Study of the K_{L}→π

The rare decay K_{L}→π^{0}νν[over ¯] was studied with the dataset taken at the J-PARC KOTO experiment in 2016, 2017, and 2018. With a single event sensitivity of (7.20±0.05_{stat}±0.66_{syst})×10^{-10}, three candidate events were observed in the signal region. After unveiling them, contaminations from K^{±} and scattered K_{L} decays were studied, and the total number of background events was estimated to be 1.22±0.26. We conclude that the number of observed events is statistically consistent with the background expectation. For this dataset, we set an upper limit of 4.9×10^{-9} on the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level.

Impact of kinetics on the growth of GaN on graphene by plasma-assisted molecular beam epitaxy.

The growth of GaN on graphene by molecular beam epitaxy was investigated. The most stable epitaxial relationship, i.e. [00.1]-oriented grains, is obtained at high temperature and N-rich conditions, which match those for nanowire growth. Alternatively, at moderate temperature and Ga-rich conditions, several metastable orientations are observed at the nucleation stage, which evolve preferentially towards [00.1]-oriented grains. The dependence of the nucleation regime on growth conditions was assigned to Ga adatom kinetics. This statement is consistent with the calculated graphene/GaN in-plane lattice coincidence and supported by a combination of transmission electron microscopy, x-ray diffraction, photoluminescence, and Raman spectroscopy experiments.

Search for K_{L}→π

A search for the rare decay K_{L}→π^{0}νν[over ¯] was performed. With the data collected in 2015, corresponding to 2.2×10^{19} protons on target, a single event sensitivity of (1.30±0.01_{stat}±0.14_{syst})×10^{-9} was achieved and no candidate events were observed. We set an upper limit of 3.0×10^{-9} for the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level (C.L.), which improved the previous limit by almost an order of magnitude. An upper limit for K_{L}→π^{0}X^{0} was also set as 2.4×10^{-9} at the 90% C.L., where X^{0} is an invisible boson with a mass of 135 MeV/c^{2}.

Remote epitaxy using graphene enables growth of stress-free GaN.

The properties of group III-Nitrides (III-N) such as a large direct bandgap, high melting point, and high breakdown voltage make them very attractive for optoelectronic applications. However, conventional epitaxy on SiC and sapphire substrates results in strained and defective films with consequently poor device performance. In this work, by studying the nucleation of GaN on graphene/SiC by MOVPE, we unambiguously demonstrate the possibility of remote van der Waals epitaxy. By choosing the appropriate growth conditions, GaN crystals can grow either in-plane misoriented or fully epitaxial to the substrate. The adhesion forces across the GaN and graphene interface are very weak and the micron-scale nuclei can be easily moved around. The combined use of x-ray diffraction and transmission electron microscopy demonstrate the growth of stress-free and dislocation-free crystals. The high quality of the crystals was further confirmed by photoluminescence measurements. First principles calculations additionally highlighted the importance of the polarity of the underlying substrate. This work lays the first brick towards the synthesis of high quality III-N thin films grown via van der Waals epitaxy.

Large magnetic anisotropy enhancement in size controlled Ni nanowires electrodeposited into nanoporous alumina templates.

A large enhancement of the magnetic anisotropy of Ni nanowires (NWs) embedded in anodic aluminium oxide porous membranes is obtained as a result of an induced magnetoelastic (ME) anisotropy contribution. This unusual large anisotropy enhancement depends on the diameter of the NWs and exceeds the magnetostatic (MS) contribution. As a consequence, it leads to effective magnetic anisotropy energies as large as 1.4 × 10(6) erg cm(-3), which are of the same order of magnitude and comparable to the MS energies of harder magnetic materials like Co NWs. Specifically, from ferromagnetic resonance experiments, the magnetic anisotropy of the NWs has been observed to increase as its diameter is decreased, leading to values that are about four times larger than the corresponding value when only the MS anisotropy is present. Our results are consistent with the recently proposed growth mechanism of Ni NWs that proceeds via a poly-crystalline stage at the bottom followed by a single-crystalline stage with texture [110] parallel to the axis of the NWs. A strong correlation between reducing the diameter of the NWs with the decrease of the length of the poly-crystalline segment and the enhancement of the effective magnetic anisotropy has been shown. Magnetization curves obtained from alternating gradient magnetometry experiments show that the average ME anisotropy results from the competition between the magnetic anisotropies of both crystalline segments of the NWs. Understanding the influence of size and confinement effects on the magnetic properties of nanocomposites is of prime interest for the development of novel and agile devices.

Discharge characteristics of steady-state high-density plasma source based on cascade arc discharge with hollow cathode.

We developed a steady-state high-density plasma source by applying a hollow cathode to a cascade arc discharge device. The hollow cathode is made of a thermionic material (LaB6) to facilitate plasma production inside it. The cascade arc discharge device with the hollow cathode produced a stationary plasma with an electron density of about 1016 cm-3. It was found that the plasma source produces a strong pressure gradient between the gas feed and the vacuum chamber. The plasma source separated the atmospheric pressure (100 kPa) and a vacuum (100 Pa) when the discharge was performed with an argon gas flow rate of 5.0 l/min and a discharge current of 40 A. An analysis of the pressure gradient along the plasma source showed that the pressure difference between the gas feed and the vacuum chamber can be well described by the Hagen-Poiseuille flow equation, indicating that the viscosity of the neutral gas is the dominant factor for producing this pressure gradient. A potential profile analysis suggested that the plasma was mainly heated within cylindrical channels whose inner diameter was 3 mm. This feature and the results of the pressure ratio analysis indicated that the temperature, and, thus, viscosity, of the neutral gas increased with the increasing number of intermediate electrodes. The discharge characteristics and shape of the hollow cathode are suitable for plasma window applications.

Characteristics of plasma window with various channel diameters for accelerator applications.

Plasma window is a feasible device as an atmosphere-vacuum interface, which can withstand energetic particle beams. It is, however, essential to enlarge the diameter to several tens of millimeters for actual beam passing in the accelerator applications. The pressure separation performance and discharge voltage V current I characteristics should be investigated in detail to design the plasma window for each purpose. Therefore, a cascade arc discharge device with a diameter of up to 20 mm was developed, and its characteristics as a function of diameter were examined. As a result, with an increase in the channel diameter, the discharge pressure that was achieved decreased, whose values were smaller compared with the values by the prediction formula, assuming the viscous gas flow with a constant plasma temperature. It showed that the bulk plasma temperature for the larger discharge channel was low because of the low-current density over the channel. Furthermore, the transition of the V-I slope was observed with an increase in the diameter.

The evolution of the fraction of Er ions sensitized by Si nanostructures in silicon-rich silicon oxide thin films.

Photoluminescence (PL) and time-resolved PL experiments as a function of the elaboration process are performed on Er-doped silicon-rich silicon oxide (SRO:Er) thin films grown under NH(3) atmosphere. These PL measurements of the Er(3+) emission at 1.54 microm under non-resonant pumping with the Er f-f transitions are obtained for different Er(3+) concentrations, ranging from 0.05 to 1.4 at.%, and various post-growth annealing temperatures of the layers. High resolution transmission electron microscopy (HRTEM) and energy-filtered TEM (EFTEM) analysis show a high density of Si nanostructures composed of amorphous and crystalline nanoclusters varying from 2.7 x 10(18) to 10(18) cm(-3) as a function of the post-growth annealing temperature. Measurements of PL lifetime and effective Er excitation cross section for all the samples under non-resonant optical excitation with the Er(3+) atomic energy levels show that the number of Er(3+) ions sensitized by the silicon-rich matrix decreases as the annealing temperature is increased from 500 to 1050 degrees C. The origin of this effect is attributed to the reduction of the density of sensitizers for Er ions in the SRO matrix when the annealing temperature increases. Finally, extended x-ray absorption fine-structure spectroscopy (EXAFS) shows a strong correlation between the number of emitters and the mean local order around the erbium ions.

Broad-spectrum antibiotic prescriptions are discontinued unevenly throughout the week.

In order to investigate prescribing patterns of in-hospital broad-spectrum antibiotics (antimeticillin-resistant Staphylococcus aureus drugs, carbapenems and piperacillin/tazobactam), data on the distribution of antibiotic initiation and discontinuation throughout the week were analysed at Osaka University Hospital, Japan. No significant differences in the number of initiations were found between weekdays. However, broad-spectrum antibiotics were disproportionately discontinued on Tuesdays or on the second day after a holiday. This study suggests that broad-spectrum antibiotics tend to be continued over weekends or holidays and discontinued thereafter; this is likely to be due to behavioural factors beyond medical indications, and needs to be addressed in future antimicrobial stewardship initiatives.

BDNF upregulation during declarative memory formation in monkey inferior temporal cortex.

In primates, visual long-term memory of objects is presumably stored in the inferior temporal (IT) cortex. Because brain-derived neurotrophic factor (BDNF) is involved in activity-dependent neural reorganization, we tested the hypothesis that BDNF would be upregulated in IT cortex during formation of visual pair-association memory. To eliminate genetic and cognitive variations between individual animals, we used split-brain monkeys for intra-animal comparison in PCR-based mRNA quantitation. The monkeys learned a pair-association (PA) task using one hemisphere and a control visual task using the other, to balance the amount of visual input. We found that BDNF was upregulated selectively in area 36 of IT cortex during PA learning, but not in areas involved in earlier stages of visual processing. In situ hybridization showed that BDNF-expressing cells were localized in a patchlike cluster. The results suggest that BDNF contributes to reorganization of neural circuits for visual long-term memory formation in the primate.

Evidence for spin-to-charge conversion by Rashba coupling in metallic states at the Fe/Ge(111) interface.

The spin-orbit coupling relating the electron spin and momentum allows for spin generation, detection and manipulation. It thus fulfils the three basic functions of the spin field-effect transistor. However, the spin Hall effect in bulk germanium is too weak to produce spin currents, whereas large Rashba effect at Ge(111) surfaces covered with heavy metals could generate spin-polarized currents. The Rashba spin splitting can actually be as large as hundreds of meV. Here we show a giant spin-to-charge conversion in metallic states at the Fe/Ge(111) interface due to the Rashba coupling. We generate very large charge currents by direct spin pumping into the interface states from 20 K to room temperature. The presence of these metallic states at the Fe/Ge(111) interface is demonstrated by first-principles electronic structure calculations. By this, we demonstrate how to take advantage of the spin-orbit coupling for the development of the spin field-effect transistor.

Escape from redox regulation enhances the transforming activity of Fos.

Fos and Jun form dimeric complexes that bind to DNA sequences containing activator protein 1 (AP-1) sites and regulate gene expression. The in vitro DNA-binding activity of these proteins is sensitive to reduction-oxidation (redox). Reduction of a single conserved cysteine residue, located in the DNA-binding domain, either by reducing agents or by a nuclear redox factor (Ref-1), is required for AP-1 DNA-binding activity. Replacing the critical cysteine with serine results in a protein that can bind to DNA in vitro even under oxidizing conditions. To determine whether redox control affects the function of Fos in vivo, we have constructed, and compared the properties of, retroviral vectors expressing either a truncated Fos protein (F118-211) or a truncated Fos protein in which the critical cysteine was replaced by serine (FC154S). In infected chicken embryo fibroblasts (CEFs), both vectors expressed similar levels of Fos protein, which formed heterodimers with Jun at equivalent efficiencies. However, extracts from cells expressing FC154S exhibited a threefold increase in AP-1 DNA-binding activity compared with cells expressing F118-211. Furthermore, this enhanced binding activity was resistant to treatment with the oxidizing agent diamide. Infection of CEFs by virus expressing FC154S resulted in increased numbers of transformed colonies and an increase in colony size compared with those obtained following infection by virus expressing Fos 118-211. These results suggest that redox regulation may limit the total level of functional Fos-Jun complexes in vivo and that escape from this control enhances transforming activity.

Inhibition of jun transformation by a mutated fos gene: design of an anti-oncogene.

The protein products of the fos and jun oncogenes (Fos and Jun) function as transcriptional regulators in the form of homo- or heterodimeric complexes that bind to DNA. Dimerization is mediated by a leucine zipper structure that serves to juxtapose alpha-helical regions of each protein, rich in basic amino acids, that form a bipartite DNA-binding domain. Although Fos participates exclusively in heterodimeric complexes, Jun can function either as a homodimer that has a low apparent affinity for DNA or as a more stable heterodimer with Fos that has a higher apparent affinity for DNA. We have used these properties of Fos and Jun to design a mutated fos gene, lacking a functional DNA-binding domain (supfos1), that suppresses the transforming activity of jun in trans. Here we show that chicken embryo fibroblasts transformed by jun revert to a normal phenotype after infection by a retroviral vector encoding supFos1. Furthermore, infection of normal cells with the supfos1 vector renders them resistant to subsequent transformation by jun. Inhibition of jun transformation was associated with the appearance of supFos1-Jun heterodimers and a reduction in the AP-1 DNA-binding activity contributed by Jun homodimers. These findings demonstrate that the function of leucine zipper-containing transcription factors can be investigated by the procedure of intracellular immunization.

Spatiotemporal dynamics of brain-derived neurotrophic factor mRNA induction in the vestibulo-olivary network during vestibular compensation.

Vestibular compensation, which is the behavioral recovery from vestibular dysfunction produced by unilateral labyrinthectomy (UL), is attributed to functional and structural reorganization of neural networks in the central vestibular system. To assess the possible contribution of brain-derived neurotrophic factor (BDNF) to this recovery process, we investigated changes in mRNA expression levels in the central vestibular system after UL. We evaluated BDNF mRNA expression levels by quantitative reverse transcription-PCR and in situ hybridization. We found that BDNF mRNA is differentially induced in the medial vestibular nucleus ipsilateral to UL and in the prepositus hypoglossi and inferior olive on the contralateral side. The BDNF mRNA induction lasted for at least 24 hr and returned to the basal expression level within 72 hr after UL. In contrast to BDNF mRNA induction, the expression of an immediate-early gene, c-fos, quickly reached the maximum level at 3 hr and decreased to the basal level within 24 hr after UL. Neither BDNF or c-fos induction was observed in sham-operated animals. The persistent induction of BDNF after UL temporally corresponded to early behavioral manifestations of vestibular compensation. We further found that trkB mRNA was expressed in the central vestibular network at high levels, although its expression levels did not change over time after UL. Because BDNF is implicated in regulating synaptic structure and function, these results provide support for the hypothesis that BDNF is involved in neuronal reorganization that allows vestibular compensation.

Difference between cancer cells and the corresponding normal tissue in view of stereoselective hydrolysis of synthetic esters.

This study has aimed at taking information necessary for design of anticancer prodrugs modified with chiral acyl group, especially about the effect of chirality of the acyl group on its enzymic removal in specific cells. Thus, 13 species of chiral esters were synthesized and stereoselectivity in their enzymic hydrolysis was investigated with six cancer cell lines, solid tumors, and the corresponding normal tissues. Cultured cancer cells from rat liver, pancreas, and muscle hydrolyzed the R enantiomer of (+/-)-ethyl 2-methoxy-2-phenylacetate (3c) more preferentially than its antipode, whereas this stereoselectivity was reversed in the reaction by homogenate of the corresponding normal tissue of rat. The difference in stereoselectivity between cancer cells and normal tissue was also found in the hydrolysis of other esters including those of actual anticancer agents, p-hydroxyaniline mustard and 5-fluorouridine. The investigation was expanded to real tumor to show that the degree of stereoselectivity or the hydrolytic activity was significantly different between a human brain tumor and its surrounding normal tissue for such substrates as (+/-)-ethyl 2-phenoxypropanoate and N-trifluoroacetylphenylalaninate. The esterases of rat liver cancer cells (Anr4) and normal rat liver gave different band patterns in active staining after gel electrophoresis. The enzymes were fractionated by ion exchange column chromatography and then tested on their stereoselectivity against (+/-)-3c. Comparison of the results and electrophoretograms of the fractions suggests that esterases with different stereoselectivity are expressed in different ways by normal and cancer cells. These results show that stereoselectivity in enzymic hydrolysis of some synthetic chiral esters is different between cancer and normal cells, leading to the possibility that specific activation of ester-type anticancer prodrugs in cancer cells would be controlled by the chiral structure of the acyl group.

Shortening of distal motor latency in anode distal stimulation.

OBJECTIVE: Distal motor latency (DML) is shortened when the anode is held distally instead of the cathode by increasing the stimulus intensity. The objective of this study was to clarify the mechanism responsible for this shortening. METHODS: In seven healthy subjects, compound muscle action potential (CMAP) was obtained from the thenar muscle by bipolar stimulation of the median nerve at the wrist, and the intensity at which the first motor units were stimulated was defined as the threshold. Bipolar stimulation with extended interpole distance was employed to identify the generating site of the CMAP and F-wave. RESULTS: The shortening of DML was dependent on the stimulus intensity and threshold. For the low threshold condition, the CMAP generating site was replaced from the proximal cathodal pole to the distal anodal pole by increasing the stimulus intensity. The generating site of the F-wave remained at the proximal cathodal pole irrespective of stimulus intensity. CONCLUSIONS: Replacement of the generating site results in the shortening of DML. When the F-wave is recorded after being induced by anode distal stimulation, CMAP should not be simultaneously evaluated. SIGNIFICANCE: This study clarified the generation sites of CMAP and the F-wave when induced by anode distal stimulation.

Cloning of human cDNAs for Apg-1 and Apg-2, members of the Hsp110 family, and chromosomal assignment of their genes.

In mice, the Hsp110/SSE family is composed of the heat shock protein (Hsp)110/105, Apg-1 and Apg-2. In humans, however, only the Hsp110/105 homolog has been identified as a member, and two cDNAs, Hsp70RY and HS24/p52, potentially encoding proteins structurally similar to, but smaller than, mouse Apg-2 have been reported. To clarify the membership of Hsp110 family in humans, we isolated Apg-1 and Apg-2 cDNAs from a human testis cDNA library. The human Apg-1 was 100% and 91.8% identical in length and amino acid (aa) sequence, respectively, to mouse Apg-1. Human Apg-2 was one aa shorter than and 95.5% identical in sequence to mouse Apg-2. In ECV304, human endothelial cells Apg-1 but not Apg-2 transcripts were induced in 2 h by a temperature shift from 32 degrees C to 39 degrees C. As found in mice, the response was stronger than that to a 37-42 degrees C shift. The human Apg-1 and Apg-2 genes were mapped to the chromosomal loci 4q28 and 5q23.3-q31.1, respectively, by fluorescence in-situ hybridization. We isolated cDNA and genomic clones encompassing the region critical for the difference between Apg-2 and HS24/p52. Although the primer sets used were derived from the sequences common to both cDNAs, all cDNA and genomic clones corresponded to Apg-2. Using a similar approach, the relationship between Apg-2 and Hsp70RY was assessed, and no clone corresponding to Hsp70RY was obtained. These results demonstrated that the Hsp110 family consists of at least three members, Apg-1, Apg-2 and Hsp110 in humans as well as in mice. The significance of HS24/p52 and Hsp70RY cDNAs previously reported remains to be determined.

Quantitative evaluation of neurotrophin and trk mRNA expression in visual and limbic areas along the occipito-temporo-hippocampal pathway in adult macaque monkeys.

The neurotrophins have been implicated in shaping and remodeling the connectivity of neural circuits. To explore the role of neurotrophins and their receptors, Trks, in cortical neural circuits of adult macaque monkeys, we determined mRNA expression levels of neurotrophins and Trk receptors in various visual and limbic areas along the occipito-temporo-hippocampal pathway by using a quantitative reverse-transcription polymerase chain reaction technique. The expression level of brain-derived neurotrophic factor (BDNF) mRNA was lowest in the primary visual cortex (V1), moderate in the temporal visual association area, and highest in the hippocampus. The expression levels of trkB mRNA isoforms, the full-length form that encodes a receptor tyrosine kinase and the truncated form that encodes a noncatalytic receptor, were also low in V1, moderate in the visual association area, and high in the entorhinal cortex. However, in contrast to their ligand BDNF, the expression levels of both trkB isoforms in the hippocampus were significantly lower than those in the entorhinal cortex. NT-3 mRNA was detectable only in the hippocampus and the entorhinal cortex, whereas both the full-length and the truncated forms of trkC mRNA were widely distributed throughout the neocortex and the limbic cortex. The expression levels of NGF and trkA mRNAs in these cortical areas were too low to determine quantitatively. The present findings suggest that, among neurotrophin/Trk signaling systems, the BDNF/TrkB-mediated signal most likely contributes to stabilization, remodeling, or both, of neural circuits in cortical areas along the occipito-temporo-hippocampal pathway in the adult macaque monkey.

A novel in vitro assay system for transendothelial tumor cell invasion: significance of E-selectin and alpha 3 integrin in the transendothelial invasion by HT1080 fibrosarcoma cells.

The interaction of tumor cells with endothelial cells is a key event in tumor metastasis. We established an in vitro invasion assay system, in which the invasion of tumor cells after interaction with endothelial cells can be examined. Two chamber culture wells separated by porous membrane were used. Human umbilical vein endothelial cells (HUVEC) were placed on porous membranes coated with matrix components. The invasion by HT1080 fibrosarcoma cells was determined in this system by counting the number of cells that moved through the membranes from upper to lower chambers. HUVEC cells did not migrate through the membranes as judged by the staining with UEA-I. Observation by scanning electron microscopy revealed that HT1080 cells bound to HUVEC surfaces and migrated underneath the HUVEC monolayer. Effects of antibodies specific for cell surface adhesion molecules on the migration of HT1080 cells were examined. Invasion of uncoated membranes and membranes coated with HUVEC cells was compared. Antibody against E-selectin significantly suppressed an increase of HT1080 cell invasion of HUVEC monolayers stimulated by IL-1 beta or TNF alpha. Antibody against integrin alpha 3 subunit remarkably inhibited the invasion of HUVEC cell-coated membranes, suggesting that integrins with the alpha 3 subunit may play an important role in the transendothelial invasion by HT1080 cells.

Enhancement of type IV collagenases by highly metastatic variants of HT1080 fibrosarcoma cells established by a transendothelial invasion system in vitro.

A novel in vitro invasion assay system was established in this laboratory, in which the invasion of tumor cells after interaction with endothelial cells could be examined. Two variant cell lines (FP-10, FP-21) were established from parental HT1080 cells using this assay system. FP-10 and FP-21 cells had higher invasive and metastatic potential than the parental cells both in vitro and in vivo. The activity of anchorage-independent proliferation and the adhesion to the HUVEC monolayer of FP-10 and FP-21 was greater than the parental cells. The secretion of type IV collagenase (both MMP-2 and MMP-9) was also increased more significantly by the variant cells than by the parental cells, and the expression of uPA mRNA was higher in FP-10 and FP-21. Treatment of variant cells with human TIMP-2 remarkably suppressed the increment of the in vitro invasion to the same level as parental cells. These results suggest that this in vitro transendothelial invasion system accelerates multiple mechanisms of the metastasis by HT1080, especially the production of type IV collagenases. It can thus provide a useful model of tumor metastasis.