Scanning near-field optical spectroscopy and carrier transport based analysis in mesoscopic regions for two-dimensional semiconductors.

The measurements of photoexcited transport in mesoscopic regimes reveal the states and properties of mesoscopic systems. In this study, we focused on direct measurements of electromagnetic energy transports in the mesoscopic regions and constructed a scanning tunnelling microscope-assisted multi-probe scanning near-field optical microscope spectroscopy system. After producing an emission energy map through a single-probe measurement, two-probe measurement enables us to observe and analyse carrier transport characteristics. It suggests that exciton generation and transport in the mesoscopic region of semiconductors with quantum structure changes, such as the bias of dopant, affect the excited carrier emission recombination process. The measured probability density of the carrier transported with quantum effects can be used for applications in natural intelligence research by combining it with the analysis using tournament structures. Our developed measurement and analysis methods are expected to clarify the details of carrier's behaviour in the mesoscopic region in various materials and lead to applications for novel optoelectronic devices.

Note: An innovative method for 12C4+ suppression in 18O6+ beam production in an electron cyclotron resonance ion source.

It is a major and complex task to accelerate an ion which has the same charge to mass ratio with strong contaminant ions, such as 12C4+ in the 18O6+ beam. An innovative method has been developed to suppress the contaminant ions in the Electron Cyclotron Resonance (ECR) ion source by introducing Li vapor. The ion distribution inside the ECR zone was obtained by the optical analysis of ions inside the ECR ion source. The 12C4+ ions were suppressed as much as by a factor of 10, whereas the 18O6+ beam changed little with the use of this technique.

Pharmacokinetics of QMF149 in Japanese versus Caucasian subjects: an open-label, randomized phase I study.

OBJECTIVES: This study aimed to evaluate influence of ethnic factors on the pharmacokinetics of orally inhaled QMF149, a novel combination of an approved longacting ß2-agonist, indacaterol (Onbrez® Breezhaler® for COPD), and an approved inhaled corticosteroid, mometasone furoate (MF), (Asmanex® Twisthaler® for asthma), following multiple dose administration of QMF149 (indacaterol acetate/MF) 150/80 µg and 150/320 µg via the Breezhaler® device in healthy Japanese and Caucasian subjects. METHODS: This was a single-center, openlabel, multiple-dose, two-period, complete crossover study that randomized healthy Japanese and, age and weight matched Caucasian subjects to QMF149 150/80 µg or 150/320 µg once daily (o.d.) for 14 days in each period. Pharmacokinetics (PK) were assessed up to 24 hours on days 1 and 14. RESULTS: 24 Japanese and 24 Caucasian healthy subjects were enrolled. Indacaterol and MF had similar PK profiles across both the doses and both ethnic groups. The maximum geometric mean ratios (90% confidence interval (CI)) for Japanese vs. Caucasian subjects for Cmax were 1.23 (1.11 - 1.38) and 1.24 (1.11 - 1.38) for indacaterol and MF, respectively. For AUC, the maximum ratios were 1.22 (1.09 - 1.36) and 1.30 (1.18 - 1.44) for indacaterol and MF, respectively. The mild trend towards higher exposure in Japanese subjects could be explained by the fact that the mean body weight was 14% higher for Caucasians compared to their Japanese counterparts. No serious adverse events or discontinuations related to study medication were reported. CONCLUSION: The study demonstrated increase of mean exposure parameters in Japanese subjects vs. Caucasian subjects, which ranged between 19 - 23% and 17 - 30%, for indacaterol and MF components, respectively. Multiple doses of both the QMF149 dose levels were safe and well-tolerated in all subjects. Body weight was considered a key contributory factor for the observed difference in exposure. These results suggest no dose adjustment for QMF149 is required in Asian populations.

Note: 6Li III light intensity observation for 6Li3+ ion beam operation at Hyper-Electron Cyclotron Resonance ion source.

The light intensity of (6)Li III line spectrum at λ = 516.7 nm was observed during (6)Li(3+) beam tuning at the Hyper-Electron Cyclotron Resonance (ECR) ion source. Separation of ion species of the same charge to mass ratio with an electromagnetic mass analyzer is known to be an exceptionally complex process. However, (6)Li III line intensity observation conducted in this study gives new insights into its simplification of this process. The light intensity of (6)Li III line spectrum from the ECR plasma was found to have a strong correlation with the extracted (6)Li(3+) beam intensity from the RIKEN Azimuthal Varying Field cyclotron.

Phase relationships in the quasi-ternary LaO1.5-SiO2-MgO system at 1773 K.

Phase relationships in the LaO1.5-SiO2-MgO quasi-ternary system at 1773 K were investigated by powder x-ray diffraction (XRD) analysis applying single- and multiple-phase Rietveld methods. Most of the formed phases satisfied the Gibbs' phase rule, except for the samples containing LaO1.5 and a liquid phase at 1773 K. The detection of segregated MgO phases was difficult in the XRD profiles of the compositional samples around the oxyapatite single phase because the MgO peaks were weak and heavily overlapped by peaks from the oxyapatite and La(OH)3 phases. The solid solubility limit of MgO in oxyapatite was determined not only from the chemical composition of the oxyapatite phase, which was confirmed by XRD, but also from several phase boundary compositions among the two-phase and three-phase regions based on the Gibbs' phase rule. Formation of a liquid phase at 1773 K was observed in a wide range of compositions and considered when constructing the phase diagram.

The effect of probiotics on gastric mucosal permeability in humans administered with aspirin.

OBJECTIVE: To examine whether a probiotic strain, Lactobacillus gasseri OLL2716 (LG21), can protect the gastric mucosal integrity from aspirin using urinary sucrose excretion (USE) test. MATERIALS AND METHODS: In the study using high-dose aspirin, the USE tests were carried out in 29 volunteers before and after LG21 treatment for 4 weeks. In the study using patients undergoing low-dose aspirin therapy, USE tests were performed in 37 subjects who took LG21 for 16 weeks. Stool occult blood was examined by the guaiac method. RESULTS: In the former study, the elevation in the USE value after aspirin loading significantly decreased after LG21 treatment (Median ± SD; 0.244 ± 0.237 vs. 0.208 ± 0.112%, p = 0.018). In the latter study, the USE value significantly decreased in the period with LG21 treatment (p = 0.033), while no significant difference was found in the period without LG21 (p = 0.113). The number of positive occult blood tests decreased during LG21 treatment. CONCLUSIONS: The regular ingestion of LG21 may protect the integrity of the gastric mucosal permeability against aspirin.

Lower bound of energy dissipation in optical excitation transfer via optical near-field interactions.

We theoretically analyzed the lower bound of energy dissipation required for optical excitation transfer from smaller quantum dots to larger ones via optical near-field interactions. The coherent interaction between two quantum dots via optical near-fields results in unidirectional excitation transfer by an energy dissipation process occurring in the larger dot. We investigated the lower bound of this energy dissipation, or the intersublevel energy difference at the larger dot, when the excitation appearing in the larger dot originated from the excitation transfer via optical near-field interactions. We demonstrate that the energy dissipation could be as low as 25 µeV. Compared with the bit flip energy of an electrically wired device, this is about 104 times more energy efficient. The achievable integration density of nanophotonic devices is also analyzed based on the energy dissipation and the error ratio while assuming a Yukawa-type potential for the optical near-field interactions.

Long-term administration of probiotics to asymptomatic pre-school children for either the eradication or the prevention of Helicobacter pylori infection.

BACKGROUND: The role of probiotics in the armamentarium remains to be defined. The aims of this study were to investigate whether the long-time administration of Lactobacillus gasseri OLL2716 (LG21) strain can eradicate H. pylori in asymptomatic pre-school children and/or prevent H. pylori infection. METHODS: A total of 440 children, from 5-7 years of age, attending a kindergarten in Thailand were screened by the Helicobacter pylori stool antigen (HpSA) test. Thereafter 132 H. pylori positive and 308 H. pylori negative children were recruited to eradication and randomized prevention arms, respectively. Children in the active and placebo treatment groups received Lactobacillus gasseri OLL2716 (LG21) containing cheese and ordinary cheese, respectively, for 12 months. Eradication was defined as reversion by HpSA at 12 months. Prevention was defined as persistently HpSA negative at 12 months. RESULTS: Eighty-two of 132 H. pylori positive (62%) completed the eradication arm, of which 24 (29.3%) were negative at 12 months according to the HpSA test. In the randomized prevention arm, 123 of 156 (79%) and 99 of 122 (81%) completed active and placebo arms, respectively, of which 4.1% and 8.1%, respectively, were HpSA positive at 12 months based on a per-protocol analysis (p = .21). CONCLUSION: Further trials are needed.

Tamper resistance in optical excitation transfer based on optical near-field interactions.

We present tamper resistance in optical excitation transfer via optical near-field interactions based on the energy dissipation process occurring locally in nanometric devices such as quantum dots. A theoretical comparison with electrical systems is also shown, focusing on the required environmental conditions. Numerical simulations based on virtual photon models demonstrate high tamper resistance.

Role of the indigenous microbiota in maintaining the virus-specific CD8 memory T cells in the lung of mice infected with murine cytomegalovirus.

The potent role of indigenous microbiota in maintaining murine CMV (MCMV)-specific memory T cells, which were measured by multimer staining, was investigated using germfree (GF) mice. When the BALB/c mice bred under specific pathogen-free (SPF) conditions were i.p. infected with 0.2 LD(50) of MCMV, high frequencies of CD69(+)/CD44(+) MCMV-specific CD8 T cells were noted in the lungs even at 6-12 mo after infection (11.1 +/- 3.2 and 9.8 +/- 0.9%, respectively). In contrast, even though the viral load and expression levels of mRNA of such cytokines as IL-2, IL-7, IL-15, and IFN-gamma in the lungs of MCMV-infected GF mice were comparable to those of infected SPF mice, the frequencies of MCMV-specific CD8 T cells in the lungs of infected GF mice were kept lower than 1% at 6-12 mo after infection. In addition, the reconstitution of microbiota of MCMV-infected GF mice by orally administering a fecal suspension prepared from SPF mice restored the frequencies of both CD8(+)/multimer(+) and CD8(+)/multimer(-) T cells to levels similar to those found in SPF mice. These results suggested the indigenous microbiota to play a crucial role in the expansion and maintenance of viral-specific CD8 memory T cells, probably by cross-reactivity between the antigenic epitope of the MCMV-specific memory T cells and the variety of peptides derived from the members of the microbiota. Such cross-reactivity may thus be a major feature of those cells.

Optical interconnects based on optical far- and near-field interactions for high-density data broadcasting.

Ultrahigh-density data-broadcasting optical interconnects are proposed and experimentally demonstrated using optical near-field interactions between quantum dots, which cannot be driven by far-field light, allowing sub-wavelength device operation, and far-field excitation for global interconnects. The proposed scheme helps to solve interconnection difficulties experienced in nano-scale device arrays since components for individually guiding light from external systems are not required. Combining the broadcasting mechanism with switching and summation architectures will allow nano-scale integration of parallel processing devices.

Nanometric summation architecture based on optical near-field interaction between quantum dots.

A nanoscale data summation architecture is proposed and experimentally demonstrated based on the optical near-field interaction between quantum dots. Based on local electromagnetic interactions between a few nanometric elements via optical near fields, we can combine multiple excitations at a certain quantum dot, which allows construction of a summation architecture. Summation plays a key role for content-addressable memory, which is one of the most important functions in optical networks.

Nonadiabatic photodissociation process using an optical near field.

We demonstrated the deposition of nanometric Zn dots using photodissociation with gas-phase diethylzinc and an optical near field under nonresonant conditions. To explain the experimental results, we proposed an exciton-phonon polariton model, and discuss the quantitative experimental dependence of the deposition rate on the optical power and photon energy based on photodissociation involving multiple-step excitation via molecular vibration modes. The physical basis of this process, which seems to violate the Franck-Condon principle, is the optically nonadiabatic excitation of the molecular vibration mode due to the steep spatial gradient of the optical near-field energy.

Sodium iodoacetate-induced experimental osteoarthritis and associated pain model in rats.

Degenerative lesions were induced in the knee joint of Wistar rats by intraarticular injection of chondrocyte metabolism inhibitor mono-iodoacetate (MIA) at doses of 0, 0.3 or 3 mg/joint. Histopathological examination and the measurement of hind paw weight ratio as an index of joint pain by incapacitance tester were performed. Histological findings that are similar to those observed in human osteoarthritis (OA), such as disorganization of chondrocytes, erosion and fibrillation of cartilage surface, and subchondral bone exposure etc., were observed in a MIA-dose-dependent manner. Saflanin-O fast green staining revealed that marked diffuse reduction of proteoglycan in cartilage tissue of rats treated with MIA. The clinical scores of the joint pain were closely correlated to the grade of histological findings. We conclude that the present experimental model in combination with a novel dual channel weight averager would be very useful for the study of human OA, and could be applied for estimation of therapeutic effect of new anti-OA drugs.

One-step RT-PCR without initial RNA isolation sStep for laser-microdissected tissue sample.

One-step RT-PCR procedure without initial RNA extraction step is tested for laser microdissected tissue sample. Unfixed cryosections of liver and kidney tissue of male SD rats were cut using laser microdissection system and directly used as templates for RT-PCR study. To check the sensitivity, 5, 25, 125, and 625 hepatocytes were cut and put in PCR-tube. After DNase treatment and cDNA synthesis with pd(N)6 random primer, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) cDNAs were amplified by 60 thermal cycles. GAPDH-specific bands were observed at as few as 25 hepatocytes. Specificity of this procedure was tested for hepatocytes, renal tubular epithelium and glomerular tissue using albumin PCR primers. Approximately 250 cells were cut and albumin cDNA was amplified as described above. Albumin specific band was observed only in hepatocytes sample. To apply this approach to quantitative PCR, various numbers of hepatocytes were cut and put in 0.2 mL PCR tube. After reverse transcription and 10 cycles of GAPDH cDNA amplification by regular thermal-cycler, PCR solution was transferred to 96-well plate designed for real-time PCR system, and further 40 cycles were performed. As a result, GAPDH cDNAs were successfully amplified with a good correlation between the number of template hepatocytes and the intensity of PCR signal. From these results, we concluded this approach would be very useful for the expression analysis of microdissected pathology samples.

Interlaboratory comparison of short-term carcinogenicity studies using CB6F1-rasH2 transgenic mice.

In order to evaluate a short-term carcinogenicity testing system using CB6F1 -Tg rasH2 (rasH2-Tg) mice carrying a human prototype c-Ha-ras gene, 26-week studies were conducted in 12 different facilities as a part of an International Life Science Institute Health and Environmental Science Institute (ILSI HESI) international collaborative project. In each study N-methyl-N-nitrosourea (MNU) was administered to a separate group of rasH2-Tg mice by single intraperitoneal injection (75 mg/kg) as a positive control. We herein have summarized the mortality, body weight change, and neoplastic and nonneoplastic lesions detected in these positive control groups as representative historical positive control data. Also, we performed an interlaboratory comparison of the response of rasH2-Tg mice to MNU based on the data of 11 positive control groups from these studies. Although the body weight of rasH2-Tg mice showed lower values than that of non-Tgmice during the experimental period, body weight gain in the rasH2-Tg mice was similar to that in non-Tg mice. The mortality of rasH2-Tg mice during the study period was very low, the same as for the non-Tg mice. Incidences of spontaneous alveolar/bronchiolar adenomas and splenic hemangiomas/hemangiosarcomas were also low in the rasH2-Tg mice. Nonneoplastic lesions detected in the rasH2-Tg mice were similar to those in non-Tg mice, excluding the incidence of myopathy. There were interlaboratory differences in mortality and incidence of some lesions in the MNU-treated groups. However, the causes of death were common among the 11 laboratories and almost all the MNU-treated rasH2-Tg mice developed forestomach squamous cell papillomas/carcinomas or malignant lymphomas. This suggests that there is no appreciable difference in the response of the rasH2-Tg mouse to MNU used as a positive control. Therefore, it is concluded that MNU would be an adequate positive control compound in this testing system.

Immunohistochemical localization of transforming growth factor alpha in regenerating rat liver.

Immunohistochemical localization of TGF-alpha and cell proliferation kinetics during liver regeneration after two-thirds partial hepatectomy (PH) were investigated. Twenty-four to 72 hr after PH, appreciable increase in the number of TGF-alpha-positive hepatocytes was observed in zones 1 and 2. At the peak at 36 hr, almost all positive cells were stained in their nuclei. Considerable increase in the BrdU labeling index was observed 24-36 hr after PH with a peak at 24 hr in zones 1 and 2. These results indicated an association between TGF-alpha expression and hepatocyte regeneration. It is suggested that immunohistochemical localization of TGF-alpha may be a useful marker of cell proliferation activity in rat liver.

Distinction of carcinogens from mutagens by induction of liver cell foci in a model for detection of initiation activity.

Initiating activities of 26 chemicals were investigated in an in vivo 5 week initiation assay model with evaluation of the induction of glutathione S-transferase placental form (GST-P) positive foci as end-point lesions. With the five genotoxic hepatocarcinogens (diethylnitrosamine, dimethylnitrosamine, 2-acetylaminofluorene, N-bis(2-hydroxypropyl)-nitrosamine and safrole) and 11 genotoxic non-hepatocarcinogens, (2-(2-furyl)-3-(5-nitro-2-furyl)-acrylamide, benzo[a]pyrene, N-butyl-N-(4-hydroxybutyl)nitrosamine, 7,12-dimethylbenz[a]anthracene, 1,2-dimethylhydrazine, N-ethyl-N-hydroxyethylnitrosamine, 3-methylcholanthrene, N-methyl-N-nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine, 4-nitroquinoline 1-oxide and 8-hydroxyquinoline), the numbers of GST-P positive foci were significantly higher than in the controls. On the other hand, the mutagenic non-carcinogens (quercetin, p-phenylenediamine dihydrochloride, 2-chloroethanol and 6-hydroquinoline) did not cause a significant increase. Similarly, non-genotoxic hepatocarcinogens of the hepatopromotor class and promotors which target organs other than the liver did not induce GST-P positive foci. The specificity was thus remarkable. Moreover, regardless of the target organ, mutagenic carcinogens were detected by this in vivo 5 week initiation assay, which therefore constitutes a powerful method for screening for carcinogenic potential, especially in the initiation stage of carcinogenesis.

Skeletal myopathy in transgenic mice carrying human prototype c-Ha-ras gene.

Skeletal myopathy was found in almost all-transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mouse). Microscopically, variation of the muscle fiber size, centrally placed nuclei, regenerating fibers, and interstitial fibrosis were evident; hyalinization and necrosis were sometimes observed in the skeletal muscle (femoralis and pectoralis) of the rasH2 mice. Inflammatory changes in the skeletal muscle or abnormality of adjacent peripheral nerve were not observed. The features were essentially similar to those of muscular dystrophy. Although the severity was relatively mild compared to 34-week-old rasH2 mice, the skeletal myopathy was also observed in younger male (10 weeks of age) rasH2 mice. In nontransgenic littermates, skeletal myopathy was not observed. The mRNA of human c-Ha-ras product was detected in femoral muscle from the rasH2 mice by RT-PCR. In conclusion, these data suggest that skeletal myopathy is occurring in almost all rasH2 mice. Integration of c-Ha-ras gene is thought to be crucial to pathogenesis of skeletal myopathy in the rasH2 mice. Further characterization of the muscular lesion and its pathogenesis are needed to explore the possibility of rasH2 mouse becoming a new model for muscular dystrophy.