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Background Human epidermal growth factor 2 (HER2) is a potential driver oncogene. Although HER2-targeted precision therapy has been tested in non-small cell lung cancer (NSCLC), the demographic characteristics of HER2-positive NSCLC have not been systematically defined. Methods Patients with pathologically confirmed stage IIIB/IV or recurrent NSCLC, Eastern Cooperative Oncology Group performance status 0 to 2, were prospectively registered. HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays were performed to screen patients. HER2 mutations were identified by using direct gene sequencing. The aim of this study was to clarify the frequency, characteristics, and outcome of HER2-positive NSCLC. HER2 was defined as positive if the tumor harbored IHC3+, IHC2+/FISH+, or exon 20 insertion mutations. Results Of the 1,126 tumors screened, 34 (3.0%) were IHC3+, and 34 (3.0%) were IHC2+/FISH+. Among the 724 epidermal growth factor receptor wild-type tumors, 21 (2.9%) were HER2-mutant tumors, including A775-G776insYVMA (n = 15). Interestingly, the IHC3+ tumors and mutant tumors were entirely exclusive. Female patients had HER2-mutant tumors more frequently, whereas both IHC3+ and IHC2+/FISH+ tumors were detected more often in male subjects and smokers. Patients with an HER2-aberrant tumor had a significantly worse prognosis than those with epidermal growth factor receptor-positive and anaplastic lymphoma kinase-positive tumors, possibly due to the low proportion that received HER2-targeted therapies (n = 15 [26%]) and low response rates of 0% and 14% in patients with HER2-overexpressing and HER2-mutant tumors, respectively. Conclusions This prospective large-scale cohort study is the first to show comprehensively the frequency and clinical demographic characteristics of those with HER2-positive advanced lung tumors in detail, providing critical historical data for future drug development against HER2-positive NSCLC. Future treatment strategies would be developed stratified according to the types of HER2 aberrations. Trial Registry UMIN Registration No. 000017003; URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019691

We experimentally show that half-metallic Co2MnSi films can be grown on SrTiO3(001) at around 350 °C by molecular beam epitaxy. Despite relatively low-temperature grown Co2MnSi films, L 2 1 -ordered structures, high saturation magnetic moments of ∼ 5.0 μ B /f.u., and the negative sign of the anisotropic magnetoresistance (AMR) indicating half-metallic nature are obtained. For the 350°C-grown Co2MnSi films, a low Gilbert damping constant of ∼ 0.0035, implying the high spin polarization, is evaluated. This study will open a way for developing novel spintronic applications consisting of Co2MnSi and perovskite oxides such as high-performance interfacial multiferroic systems and efficient spin-to-charge conversion systems.

We have applied an ultrashort-pulse reflectometer (USRM) to an inductively coupled plasma for density profile measurement along with a plasma absorption probe (PAP). It is found that the density in the edge plasma region measured by USRM is in good agreement with that by PAP, however, the measured density in core region shows large discrepancy between two methods. This difference is considered to occur due to difference of optical path route within utilized frequency band. We have rearranged experimental setup to avoid this improper situation, and confirmed that the density in core region measured by both methods is becoming in good agreement.

The inhomogeneity of the impurity- and field-induced magnetic order and superconductivity has been investigated in the hole-doped La 2− x Sr x CuO 4 (LSCO), La 2− x Ba x CuO 4 (LBCO) and the electron-doped Pr 1− x LaCe x CuO 4 (PLCCO). For the hole-doped cuprates, it has been found from the muon-spin-relaxation measurements that both Zn and Ni impurities tend to develop a magnetic order and to destroy the superconductivity around themselves not only around p (the hole concentration per Cu) = 1/8 but also at x = 0.15 and 0.18 in LSCO, though the development of the magnetic order by Zn is more marked than by Ni. Moreover, it has been found from the thermal conductivity measurements that the development of the magnetic order by the application of magnetic field is marked not just at p = 1/8 but in the neighborhood of p = 1/8 in LSCO and LBCO. The impurity- and field-induced magnetic order in the hole-doped cuprates can be interpreted as being due to pinning of the dynamical stripes of holes and spins by impurities and vortex cores in the CuO 2 plane, respectively. For the electron-doped PLCCO with x = 0.14, on the contrary, no impurity-induced magnetic order has been observed. The reason is discussed.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive approach used for stimulating the brain, and has proven effective in the treatment of depression, however the mechanism of its antidepressant action is unknown. Recently, we have reported the induction of kf-1 in rat frontal cortex and hippocampus after chronic antidepressant treatment and repeated electroconvulsive treatment (ECT). In this study, we demonstrated the induction of kf-1 after rTMS in the rat frontal cortex and hippocampus, but not in hypothalamus. Our data suggest that kf-1 may be a common functional molecule that is increased after antidepressant treatment, ECT and rTMS. In conclusion, it is proposed that induction of kf-1 may be associated with the treatment induced adaptive neural plasticity in the brain, which is a long-term target for their antidepressant action.

Since liquid chromatography/mass spectrometry (LC/MS) was introduced in the field of forensic toxicology in Japan, many challenges were considered using this technique in an attempt to overcome the problems which remained unsolved using other techniques such as gas chromatography (GC), liquid chromatography (LC) and gas chromatography/mass spectrometry (GC/MS). We here review the analytical challenges carried out in Japan using LC/MS from 1992 to 2002. The studied compounds include abused drugs, hypnotics, antipsychotics, ethyl glucuronide, muscle relaxants, pesticides, surfactants, natural toxins such as tetrodotoxin and cardiac glycosides, etc. We also describe the background of the research and some cases of poisoning which provided the opportunity to begin these researches. Although GC/MS and LC/diode array detector (DAD) are mainly used in Japan for comprehensive screening and confirmation of drugs and poisons, the requirements of LC/MS in the field of forensic toxicology is expected to increase. This field which makes use of LC/MS is indeed expanding.

The KEKB accelerator control system including a control computer system, a timing distribution system, and a safety control system are described. KEKB accelerators were installed in the same tunnel where the TRISTAN accelerator was. There were some constraints due to the reused equipment. The control system is based on Experimental Physics and Industrial Control System (EPICS). In order to reduce the cost and labor for constructing the KEKB control system, as many CAMAC modules as possible are used again. The guiding principles of the KEKB control computer system are as follows: use EPICS as the controls environment, provide a two-language system for developing application programs, use VMEbus as frontend computers as a consequence of EPICS, use standard buses, such as CAMAC, GPIB, VXIbus, ARCNET, RS-232 as field buses and use ergonomic equipment for operators and scientists. On the software side, interpretive Python and SAD languages are used for coding application programs. The purpose of the radiation safety system is to protect personnel from radiation hazards. It consists of an access control system and a beam interlock system. The access control system protects people from strong radiation inside the accelerator tunnel due to an intense beam, by controlling access to the beamline area. On the other hand, the beam interlock system prevents people from radiation exposure by interlocking the beam operation. For the convenience of accelerator operation and access control, the region covered by the safety system is divided into three major access control areas: the KEKB area, the PF-AR area, and the beam-transport (BT) area. The KEKB control system required a new timing system to match a low longitudinal acceptance due to a low-alpha machine. This timing system is based on a frequency divider/multiply technique and a digital delay technique. The RF frequency of the KEKB rings and that of the injector Linac are locked with a common divisor frequency. The common divisor frequency determines the injection timing. The RF bucket selection system is also described. r 2002 Elsevier Science B.V. All rights reserved.

This study presents a hybrid monitoring system for nuclear reactor utilizing neural networks and a rule-based real-time expert system. The whole monitoring system including a data acquisition system and the advisory displays has been tested by an online simulator of pressurized water reactor. From the testing results, it was shown that the neural network in the monitoring system successfully modeled the plant dynamics and detected the symptoms of anomalies earlier than the conventional alarm system. The real-time expert system also worked satisfactorily in diagnosing and displaying the system status by using the outputs of neural networks and a priori knowledge base.

We report systematic high-resolution angle-resolved photoemission results on single-layered Pb-substituted Bi 2 Sr 2 CuO 6+ δ . We found that the intensity of shadow bands is invariable with respect to temperature and doping. This result rules out the possibility of short-range antiferromagnetic correlation and supports the structural origin of shadow bands.

Analytical expressions of the output power spectra are derived for spin-transfer nano-oscillators, by using the phase-noise theories, which have been developed for electronic oscillators. The output spectra, which are proportional to the power spectra of transverse component of magnetization, are calculated under the thermal fluctuation with a small amplitude approximation.

To develop the method to analyze transient characteristics of the combined radiative and conductive heat transfer in the industrial furnaces, heat transfer in vacuum furnaces is numerically analyzed. The vacuum furnace is heated by several radiant tube burners and enclosed with thermal insulation walls. Object materials to be heated are placed at the central region of the furnace. A three-dimensional computer program for general purpose is developed to solve radiative heat transfer within enclosure including the transient conductive heat transfer within the insulation walls surrounding the system. The Monte Carlo method is used for the radiative heat exchange calculation. The results of the numerical simulation are compared with the results of experiment. The simulated results fit very well with the experimental ones, which shows the validity of the present simulation method.

The use of commercially available bubble detectors for gamma and neutron detection has been reported by several groups. We have carried out systematic investigations to study the response of gamma bubble detector as a function of energy, the effect of waiting time on sensitivity of BD-100R neutron bubble detector and the effect of shelf life on both types of bubble detectors. Our results show that the response of the gamma bubble detector is energy dependent. Waiting time of up to 260 hours for BD-100R neutron detector has no significant effect. Both the detectors have a limited shelf life. These factors must be taken into account while using these detectors.

With the use of a numerical method by linearizing the nonlinearities caused by an amplifier-analyzer system, we can reproduce a pulse height spectrum reflecting the actual characteristics of a radiation detector itself. This method was applied to spectrometer systems of a 3He proportional counter for fast neutron measurements and a high-purity Ge detector for gamma-ray measurements. As the pulse height spectrum distortion due to the nonlinearities of the measuring system was improved especially in the lower pulse height region, we can discuss the precise pulse height relations and the intrinsic nonlinearities caused in radiation detectors.

After achieving a reasonable success in BD-100R neutron-bubble detectors, the Bubble Technology Industries (Canada) has recently developed a new type of γ-bubble detector and is commercially available. A series of experiments were carried out to determine the sensitivity and the effect of temperature on both of the above mentioned detectors. The response of these detectors is found to be strongly dependent upon the temperature during irradiation. The γ-bubble detector needs a lot of improvements before it can be used in actual measurements. Although BD-100R detector has a lot of promising properties, it cannot replace CR-39 based personnel neutron dosimeters, but they complement each other.

In Part-I of this paper, computer calculations for determining the calibration factors of CR-39 based neutron dosimeters were described. Here in Part-II, related experimental work is presented. Rem counters, bubble detectors and different types CR-39 based neutron dosimeter were irradiated in free air and on a water phantom with known fluences of monoenergetic neutrons. Irradiations were also performed in a D2O moderated 252Cf neutron field. From the observed readings (number of bubbles or counts or track/cm2 or ECE spots/cm2), calibration factors were determined.

Measurements concerning radon and its daughter products' concentration levels have been performed in 42 selective houses of the Tsukuba Science City (Japan) using CR-39 and LR-115 nuclear track detectors. These included both single story houses and flats in multi-storied buildings. Four CR-39 and four LR-115 detectors were put into a zippable polyethylene bag and a number of such bags were prepared. These detector loaded bags were then installed in two bedrooms of each of the houses/flats and were exposed for a period of three months during the winter season (i.e. from December to February). These radon exposed samples were then processed, analyzed and related to the Bq/m 3 . These studies indicated that the radon levels are very low in the houses surveyed and do not pose any serious threat to the occupants.

Recently, the Bubble Technology Industries has developed a new type of γ-bubble detector for measurement of γ doses and have made it commercially available. A series of experiments were carried out at the Electrotechnical Laboratory (ETL) and Centre for Nuclear Studies (CNS) to determine the sensitivity of the detector, effect of temperature and recompression time on the sensitivity and to find out whether such detectors can be used for the measurement of the γ-rays that are always associated with neutron fields. The sensitivity of the detector is found to be about 15 bubbles/μSv at 21.8°C. The response of the detector is strongly dependent upon the temperature during irradiation. In the light of our results, this detector needs many improvements before it can be used for accurate measurements of γ doses in routine dosimetry.

The response of our previously reported cubical fast neutron dosimeter is studied in terms of 10 mm directional dose equivalent, H'(10), both in free air and on a tissue phantom. Its response has been extended to thermal neutrons by introducing a 0.045 μm thick layer of LiF converter between the detector and radiator stack (i.e. 150 μm polyimide + 800 μm polystyrene + 3 μm polyethylene). Our studies predict that the above radiator-detector assembly would yield a flat response over the neutron energy range of thermal to 15 MeV (within 26% variation) on a tissue phantom. A cubical dosimeter based on the above radiator-detector assembly (only one part of the assembly containing a 0.045 μm thick layer of LiF) would yield an angular response reasonably close to that required (i.e. H'(10)) over a wide neutron energy range.

An experiment was carried out to measure the radon and its airborne daughter product levels in the bed rooms of 40 houses. The houses chosen for this experiment were constructed from same building material and the bed rooms chosen were approximately of similar dimensions. The main objective of this experiment was to study the living standards (e.g. ventilation of the houses) of the residents from the measured values of radon and its daughter product concentration levels. Our results indicate that, except for a few cases, one can predict the living habits of the occupants from the measured values of radon and its daughter concentration levels.

Following the development of an isotropic personnel fast-neutron dosimeter having an approximately flat dose-equivalent response to fast neutrons (from 0.1 to 19 MeV) in free air, which was reported elsewhere, we developed a thermal-neutron dosimeter having an approximately similar dose-equivalent response as that of fast neutrons under the same processing conditions. We now combine the above dosimeters into a single one and study its response on a tissue phantom. Our results show that the dose-equivalent response of the dosimeter in question will no longer be energy- and direction-independent when irradiated with mixed-energy and multidirectional neutrons on a tissue phantom.

Introduction: Streptococcus pneumoniae is an important human pathogen in community-acquired respiratory infections. S. pneumoniae with resistance to penicillin and other antibiotics is becoming prevalent. In particular, macrolide resistance among S. pneumoniae isolates has risen in recent years worldwide. The increasing incidence of macrolideand penicillin-resistant S. pneumoniae has been a serious problem in Japan. Objectives: The objective of this study was to investigate the prevalence of serotypes, and macrolideand penicillin-resistance among pneumococcal isolates from outpatients with non-invasive infections. Methods: A total of 1,061 non-invasive S. pneumoniae strains isolated from outpatients who visited various hospitals and clinics in Hokkaido, northern main island of Japan in 2011 were analyzed. The presence of macrolide-resistance genes erm (B ) and mef (A/E ), and 3 unaltered pbp genes (pbp1a, pbp2x, and pbp2b) were detected by multiplex PCR. MICs of all isolates against erythromycin and penicillin were measured by E-test. Serotyping of these isolates was performed genetically by sequential multiplex PCR and direct sequencing. Additionally, we developed a novel mutagenic PCR-RFLP assay for discrimination of serotypes 6A, 6B, 6C, and 6D. Results: Among the 1,061 strains, 95.8% and 7.7% isolates were resistant to erythromycin and penicillin, respectively. The erm (B ) and mef (A/E ) genes were detected in 66.4% and 40%, respectively (including 10.7% of the strains carrying both genes). The rate of strains with a single altered pbp gene was 38.8%, with two and three altered pbp genes being 18.4% and 37.9%, respectively. The most frequent serotypes were 6B (17.0%), 19F (15.6%), 23F (12.1%). While most of strainswith these three serotypes harbored erm (B ) and/ormef (A/E ) (>98%), rate of PRSP with three altered pbp genes was highest in 23F (83.6%), followed by 6B (70.3%) and 19F (62.4%). All the serotype15B/C isolates were resistant to erythromycin (MIC: >256 mg/ml). Serotypes included in the 7and 13-valent conjugate vaccines covered 47.7% and 69.3% of isolates, respectively. Conclusion:The present study indicated the spreadofmacrolideand penicillin-resistant strains among non-invasive S. pneumoniae isolates in Hokkaido.

Congenital generalized lipodystrophies are rare autosomal recessive disorders which are characterized by near total loss of subcutaneous adipose tissue since birth, insulin resistance, diabetes, hypertriglyceridemia and hepatic steatosis. Recently Hayashi et al. described congenital generalized lipodystrophy type 4 with muscular dystrophy caused by PTRF (polymerase I and transcript release factor) mutations. Since the disease is a rare disorder, when and how the disease characteristic symptoms appear remains unknown. We followed a Japanese boy from early infancy to 3 years and 11 months (3 y 11 m). He was noticed to have decreased subcutaneous fat tissue on his face at 7 m. The lip dystrophy progressed to extremities and muscle appeared to be hypertrophic at 1 y 4 m, but developmental mile stones were delayed; he sat alone at 1 y 4 m and walked alone at 2 y 6 m. Muscle biopsy done at 1 y 4 m showed fiber necrosis and regeneration with fibrosis consistent with muscular dystrophy. Strikingly PTRF protein was absent with an immunohistochemical staining though caveolin-3 was positive. He had a homozygous mutation of c.696_697insC in PTRF gene. He had no insulin resistant diabetes but insulin resistant index was already elevated at 3 y 11 m though it was normal level at 2 y 6 m. Caveolin-1 deficient mice that demonstrate a loss of caveolae, have been reported to show insulin resistance due to decrease of insulin receptor. Because PTRF is an essential compartment for stabilization of caveolae, PTRF-deficient mice have been described to have no detectable caveolae and show decreased level of insulin receptor. Therefore patients with deficiency of PTRF are thought to have insulin resistance as same as those with caveoline-1-deficiency. Caveolin-3 expression in our patient was almost normal despite PTRF deficiency, but it is likely that caveolins decrease secondarily with disease progression, then the insulin resistance progresses.

Use of the latest PC version of the computer code SAIPS in neutron spectrum unfolding is described. Guidelines for extending the use of SAIPS to unfold the spectrum from a CR-39-based spectrometer are presented.

A personnal neutron dosimeter based on electrochemically etched CR-39 detector has been developed. The dosimeter has approximately a flat response on a tissue-equivalent phantom over the fission neutron spectrum (i.e. thermal to 15 MeV). A method concerning the achievement of an almost angle independent dose equivalent response on a tissue-equivalent phantom is described.

In Part I of this paper, we described the use of the computer code SAIPS in neutron spectrum unfolding. Here in Part II, we present our experimental work carried out to study the shape of the neutron spectrum in different experimental channels of a 5 MW light-water cooled and moderated research reactor. The spectral neutron flux was determined using various fission foils (placed in close contact with mica track detectors) and activation detectors. From the measured activities, the neutron spectrum was unfolded by SAIPS.

A fast neutron spectrometer based on electrochemically etched CR-39 detector has been developed. The spectrometer consists of a 500 μ m thick CR-39 detector placed in closed contact with judiciously chosen thicknesses of a polyethylene radiator and a gold degrader. The problems associated with our previously reported spectrometer are outlined and a method for neutron spectrum unfolding is suggested.

We propose a general form for the statistical bootstrap equation by means of a convolution formula for the thermodynamical system of hadronic matter. In connection with a phase transition of hadronic matter to a state of quark liberation, we predict the negative binomial distribution with k ∼1 for the multiplicity distributions in the central pseudorapidity region at high energies.

The electrical properties of 10 BP wafers grown by chemical vapour deposition at room temperature before and after irradiation by thermal neutrons were measured by the van der Pauw method. No appreciable change in electrical properties was observed for the (100) wafer. In the case of the (111) wafer, the carrier concentration for the n type increased and decreased for the p type after irradiation with thermal neutrons owing to the formation of donors caused by nuclear reaction of 10 B(n,α) 7 Li. The electrical conductivity σ, the carrier concentration n and the mobility μ of the (111) wafer after irradiation were measured at high temperatures: n decreased and μ increased for the p type (and vice versa for the n type) compared with the values before irradiation. The temperature dependence of carrier concentration before and after irradiation was correlated with the theoretical curves to calculate the donor and acceptor concentrations and their activation energies.

Ellipsometric and electrochemical measurements of the anodic passivation and secondary passivation films on nickel in borate buffer solution at pH 8·42 were made. The reference bare surface, obtained by cathodic reduction of electropolished nickel, gives the optical constants N 3 = 1·65−3·81 i for nickel. In the passivity region, where a little dissolution of nickel occurs, the surface film has the optical constants N 2 = 2·7−0·25 i and the film thickness as estimated by ellipsometry increases linearly with rise of the potential, from 4 to 13 A, which is in fairly good agreement with the coulometrically estimated film thickness. In the oxygen evolution region, secondary passivation occurs with an abrupt increase in both optical constants and thickness of the surface film. The anodic passivation of nickel is compared with that of iron in terms of thickness of the surface film as a function of potential.

Charged multiplicity distributions obtained in pp collisions at s =540 GeV for various pseudorapidity intervals are investigated using the cluster model. It is shown that the observed pseudorapidity dependence of these distributions are well described by a simple three-cluster model. The leading-particle effect is also estimated in this model.

This paper describes the effect of solution pH on the passive film on iron which was investigated by ellipsometry and by cathodic reduction combined with chemical analysis. Anodic two-step passivation was employed to exclude anodic deposition of ferrous ion, resulting from anodic oxidation of iron. The film in acid solution is almost anhydrous oxide, whereas the film in neutral and alkaline solution has an outer hydrated oxide layer, whose thickness decreases with decreasing pH. The hydrated outer layer depends also on the anion present in solution. The transition layer model of the film is proposed to explain the results.