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We present the development of neutron-tagging techniques in Super-Kamiokande IV using a neural network analysis. The detection efficiency of neutron capture on hydrogen is estimated to be 26%, with a mis-tag rate of 0.016 per neutrino event. The uncertainty of the tagging efficiency is estimated to be 9.0%. Measurement of the tagging efficiency with data from an Americium-Beryllium calibration agrees with this value within 10%. The tagging procedure was performed on 3,244.4 days of SK-IV atmospheric neutrino data, identifying 18,091 neutrons in 26,473 neutrino events. The fitted neutron capture lifetime was measured as 218±9 μs. We present the development of neutron-tagging techniques in Super-Kamiokande IV using a neural network analysis. The detection efficiency of neutron capture on hydrogen is estimated to be 26%, with a mis-tag rate of 0.016 per neutrino event. The uncertainty of the tagging efficiency is estimated to be 9.0%. Measurement of the tagging efficiency with data from an Americium-Beryllium calibration agrees with this value within 10%. The tagging procedure was performed on 3,244.4 days of SK-IV atmospheric neutrino data, identifying 18,091 neutrons in 26,473 neutrino events. The fitted neutron capture lifetime was measured as 218 \pm 9 \mu s.

Background Coronary functional abnormalities including both epicardial and microvascular coronary artery spasm represent an important role responsible for myocardial ischemia in patients with angina and nonobstructive coronary artery disease. However, clinical characteristics associated with microvascular spasm (MVS) have not been fully evaluated. Purpose The aim of this study was to assess differences in clinical features between patients with MVS and epicardial coronary spasm. Methods A total of 732 consecutive patients with suspected angina who presented nonobstructive coronary arteries and underwent intracoronary acetylcholine provocation test were retrospectively enrolled in this study. Epicardial coronary spasm was defined as total or subtotal occlusion of epicardial coronary arteries accompanied by chest pain and/or ischemic electrocardiographic changes in response to acetylcholine provocation test. MVS was diagnosed when chest pain and/or ischemic electrocardiographic changes developed after administration of acetylcholine in the absence of epicardial coronary spasm. Clinical characteristics were compared between patients with MVS and epicardial coronary spasm. Results Of all patients, 83 patients (11%) had MVS, 367 (50%) had epicardial coronary spasm, and the other patients (39%) showed neither MVS nor epicardial coronary spasm. Patients with MVS tended to be older (65.6±12.7 vs. 63.0±12.3 years, P=0.088) and were more frequently female (60.2% vs. 41.1%, P=0.0016) in comparison with patients with epicardial coronary spasm. Patients with MVS were less likely to be smokers (8.6% vs. 22.9%, P=0.0018), while there were no significant differences in the other coronary risk factors such as hypertension, dyslipidemia, and diabetes mellitus. Serum uric acid were significantly lower in patients with MVS (4.9±1.1 vs. 5.4±1.3 mg/dl, P=0.0018). Conclusion Our study demonstrated that patients with MVS had distinctive clinical background from those with epicardial coronary spasm, suggesting different mechanisms may involve the development of MVS. Funding Acknowledgement Type of funding source: None

Background Vasospastic angina (VSA) is considered as a cause of myocardial infarction with nonobstructive coronary arteries. Given the previous reports of higher incidence of cardiovascular events in young VSA patients, early diagnosis and optimal treatment are important for these patients. While acetylcholine provocation test (ACh test) for VSA diagnosis is well reported, ACh test among young patients is not as commonly performed, therefore its safety and usefulness for this patient subset have not been fully evaluated. Purpose The purpose of this study was to evaluate the safety and the proportion of positive results of ACh test for young patients. Methods Data from patients who underwent ACh test in our institution from May 2012 to September 2018 were retrospectively analyzed. A total of 669 patients were enrolled and divided into 2 groups according to age: Young group (Age≤50, n=106); and Senior group (Age>50, n=563). Results The senior group had a higher incidence of hypertension, dyslipidemia, diabetes mellitus, and coronary artery disease. On the other hand, the young group had a significantly higher incidence of current smoker and tendency of daily alcohol. The rate of positive ACh test was similar, and there were no significant differences in major or minor complications between the 2 groups. Patient characteristics and outcome Young group Senior group p (n=106) (n=563) Age (years) 42.8±7.3 68.0±9.0 Conclusion ACh provocation test for young patients can be safely performed, and the rate of positive results was similar to that of senior patients. In young patients suspected of having VSA, ACh test should be actively performed to identify optimal medical therapy for prevention of cardiovascular events. Acknowledgement/Funding None

We present a real-time supernova neutrino burst monitor at Super-Kamiokande (SK). Detecting supernova explosions by neutrinos in real time is crucial for giving a clear picture of the explosion mechanism. Since the neutrinos are expected to come earlier than light, a fast broadcasting of the detection may give astronomers a chance to make electromagnetic radiation observations of the explosions right at the onset. The role of the monitor includes a fast announcement of the neutrino burst detection to the world and a determination of the supernova direction. We present the online neutrino burst detection system and studies of the direction determination accuracy based on simulations at SK., 15 pages, 8 figures, accepted for publication in Astroparticle Physics

Aims The aim of this study was to determine whether chilled irrigation saline decreases the incidence of clinical upper limb palsy (ULP; a reduction of one grade or more on manual muscle testing; MMT), based on the idea that ULP results from thermal damage to the nerve roots by heat generated by friction during bone drilling. Methods Irrigation saline for drilling was used at room temperature (RT, 25.6°C) in open-door laminoplasty in 400 patients (RT group) and chilled to a mean temperature of 12.1°C during operations for 400 patients (low-temperature (LT) group). We assessed deltoid, biceps, and triceps brachii muscle strength by MMT. ULP occurring within two days post-operatively was categorised as early-onset palsy. Results The incidence of ULP (4.0% vs 9.5%, p = 0.003), especially early-onset palsy (1.0% vs 5.5%, p < 0.001), was significantly lower for the LT group than for the RT group. Multivariate analysis indicated that RT irrigation saline use, concomitant foraminotomy, and opened side were significant predictors for ULP. Discussion Using chilled irrigation saline during bone drilling significantly decreased the ULP incidence, particularly the early-onset type, and shortened the recovery period for ULP. Chilled irrigation saline can thus be recommended as a simple method for preventing ULP. Take home message: Chilled irrigation during laminoplasty reduces C5 palsy. Cite this article: Bone Joint J 2016;98-B:117–24.

Aims Primary central nervous system lymphoma (PCNSL) manifest aggressive clinical behaviour and have poor prognosis. Although constitutive activation of the nuclear factor-κB (NF-κB) pathway has been documented, knowledge about the genetic alterations leading to the impairment of the NF-κB pathway in PCNSLs is still limited. This study was aimed to unravel the underlying genetic profiles of PCNSL. Methods We conducted the systematic sequencing of 21 genes relevant to the NF-κB signalling network for 71 PCNSLs as well as the pyrosequencing of CD79B and MYD88 mutation hotspots in a further 35 PCNSLs and 46 glioblastomas (GBMs) for validation. Results The results showed that 68 out of 71 PCNSLs had mutations in the NF-κB gene network, most commonly affecting CD79B (83%), MYD88 (76%), TBL1XR1 (23%), PRDM1 (20%) and CREBBP1 (20%). These mutations, particularly CD79B and MYD88, frequently coincided within each tumour in various combinations, simultaneously affecting diverse pathways within the network. No GBMs had hotspot mutation of CD79B Y196 and MYD88 L265. Conclusions The prevalence of CD79B and MYD88 mutations in PCNSLs was considerably higher than reported in systemic diffuse large B-cell lymphomas. This observation could reflect the paucity of antigen stimuli from the immune system in the central nervous system (CNS) and the necessity to substitute them by the constitutive activation of CD79B and MYD88 that would initiate the signalling cascades. These hotspot mutations may serve as a genetic hallmark for PCNSL serving as a genetic marker for diagnose and potential targets for molecular therapy.

Four new metabolites related to IAA (indole-3-acetic acid) were isolated from an aqueous methanol extract of rice bran and were elucidated by spectroscopic methods to be a pair of diastereomers of 5-O-β-D-glucopyranosyl 3,5-dihydroxy-2-indolinone-3-acetic acid (A-1 and A-2) and of 5-O-β-D-cellobiosyl 3,5-dihydroxy-2-indolinone-3-acetic acid (B-1 and B-2). Compound B-1 was also a diastereomer of compound B-2 at the C3 position with an asymmetric carbon atom on an indolinone skeleton, like the relationship between compounds A-1 and A-2.

The phylogenetically-conserved vertebrate transcription factor, NFIB, is an orchestrator of glial differentiation in the developing mammalian central nervous system. We found NFIB expression to be reduced in glioblastoma (GBM), the commonest and most lethal primary adult brain cancer, so investigated what effect increased expression of NFIB had on GBM. Increased expression of NFIB in primary GBM cell lines induced expression of markers of glial differentiation, inhibited cell proliferation, reduced stem/progenitor cell growth, altered cell cycle progression and inhibited tumor growth in murine models of GBM. We thus identified NFIB to be a novel tumor suppressor gene in GBM.

Microwave-assisted magnetization reversal of 1.3×0.3×0.035 μm3 NiFe element with a natural ferromagnetic resonance frequency of 8.3 GHz was experimentally investigated by means of vector network analyzer ferromagnetic resonance measurement. The irreversible switching of magnetization after the application of ac magnetic field with an appropriate frequency was detected from a discontinuous increase of ferromagnetic resonance frequency in the NiFe element at a non-zero dc bias field. The switching field can be reduced from 300 to 192 Oe when the ac magnetic field with the frequency of 7GHz and the amplitude of 130 Oe is applied along the short axis of the NiFe element.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, A search for neutrino oscillations induced by Lorentz violation has been performed using 4,438 live-days of Super-Kamiokande atmospheric neutrino data. The Lorentz violation is included in addition to standard three-flavor oscillations using the nonperturbative standard model extension (SME), allowing the use of the full range of neutrino path lengths, ranging from 15 to 12,800 km, and energies ranging from 100 MeV to more than 100 TeV in the search. No evidence of Lorentz violation was observed, so limits are set on the renormalizable isotropic SME coefficients in the eμ, μτ, and eτ sectors, improving the existing limits by up to 7 orders of magnitude and setting limits for the first time in the neutrino μτ sector of the SME, We would like to thank A. Kostelecky for his advice and support and we are grateful to J. S. Diaz for working closely with us to calculate and implement the Lorentz-violating oscillation probabilities. The authors gratefully acknowledge the cooperation of the Kamioka Mining and Smelting Company. Super-K has been built and operated from funds provided by the Japanese Ministry of Education, Culture, Sports, Science and Technology, the U.S. Department of Energy, and the U.S. National Science Foundation. This work was partially supported by the Research Foundation of Korea (BK21 and KNRC), the Korean Ministry of Science and Technology, the National Science Foundation of China, the European Union FP7 (DS laguna-lbno PN- 284518 and ITN invisibles GA-2011-289442), the National Science and Engineering Research Council (NSERC) of Canada, and the Scinet and Westgrid consortia of Compute Canada

Primary central nervous system lymphoma (PCNSL) manifest aggressive clinical behaviour and have poor prognosis. Although constitutive activation of the nuclear factor-κB (NF-κB) pathway has been documented, knowledge about the genetic alterations leading to the impairment of the NF-κB pathway in PCNSLs is still limited. This study was aimed to unravel the underlying genetic profiles of PCNSL.We conducted the systematic sequencing of 21 genes relevant to the NF-κB signalling network for 71 PCNSLs as well as the pyrosequencing of CD79B and MYD88 mutation hotspots in a further 35 PCNSLs and 46 glioblastomas (GBMs) for validation.The results showed that 68 out of 71 PCNSLs had mutations in the NF-κB gene network, most commonly affecting CD79B (83%), MYD88 (76%), TBL1XR1 (23%), PRDM1 (20%) and CREBBP1 (20%). These mutations, particularly CD79B and MYD88, frequently coincided within each tumour in various combinations, simultaneously affecting diverse pathways within the network. No GBMs had hotspot mutation of CD79B Y196 and MYD88 L265.The prevalence of CD79B and MYD88 mutations in PCNSLs was considerably higher than reported in systemic diffuse large B-cell lymphomas. This observation could reflect the paucity of antigen stimuli from the immune system in the central nervous system (CNS) and the necessity to substitute them by the constitutive activation of CD79B and MYD88 that would initiate the signalling cascades. These hotspot mutations may serve as a genetic hallmark for PCNSL serving as a genetic marker for diagnose and potential targets for molecular therapy.

Light-emitting diodes (LEDs) have been demonstrated with a thin p-type layer using the plasmonic effect. Optimal LED device operation was found when using a 20-nm-thick p+-GaN layer. Ag of different thicknesses was deposited on the thin p-type layer and annealed to form the localized Ag particles. The localized Ag particles were embedded by indium tin oxide to form a p-type electrode in the LED structure. By optimization of the plasmonic LED, the significant electroluminescence enhancement was observed when the thickness of Ag was 9.5 nm. Both upward and downward electroluminescence intensities were improved, and the external quantum efficiency was approximately double that of LEDs without the localized Ag particles. The time-resolved photoluminescence (PL) decay time for the LED with the localized Ag particles was shorter than that without the localized Ag particles. The faster PL decay time should cause the increase in internal quantum efficiency by adopting the localized Ag particles. To validate the l...

Joining between copper and resin on commutator of electromotor is usually executed by injection molding method and copper is embedded in resin. In this case, clear boundary exists between copper and resin because copper and resin are not combined chemically. This boundary will change to be gaps or cracks after a long time use. In most cases, an abrupt fracture occurs when a force is greater than a certain value applied to this cracks or crack-like defects. In this study, so as to solve this problem, trial manufacture of functionally graded commutator made from copper and resin powder has been executed by spark plasma sintering method. The third element is added into resin powder and resin powder is prepared so that the coefficient of linear thermal expansion may become low. Several mechanical and thermophysical properties have been investigated. The value of shearing stress between copper and copper-resin mixed layer is more than 50Mpa. It shows that the joint strength between copper and resin of this functionally graded commutator without clear boundary is high enough. The more the content of resin increases, the higher the coefficient of thermal expansion becomes. The thermal conductivity in onedimensional and non-steady state at 296K indicates that the change is due to the mixing ratio of copper and resin.

The trilepton nucleon decay modes p→e+νν and p→μ+νν violate |Δ(B-L)| by two units. Using data from a 273.4 kt yr exposure of Super-Kamiokande a search for these decays yields a fit consistent with no signal. Accordingly, lower limits on the partial lifetimes of τp→e+νν>1.7×10(32) years and τp→μ+νν>2.2×10(32) years at a 90% confidence level are obtained. These limits can constrain Grand Unified Theories which allow for such processes.

The trilepton nucleon decay modes p→e+νν and p→μ+νν violate |Δ(B-L)| by two units. Using data from a 273.4 kt yr exposure of Super-Kamiokande a search for these decays yields a fit consistent with no signal. Accordingly, lower limits on the partial lifetimes of τp→e+νν1.7×10(32) years and τp→μ+νν2.2×10(32) years at a 90% confidence level are obtained. These limits can constrain Grand Unified Theories which allow for such processes.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, We present limits on sterile neutrino mixing using 4,438 live-days of atmospheric neutrino data from the Super-Kamiokande experiment. We search for fast oscillations driven by an eV2-scale mass splitting and for oscillations into sterile neutrinos instead of tau neutrinos at the atmospheric mass splitting. When performing both of these searches we assume that the sterile mass splitting is large, allowing sin2(Δm2L/4E) to be approximated as 0.5, and we assume that there is no mixing between electron neutrinos and sterile neutrinos (|Ue4|2=0). No evidence of sterile oscillations is seen and we limit |Uμ4|2 to less than 0.041 and |Uτ4|2 to less than 0.18 for Δm2>0.1eV2 at the 90% C.L. in a 3+1 framework. The approximations that can be made with atmospheric neutrinos allow these limits to be easily applied to 3+N models, and we provide our results in a generic format to allow comparisons with other sterile neutrino models, The authors gratefully acknowledge the cooperation of the Kamioka Mining and Smelting Company. Super-K has been built and operated from funds provided by the Japanese Ministry of Education, Culture, Sports, Science and Technology, the U.S. Department of Energy, and the U.S. National Science Foundation. This work was partially supported by the Research Foundation of Korea (BK21 and KNRC), the Korean Ministry of Science and Technology, the National Science Foundation of China, the European Union FP7 (DS laguna-lbno PN- 284518 and ITN invisibles GA-2011-289442) the National Science and Engineering Research Council (NSERC) of Canada, and the Scinet and Westgrid consortia of Compute Canada

In situ radiation damage and thermal pulses considerably modify the high cycle fatigue property of solution treated specimens of the modified 316L stainless steels, where the observed effects show a characteristic relationship with the chemical composition of the specimens. For the specimens which show a low work-hardening exponent, the fatigue life elongates under irradiation. In contrast, the fatigue life of the specimens which show a high work-hardening exponent is shortened under irradiation. A probable dislocation–defect interaction responsible for these effects is discussed.

Pneumatic slug conveying in a horizontal straight pipeline is analyzed numerically. The gas flow is calculated by the method of characteristics, divided into three regions: 1, particle slugs; 2, particle free layers; and 3, particle settled layers. It is assumed that: (1) the shear stress on the surface of the settled layer is within a saltation limit; (2) the pressure drop through the particles obeys the Ergun equation; (3) the frictional force on the slug is due to the slug weight alone; (4) the height of the settled layer is constant; and (5) the voidage is constant. The particles are fed continuously into the pipe to form a slug. The feeding is stopped when the slug length exceeds a certain fixed value and generation of a slug is completed. Calculations are carried out for a constant gas mass flow rate under similar conditions to our previous experimental measurements.

For the modified 316L stainless steel in which the dislocation interaction governs the fatigue hardening process, the high-cycle fatigue tests were carried out between 300 and 403 K. The in situ irradiation tests and the in situ thermal-pulse tests indicate that dislocation rearrangements due to thermal-pulse give rise to an increase in the areal density of persistent slip bands (PSBs), resulting in elongation of the fatigue life N f, and an introduction of obstacles to dislocation motions, irradiation induced lattice defects or the fatigue induced precipitates, brings about a decrease in the areal density of PSBs, giving shortening of N f .

Fasting plasma GLP-1 levels were significantly higher in hypophysectomized (hypox) rats (n = 6) than in intact (normal) rats (n = 7) (54.3 +/- 5.2 vs. 33.3 +/- 2.4 pmol/L, p < 0.001). To examine the influence of pituitary hormones on plasma GLP-1 levels, concentrations of plasma glucose, insulin and GLP-1 after an oral glucose load to hypox rats that were given either rat growth hormone (rGH) (n = 7), cortisol and thyroxine (n = 7) or no substitution (n = 6) were compared with those of normal rats (n = 7). Plasma glucose levels in the fasting state and after the glucose ingestion were significantly lower in hypox rats, but the hormonal replacements to hypox rats increased their total glucose levels to those of normal rats, although the increasing patterns were different from those in normal rats. Insulin levels both in the fasting state and after the glucose ingestion were significantly decreased in hypox rats and the fasting and total GLP-1 levels were significantly increased in those rats. rGH substitution significantly increased the total insulin levels in hypox rats and decreased the fasting and total GLP-1 levels closely to levels in normal rats, while substitution with cortisol and thyroxine failed to introduce such a significant effect. These results suggested that secretion of GLP-1 might be influenced by the function of GH.

We are developing a hybrid photo detector (HPD) for the Hyper-Kamiokande Project. Eight-inch HPDs were prepared to evaluate their performance. Based on the results from these measurements, HPDs achieve a better performance such as single photon separation than conventional PMTs. A verification study lasting a few years in a water tank is planned in 2013 to check their feasibility.

Bis-branched urea oligomers (B-urea) mainly composed of hexakis(N-arylcarbamoyl)-[3N,4N-bis(ethylamino)]pentaethylenehexamine were obtained by the reaction of triethylenetetramine with 1,2-dibromoethane followed by ureanization with PhNCO. Under neutral conditions the B-urea readily forms stable mononuclear Cu(II) complexes in which a Cu(II) ion is almost fully surrounded by the B-urea ligand, as evidenced by magnetic susceptibility measurements. In the presence of oxygen, this Cu(II) complex (B-urea-Cu(II)) effectively catalyzes oxidative coupling of various substituted phenols. At the same time the Cu(II) ion is reduced to form the corresponding yellow B-urea-Cu(I) complex quantitatively. The Cu(I) state is highly stable for storage in the solid state but can readily be reacted with oxygen in a reversible manner in solution.

We propose a new parameter obtained by three-fiber-based diffuse reflectance spectroscopy for nondestructive measurement, demonstrating a good linear correlativity of the parameter with the fruit sugar content by employing LEDs as light sources.

In wireless sensor networks, location estimation of sensor nodes is important. Therefore some location estimation methods have been proposed. Especially, in wireless sensor networks based on IEEE802.15.4, a method using received signal strength indicator (RSSI) which can be measured by each sensor node is one of the most practicable methods in the way that new hardware is not needed and it is suitable also for the miniaturization. However this technique has a weak point that it needs to investigate the propagation environment of the sensor field to estimate the location of sensor nodes in advance. This paper proposes the method that the decision of the parameter of the propagation environment using only measurements obtained during localization without investigating prior. Evaluation of this method is shown by simulation and experiment that it is able to decide the propagation parameter of an extent that doesnpsilat influence the location estimation accuracy without investigating the propagation environment of the sensor field.

This paper presents statistical inference of computer virus propagation using non-homogeneous Poisson processes (NHPPs). Under some mathematical assumptions, the number of infected hosts can be modeled by an NHPP In particular, this paper applies a framework of mixed-type NHPPs to the statistical inference of periodic virus propagation. The mixed-type NHPP is defined by a superposition of NHPPs. In numerical experiments, we examine a goodness-of-fit criterion of NHPPs on fitting to real virus infection data, and discuss the effectiveness of the model-based prediction approach for computer virus propagation.

This paper presents the relation between the partial pressures and growth rate on forming Er-Si-O crystalline thin films used by MOMBE.

Introduction: A short high-intensity exercise test (e.g., the Wingate test) has been commonly used to measure the anaerobic power and muscle metabolism. The monitoring of salivary biomarkers in response to high intensity exercise-induced stress provides insights into the assessment ofmucosal immune function. The purpose of this study was to examine the effect of repeated bouts of Wingate tests (short-duration intermittent and maximal effort exercise) on the levels of salivary -amylase and IgA levels in male collegiate cyclists. Methods: Twelve male collegiate cyclists [age: 20.3±0.6 year; height: 170.7±3.9 cm; body mass: 63.3±7.3 kg; BMI: 21.7±2.2 kg/m2; body fat: 13.8±4.3%; VO2peak: 58.8±9.0mL/kg/min (mean± SD)] served as the subjects. The exercise intervention consisted of two consecutive, all-out 30secondWingate leg cycling tests (0.075kg/kg body weight), which were separated by ten minutes of recovery. Unstimulated saliva was collected before (PRE) and immediately after first (WIN1POST) and second (WIN2-POST) completion of each exercise testing protocol for the later analysis of salivary -amylase and IgA levels. Salivary -amylase and IgA levels were determined by an enzymatic assay and turbidimetric immunoassay, respectively. Results: In light of salivary -amylase activity, one-way analysis of variance (ANOVA) showed a significant elevation (WIN1-PRE=81.6±50.5, WIN1-POST=215.0±140.1, WIN2POST=315.4±246.5 U/mL, p

We have investigated the coherent dynamics of the collective motions of phonons in the commensurate phase of quasi-two-dimensional $1T\text{\ensuremath{-}}{\mathrm{TaS}}_{2}$ using femtosecond laser pulses. One of the coherent phonons increased in intensity as a function of time, this behavior being strongly correlated with the decay of charge-density-wave oscillations as well as the slow decay component in single-particle relaxation.

It has recently been determined that the proteolytic destruction of IkappaB (inhibitor of NF-kappaB) by the ubiquitin-proteasome system plays a key role in the immediate elimination of IkappaB from the IkappaB-(NF-kappaB) complex which allows nuclear translocation of free NF-kappaB, thus leading to activation of a multitude of target genes. The SCF(Fbw1) (composed of Skp1, Cul-1, Roc1, and Fbw1) complex, identified as an IkappaBalpha-E3 ligase, binds and ubiquitylates IkappaBalpha phosphorylated by IkappaB kinase that has been activated in response to extracellular signals. The generating poly-ubiquitin chain is finally recognized by the 26S proteasome for ultimate degradation. In this NF-kappaB signalling pathway, it becomes clear that the SCF(Fbw1) activity is enhanced by a ubiquitin-like protein NEDD8 (equivalent to Rub1) that modifies Cul-1 in a manner analogous to ubiquitylation, and consequently, IkappaBalpha proteolysis is induced. NEDD8 is a new regulator of the SCF ubiquitin-ligase, functioning as a covalent modifier for proteolytic targeting at a physiological level.

Rat cDNA encoding a 376-amino acid peroxin was isolated by functional complementation of a peroxisome-deficient Chinese hamster ovary cell mutant, ZP110, of complementation group 14 (CG14). The primary sequence showed 28 and 24% amino acid identity with the yeast Pex14p from Hansenula polymorpha and Saccharomyces cerevisiae, respectively; therefore, we termed this cDNA rat PEX14 (RnPEX14). Human and Chinese hamster Pex14p showed 96 and 94% identity to rat Pex14p, except that both Pex14p comprised 377 amino acids. Pex14p was characterized as an integral membrane protein of peroxisomes, exposing its N- and C-terminal parts to the cytosol. Pex14p interacts with both Pex5p and Pex7p, the receptors for peroxisome targeting signal type 1 (PTS1) and PTS2, respectively, together with the receptors' cargoes, PTS1 and PTS2 proteins. Mutation in PEX14 from ZP161, the same CG as ZP110, was determined by reverse transcription-PCR as follows. A 133-base pair deletion at nucleotide residues 37-169 in one allele created a termination codon at 40-42; in addition to this mutation, 103 base pairs were deleted at positions 385-487, resulting in the second termination immediately downstream the second deletion site in the other allele. Neither of these two mutant forms of Pex14p restored peroxisome biogenesis in ZP110 and ZP161, thereby demonstrating PEX14 to be responsible for peroxisome deficiency in CG14.

5-fluorouracil (5-FU), although a widely used chemotherapeutic agent, has a limited effect in the treatment of human solid tumors due to their resistance to the cytotoxic effects of 5-FU. Escherichia coli uracil phosphoribosyltransferase (UPRT) is a pyrimidine salvage enzyme that catalyzes the synthesis of UMP from uracil and 5-phosphoribosyl-alpha-1-diphosphate. The present study demonstrates that adenovirus-mediated transduction of E. coli UPRT gene results in marked sensitization of colon, gastric, liver, and pancreas cancer cell lines to low concentration of 5-FU in vitro. The in vitro bystander effect was observed when only 10% of the hepatoma Hep3B cells were infected with UPRT-expressing adenovirus. In addition, 5-FU treatment of human hepatoma or gastric cancer xenografts in nude mice transduced with UPRT was demonstrated to result in significant in vivo antitumor effects. The adenovirus vector transduction of the UPRT gene followed by 5-FU administration is representative of a new chemosensitization strategy for cancer gene therapy.

We isolated peroxisome biogenesis mutants from Chinese hamster ovary (CHO) cells, using the 9-(1'-pyrene)nonanol/ultraviolet (P9OH/ UV) method and wild-type CHO-K1 cells that had been stably transfected with cDNA encoding Pex2p (formerly peroxisome assembly factor-1, PAF-1). Three mutant cell clones, ZP110, ZP111, and ZP114, showed cytosolic localization of catalase, thereby indicating a defect in peroxisome biogenesis, whereas ZP112 and ZP113 contained fewer but larger catalase-positive particles. Mutant ZP115 displayed an aberrant, tubular structure immunoreactive to anti-catalase antibody. Mutants lacking morphologically recognizable peroxisomes also showed the typical peroxisome assembly-defective phenotype such as severe loss of catalase latency and resistance to 12-(1'-pyrene)dodecanoic acid (P12)/UV treatment. ZP110 and ZP111, and ZP114 were found to belong to two novel complementation groups, respectively, by complementation group analysis with cDNA transfection and cell fusion. Cell fusion with fibroblasts from patients with peroxisome biogenesis disorders such as Zellweger syndrome revealed that ZP110 and ZP114 could not be classified to any of human complementation groups. Thus, ZP110/ZP111 and ZP114 are the first, two peroxisome-deficient cell mutants of newly identified complementation groups distinct from the ten mammalian groups previously characterized.

Three-dimensional interactions between gasdynamics and electrodynamics near electrode in a supersonic Faraday type MHD generator are studied by means of numerical analyses. Time-dependent three-dimensional Navier-Stokes equations without a turbulence model are solved by using an explicit TVD method, while the steady three-dimensional Maxwell equations together with the generalized Ohm's law are solved with Galerkin FEM and GMRES scheme for linear equations. The following results are obtained. (1) Periodic spots of current concentration along the magnetic field are obtained as a result of three-dimensi onal interaction. (2) A boundary layer separation is induced at arcing spots, whereas the flow is strongly accelerated between the arcing spots. (3) The Hall effect and the effect of back flow is balanced and therefore the arcing spots do not move. (4) Three-dimensional vortex is produced near the arcing spots, caused by the three-dimensional MHD interaction.

Concentrations of eosinophil cationic protein (ECP) were measured in serum from patients with asthma, patients with chronic obstructive pulmonary disease (COPD), and healthy subjects. The relationships between serum ECP concentration and percent of predicted FEV1 (%FEV1), and between serum and sputum ECP concentrations were also examined in patients with asthma. Serum ECP concentration in asthma was significantly higher than those in COPD patients and healthy subjects. There was a significant inverse correlation between serum ECP concentration and %FEV1 when analysis was restricted to data from asthma patients less than 60 years old. ECP concentration in serum and in sputum were significantly correlated. These results suggest that in asthma patients, eosinophils are activated in serum, and that the degree of eosinophil activation in the airway can be estimated by measuring serum ECP to some extent. Because it does not require bronchial biopsy or bronchoalveolar lavage, measurement of serum ECP may be useful as a minimally invasive monitoring of asthma.

A 21-year-old man was troubled with a subacute history of brainstem involvement and a leukocyte pleocytosis in the cerebrospinal fluid. Magnetic resonance imaging (MRI) demonstrated a massive lesion with Gd enhancement in the pons. Steroid therapy, not antiviral drugs, was dramatically effective for the mass reduction and symptom improvement. Over 4 years no recurrence has been recognized, so this case was diagnosed to be an unusual case of acute disseminated encephalomyelitis (ADEM). ADEM must be included in the differential diagnosis for a brainstem mass in MRI.

We report the case of a 8-month-old boy with atrial septal defect associated with congenital atrial flutter. He was operated on for ASD successfully. Atrial flutter in infants has been reported to be uncommon and to have a poor prognosis when associated with underlying cardiac disease. Therefore, early surgical intervention may improve the prognosis.