Photocurrent generation of a single-gate graphene p-n junction fabricated by interfacial modification.

A back-gate graphene p-n junction was achieved by selective interfacial modification of a chemical vapor deposition (CVD)-grown graphene field effect transistor (FET). Silane self-assembled monolayer (SAM) patterns were used to fabricate uniform p- and n-doped regions and a sharp p-n junction in the graphene FET channel. A gate-dependent photocurrent response was observed at the graphene p-n junction, and exhibited a maximum signal between two Dirac point voltages of SAM-doped graphene regions. A spatial photocurrent map shows that the photocurrent generated at the junction region was much larger than that from graphene/electrode junctions under the same incident laser power. This single-peak characteristic photocurrent in CVD graphene is dominated by the photothermoelectric contribution, and is highly sensitive to the power of incident laser. The SAM interfacial modification method provides a feasible route for the fabrication of efficient graphene-based photodetectors.

Resonant edge magnetoplasmons and their decay in graphene.

We investigate resonant edge magnetoplasmons (EMPs) and their decay in graphene by high-frequency electronic measurements. From EMP resonances in disk shaped graphene, we show that the dispersion relation of EMPs is nonlinear due to interactions, giving rise to the intrinsic decay of EMP wave packets. We also identify extrinsic dissipation mechanisms due to interaction with localized states in bulk graphene from the decay time of EMP wave packets. We indicate that, owing to the linear band structure and the sharp edge potential, EMP dissipation in graphene can be lower than that in GaAs systems.

Dynamics of the silicon (111) surface phase transition

The manner in which phase transformations occur in solids determines important structural and physical properties of many materials. The main problem in characterizing the kinetic processes that occur during phase transformations is the difficulty of observing directly, in real time, the growth of one phase at the expense of another. Here we use low-energy electron microscopy to study the real-time kinetics of a phase transformation confined to the silicon (111) surface. We show that the transformation is governed by the rate at which material is exchanged between the first layer of the crystal and the surface. In bulk phase transformations, the dynamics are usually governed either by the rate of diffusion of material to the phase boundaries or by the structural rearrangement of atoms at the phase boundary. The kinetic process that we have identified here has no bulk analogue and leads to domain dynamics that are qualitatively different from those expected for bulk systems.

Local conductance measurements of double-layer graphene on SiC substrate.

The microscopic structural and electrical properties of few-layer graphene grown on an SiC substrate were characterized by low-energy electron microscopy, transmission electron microscopy and scanning probe microscopy measurements of local conductance. The double-layer graphene sheet was confirmed to be continuous across the atomic steps on the buried SiC substrate surface, and the measured local conductance was clearly modified in the vicinity of the steps. The conductance decreased (slightly increased) at the lower (upper) side of the steps, suggesting deformation-induced strain is the origin of the conductance modification. From the contact force dependence of the conductance images, the effective contact areas for both nanogap-probe and point-probe measurements were estimated.

RIM binding proteins (RBPs) couple Rab3-interacting molecules (RIMs) to voltage-gated Ca(2+) channels.

Ca(2+) influx through voltage-gated channels initiates the exocytotic fusion of synaptic vesicles to the plasma membrane. Here we show that RIM binding proteins (RBPs), which associate with Ca(2+) channels in hair cells, photoreceptors, and neurons, interact with alpha(1D) (L type) and alpha(1B) (N type) Ca(2+) channel subunits. RBPs contain three Src homology 3 domains that bind to proline-rich motifs in alpha(1) subunits and Rab3-interacting molecules (RIMs). Overexpression in PC12 cells of fusion proteins that suppress the interactions of RBPs with RIMs and alpha(1) augments the exocytosis triggered by depolarization. RBPs may regulate the strength of synaptic transmission by creating a functional link between the synaptic-vesicle tethering apparatus, which includes RIMs and Rab3, and the fusion machinery, which includes Ca(2+) channels and the SNARE complex.

Biology and epidemiology of rice viruses.

The 15 known viruses that occur in rice are rice black-streaked dwarf, rice bunchy stunt, rice dwarf, rice gall dwarf, rice giallume, rice grassy stunt, rice hoja blanca, rice necrosis mosaic, rice ragged stunt, rice stripe necrosis, rice stripe, rice transitory yellowing, rice tungro bacilliform, rice tungro spherical, and rice yellow mottle viruses. This paper describes their geographical distribution, relation to vectors, infection cycles, field dispersal, and development, and lists recorded outbreaks of the viruses. Many rice viruses have become serious problems since rice cultivation has been intensified. Double-cropping of rice using improved, photo-insensitive cultivars of short growth duration has significantly influenced the incidence of these viruses.

Quantum Hall effect in epitaxial graphene with permanent magnets.

We have observed the well-kown quantum Hall effect (QHE) in epitaxial graphene grown on silicon carbide (SiC) by using, for the first time, only commercial NdFeB permanent magnets at low temperature. The relatively large and homogeneous magnetic field generated by the magnets, together with the high quality of the epitaxial graphene films, enables the formation of well-developed quantum Hall states at Landau level filling factors v = ±2, commonly observed with superconducting electro-magnets. Furthermore, the chirality of the QHE edge channels can be changed by a top gate. These results demonstrate that basic QHE physics are experimentally accessible in graphene for a fraction of the price of conventional setups using superconducting magnets, which greatly increases the potential of the QHE in graphene for research and applications.

AML1(-/-) embryos do not express certain hematopoiesis-related gene transcripts including those of the PU.1 gene.

The AML1 and PEBP2beta/CBFbeta genes encode the DNA-binding and non-binding subunits, respectively, of the heterodimeric transcription factor, PEBP2/CBF. Targeting each gene results in an almost identical phenotype, namely the complete lack of definitive hematopoiesis in the fetal liver on embryonic day 11.5 (E11.5). We examined and compared the expression levels of various hematopoiesis-related genes in wild type embryos and in embryos mutated for AML1 or PEBP2beta/CBFbeta. The RNAs were prepared from the yolk sacs of E9.5 embryos, from the aorta-gonad- mesonephros regions of E11.5 embryos and from the livers of E11.5 embryos and RT-PCR was performed to detect various gene transcripts. Transcripts were detected for most of the hematopoiesis-related genes that encode transcription factors, cytokines and cytokine receptors, even in tissues from homozygously targeted embryos. On the other hand, PU.1 transcripts were never detected in any tissue of AML1(-/-) or PEBP2beta/CBFbeta(-/-) embryos. In addition, transcripts for the Vav, flk-2/flt-3, M-CSF receptor, G-CSF receptor and c-Myb genes were not detected in certain tissues of the (-/-) embryos. The results suggest that the expression of a particular set of hematopoiesis-related genes is closely correlated with the PEBP2/CBF function.

Transduction of LacZ gene into leukemia cells using viral vectors of retrovirus and adenovirus.

Recent developments in gene therapy techniques enable us to introduce new genetic information into hematopoietic cells. Among the various techniques, we focused on two viral vector systems, one using a retrovirus and the other an adenovirus. By using an adenoviral vector we could transduce and highly express bacterial beta-galactosidase (LacZ) gene under the control of the CAG (cytomegalovirus enhancer with chicken beta-actin promoter) promoter in various hematopoietic cells, although the expression persisted for only two weeks. The retroviral vector (MFG) could transduce the LacZ gene into hematopoietic cells almost as well as the adenoviral vector using the repetitive infection protocol. The retroviral system could maintain the expression of transduced cells quite longer than the adenoviral system. Differential use of these two vector systems may be helpful for the gene transduction into various kinds of hematopoietic cells (Lin et al., manuscript in preparation).

Significant expression of G-CSF-induced gene-1 (GIG-1) protein in myeloid cells and NK cells.

The granulocyte colony-stimulating factor (G-CSF)-induced gene, GIG-1, was originally cloned from G-CSF-stimulated bone marrow mononuclear cells obtained from a patient with chronic myelogenous leukemia (CML). We have characterized the GIG-1 gene and its protein product. Expression of GIG-1 mRNA was elevated by treatment with G-CSF in normal bone marrow mononuclear cells, as well as in some cases of blast cells obtained from patients with acute myelogenous leukemia (AML) and CML. Western blot analysis with anti-GIG-1 peptide antiserum showed the molecular mass of GIG-1 product was about 17 kDa. Immunostaining of the hematopoietic cells demonstrated that GIG-1 product was mainly localized to the cytoplasm of both myeloid and natural killer (NK) cells. These results suggested that GIG-1 protein is an integral component that is accumulated during the differentiation of myeloid cells toward the stage of mature neutrophils. Expression of GIG-1 gene in mature neutrophils was tightly regulated and reactivation of GIG-1 gene by G-CSF in mature neutrophils may represent a compensation process for the protein lost through the activation of these cells, thus implying an important role for this protein in host defense mechanisms.

Shot noise generated by graphene p-n junctions in the quantum Hall effect regime.

Graphene offers a unique system to investigate transport of Dirac Fermions at p-n junctions. In a magnetic field, combination of quantum Hall physics and the characteristic transport across p-n junctions leads to a fractionally quantized conductance associated with the mixing of electron-like and hole-like modes and their subsequent partitioning. The mixing and partitioning suggest that a p-n junction could be used as an electronic beam splitter. Here we report the shot noise study of the mode-mixing process and demonstrate the crucial role of the p-n junction length. For short p-n junctions, the amplitude of the noise is consistent with an electronic beam-splitter behaviour, whereas, for longer p-n junctions, it is reduced by the energy relaxation. Remarkably, the relaxation length is much larger than typical size of mesoscopic devices, encouraging using graphene for electron quantum optics and quantum information processing.

Immunolocalization of an inwardly rectifying K+ channel, K(AB)-2 (Kir4.1), in the basolateral membrane of renal distal tubular epithelia.

Immunolocalization of K(AB)-2 (Kir4.1), an inwardly rectifying K+ channel with a putative ATP-binding domain, was examined in rat kidney where expression of K(AB)-2 mRNA was previously shown. Anti-K(AB)-2 antibody was raised in rabbit and then affinity-purified. An immunohistochemical study revealed that K(AB)-2 immunoreactivity was detected specifically in the basolateral membrane of distal tubular epithelia. Therefore, K(AB)-2 is the first K+ channel shown to be localized in the basolateral membrane of renal epithelia. The finding suggests that K(AB)-2 may contribute to supplying K+ to the Na(+)-K+ pump, which is abundant in the basolateral membrane of distal tubular epithelia, as well as to maintenance of the deep negative membrane potential of these cells.

Superiority of interleukin-12-transduced murine lung cancer cells to GM-CSF or B7-1 (CD80) transfectants for therapeutic antitumor immunity in syngeneic immunocompetent mice.

Interleukin-12 (IL-12) is a heterodimeric cytokine that consists of p40 and p35 subunits. IL-12 has been regarded as a potent inducer of host antitumor immunity through interferon-gamma (IFN-gamma) production and development of Th1 helper T cells from Th0 cells. Here, we demonstrate the immunomodulatory actions of an IL-12-transduced murine lung cancer cell line, Lewis lung carcinoma (LLC) (LLC/IL12) cells, in syngeneic C57BL/6 mice. We also report on their therapeutic potency. Three LLC/IL12 cells producing different levels of IL-12 were cloned and found to have diminished tumorigenicity in C57BL/6 mice depending on their level of IL-12 production. In vivo depletion assay demonstrated that the loss of tumorigenicity of LLC/IL12 depended on both CD4+ and CD8+ T cells, and that natural killer (NK) cells were involved, especially in the early phase of immunity. The strong systemic antitumor immunity against challenge with wild type LLC (LLC/wt) cells was also induced by LLC/IL12 cells. The systemic antitumor memory was found to be dependent mainly on the CD4+ T-cell subset. 51Cr-release assay revealed that the killer activity consisted of a specific killer activity directed at the parental LLC/wt cells and a nonspecific killer activity directed at both LLC/wt and syngeneic EL-4 thymoma cells. In addition, LLC/IL12 apparently had a much stronger antitumor effect against the established LLC/wt tumor than LLC transduced with B7-1 or GM-CSF cDNA. IL-12 can be considered an efficient candidate molecule for immunogene therapy for lung cancer in this experimental system.

Three novel connexin26 gene mutations in autosomal recessive non-syndromic deafness.

Since the first identification of an association between mutations in the connexin26 (Cx26) gene and autosomal recessive non-syndromic deafness it has been shown that several mutations in this gene cause recessive, sporadic, and dominant non-syndromic deafness. Three novel mutations in the Cx26 gene were identified in four of 20 Japanese families with autosomal recessive non-syndromic deafness. Seven of 40 chromosomes contained a 233delC allele, while Tyr136Stop (408C-->A) and Gly45Glu (134G-->A) were detected in two of 40 chromosomes, respectively. These mutations were not found in chromosomes in cases of sporadic congenital deafness (0/60) or in control groups (0/100). This indicates that 27.5% (11/40 chromosomes) of cases of autosomal recessive non-syndromic deafness among the Japanese are caused by mutations in the Cx26 gene.

Inhibitory effect of docosahexaenoic acid-containing phospholipids on 5-lipoxygenase in rat basophilic leukemia cells.

5-Lipoxygenase has been recognized to be an important enzyme that catalyzes the first step in leukotriene production. In this study we examine whether or not phospholipids containing docosahexaenoic acid (DHA) affect 5-lipoxygenase activity of a rat basophilic leukemia cell line (RBL-1). Among the synthesized phospholipids examined, 1-oleoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (1-oleoyl-2-DHA-PC) was found to be the most potent inhibitor of 5-lipoxygenase. The inhibition was dose-dependent and the ID50 value was 4.0 microM. When the fatty acid at the sn-2-position was replaced by other unsaturated fatty acids, the inhibitory activity decreased with decreasing numbers of both carbon atoms and double bonds in the fatty acids. Substitution at the 1-position of the DHA-containing PC also affected the inhibitory potency. If oleic acid was substituted with palmitic acid, the inhibition activity was completely abolished. Lineweaver-Burk plot analysis showed that the inhibition of 5-lipoxygenase by 1-oleoyl-2-DHA-PC was non-competitive. The inhibition by this synthesized phospholipid was very specific to 5-lipoxygenase; that is, it did not extend to fatty acid cyclooxygenase, 12-lipoxygenase or 15-lipoxygenase. These results suggest that endogenously existing DHA-containing phospholipids may affect 5-lipoxygenase activity and thus control leukotriene biosynthesis in vivo.

Evening primrose oil and fish oil in non-insulin-dependent-diabetes.

The effects of two anti-thrombotic and anti-lipidemic oils, evening primrose oil and fish oil, on glucose and lipid metabolism, prostaglandin (PG) levels and body composition were studied in patients with non-insulin-dependent diabetes. Seven patients were administered 4 g evening primrose oil, 2.4 g sardine oil and 200 mg vitamin E for 4 weeks. Fasting plasma glucose, hemoglobin A1c, total cholesterol, body weight and % body fat mass were significantly decreased after the treatment, and levels of changes in these parameters were not different from 11 patients who did not receive the oils. In the treatment group, concentrations of (e) icosapentaenoic acid (EPA) increased significantly in all the lipoprotein fractions, but dihomo-gamma-linolenic acid (DGLA) increased only in the high-density lipoprotein (HDL) fraction. The treatment decreased urinary 11-dehydro-thromboxane B2 excretion (32.7% decrease, P < 0.05), but did not alter significantly plasma PGE1 or 6-keto-PGF1 alpha levels. The ratio of 6-keto-PGF1 alpha and PGE1 to 11-dehydro-thromboxane B2 increased significantly after the treatment. These results suggest that these oil treatments are useful in improving abnormal lipid and thromboxane (TX)A2 metabolism in diabetic patients.

Eicosapentaenoic acid abolishes the proatherogenic effects of cholesterol: effects on migration of bovine smooth muscle and endothelial cells in vitro.

It is well known that vascular endothelial cell (EC) migration plays a major role in regeneration of the injured endothelium and also that smooth muscle cell (SMC) migration is the important step for atheromatous plaque formation. In the present study, we investigated the effects of cholesterol and eicosapentaenoic acid (EPA) on bovine carotid artery EC and SMC migration using the modified Boyden chamber technique. The migration activity of the cholesterol-enriched ECs loaded with cholesterol-rich liposomes was significantly suppressed, whereas that of the cholesterol-enriched SMCs was enhanced. Next, we examined the effects of EPA pretreatment on the migration of both cell types. When ECs and SMCs were treated with EPA (5 micrograms/ml) for 2 days, the EPA content increased from 0.55 +/- 0.04% to 11.72 +/- 0.19% and 1.22 +/- 0.09% to 9.69 +/- 0.07% in cellular phospholipids, respectively. Although pretreatment of the ECs with EPA caused a significant increase in serum-induced cell migration, pretreatment of SMCs had no effect. If both cell types were concomitantly pretreated with EPA and cholesterol-rich liposomes, EPA abolished the effects of cholesterol on the migration of both cell types, but did not affect the content of cholesterol in both cells. These data indicate the possibility that EPA counteracts the atherogenic effect of cholesterol on EC and SMC migration.

Effects of bifemelane hydrochloride on cerebral circulation and metabolism in patients with aphasia.

The effects of bifemelane hydrochloride on aphasia and on cerebral circulation and metabolism were studied using positron emission tomography (PET) in 10 aphasic patients with cerebrovascular disease. After the first PET scan, bifemelane was administered orally three times in a daily dose of 150 mg. Aphasic features, such as fluency, auditory comprehension, object naming, and repetition, were evaluated by using the Western Aphasia Battery (Japanese edition) before and at least 2 months after bifemelane treatment. Simultaneous with the evaluation of aphasia, the PET scans were performed by using the steady-state method with 15O gases inhalation. All aphasic features, except fluency, improved significantly after bifemelane treatment. Regional cerebral blood flow (rCBF) and the cerebral metabolic rate for oxygen (CMRO2) were increased at every brain region of interest, and the oxygen extraction fraction was decreased. Both rCBF and CMRO2 were significantly increased on the left inferior frontal gyrus, superior temporal gyrus, white matter of the parietal lobe, and insula. These results suggest that bifemelane improves both cerebral oxygen metabolism and cerebral circulation and contributes to the improvement of aphasia caused by cerebrovascular disease.

1-Oleoyl-2-docosahexaenoyl phosphatidylcholine increased paradoxical sleep in F344 rats.

The effects of administration of 1-oleoyl-2-docosahexaenoyl-sn-glycero-3-phosphorylcholine (O-DH-PC), a kind of lecithin, and of glycerophosphorylcholine (GPC) on sleep were investigated in male F344 rats. Intracerebroventricular administration of O-DH-PC at a dose of 10 micrograms/rat induced significant increase in paradoxical sleep time and total sleep time in the following 24 h, while administration of GPC did not. Results suggest that O-DH-PC affects on neuronal mechanism relating to paradoxical sleep, and that the effect of O-DH-PC might be caused by fatty acid residues, rather than choline residue.

Intraperitoneal injection of 1-oleoyl-2-docosahexaenoyl phosphatidylcholine enhances discriminatory shock avoidance learning in rats.

Effects of injection of 1-oleoyl-2-docosahexaenoyl-sn-glycero-3-phosphorylcholine (ODHPC) on learning ability were investigated in rats using discriminatory shock avoidance learning task. When ODHPC (2 mumol) was intraperitonealy administered 5 min before the beginning of the first trial of learning task from the second to fifth sessions, avoiding rates of the ODHPC-injected group were significantly higher than those of the control group. However, any injection of ODHPC derivatives, such as 1-oleoyl-2-docosahexaenoyl-diacylglycerol, 1,2-dioleoyl-sn-glycero-3-phosphorylcholine, glycerophosphorylcholine, docosahexaenoate, oleate and choline chloride, did not affect learning. These results suggest that intraperitoneal ODHPC injection enhances learning ability by its specific conformation.