Showing papers by "Takashi Saito published in 2005"

Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76.

Abstract: T cell receptor (TCR) activation and signaling precede immunological synapse formation and are sustained for hours after initiation. However, the precise physical sites of the initial and sustained TCR signaling are not definitively known. We report here that T cell activation was initiated and sustained in TCR-containing microclusters generated at the initial contact sites and the periphery of the mature immunological synapse. Microclusters containing TCRs, the tyrosine kinase Zap70 and the adaptor molecule SLP-76 were continuously generated at the periphery. TCR microclusters migrated toward the central supramolecular cluster, whereas Zap70 and SLP-76 dissociated from these microclusters before the microclusters coalesced with the TCR-rich central supramolecular cluster. Tyrosine phosphorylation and calcium influx were induced as microclusters formed at the initial contact sites. Inhibition of signaling prevented recruitment of Zap70 into the microclusters. These results indicated that TCR-rich microclusters initiate and sustain TCR signaling.

Designed ferromagnetic, ferroelectric Bi(2)NiMnO(6).

Abstract: A newly designed ferromagnetic, ferroelectric compound, Bi(2)NiMnO(6), was prepared by high-pressure synthesis at 6 GPa. The crystal structure, as determined by synchrotron X-ray powder diffraction, is a heavily distorted double perovskite with Ni(2+) and Mn(4+) ions ordered in a rock-salt configuration. The presence of 6s(2) lone pairs of Bi(3+) ions and the covalent Bi-O bonds give ferroelectric properties with T(CE) of 485 K, while -Ni(2+)-O-Mn(4+)-O-Ni(2+)- magnetic paths lead to a ferromagnetism with T(CM) of 140 K. This simple material design to distribute two magnetic elements with and without e(g) electrons on B sites of Bi- and Pb-based perovkites can be applied to other Bi(2)M(2+)M'(4+)O(6) and Pb(2)M(3+)M'(5+)O(6) systems to search for newer ferromagnetic ferroelectrics.

Somatostatin regulates brain amyloid beta peptide Abeta42 through modulation of proteolytic degradation.

Abstract: Expression of somatostatin in the brain declines during aging in various mammals including apes and humans. A prominent decrease in this neuropeptide also represents a pathological characteristic of Alzheimer disease. Using in vitro and in vivo paradigms, we show that somatostatin regulates the metabolism of amyloid beta peptide (Abeta), the primary pathogenic agent of Alzheimer disease, in the brain through modulating proteolytic degradation catalyzed by neprilysin. Among various effector candidates, only somatostatin upregulated neprilysin activity in primary cortical neurons. A genetic deficiency of somatostatin altered hippocampal neprilysin activity and localization, and increased the quantity of a hydrophobic 42-mer form of Abeta, Abeta(42), in a manner similar to presenilin gene mutations that cause familial Alzheimer disease. These results indicate that the aging-induced downregulation of somatostatin expression may be a trigger for Abeta accumulation leading to late-onset sporadic Alzheimer disease, and suggest that somatostatin receptors may be pharmacological-target candidates for prevention and treatment of Alzheimer disease.

Mechanism of vasodilation to adenosine in coronary arterioles from patients with heart disease

Abstract: Adenosine is a key myocardial metabolite that elicits coronary vasodilation in a variety of pathophysiological conditions. We examined the mechanism of adenosine-induced vasodilation in coronary ar...

DNA polymerase θ contributes to the generation of C/G mutations during somatic hypermutation of Ig genes

Abstract: Somatic hypermutation of Ig variable region genes is initiated by activation-induced cytidine deaminase; however, the activity of multiple DNA polymerases is required to ultimately introduce mutations. DNA polymerase η (Polη) has been implicated in mutations at A/T, but polymerases involved in C/G mutations have not been identified. We have generated mutant mice expressing DNA polymerase (Polθ) specifically devoid of polymerase activity. Compared with WT mice, Polq-inactive (Polq, the gene encoding Polθ) mice exhibited a reduced level of serum IgM and IgG1. The mutant mice mounted relatively normal primary and secondary immune responses to a T-dependent antigen, but the production of high-affinity specific antibodies was partially impaired. Analysis of the JH4 intronic sequences revealed a slight reduction in the overall mutation frequency in Polq-inactive mice. Remarkably, although mutations at A/T were unaffected, mutations at C/G were significantly decreased, indicating an important, albeit not exclusive, role for Polθ activity. The reduction of C/G mutations was particularly focused on the intrinsic somatic hypermutation hotspots and both transitions and transversions were similarly reduced. These findings, together with the recent observation that Polθ efficiently catalyzes the bypass of abasic sites, lead us to propose that Polθ introduces mutations at C/G by replicating over abasic sites generated via uracil-DNA glycosylase.

IFN Regulatory Factor-2 Deficiency Revealed a Novel Checkpoint Critical for the Generation of Peripheral NK Cells

Abstract: NK cell development is far less understood compared with that of T and B cells despite the critical importance of NK cells in innate immunity. Mice lacking the transcription factor IFN regulatory factor-2 (IRF-2) are known to exhibit NK cell deficiency. However, the role of IRF-2 in NK cell development has remained unclear. In this study we found that NK cell deficiency in the periphery in IRF-2-deficient mice was due to selective loss of mature NK cells, but not to maturation arrest, and NK cells in these mice exhibited very immature surface phenotypes (CD11b low Dx5 low ) with highly compromised NK receptor expression. In contrast, IRF-2-deficient NK cells in bone marrow (BM) showed relatively mature phenotypes (CD11b low Dx5 high ) with less compromised NK receptor repertoire. Furthermore, BM NK cells in IRF-2-deficient mice were found to proliferate almost normally, but underwent accelerated apoptosis. These observations indicated that NK cell maturation could advance up to a late, but not the final, stage in the BM, whereas these cells were incapable of contributing to the peripheral NK cell pool due to premature death in the absence of IRF-2. In contrast, NK cell numbers and Ly49 expression were much more severely reduced in BM in IL-15-deficient mice than in IRF-2 −/− mice. The differential peripheral and central NK cell deficiencies in IRF-2 −/− mice thus revealed a novel late checkpoint for NK cell maturation, distinct from the early IL-15-dependent expansion stage.

Down-Regulation of Basophil Function by Human CD200 and Human Herpesvirus-8 CD200

Abstract: Human and rodent CD200 are recognized by the inhibitory CD200R, and these molecules play an important role in the regulation of the immune system. Several viruses, such as human herpesvirus-6 (HHV-6), HHV-7, and HHV-8, possess a CD200 homologue, suggesting that these viruses regulate the immune response via CD200R. In this study, we analyzed the effect of human CD200 and the viral CD200 homologues on human CD200R-expressing cells. We found that human CD200R is predominantly expressed on basophils in amounts higher than on other human peripheral blood leukocytes. Furthermore, the viral CD200 homologues as well as human CD200 were recognized by human CD200R, and the activation of basophils was down-regulated by these CD200 proteins. These results suggested that CD200R is an important regulatory molecule of basophil activation. In addition, the presence of CD200 homologues on several viruses suggests a potentially unique relationship between basophil function and viral infection.

Heterotypic interaction of CRTAM with Necl2 induces cell adhesion on activated NK cells and CD8+ T cells.

Abstract: NK cells and CD8 1 T cells exhibit cytotoxicity and cytokine production upon recognizing target cells through cell–cell interaction. We screened the molecules involved in the recognition and regulation of these cells using cDNA subtraction between naive and activated NK cells. We identified class I-restricted T cell-associated molecule (CRTAM), a two Ig domain-bearing surface receptor, as a molecule rapidly and transiently expressed on NK cells and CD8 1 T cells upon activation. CRTAM is expressed as a dimer on the cell surface, and its expression is transcriptionally regulated. Using an expression-cloning system, we then further identified Nectin-like (Necl) molecule 2, a three Ig domaincontaining receptor, as a ligand of CRTAM. While Necl2 mediates homotypic interaction, CRTAM interacts with Necl2 but not with CRTAM itself. The heterotypic CRTAM–Necl2 interaction has a higher affinity than the homotypic Necl2 interaction. Although there was no clear alteration in the cytotoxic function of the NK cells and CD8 1 T cells against the Necl2-expressing target cells, T cells expressing CRTAM tightly bound to Necl2-expressing cells. CRTAM 1 cells did not induce homotypic aggregation but they did exert strong heterotypic binding with Necl2 1 cells, which was inhibited by the addition of the CRTAM-Ig fusion protein. These results suggest that the heterotypic interaction between CRTAM and Necl2 plays an important role in the adhesion, interaction or migration of NK cells and CD8 1

CD25(+)CD4(+) regulatory T cells exert in vitro suppressive activity independent of CTLA-4.

Abstract: Cytotoxic T lymphocyte antigen-4 (CTLA-4) is constitutively expressed on CD25 1 CD4 1 regulatory T cells (Treg) and is suggested to play a role in Treg-mediated suppression. However, the results of analysis with anti-CTLA-4 have been controversial. We addressed this issue by analyzing mice over-expressing or deficient in CTLA-4. For over-expression, CTLA-4 transgenic mice expressing a full-length (FL) or a truncated (TL) mutant of CTLA-4 were analyzed. FL T cells expressed similar levels of CTLA-4 to Treg, whereas TL T cells expressed much higher levels on the cell surface. The number of Treg in both mice was decreased, although Foxp3 expression was not altered. Treg from both mice exerted suppressive activity, whereas CD25 T cells from FL mice showed no suppression. Furthermore, CD25 1 CD4 thymocytes from young CTLA-4-deficient mice were analyzed and found to exhibit suppressive activity. These results indicate that Treg exert in vitro suppressive activity independent of CTLA-4 expression.

In vivo overexpression of CTLA-4 suppresses lymphoproliferative diseases and thymic negative selection

Abstract: Cytotoxic T lymphocyte antigen-4 (CTLA-4) induces major inhibitory signals for T cell activation. From analyses of TCR-transgenic (Tg) CTLA-4-deficient mice, it has been believed that CTLA-4 does not affect thymocyte development. To focus upon the in vivo function of CTLA-4 in thymocyte development from a different aspect, we have established Tg mice expressing either full-length CTLA-4 (FL-Tg) or a mutant CTLA-4 lacking the cytoplasmic region (truncated, TR-Tg), and analyzed thymocyte development. TR-T cells express much higher CTLA-4 on the cell surface than FL-T cells, in which most CTLA-4 was localized in intracellular vesicles. While CTLA-4-/- mice exhibit lymphoproliferative disease, neither of the Tg mice with CTLA-4-/- background developed the disorder. Although the development of thymocytes appeared normal in both Tg mice, in vivo depletion of double-positive thymocytes by injection of anti-CD3 Ab as well as the elimination of minor lymphocyte-stimulating antigen-reactive thymocytes were impaired in FL-Tg mice but not in TR-Tg mice. Functionally, cross-linking of CTLA-4 on thymocytes from FL-Tg mice, but not from TR-Tg mice, inhibited proliferation. These results reveal a potential role of CTLA-4, through its cytoplasmic domain, in the negative selection of thymocytes and in the prevention of lymphoproliferative disease.

Tuning of g -factor in self-assembled In(Ga)As quantum dots through strain engineering

Abstract: We have investigated the effect of strain on the $g$-factors of self-assembled In(Ga)As dots by single-dot spectroscopy and an eight-band effective mass calculation taking into account the influence of the strain distribution and the Zeeman effect. The strain and its distribution in and around the quantum dots are varied by thermal annealing or by introducing an strain reducing layer. Thermal annealing produces a graded composition profile due to $\mathrm{In}\mathrm{Ga}$ intermixing. The graded composition profile reduces both hydrostatic and biaxial strain near the bottom of the dot, and enhances them near the top. This strain variation results in a large reduction of the absolute hole $g$-value and a small reduction of the absolute electron $g$-value. On the other hand, the covering of InAs dots with an ${\mathrm{In}}_{0.17}{\mathrm{Ga}}_{0.83}\mathrm{As}$ strain reducing layer decreases mainly the hydrostatic strain. The variation of the strain and the band edge alignment enhance the electron $g$-value while they reduce the hole $g$-value. These results should provide insights to control the $g$-factors in pyramidal self-assembled dots.

Strain distribution and electronic states in stacked InAs/GaAs quantum dots with dot spacing 0-6nm

Abstract: We have calculated the strain distribution and electronic structures in stacked InAs/GaAs quantum dots (QDs) with the dot spacing 6– 0 nm . We used the elastic continuum theory for the strain distribution, and the 8-band k · p theory for the electronic structures. For the triply stacked QDs, the light-hole (LH) component of the hole ground state increases with decreasing the dot spacing. The LH component in the columnar QD (dot spacing 0 nm ) reaches 21.1% which is 4.8 times larger than that in the single QD due to the reduction of the biaxial strain. Further increase of the LH component (up to 28.6%) is obtained in the fivefold-stacked columnar QD. This result suggests a possibility of increase in the TM-mode transition in the columnar QDs.

Reconstitution of photosynthetic reaction centers and core antenna-reaction center complexes in liposomes and their thermal stability.

Abstract: Photosynthetic reaction centers (RCs) and their core light-harvesting complexes (LH1-RCs), purified from a thermophile, Thermochromatium (T.) tepidum, and a mesophile, Allochromatium (A.) vinosum, were reconstituted into liposomes. The RC and the LH1-RC in the reconstituted liposomes were found intact from the absorption spectra at about 4 and 40 °C respectively. The thermal stability of the RCs of T. tepidum in the liposome was dependent on whether they were surrounded directly by lipids or by the core light-harvesting complexes. The results show that the RC of T. tepidum gains its thermostability through interactions with the LH1. These results are consistent with the result that the thermal stability of the LH1 in T. tepidum is similar in both the reconstituted LH1-RC liposome and ICM. This is clearly different from the mesophilic bacterium, A. vinosum. The thermal stability of RC was also affected by its subunit constitution: the RC containing a cytochrome subunit was more thermostable than the cytoch...

Regulation of Mast Cell Activation through FcεRI

Abstract: The cross-linking of FceRI on mast cells by IgE and antigen (Ag) initiates activation cascades that lead to allergic responses. FceRI is composed of an α and a Β monomer, and a γ homodimer, and the

The FcRgamma chain is not essential for induction of experimental allergic encephalomyelitis (EAE) or anti-myelin antibody-mediated exacerbation of EAE.

Abstract: Macrophages are considered essential mediators in multiple sclerosis (MS) pathogenesis, presumably through myelin phagocytosis and release of inflammatory mediators. Macrophages and microglia express activating Fcgamma receptors (FcgammaRI and FcgammaRIII), which depend on the FcRgamma chain for surface expression and signaling. In MS lesions, crosslinking of FcgammaR by immunoglobulins (IgG) directed against myelin may enhance myelin phagocytosis and inflammation. We studied the role of FcgammaR and anti-myelin antibodies in MOG35-55-induced experimental allergic encephalomyelitis (EAE) in C57BL/6 mice, a model of MS-like disease. Incidence and severity of EAE were similar in FcRy chain-/- (FcRgamma-/-) and wild-type (wt) mice, albeit with delayed onset in FcRgamma-/- mice. This demonstrates that the FcRy chain is not essential for induction of EAE, but that FcRgamma signaling may contribute to the preclinical phase. The role of FcgammaR in antibody-mediated demyelination was addressed by injection of anti-myelin antibodies (Z12 mAb) at onset of MOG35-55-induced EAE. Injection of Z12 mAb rapidly reduced survival time in both wt and FcRgamma-/- mice, demonstrating that antibody-mediated exacerbation of EAE is independent of the FcRgamma chain. Interestingly, Z12-induced exacerbation of inflammation and demyelination persisted longer in wt than FcRgamma-/- mice, suggesting that IgG-FcgammaR interactions may contribute to a sustained pathologic effect of anti-myelin antibodies in the CNS.

Inhibition of the antigen-induced activation of rodent mast cells by putative Janus kinase 3 inhibitors WHI-P131 and WHI-P154 in a Janus kinase 3-independent manner

Abstract: We analyzed the effects of the Janus kinase 3 (Jak3)-specific inhibitor WHI-P131 (4-(4′-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline) and the Jak3/Syk inhibitor WHI-P154 (4-(3′-bromo-4′-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline) on the antigen-induced activation of mast cells. In the rat mast cell line RBL-2H3, both WHI-P131 and WHI-P154 inhibited the antigen-induced degranulation and phosphorylation of p44/42 mitogen-activated protein kinase (MAPK), p38 MAPK and c-Jun N-terminal kinase (JNK). The phosphorylation of Gab2, Akt and Vav was also inhibited by WHI-P131 and WHI-P154, indicating that these inhibitors suppress the activation of phosphatidylinositol 3-kinase (PI3K). In bone marrow-derived mast cells (BMMCs) from Jak3-deficient (Jak3−/−) mice, degranulation and activation of MAPKs were induced by the antigen in almost the same extent as in BMMCs from wild-type mice. In addition, the antigen-induced degranulation and activation of MAPKs were inhibited by WHI-P131 and WHI-P154 in both groups of BMMCs, indicating that these compounds inhibit a certain step except for Jak3. The antigen-induced increase in the activity of Fyn, a probable tyrosine kinase of Gab2, was also inhibited by WHI-P131 and WHI-P154 in RBL-2H3 cells. In BMMCs from Jak3−/− mice, the antigen stimulation induced tyrosine phosphorylation of Fyn, which was inhibited by WHI-P131, as well as in BMMCs from wild-type mice and in RBL-2H3 cells. These findings suggest that Jak3 does not play a significant role in the antigen-induced degranulation and phosphorylation of MAPKs, and that WHI-P131 and WHI-P154 inhibit the PI3K pathway by preventing the antigen-induced activation of Fyn, thus inhibiting the antigen-induced degranulation and phosphorylation of MAPKs in mast cells. Keywords: Mast cells, WHI-P131, WHI-P154, p44/42 MAP kinase, p38 MAP kinase, c-Jun N-terminal kinase, phosphatidylinositol 3-kinase, Fyn Introduction Mast cells contribute to inflammatory responses by releasing preformed mediators such as histamine and serine proteases, and generating eicosanoids and cytokines (Williams & Galli, 2000). The early signaling events in antigen-stimulated mast cells are initiated by the tyrosine kinases Lyn and Syk (Beaven & Metzger, 1993; Beaven & Ozawa, 1996). The aggregation of the IgE high-affinity receptor I (FcɛRI) induced by the antigen results in the tyrosine phosphorylation of the β- and γ-chains of FcɛRI by Lyn. The phosphorylation of these chains promotes the recruitment of Lyn and Syk to the β-chain and the γ-chain, respectively, resulting in the tyrosine phosphorylation of linker proteins such as linker for activation of T cells (LAT). Furthermore, the tyrosine kinase Fyn is required for mast cell degranulation (Parravicini et al., 2002). Fyn phosphorylates a linker protein Gab2 (Parravicini et al., 2002), and leads to the activation of phosphatidylinositol 3-kinase (PI3K) (Gu et al., 2001; Wilson et al., 2001). PI3K regulates the translocation of Bruton's tyrosine kinase (Btk) (Buhl & Cambier, 1999; Varnai et al., 1999) to membrane, promoting the activation of Btk by Lyn/Syk (Rawlings et al., 1996; Baba et al., 2001). The activation of these tyrosine kinases induces the tyrosine phosphorylation of phospholipase (PL) Cγ (Li et al., 1992) and Vav (Hirasawa et al., 1995b). The former leads to the generation of inositol 1, 4, 5-trisphosphate and diacylglycerol, which induce an increase in the intracellular Ca2+ level and the activation of protein kinase C, respectively. The latter activates low molecular weight G proteins such as Ras and Rac (Gulbins et al., 1994; Han et al., 1998; Abe et al., 2000), resulting in the activation of the mitogen-activated protein kinase (MAPK) family. The activation of MAPKs in mast cells causes the release of arachidonic acid (Hirasawa et al., 1995a) and the production of cytokines such as interleukin (IL)-4 (Hirasawa et al., 2000) and IL-13 (Hirasawa et al., 2003). Janus kinase 3 (Jak3), a member of the Jak family of cytoplasmic nonreceptor tyrosine kinases, is selectively expressed in hematopoietic cells (Johnston et al., 1994; Witthuhn et al., 1994) and associates with the γc-chain of receptors for IL-2, 4, 7, 9, 15 and 21 (Chen et al., 1997; Asao et al., 2001). Jak3 mediates cytokine-induced responses by activating the cytoplasmic latent forms of signal transducers and activators of transcription (STATs) via phosphorylation of a specific tyrosine residue near the SH2 domain (Leonard & O'Shea, 1998). In addition, Jak3 has been suggested to play important roles in the FcɛRI-mediated activation of mast cells (Malaviya & Uckun, 1999; Malaviya et al., 1999, 2000) and T-cell receptor-mediated activation of T cells (Tomita et al., 2001). In Jak3-deficient (Jak3−/−) mice, the anaphylactic reaction was impaired with defective immune responses (Malaviya & Uckun, 1999; Malaviya et al., 1999). Jak3 also plays roles in bacterial clearance and neutrophil recruitment to the sites of infection by regulating the release of tumor necrosis factor-α from mast cells (Malaviya et al., 2001). In addition, stimulation of the rat mast cell line RBL-2H3 with antigen induced the activation of Jak3 and the specific Jak3 inhibitor WHI-P131 (4-(4′-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline) (Sudbeck et al., 1999) inhibited the antigen-induced degranulation, production of tumor necrosis factor-α and increase in the cytosolic Ca2+ level without affecting the activation of Syk (Malaviya et al., 1999). However, the precise role of Jak3 in the antigen-triggered signaling events in mast cells remains to be clarified. In this study, we evaluated the effects of the specific Jak3 inhibitor WHI-P131 and the Jak3/Syk inhibitor WHI-P154 (4-(3′-bromo-4′-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline) (Ghosh et al., 1999) on the IgE/FcɛRI-mediated activation of RBL-2H3 cells and bone marrow-derived mast cells (BMMCs) from Jak3−/− mice and wild-type mice, and found that these inhibitors strongly suppressed the antigen-induced degranulation and phosphorylation of MAPKs in mast cells via the Jak3-independent pathway.

IRAKs: Key Regulatory Kinases of Innate Immunity

Abstract: Toll-like receptors (TLRs), interleukin 1 receptor (IL-1R), IL-18 receptor (IL-18R) and plant R are vital to the induction of acute inflammation as well as various adaptive immune responses upon invasion of microorganisms. These receptors share a common cytoplasmic domain called the TIR (TLR/IL-1R/plant R) domain and the signaling cascade involving the TIR domain is conserved from invertebrate to vertebrate. The engagement of TIR domain containing receptors initiates their signaling through several intermediate proteins including serine-threonine kinase IL-1 receptor associated kinases (IRAKs). The IRAK family has four members and the newest member, IRAK-4, is indispensable to the TIR-mediated signaling pathway. The improper regulation of TIR receptor signaling leads to the development of such severe inflammatory diseases as sepsis, asthma, rheumatoid arthritis and even cancer. Therefore, it is very important to determine precisely the implications of TIR signaling in those inflammatory diseases for appropriate medical treatment and drug development. As IRAK-4 is the critical molecule for TIR-mediated signaling, it is a promising therapeutic target for many inflammatory diseases. In this review, we discuss the functions of the IRAK family members with focus on IRAK-4, to seek the possibility of yielding new therapeutic strategies.

Electronic properties and thermal stability of soluble redox proteins from a thermophilic purple sulfur photosynthetic bacterium, Thermochromatium tepidum

Abstract: The electronic properties of soluble redox proteins from a thermophilic purple sulfur photosynthetic bacterium Thermochromatium (T.) tepidum have been studied in terms of electronic absorption, mag...

Differential display analysis reveals the expression of glutathione S-transferase ω and novel genes through an ITAM-containing receptor in ascidian immunocytes

Abstract: The immunoreceptor tyrosine-based activation motif (ITAM) plays an important role in signal transduction through antigen receptors in mammalian lymphocytes. We previously reported that an ITAM-containing receptor, ascidian hemocyte ITAM-containing receptor 1 (AhITAMR1), exists on the hemocyte surfaces of the ascidian Halocynthia roretzi, and is involved in both phagocytosis and hemocyte aggregation. In this study, we carried out differential display screening of upregulated genes during H. roretzi hemocyte aggregation and found that at least three genes are upregulated. One encodes glutathione S-transferase omega (GSTomega), while the other two encode novel proteins. The expression of all three genes was induced by treatment with a specific monoclonal antibody against AhITAMR1, while their expression was inhibited by wortmannin, BAPTA-AM, and cyclosporin A. We also found that the expression of GSTomega was induced by treatment with anti-T cell receptor antibody in mouse peripheral T cells. We propose that signal transduction pathways mediated by ITAM-containing receptors are conserved from ascidian hemocytes to mammalian T cells.

Relationship between Interface Motion of an Isolated Bubble and Its Zigzagging Motion of the Center of Gravity

Abstract: The motion of the center of gravity and the interface motion of a bubble are essential for deep understanding of the mass transfer mechanism between gas and liquid phases in a bubble column, a gas-lift reactor, and so on. Since the two-phase flows have the hierachical structure, the interaction between the interface motion of the individual bubbles and the local-scale motion of the surrounding liquid plays a role important for the mass transfer process in the vicinity of their surfaces. In the present study, the interrelation between the motion of the center of gravity and the interface motion of a zigzag rising bubble in rest water has been investigated. The bubble of 2.64 mm in equivalent diameter was microscopically visualized by high-speed video camera, in order to catch minute interface motion. Statistical analysis of the bubble interface motion has been achieved by maintaining the high reproducibility of bubble release with a hypodermic needle. Analyzing the fluctuation of the curvature in right-and-left bubble shape edges, the relationship between the asymmetrical interface motion and the zigzagging motion was elucidated.

Method for producing mandelic acid and crystal of mandelic acid

Abstract: PROBLEM TO BE SOLVED: To provide a method for producing high purity mandelic acid useful as a medicinal and agrochemical row material, a liquid crystal material and a reagent for optical resolution, and to provide crystal of mandelic acid SOLUTION: The method for producing the high purity mandelic acid comprises acid hydrolysis of mandelonitrile, aging of the produced mandelic acid in a state of precipitating a part thereof, and recovery of the crystal of the mandelic acid The crystal of mandelic acid contains the dimer of not more than 01% (surface percentage) based on 100 surface% total of the mandelic acid and the dimer thereof in high performance liquid chromatographic measurement COPYRIGHT: (C)2006,JPO&NCIPI

Observation of PeV Gamma Rays from the Monogem Ring with the Tibet Air Shower Array

Abstract: We searched for steady PeV gamma-ray emission from the Monogem ring region with the Tibet air shower array from 1997 February to 2004 October. No evidence for statistically significant gamma-ray signals was found in a region 111° ≤ R.A. < 114°, 125 ≤ decl. < 155 in the Monogem ring where the MAKET-ANI experiment recently claimed a positive detection of PeV high-energy cosmic radiation, although our flux sensitivity is approximately 10 times better than MAKET-ANI's. We set the most stringent integral flux upper limit at a 99% confidence level of 4.0 × 10-12 cm-2 s-1 sr-1 above 1 PeV on diffuse gamma rays extended in the 3° × 3° region.

Double-outlet technique for tetralogy of Fallot-type disease with an anomalous coronary artery.

Abstract: To reduce the right ventricular (RV) pressure and the pressure gradient between the RV and the pulmonary artery (PA) in Tetralogy of Fallot (TOF) with small pulmonary annulus, it is inevitable to enlarge the small annulus by incising and patching from RV to PA via PA annulus. If the anomalous coronary artery exists in the RV outflow tract, the procedure can not be done.

Plastic Deformation of Mg-Zn-Y Icosahedral Quasicrystals under Confining Pressure

Abstract: Deformation experiments of Mg-Zn-Y icosahedral quasicrystals under a hydrostatic confining pressure have been performed to investigate their deformation mechanism in a low temperature range. The temperature dependence of the yield stress has been successfully measured, for the first time, down to room temperature. An irregular behavior has been found in the temperature dependence: the yield stress increases rapidly with lowering temperature down to 373 K and it becomes almost constant in the temperature region lower than 373 K. The origin of such an irregular temperature dependence is discussed in terms of possible transition between two different dislocation processes: glide and climb.

Method for purifying mandelic acids

Abstract: PROBLEM TO BE SOLVED: To provide a method for purifying mandelic acids, capable of giving a high-purity crystal of the mandelic acids having a low content of a dimer of the mandelic acids, without using an organic solvent. SOLUTION: This method for purifying the mandelic acids comprises mixing contact of a crystal containing the dimer of the mandelic acids and the mandelic acids with an aqueous solvent not containing the organic solvent (a mixed liquid after mixed may be such a solution that the mandelic acids are completely dissolved in water or may be such a mixed suspension that the mandelic acids are not completely dissolved therein), and then subjecting the mixed liquid to solid-liquid separation at 0-60°C under an acidic condition of a pH of 7.0 or less. COPYRIGHT: (C)2007,JPO&INPIT

Measurements of the response functions of a large size NE213 organic liquid scintillator for neutrons up to 800 MeV

Abstract: The response functions of 25.4 cm (length) x 25.4 cm (diameter) NE213 organic liquid scintillator have been measured for neutrons in the energy range from 20 to 800 MeV at the Heavy-Ion Medical Accelerator in Chiba (HIMAC) and at the Research Center for Nuclear Physics (RCNP) of Osaka University. At HIMAC, white (continuous) energy spectrum neutrons were produced by the 400 MeV per nucleon carbon ion bombardment on a thick graphite target, whose energy spectrum has already been measured by Kurosawa et al., [Nucl. Sci. Eng. 132, 30 (1999)] and the response functions of the time-of-flight-gated monoenergetic neutrons in a wide energy range from 20 to 800 MeV were simultaneously measured. At RCNP, the quasi-monoenergetic neutrons were produced via 7Li(p,n)7Be reaction by 250 MeV proton beam bombardment on a thin 7Li target, and the TOF-gated 245 MeV peak neutrons were measured. The absolute peak neutron yield was obtained by the measurement of 478 keV gamma rays from the 7Be nuclei produced in a Li target. The measured results show that the response functions for monoenergetic neutrons 250 MeV, the plateau and the edge become unclear because the proton range becomes longer than the detector size and the escaping protons increase. It can be found that the efficiency of the 24.5 cm (diameter) x 25.4 cm (length) NE213 for the 250 MeV neutrons is -10 times larger than the 12.7 cm (length) x 12.7 cm (diameter) NE213, which is widely used as a neutron spectrometer.