next, DLIs using CD8+ T cells only, or both CD8+ and CD4+ (CD8+/CD4+) T cells from naïve mice were carried out at 4 or 2 weeks after BMT. No apparent effect of CD4+ T cell co-infusion on tumor growth and GVHD was observed in both types of donor T cell recipients when DLI was carried out at 4 weeks after BMT. However, GVHD was aggravated in CD8+/CD4+ T cell recipients from both types of donors when DLI was carried out at 2 weeks after BMT, and no CD4-driven additional anti-tumor effect was observed in DUC18 T cell recipients. We then performed DLI using in vitro activated/expanded T cells including both CD8+ and CD4+ as a more clinically relevant model. BALB/c and DUC18 splenocytes were activated and expanded in vitro and infused (adjusted CD8+ T cell number to 4x106/mouse) into recipients at 2 or 8 weeks after BMT. Aggravation of GVHD was observed in either BALB/c or DUC18 activated/expanded T cell recipients when DLI was carried out at 2 weeks after BMT. On the other hand, it was not observed when DLI was carried out at 8 weeks after BMT. Anti-tumor effect of DUC18 T cells was observed regardless of timings of DLI. Taken together, infusion of tumor-specific donor lymphocytes with reduced allo-reactivity for tumor relapse after MHC-haploidentical HSCT will be promising strategy. Timing of DLI and condition of recipients such as inflammatory status may affect GVHD. Multiple model studies are required for development of more effective DLI strategies without aggravation of GVHD. Disclosures Tawara: Astellas: Honoraria. Katayama:Nippon Shinyaku: Honoraria; Chugai: Honoraria, Research Funding; Alexion Pharmaceuticals: Honoraria; Dainippon Sumitomo Pharma: Honoraria; Pfizer: Honoraria; Celgene: Honoraria; Shionogi: Honoraria; Kyowa Hakko Kirin: Honoraria, Research Funding; Taisho Toyama Pharma: Honoraria; Shire: Honoraria; Astellas: Honoraria, Research Funding; Daiichi Sankyo: Honoraria; Eisai: Honoraria; Takeda: Honoraria; Bristol-Myers Squibb Japan: Honoraria. Ikeda:Ono Pharmaceutical Co., Ltd: Honoraria; Daiichi Sankyo Co., Ltd: Honoraria.

CD4+ Th cells, in particular IFN-γ-producing Th1 cells, play a critical role in the activation and maintenance of CD8+ Tc1 cells that are essential for tumor eradication. Recent identification of MHC class II binding peptides derived from tumor antigens theoretically made possible to tumor-specific CD4+ T cells in addition to CD8+ T cells induced by MHC class I binding tumor antigen peptides. However, the generation of tumor-specific T cells is still a practically challenging and time-consuming procedure. This fact makes difficult the application of tumor-specific T cells to adoptive immunotherapy of cancer patients. Recently, novel methods have been developed to prepare tumor-specific T cells from nonspecifically activated T cells by gene transfer. Specifically, two types of genes were shown to be successful when they were introduced into nonspecific-T cells to generate genetically engineered tumor-specific T cells. One is the TCR α and β chain genes obtained from tumor-specific T cells, and the other is the chimeric immunoglobulin-T cell receptor (cIgTCR) gene which contains a single chain variable fragment from antitumor monoclonal antibody. In this review, we overviewed these methods briefly, and showed our recent results generating genetically engineered tumor-specific Th1 cells successfully by both these methods. In both mouse and human systems, non-specifically activated Th1 cells transduced with TCR genes specific for tumor antigen-derived peptide showed potent antitumor activity against tumor cells when they recognized tumor antigen peptide presented on MHC molecules. On the other hand, Th1 cells transduced with a cIgTCR gene specific for carcinoembryonic antigen, CEA, were shown to be reactive with cell surface CEA in an MHC independent manner. Taken together, these results strongly suggest that it is possible to prepare tumor-specific human Th1 cells by gene transfer technique that is applicable to adoptive tumor immunotherapy for cancer patients.

Background The patients with relapsed hematological malignancy after allogeneic hematopoetic stem cell transplantation (HSCT) can be treated by donor lymphocyte infusion (DLI). However, the efficacy is often limited in association with the development of Graft-versus-Host Disease (GVHD) as a serious adverse event. By the use of the novel retrovirus vector that specifically silences endogenous T cell receptor (TCR) in gene-engineered T cells, here we demonstrate the development of DLI with lymphocytes engineered to express tumor-specific TCR that exhibit increased tumor-specificity in combination with decreased GVHD-inducing potential (Summarized in the figure). Methods Human PBMC were transduced with a high affinity TCR specific to a cancer/testis antigen, NY-ESO-1, by the retrovirus vector with siRNA specific to the endogenous TCR (siTCR vector). Resulting TCR gene-transduced T cells were examined for the expression of their endogenous TCR by flow cytometry and for their reactivity to allogeneic LCL by 3H uptake proliferation assay. Immunodeficient NOG mice were innoculated with a NY-ESO-1 expressing human tumor cell line NW-MEL-38, received TCR gene-transduced T cells, and monitored for the tumor growth and the development of GVHD. Results Human lymphocytes that were genetically engineered to express a high affinity NY-ESO-1-specific TCR with siTCR vector showed significantly reduced expression of endogenous TCR associated with dramatically diminished reactivity to allogeneic LCL. When adoptively transferred into NOG mice, control non-engineered T cells failed to control the growth of human tumor cells despite the fact that the lymphocytes were allogeneic to the tumor cells and developed lethal GVHD including severe bone-marrow destruction. The development of GVHD was dependent on both the CD4+ and CD8+ T cells suggesting that the simple purification of CD8+ T cells was not a sufficient enough strategy to prevent GVHD. In contrast, adoptive transfer of NY-ESO-1-specific TCR gene-transduced T cells induced complete tumor regression without the development of GVHD. Conclusions The results here suggest that the allogeneic T cells transduced with a tumor-specific TCR by siTCR vector showed increased tumor-reactivity with diminished GVHD potential. These T cells will be applicable to the donor lymphocytes infusion therapy after allogeneic stem cell transplantation for the treatment of hematological malignacy. Currently we plan a clinical trial of DLI with siTCR technology for the patients with relapsed NY-ESO-1 positive adult T cell leukemia/lymphoma after HSCT. Figure 1 Figure 1. Disclosures Ikeda: Takara Bio Inc.: Research Funding. Kawamura:Takara Bio Inc.: Employment. Imai:Takara Bio Inc.: Research Funding. Okamoto:CDM Center, Takara Bio Inc.: Employment. Mineno:Takara Bio Inc.: Membership on an entity's Board of Directors or advisory committees. Takesako:Takara Bio Inc.: Membership on an entity's Board of Directors or advisory committees. Shiku:Takara Bio Inc.: Research Funding.

Recently, we demonstrated a speckle velocimeter to measure both velocity and length of a moving plate using a self-mixing laser diode (SM-LD).(1),(2) Although the measurement error by the previous velocimeter was 1% for velocity and a few % for length, it requires advance calibration to determine a pair of constants which depend on a beam spot size and material surface to be measured.

A clear nonlinear Zeeman effect of magnon side band lines in a uniaxial antiferromagnet Rb 2 CoF 4 is observed above 100 kOe by using a pulsed high magnetic field. The nonlinearity is explained by considering the spin-orbit interaction in the excited 2 T 1 ( 2 P) triplet of the Co 2+ ion.

A new convenient circuit for computing the magnitude of the sum of two vectors which are perpendicular to each other is described. The circuit consists of operational amplifiers and logic gates, and its main function is achieved by charging and discharging a capacitor. Since input and output signals are all given in analogue values, represented by pulse width, they can easily be converted into digital codes to interface a sampled-data system, if necessary.

Because WT1 is expressed in leukemia cells, the development of cancer immunotherapy targeting WT1 has been an attractive translational research topic. However, concern of this therapy still remains, since WT1 is abundantly expressed in renal glomerular podocytes. In the present study, we clearly showed that WT1-specific cytotoxic T lymphocytes (CTLs) certainly exerted cytotoxicity against podocytes in vitro; however, they did not damage podocytes in vivo. This might be due to the anatomical localization of podocytes, being structurally separated from circulating CTLs in glomerular capillaries by an exceptionally thick basement membrane.

Meeting abstracts Engineering the antigen receptor gene in patients' lymphocytes is one promising strategy to create antigen-specific lymphocytes without senescent phenotypes. The strategy provides an opportunity to extend the application of adoptive T cell therapy for cancer patients. However