Spin-Polarized Positronium Time-of-Flight Spectroscopy for Probing Spin-Polarized Surface Electronic States.

The energy spectrum of positronium atoms generated at a solid surface reflects the electron density of states (DOS) associated solely with the first surface layer. Using spin-polarized positrons, the spin-dependent surface DOS can be studied. For this purpose, we have developed a spin-polarized positronium time-of-flight spectroscopy apparatus based on a ^{22}Na positron source and an electrostatic beam transportation system, which enables the sampling of topmost surface electrons around the Γ point and near the Fermi level. We applied this technique to nonmagnetic Pt(111) and W(001), ferromagnetic Ni(111), Co(0001) and graphene on them, Co_{2}FeGa_{0.5}Ge_{0.5} (CFGG) and Co_{2}MnSi (CMS). The results showed that the electrons of Ni(111) and Co(0001) surfaces have characteristic negative spin polarizations, while these spin polarizations vanished upon graphene deposition, suggesting that the spin polarizations of graphene on Ni(111) and Co(0001) were mainly induced at the Dirac points that were out of range in the present measurement. The CFGG and CMS surfaces also exhibited only weak spin polarizations suggesting that the half-metallicity expected for these bulk states was not maintained at the surfaces.

Serum cell-free DNA levels are a useful marker for extramammary Paget disease.

BACKGROUND: Although carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) are useful markers for extramammary Paget disease (EMPD), serum CEA and CYFRA levels are not elevated in most patients with EMPD without metastasis. Cell-free (cf)DNA has attracted attention as an indicator of clinical conditions in several cancers. OBJECTIVES: To identify further useful biomarkers for the detection of EMPD, including early lesions, and to study the clinical implications of cfDNA in EMPD. METHODS: cfDNA were isolated from serum of patients with EMPD with and without metastasis, and from healthy volunteers. Serum extracts were amplified using polymerase chain reaction. RESULTS: Serum cfDNA levels were significantly elevated in patients with EMPD with or without metastasis compared with those in healthy controls. Serum cfDNA was a better diagnostic marker for the presence of EMPD than serum CYFRA. Moreover, the postoperative serum cfDNA levels were significantly lower than those from the preoperative samples, and the change in serum cfDNA levels reflected the clinical courses of patients with EMPD treated with chemotherapy. CONCLUSIONS: Taking the evidence together, serum cfDNA levels may be a useful marker for diagnosis and disease progression in EMPD. What's already known about this topic? Serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) are not elevated in most patients with extramammary Paget disease (EMPD) without metastasis. Cell-free (cf)DNA has attracted attention as an indicator of clinical conditions in several cancers. There are few reports of the clinical implications of cfDNA in dermatology. What does this study add? Serum cfDNA levels were significantly elevated in patients with EMPD with or without metastasis compared with those in healthy controls. Postoperative serum cfDNA levels were significantly lower than those from the preoperative samples. Changes in serum cfDNA levels reflected the clinical courses of patients with EMPD treated with chemotherapy. What is the translational message? Serum cfDNA levels in patients with EMPD are a useful marker for the detection of EMPD, including localized EMPD. Changes in serum cfDNA levels in an individual patient may reflect the clinical course of EMPD.

Candidate genes in panic disorder: meta-analyses of 23 common variants in major anxiogenic pathways.

The utilization of molecular genetics approaches in examination of panic disorder (PD) has implicated several variants as potential susceptibility factors for panicogenesis. However, the identification of robust PD susceptibility genes has been complicated by phenotypic diversity, underpowered association studies and ancestry-specific effects. In the present study, we performed a succinct review of case-control association studies published prior to April 2015. Meta-analyses were performed for candidate gene variants examined in at least three studies using the Cochrane Mantel-Haenszel fixed-effect model. Secondary analyses were also performed to assess the influences of sex, agoraphobia co-morbidity and ancestry-specific effects on panicogenesis. Meta-analyses were performed on 23 variants in 20 PD candidate genes. Significant associations after correction for multiple testing were observed for three variants, TMEM132D rs7370927 (T allele: odds ratio (OR)=1.27, 95% confidence interval (CI): 1.15-1.40, P=2.49 × 10(-6)), rs11060369 (CC genotype: OR=0.65, 95% CI: 0.53-0.79, P=1.81 × 10(-5)) and COMT rs4680 (Val (G) allele: OR=1.27, 95% CI: 1.14-1.42, P=2.49 × 10(-5)) in studies with samples of European ancestry. Nominal associations that did not survive correction for multiple testing were observed for NPSR1 rs324891 (T allele: OR=1.22, 95% CI: 1.07-1.38, P=0.002), TPH1 rs1800532 (AA genotype: OR=1.46, 95% CI: 1.14-1.89, P=0.003) and HTR2A rs6313 (T allele: OR=1.19, 95% CI: 1.07-1.33, P=0.002) in studies with samples of European ancestry and for MAOA-uVNTR in female PD (low-active alleles: OR=1.21, 95% CI: 1.07-1.38, P=0.004). No significant associations were observed in the secondary analyses considering sex, agoraphobia co-morbidity and studies with samples of Asian ancestry. Although these findings highlight a few associations, PD likely involves genetic variation in a multitude of biological pathways that is diverse among populations. Future studies must incorporate larger sample sizes and genome-wide approaches to further quantify the observed genetic variation among populations and subphenotypes of PD.

Characterization of a retroreflector array for 320-GHz interferometer system in Heliotron J.

A retroreflector array, composed of a cluster of small retroreflectors, is experimentally studied for application to a Michelson-type interferometer system in the fusion plasma experiment. Such a new-type reflector has the potential to be a vital and effective tool at a spatially limited location, such as on the vacuum chamber wall of plasma experimental devices. To investigate the effect of retroreflector array on the reflected beam properties, a tabletop experiment is performed with the retroreflector array composed of 4 mm corner-cube retroreflectors and with a 320-GHz (λ ∼ 0.937 mm) submillimeter wave source. An imaging camera is utilized to measure the submillimeter wave beam profile and is scanned perpendicularly to the beam propagation direction if necessary. The experimental result exhibits a diffraction effect on the reflected beam, resulting in the emergence of discrete peaks on the reflected beam profile, as predicted in the past numerical study; however, the most reflected beam power converges on the one reflected into the incident direction, resulting from a property as a retroreflector. Furthermore, the dependence of the reflected beam on the incident beam angle is characterized while fixing the detector position, and the retroreflection beam intensity is found to vary due to the diffraction effect. Such an undesired variation of beam intensity induced by the diffraction can be suppressed with a focusing lens placed in front of the detector in the practical application to an interferometer.

Development and initial results of 320 GHz interferometer system in Heliotron J.

A new 320 GHz solid-state source interferometer is installed in the Heliotron J helical device to explore the physics of high-density plasmas (ne > 2-3 × 1019 m-3, typically) realized with advanced fueling techniques. This interferometry system is of the Michelson type and is based on the heterodyne principle, with two independent solid-state sources that can deliver an output power of up to 50 mW. A high time resolution measurement of <1 µs can be derived by tuning the frequency of one source in the frequency range of 312-324 GHz on the new system, which can realize the fluctuation measurement. We successfully measured the line-averaged electron density in high-density plasma experiments. The measured density agreed well with a microwave interferometer measurement using a different viewing chord, demonstrating that the new system can be used for routine diagnostics of electron density in Heliotron J.

Three-dimensional dynamics of fluctuations appearing during pellet ablation process around a pellet in a fusion plasma experiment.

Understanding pellet ablation physics is crucial to realizing efficient fueling into a high temperature plasma for the steady state operation of ITER and future fusion reactors. Here we report the first observation of the formation of fluctuation structures in the pellet plasmoid during the pellet ablation process by a fast camera in a medium-sized fusion device, Heliotron J. The fluctuation has a normalized fluctuation level of ~ 15% and propagates around the moving pellet across the magnetic field. By comparing the fluctuation structures with the shape of magnetic field lines calculated with the field line tracing code, we successfully reconstruct the spatio-temporal structure of the fluctuations during the pellet ablation process. The fluctuations are located at the locations displaced toroidally from the pellet and propagate in the cross-field direction around the pellet axis along the field line, indicating a three-dimensional behavior and structure of fluctuations. The fluctuation would be driven by a strong inhomogeneity formed around the pellet and invoke the relaxation of the gradient through a cross-field transport induced by the fluctuations, which could affect the pellet ablation and pellet fueling processes. Such fluctuations can be ubiquitously present at the inhomogeneity formed around a pellet in the pellet ablation process in fusion devices.

Sensitivity improvement of infrared imaging video bolometer for divertor plasma measurement.

The sensitivity of an infrared imaging video bolometer (IRVB) was improved for the measurement of relatively low energy plasma radiation from the viewpoint of the metal foil absorber material. The photon energy of the radiation was considered up to 1 keV for the divertor plasma measurement. The thickness of the foil absorber was evaluated not only for conventional heavy elements, e.g., platinum, but also for light elements by the relation between the photon energy and attenuation length and by mechanical strength. A heat-transfer calculation using ANSYS suggested that light elements with practical foil thickness provide a higher temperature rise of the foil absorber compared with heavier elements with practical foil thickness. The maximum of the temperature rise was evaluated using He-Ne laser irradiation onto absorber samples. The material dependence of the temperature rise has a similar tendency between calculations and experiments. Experimentally, the sensitivity of the IRVB improved from 280 to 110 µW/cm2 using titanium with 1 µm thickness compared with conventional platinum with 2.5 µm thickness. Consequently, the signal-to-noise ratio of the IRVB could be improved from 2.8 to 9.1.

High-density magnetic-vacancy inclusion in Co2MnGa single crystal probed by spin-polarized positron annihilation spectroscopy.

Co2MnGa is a Weyl semimetal exhibiting giant anomalous Hall and Nernst effects. Using spin-polarized positron annihilation spectroscopy, we examined a Bridgman-grown Co2MnGa single crystal with a nearly perfectL21-ordered structure and a reference Co2MnAl polycrystal with a Mn-Al-disorderedB2 structure. We found that a large amount of magnetic vacancies (more than 100 ppm) were included in the Co2MnGa crystal but not the Co2MnAl crystal. We discuss possible reasons for the inclusion of vacancies, the role of vacancies in the development of the ordered structure, and the electronic states associated with the vacancies. Toward the development of Co2MnGa-based devices, the manners for reducing vacancies as well as the influence of vacancies on the electrical transport properties should be considered.

Development of a multi-channel 320 GHz interferometer for high density plasma measurement in Heliotron J.

We report the development of a new interferometer with two stable, high-power, 320 GHz solid-state sources in Heliotron J. A heterodyne Michelson interferometer optical scheme is employed. Two solid-state oscillators are utilized as sources with a fixed frequency at 320 GHz and frequency tunable of 312-324 GHz. Quasi-optical techniques are used for beam transmission. The beam is elongated in the vertical direction with two off-axis parabolic mirrors and injected into the plasma as a sheet beam for the multi-channel measurement (>5 ch.). Passing through the plasma, the beam is reflected at a retroreflector-array installed at the vacuum chamber wall. The retroreflector-array is a bunch of retroreflector structures, which can suppress the beam refraction caused by plasma without much space inside a vacuum chamber unlike a single retroreflector and can facilitate the system design. The source, detectors, and the retroreflector-array are tested to evaluate their basic performance on a tabletop experiment.

Absence of microsatellite instability in extramammary Paget's disease.

Background: Deficiency of DNA mismatch repair (MMR) induces microsatellite instability (MSI). Pembrolizumab, an antibody targeting PD-1 (an immune checkpoint inhibitor), is more effective against MMR-deficient tumours than against MMR-proficient tumours. The status of MMR is a useful biomarker for predicting the effectiveness of pembrolizumab administration. Although the status of MMR has attracted attention in skin tumours, there are few reports on MSI in extramammary Paget's disease (EMPD). Objectives: To evaluate the status of MMR in patients with EMPD. Materials & Methods: One hundred one patients with EMPD were included. MMR status of the genomic DNA of each subject was analysed using Promega panel (approved as a companion diagnostic agent for the administration of pembrolizumab). Results: MSI testing showed the occurrence rates of MSI-high (more than two markers are unstable), MSI-low (one marker is unstable) and MSS (all markers are stable) tumour tissues were 0% (0/101), 1.0% (1/101) and 99.0% (100/101), respectively. Conclusion: The status of MMR may not be useful for the potential therapeutic application of pembrolizumab.

Positronium formation at 4H SiC(0001) surfaces.

Positronium formation at 4H SiC(0001) surfaces were investigated upon the removal of natural oxide layers by hydrofluoric acid etching and heat treatment at 1000 K in ultra-high vacuum. Two types of positronium were observed in the positronium time-of-flight (PsTOF) measurements irrespective of conduction type and surface polarity. One type formed the major part of the PsTOF spectrum with a maximum energy of 4.7 ± 0.3 eV. This energy exceeded the theoretical value calculated with valence electrons. The PsTOF spectrum shape was different from those of metal surfaces, suggesting that the surface state electrons or conduction electrons need to be considered as the positronium source. Another positronium appeared at 1000 K in the tail of the PsTOF spectrum with a maximum energy of 0.2-0.5 eV. This thermally-assisted athermal positronium may be formed via the surface state positrons and electrons.

Identification of independent APP locus duplication in Japanese patients with early-onset Alzheimer disease.

BACKGROUND: The occurrence of duplications of the amyloid precursor protein gene (APP) has been described in European families with early-onset familial Alzheimer disease (EO-FAD) and cerebral amyloid angiopathy. However, the contribution of APP duplication to the development of AD in other ethnic populations remains undetermined. METHODS: The occurrence of APP duplication in probands from 25 families with FAD and 11 sporadic EO-AD cases in the Japanese population was examined by quantitative PCR and microarray-based comparative genomic hybridisation analyses. APP expression level was determined by real-time quantitative reverse-transcription (RT) PCR analysis using mRNA extracted from the peripheral blood of the patients. RESULTS: We identified APP locus duplications in two unrelated EO-FAD families. The duplicated genomic regions in two patients of these families differed from each other. No APP duplication was found in the late-onset FAD families or sporadic EO-AD patients. The patients with APP duplication developed insidious memory disturbance in their fifties without intracerebral haemorrhage and epilepsy. Quantitative RT-PCR analysis showed the increased APP mRNA expression levels in these patients compared with those in age- and sex-matched controls. CONCLUSIONS: Our results suggest that APP duplication should be considered in patients with EO-FAD in various ethnic groups, and that increased APP mRNA expression level owing to APP duplication contributes to AD development.

Prediction of disease-associated single nucleotide polymorphisms using virtual genomes constructed from a public haplotype database.

OBJECTIVES: Simultaneous dealing of hundreds of thousands of single nucleotide polymorphisms (SNPs) in genome-wide association studies is laborious. The aim of our study is to develop a method to decrease the number of candidate SNPs prior to the genotyping of study subjects. METHODS: We created virtual genotype data on case and control subjects from data of the International HapMap Project by using haplotype-based simulation method. We repeated virtual case-control association studies and selected candidate SNPs. We applied the selected SNPs to previously published genetic case-control studies. Sensitivity to detect association with causative genes using our method was compared to the original studies and results using tag SNPs. RESULTS: We found a discrete distribution pattern of SNPs, which was able to produce significant results in case-control association studies. The number of candidate SNPs that we selected was 24.7% of the number of the original set of SNPs. We applied this method to previously published genetic case-control studies and found that the use of candidate SNPs improved the sensitivity for detecting significant alleles, both compared to the original studies and to the use of tag SNPs. The results were not affected by the difference of the diseases and genes involved. CONCLUSIONS: Our simulation-based approach has advantages of reducing costs and improving performance to detect significant alleles. This method can be used without considering the specific disease and genes involved.

Five different genes, Eif4a1, Cd68, Supl15h, Sox15 and Fxr2h, are clustered in a 40 kb region of mouse chromosome 11.

We characterized a region of the mouse genome disrupted by integration of a gene trap (GT) vector in ES cells. On 5' rapid amplification of cDNA ends analysis of the fusion transcripts containing the GT vector, we identified the eukaryotic protein synthesis initiation factor 4A1 gene (Eif4a1) as a promoter-trapped gene. Plasmid rescue was used to show that the other end of the integrated vector disrupted the murine homolog of the human fragile X mental retardation syndrome-related protein 2 gene (Fxr2h). Structural analysis of P1 clones, isolated from the wild-type mouse genome by PCR with Eif4a1-specific primers, indicated that the integration of the GT vector was accompanied by the deletion of about 35 kb of genomic DNA and that the disrupted region also included three genes, Cd68, Supl15h and Sox15, the latter two of which are transcribed in opposite directions with overlapping 3' ends. These five different genes at least, Eif4a1, Cd68, Supl15h, Sox15 and Fxr2h, are clustered in a 40 kb region. The chromosomal location of this region was mapped by means of interspecific backcross panel DNAs to the central part of mouse chromosome 11, exhibiting a known region of synteny with human chromosome 17.

Correlation of quantitative CT with selective alveolobronchogram and pulmonary function tests in emphysema.

BACKGROUND: Emphysema diagnosed by computed tomography (CT) has been reported to be correlated with morphologic data from autopsied lungs or resected lobes. However, autopsied lungs or resected lobes are quite different from lungs in vivo. We examined the correlation between a quantitative analysis of CT and the in vivo morphologic degree of emphysema (selective alveolobronchography [SAB]) in patients with COPD. METHODS: We measured the mean attenuation value (MAV) of the lung fields between -700 HU and -1,024 HU to exclude the effect of high-density structures in 21 patients with COPD. Low attenuation, greater than 2 SD below the mean value of five normal healthy subjects, was used as an index of emphysema. To quantitate the amount of emphysema, the relative area of low attenuation to the area of the entire lung field (2SD percent) was measured. The morphologic degree of emphysema was determined from the diameter of ring shadow (DR) of SAB. We also examined the relationship between CT data and pulmonary function tests. RESULTS: The DR was highly correlated with the CT indexes of MAV and 2SD percent; (r = -0.894, p < 0.001, and r = 0.890, p < 0.001). Both MAV and 2SD percent were correlated with pulmonary function tests such as Dco, FEV1, and residual volume (r > 0.60). CONCLUSIONS: The MAV and relative area of emphysema obtained from CT density measurements accurately assess the severity of emphysema in patients with COPD as well as SAB.

Similar increase in circulating renin after equihypotensive doses of nitroprusside, dihydralazine or isradipine in conscious rabbits.

Calcium entry blockers but not nitroprusside sodium (NPS) or dihydralazine are known to enhance renin release in vitro. Isradipine (PN200-110), NPS or dihydralazine were infused at 15 min intervals into groups of 6 conscious, chronically instrumented rabbits each, at 3 doses carefully matched to elicit comparable falls in blood pressure. Plasma renin activity increased similarly with all treatments. In intact animals, the magnitude of the pressure decrease appears to be more important for renin release than the mechanism of vasodilation and a typical calcium entry blocker was indistinguishable from other vasodilators.

Validation of a liquid chromatographic-tandem mass spectrometric method for the measurement of (R)-1-[2,3-dihydro-2-oxo-1-pivaloylmethyl-5-(2-pyridyl)-1H-1,4-benzodiazepin-3-yl]-3-(3-methylaminophenyl)urea (YF476) in human plasma.

A sensitive and specific liquid chromatographic-tandem mass spectrometric (LC-MS-MS) method has been validated for the measurement of YF476 in human plasma. The method involves a simple liquid-liquid extraction procedure, chromatography of the extracts on a C(18) column, atmospheric pressure chemical ionisation and detection in the multiple reaction monitoring mode. The calibration line was linear over the concentration range 0.1 ng/ml (the limit of quantification) to 25.0 ng/ml. Intra- and inter-batch precision was <14% and intra- and inter-batch accuracy was <11% over the entire calibration range. The bioanalytical method is robust and has been used for the analysis of many samples from human subjects involved in early clinical studies (Phase I).

A gene trap strategy for identifying the gene expressed in the embryonic nervous system.

An efficient gene trap strategy was devised for identifying the genes that are expressed in the mouse developing nervous system. Mouse embryonic stem (ES) cell lines that carried independent integrations of a gene trap vector, pSneolN/acZA, were allowed to differentiate in a suspension culture system. To select cells containing neurons, astrocytes or neuron-glia precursors, cell lines were immunohistochemically examined with antibodies against neuron-specific proteins (neurofilament protein 150 kD and microtubule associated protein 2), glial fibrillary acidic protein or nestin. Three cell clones (GT3-8, 11 and 12) were immunoreactive to either of the antibodies employed and at the same time positive for beta-galactosidase activity. When chimeric embryos were generated by the use of the above 3 cell lines, some cells in their nervous system showed X-gal staining. Thus the major advantage of the present gene trap method lies in its prescreening step of manipulated ES cells prior to generation of chimeric animals. This method holds promise as a useful tool for investigating the genes involved in the development of the nervous system.

Mucinous carcinoma of the skin: report of a case with DNA cytofluorometric study.

A 62-year-old man with a mucinous carcinoma of the skin on the left cheek is described. The excised specimen showed a characteristic histopathologic picture. The findings from histochemical, immuno-histochemical, and electron microscopic examinations suggested an eccrine differentiation of the tumor cells. The removed tumor was examined using DNA cytofluorometry in order to analyze the cell kinetics and to estimate its biological behavior and prognosis. The tumor cells showed a diploid mode with a small number of polyploid cells. Only a small number of cells in the S and G2/M phase ranges were detected. After four years, there has been no evidence of tumor recurrence nor metastasis. The results of DNA ploidy analysis were thus compatible with the nature of slow growth with a good prognosis in this case.

[Traumatic aneurysm of the posterior inferior cerebellar artery (author's transl)].

The incidence of traumatic intracranial aneurysms are rare. In review of literature, only six cases of traumatic aneurysms in posterior fossa are reported. The patient, 15-year-old girl, was admitted on Dec. 18th, 1979, presented with unconsciousness after a traffic accident. She was developed impaired consciousness and left hemiparesis with right hemotympanum and nasal bleeding. Skull film showed an occipital linear fracture and a laminal fracture of the atlas. CT scan demonstrated traumatic subarachnoid, intraventricular hemorrhage and pneumocephalus. After accident, she regained consciousness with conservative therapy, but she deteriorated on the 10th hospitalized day. On the 17th day, lumbar puncture and CT scan revealed recurrent subarachnoid and intraventricular hemorrhage. The saccular aneurysm on the lateral medullary segment of the right posterior inferior cerebellar artery was obtained by cerebral angiogram on the 35th day. The configuration and size of the aneurysm was easily demonstrated by CT scans and cerebral angigrams. On the 43rd day, the clipping of the common trunk of the right posterior inferior cerebellar artery was employed. Her postoperative course was uneventful and she was discharged on the 97th day in good condition. This aneurysm was suggested to be induced by severe head injury with clinical ad operative findings. With the introduction of CT scan, CT scan is more available diagnostic modality than cerebral angiography in the follow up study with severe head injuries. And in the absence of pathological CT scan findings, suspicion of traumatic cerebrovascular impairments such as aneurysm should be paid. As the conservative management of traumatic intracranial aneurysms carries high mortality rate up to 30-50%, the prompt diagnosis and direct surgical intervention are recommended.