Investigation of Ag and Cu Filament Formation Inside the Metal Sulfide Layer of an Atomic Switch Based on Point-Contact Spectroscopy.

The atomic switches have attracted wide attention owing to their applications in nonvolatile electric devices. The atomic switch is operated by the formation and dissipation of a metallic filament inside a metal sulfide film, which is controlled by a solid electrochemical reaction. Although the metallic filament is considered to consist of metal atoms, the chemical species of the metallic filament are difficult to be identified due to challenges in observing the metallic filament inside the solid. In this study, we report the investigation on the metallic filament in the atomic switch with metal sulfide based on point-contact spectroscopy (PCS). By cooling the atomic switch, the switch voltage increased to 1 V, which allowed for the PCS measurement. The PCS revealed that the metallic filament was composed of Ag atoms in the case of the Pt/Ag2S/Ag atomic switch. We applied this technique to the Pt/Cu2S/Ag and Pt/Ag2S/Cu atomic switches to uncover the formation process of the metallic filament. In both atomic switches, the chemical species of the metallic filament were Ag. The metal atoms were supplied from both the metal electrode and the sulfide layer.

Volatile and nonvolatile selective switching of a photo-assisted initialized atomic switch.

A photo-assisted atomic switch, which has a photoconductive molecular layer in a gap of about 20 nm between an Ag2S electrode and a Pt electrode, is set to a conventional gap-type atomic switch operation mode by light irradiation with the application of a small bias that precipitates Ag atoms from an Ag2S electrode. After this initialization, the switch operates only with application of a bias. In this study, we also found that after the set-operation a photo-assisted initialized atomic switch shows different switching modes depending on the bias range, i.e., volatile switching when the applied bias is smaller than the threshold bias, and nonvolatile switching when the applied bias is larger than the threshold bias. These characteristics can be useful in reconfiguring a circuit such as in neural computing systems.

Forming and switching mechanisms of a cation-migration-based oxide resistive memory.

We report detailed current-voltage and current-time measurements to reveal the forming and switching behaviors of Cu/Ta(2)O(5)/Pt nonvolatile resistive memory devices. The devices can be initially SET (from the OFF state to the ON state) when a low positive bias voltage is applied to the Cu electrode. This first SET operation corresponds to the first formation of a metal filament by inhomogeneous nucleation and subsequent growth of Cu on the Pt electrode, based on the migration of Cu ions in the stable Ta(2)O(5) matrix. After the forming, the device exhibits bipolar switching behavior (SET at positive bias and RESET (from the ON state to the OFF state) at negative bias) with increasing the ON resistance from a few hundred Ω to a few kΩ. From the measurements of the temperature stability of the ON states, we concluded that the RESET process consists of the Joule-heating-assisted oxidation of Cu atoms at the thinnest part of the metal filament followed by diffusion and drift of the Cu ions under their own concentration gradient and the applied electric field, disconnecting the metal filament. With ON resistances of the order of a few kΩ, the SET and RESET operations are repeated by the inhomogeneous nucleation and the Joule-heating-assisted dissolution of a small filament on a remaining filament. This switching model is applicable to the operation of cation-migration-based resistive memories using other oxide materials.

Quantized conductance atomic switch.

A large variety of nanometre-scale devices have been investigated in recent years that could overcome the physical and economic limitations of current semiconductor devices. To be of technological interest, the energy consumption and fabrication cost of these 'nanodevices' need to be low. Here we report a new type of nanodevice, a quantized conductance atomic switch (QCAS), which satisfies these requirements. The QCAS works by controlling the formation and annihilation of an atomic bridge at the crossing point between two electrodes. The wires are spaced approximately 1 nm apart, and one of the two is a solid electrolyte wire from which the atomic bridges are formed. We demonstrate that such a QCAS can switch between 'on' and 'off' states at room temperature and in air at a frequency of 1 MHz and at a small operating voltage (600 mV). Basic logic circuits are also easily fabricated by crossing solid electrolyte wires with metal electrodes.

Highly diverse TTV population in infants and their mothers.

Infants born to serum HCV-positive 12 mothers were enrolled in the study. Nucleotide sequences amplified by primers deduced from a noncoding region were compared between mothers and their infants. The rates for detection of serum TTV in 12 mothers and their infants were 10/12 (83%) and 9/12 (75%), respectively. Serum TTV DNA was not detected in any infant at 1 month of age, but was detected for the first time between 1.5 and 8 months after birth. Positivity persisted thereafter throughout the follow-up period. In seven randomly selected mother-infant pairs, intrahost TTV heterogeneity was lower in infants than in mothers. Furthermore, one of seven mother-infant pairs showed a high degree of similarity (98.7-100%) in all clones, while in four infants, all nucleotide sequences differed by >10% from those of their mothers. However, the degree of homology in the two mother-infant pairs was 89-98.7% in family 2 and 88.1-99.4% in family 5. In the present study, with only one exception, it was shown that TTV from infants is not identical to TTV from mothers. The mechanism is discussed briefly in this paper.

Detection rates of TT virus DNA in serum of umbilical cord blood, breast milk and saliva.

To date, the routes of mother-to-infant transmission of TT virus (TTV) have not been fully elucidated. The present study examines the detection rates of TTV DNA in the serum of pregnant Japanese women and in cord blood at the time of delivery, as well as in the saliva and breast milk of mothers one-month postpartum. Primers derived from the well-known translated region N22 (N22 system), as well as the untranslated region (UTR system) were used. The prevalence of TTV DNA in the serum of pregnant women was found to be 11.9% (19/160) using the N22 system and 72.4% (55/76) using the UTR system. No TTV DNA was detected in the cord blood samples (0/160) when the N22 system was used for detection but TTV DNA was detected in 11.8% (7/76) of samples studied with the UTR system. Using the N22 system, TTV DNA was not detected in breast milk, but was detected in saliva. However using the UTR system, TTV DNA was detected in both specimens. These results imply that some babies are vertically infected with TTV via cord blood at the time of delivery or via breast milk or saliva. However, further research is necessary to confirm this hypothesis. polymerase chain reaction; pregnant women; horizontal route of transmission

TT virus infection in Japanese children: isolates from genotype 1 are overrepresented in patients with hepatic dysfunction of unknown etiology.

The pathogenecity of the TT virus (TTV) especially during childhood remains obscure. We investigated the prevalence of TTV in 40 patients with non-A to C hepatic dysfunction (non-A to C hepatic dysfunction group). Five patients with fulminant hepatitis of unknown etiology were enrolled in this group. We also examined 380 children without a history of transfusion or liver disease (control group). Subsequently, the genotypes of TTV strains isolated were analyzed in terms of their nucleotide sequences including 222 bp in the open reading frame 1 region. The prevalence of serum TTV DNA was 10/40 (25%) in the non-A to C hepatic dysfunction group and 25/380 (7%) in the control group. Sixty-six percent (23/35) of all examined cases exhibited either genotype 1 or 2. However, assessment of genotype in the non-A to C hepatic dysfunction group (10 cases) revealed a higher prevalence of genotype 1 than of all other genotypes (80% vs. 20%). This result differed significantly from that of the control group (25 cases; 32% vs. 68%). Such overrepresentation of genotype 1 suggests that this type of TTV strain is associated with the development of hepatic dysfunction of unknown etiology in Japanese children.

The prevalence of serum GB virus C/hepatitis G virus RNA and anti-E2 in Japanese children without a history of blood transfusion.

The prevalence of serum GB virus C (GBV-C)/Hepatitis G virus (HGV) RNA and anti-E2 was investigated in Japanese children younger than 16 years of age without a history of blood transfusion and the family members of serum GBV-C/HGV RNA-positive children. The prevalences of serum GBV-C/HGV RNA and anti-E2 were 0.5% (5/1000) and 0% (0/330), respectively. Viral RNA was also detected in the mothers of all five GBV-C/HGV RNA-positive children and in two of their siblings. Sequence determinations indicated the likelihood of mother-to-infant transmission in all cases. The presence of the virus persisted for at least 10-18 months in all 5 children, without any appearance of anti-E2.

Prevalence of TTV DNA among children with a history of transfusion or liver disease.

The prevalence rates of serum TT virus (TTV) DNA among children with or without a history of transfusion or liver disease were studied by polymerase chain reaction (PCR) using either the Okamoto primer set or the Takahashi primer set developed more recently. Using Okamoto and Takahashi primer sets, the prevalence rates were 31.6% (12/38) and 78.9% (30/38), respectively, for children with a history of blood transfusion (including malignant and non-malignant groups) and 6.7% (2/30) and 60% (18/30), respectively, for children without a history of blood transfusion. Among pregnant women, these rates were 12.9% (4/31) and 61.3% (19/31), respectively. On the other hand, the prevalence rates were 0% (0/16) and 50% (8/16), respectively, in hepatitis B patients, 21.4% (3/14) and 71.4% (10/14), respectively, for hepatitis C patients, and 20.0% (9/45) and 57.8% (26/45), respectively, for non-A to C hepatitis patients (including 27 acute hepatitis patients, 5 fulminant patients and 13 chronic hepatitis patients). In this study, the prevalence rates determined by the Takahashi primer set tended to be 2-9 times higher than those determined using the Okamoto primer set. These results suggest that TTV infection is widespread among Japanese children. Furthermore, blood transfusion does not appear to be the major route of infection. The similar prevalence rates between control children and children with various types of hepatitis using the Takahashi primer system suggest that TTV infection does not play a direct causative role in the development of liver disease in children.

Route of TT virus infection in children.

TT virus (TTV) is a novel viral agent, detected recently in non-A to E hepatitis cases. Little is known about its natural history or routes of transmission in childhood. For the detection of serum TTV DNA, semi-nested polymerase chain reaction (PCR) was carried out using TTV-specific primers and TTV nucleotide sequences were determined by the dideoxy chain-mediated termination method. Five of the 70 children studied (including 20 hepatitis B virus [HBV] carriers, 40 children born to HBV carrier mothers and 10 children born to hepatitis C virus [HCV] carrier mothers) had serum TTV DNA. Three of the 5 children had siblings (4 in total), so that a total of 9 children were studied to determine the time of initial serum TTV DNA detection. In the 8 seropositive children, the time of serum TTV DNA detection ranged from 6 to 14 months after birth, and TTV DNA persisted thereafter throughout the follow-up period. The TTV DNA-negative child was assessed most recently at 6 months of age. TTV DNA was detected in only 2 of the 4 mothers tested (families 2 and 3). When 271-bp TTV DNA fragments from each of the 8 children were sequenced, the degree of homology between siblings in families 1-3 was 100%, 99.5%, and 92.3%, respectively. The degree of homology between child-mother pairs of families 2 and 3 was 99.5-100% and 62. 6-63.9%, respectively. The distribution of different TTV strains was consistent within families, except for family 3. None of the TTV-infected children had elevated levels of alanine aminotransferase or clinical signs of liver disease.

Evaluation of a new anti-HCV-assay kit for anti-HCV screening in early childhood.

Sera of 20 children falsely identified as positive for hepatitis C virus antibody (Anti-HCV) by a second generation anti-HCV-assay kit (Imucheck-HCV Ab "Kokusai") were re-tested using a new third generation anti-HCV-assay kit (Imucheck x F-HCV C50 Ab "Kokusai"). Seventeen of the samples were reclassified as negative and only three remained positive. Changing well solids in the anti-HCV-assay kit from casein to bovine serum albumin appears to have improved the false-positive rate, most likely as a result of decreased non-specific adsorption of casein antibodies.

Detection rates of TT virus among children who visited a general hospital in Japan.

Recently, genomic DNA of the novel TT virus (TTV) was isolated from patients suffering from posttransfusion hepatitis of unknown etiology. We examined sera from 197 children who visited the Department of Pediatrics at Toyohashi National Hospital. Sera were tested for TTV DNA by seminested polymerase chain reaction (PCR) using a set of primers synthesized according to the published TTV sequence. Ten children were found to be positive for TTV (5.1%). All positive PCR products were directly sequenced in both directions using a fluorescent dye terminator cycle sequencing system. The sequences were compared by a multiple sequence alignment and a phylogenetic tree was constructed. The phylogenetic tree showed that two of the TTV isolates found in the present experiment did not belong to any of the phylogenetic groups previously reported.

Prevalence of GB virus C/hepatitis G virus ribonucleic acid and anti-hepatitis G virus-E2 antibodies among Japanese children with histories of transfusions or with liver diseases.

To clarify the prevalence of Japanese children thought to be at a risk for infection with GB virus-C (GBV-C)/hepatitis G virus (HGV), we investigated the detection rates of serum GBV-C/ HGV ribonucleic acid (RNA) by reverse transcription-seminested PCR and serum anti-HGV-E2 antibody by ELISA in 162 children with histories of blood or plasma product transfusions or with liver diseases and performed phylogenetic analysis of the 5' noncoding region sequences of GBV-C/HGV genomes. Children with histories of transfusions were divided into those who had been treated with antineoplastic agents for malignant diseases (malignant group) and those who had received transfusions for nonmalignant diseases (nonmalignant group). Children with liver diseases were divided into hepatitis B (HBV), hepatitis C (HCV), and non-A-C hepatitis groups. We detected GBV-C/ HGV RNA in 11 of 33 (33.3%) and anti-HGV-E2 in 1 of 27 (3.7%) children in the malignant group and in 3 of 56 (5.4%) and 1 of 53 (1.9%) children, respectively, in the nonmalignant group. Neither GBV-C/HGV RNA nor anti-HGV-E2 was detected in the HBV and non-A-C hepatitis groups. GBV-C/HGV RNA and anti-HGV-E2 were detected in 7 of 23 (30.4%) and in 1 of 18 (5.6%) children, respectively, in the HCV group. All children positive for either GBV-C/HGV RNA or anti-HGV-E2, except one whose route of GBV-C/HGV infection suggested mother-to-infant transmission, had histories of transfusions. The phylogenetic analysis showed that all isolates in this study were divisible into three groups and that most of them were clustered into group 3 (Asian group).

Prevalence of GBV-C/HGV infection in pregnant Japanese women.

Recently, a novel viral agent, hepatitis G virus, was identified by independent researchers from the serum of patients with liver disease, and termed GBV-C or HGV. At present, GBV-C and HGV are considered to be separate isolates of the same virus; however, the role of this virus in acute and chronic liver disease remains uncertain. Although vertical transmission is known to be one of the routes of transmission, the prevalence of GBV-C/HGV viremia in pregnant Japanese women is unknown. Thus, we determined this prevalence using the reverse transcription polymerase chain reaction (RT-PCR).

Antitumor effect of anthocyanin fractions extracted from red soybeans and red beans in vitro and in vivo.

Many bioflavonoids extracted from petals of higher plants and from fruit rinds, as well as purified flavonoids, have been reported to have antitumor effects in vitro and in vivo. Bioflavonoids extracted from red soybeans are mostly cyanin conjugated with glucose and rhamnose, whereas bioflavonoids of red beans are cyanin conjugated with rhamnose as revealed by thin-layer chromatogram. Flavonoids extracted from red soybeans were effective in inhibiting the growth of HCT-15 cells in vitro. On the other hand, flavonoids from red beans were not effective, although their hydrolyzed sugar-free forms were growth inhibitory. Sugar-bonded bioflavonoids extracted from both red soybeans and red beans were effective in prolonging the survival of Balb/C mice bearing syngeneic tumor-Meth/A cells, when they were dissolved in drinking water and given at a dose of approximately 500 micrograms/mouse/day.

Influence of flavonoids on cell cycle phase as analyzed by flow-cytometry.

Flavonoids were previously reported to have cytostatic activity in vitro and in vivo. In the present study each phase of the cell cycle was observed by flow-cytometry after HCT-15 cells had been cultured with flavonoids for 2 days. In the control group, two peaks were observed on the histogram, the first peak representing double strands of DNA, and the second, tetra strands. Chalcone, which is known to be a precursor of all flavonoids, seemed to block the passage from S to G2 and M phase. Flavonone, which is freely transformed into chalcone in vivo, showed a similar histogram as chalcone. Among the anthocyanins most effective in suppressing the tumor cell growth, cyanin and pelargonidin made a mild rise between the 1st and 2nd peak suggesting block between G1 and S phase. Delphinidin gave a high percent of cells in G1 phase, suggesting prolongation of G1 phase. When quercetin or kaempherol, both of which are flavonols were added to the culture, the second peak rose significantly, indicating a block between G2 and M phases. Thus, the site of these cytostatic agents seems to differ depending on the kind of flavonoid.

[Clinical effects of postoperative immunochemotherapy with a combination of 5-FU, CDDP and lentinan for stage IVb gastric carcinoma and long-term pharmacokinetic studies on CDDP and 5-FU].

Eleven patients with postoperative-stage IVb gastric cancer were treated by combined administration of CDDP, 5-FU and Lentinan. CDDP was given intravenously at 20 mg/body on days one to five. At the same time, 5-FU was continuously administered 250 or 500 mg/body/day via the central venous catheter for more than two weeks, while Lentinan was given at the dose of 2 mg per week. Two courses were repeated every 3 weeks. The mean response duration and survival period for the eleven patients were 13 and 21 months, respectively, and one- and two year survival rates were 82% and 27%. This combination therapy was thus considered to be very effective. Next, the pharmacokinetics of long-term CDDP and 5-FU was studied. Our method could maintain the optimum serum concentration of total CDDP. Furthermore, the continuous infusion of 5-FU at a daily dose of 250 mg/day could sufficiently maintain the effective plasma concentration, although its peak fluctuated over time. Thus, in the plasma level of 5-FU in patients in poor condition requires periodic measurement.

Flavonoid-mediated tumor growth suppression demonstrated by in vivo study.

Many of flavonoids as well as bioflavonoids extracted from higher plants, which were earlier revealed to have tumor cell growth suppression activity in vitro, were examined for their effect on tumors in vivo. Balb/c mice were inoculated i.p. with syngeneic tumor cells, meth/a, and then provided with flavonoids dissolved in their drinking water during the course of their survival time. Many flavonoids were effective in prolonging the survival period. Furthermore, flavonoids that did not show suppressive activities in the in vitro experiments were effective in the in vivo assay. The data suggested that sugar bonded to the A ring, which suppresses tumor growth inhibition in vitro, plays an important role. Many aglycones that were effective in the in vitro assay on the tumor growth suppression were not effective in the in vivo assay. The reason for this seems to be that most aglycones are unstable and thus break down in vivo. No acute nor chronic toxicity of flavonoids was observed in the mice.

Suppression of tumor cell growth by anthocyanins in vitro.

Bioflavonoids, extracted from flower petals, were examined for their growth inhibitory effect on cells in culture. They were found to significantly suppress the growth of the cultured cells. Anthocyanins tended to show greater inhibitory effect than other flavonoids. Commercially synthesized or purified aglycones of flavonoids were also studied for their suppression of tumor cells. The anthocyanins were more effective than other flavonoid aglycones, although the aglycones were easily inactivated under the culture conditions.