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Calcineurin inhibitors (CNIs) have been used off-label for the treatment of refractory Kawasaki disease (KD). However, it remains unknown whether CNIs show protective effects against the development of coronary artery lesions in KD patients. To investigate the effects of CNIs on coronary arteries and the mechanisms of their actions on coronary arteritis in a mouse model of KD, we performed experiments with FK565, a ligand of nucleotide-binding oligomerization domain-containing protein 1 (NOD1) in wild-type, severe combined immunodeficiency (SCID), caspase-associated recruitment domain 9 (CARD9)-/- and myeloid differentiation primary response gene 88 (MyD88)-/- mice. We also performed in-vitro studies with vascular and monocytic cells and vascular tissues. A histopathological analysis showed that both cyclosporin A and tacrolimus exacerbated the NOD1-mediated coronary arteritis in a dose-dependent manner. Cyclosporin A induced the exacerbation of coronary arteritis in mice only in high doses, while tacrolimus exacerbated it within the therapeutic range in humans. Similar effects were obtained in SCID and CARD9-/- mice but not in MyD88-/- mice. CNIs enhanced the expression of adhesion molecules by endothelial cells and the cytokine secretion by monocytic cells in our KD model. These data indicated that both vascular and monocytic cells were involved in the exacerbation of coronary arteritis. Activation of MyD88-dependent inflammatory signals in both vascular cells and macrophages appears to contribute to their adverse effects. Particular attention should be paid to the development of coronary artery lesions when using CNIs to treat refractory KD. [ABSTRACT FROM AUTHOR]

We have detected DNA polymerase beta (Polβ), known as a key nuclear base excision repair (BER) protein, in mitochondrial protein extracts derived from mammalian tissue and cells. Manipulation of the N-terminal sequence affected the amount of Polβ in the mitochondria. Using Polβ fragments, mitochondrion-specific protein partners were identified, with the interactors functioning mainly in DNA maintenance and mitochondrial import. Of particular interest was the identification of the proteins TWINKLE, SSBP1, and TFAM, all of which are mitochondrion-specific DNA effectors and are known to function in the nucleoid. Polβ directly interacted functionally with the mitochondrial helicase TWINKLE. Human kidney cells with Polβ knockout (KO) had higher endogenous mitochondrial DNA (mtDNA) damage. Mitochondrial extracts derived from heterozygous Polβ mouse tissue and KO cells had lower nucleotide incorporation activity. Mouse-derived Polβ null fibroblasts had severely affected metabolic parameters. Indeed, gene knockout of Polβ caused mitochondrial dysfunction, including reduced membrane potential and mitochondrial content. We show that Polβ is a mitochondrial polymerase involved in mtDNA maintenance and is required for mitochondrial homeostasis. [ABSTRACT FROM AUTHOR]

LKB1/STK11 is a tumor suppressor gene responsible for Peutz-Jeghers syndrome, an inherited cancer disorder associated with genome instability. The LKB1 protein functions in the regulation of cell proliferation, polarization and differentiation. Here, we suggest a role of LKB1 in non-homologous end joining (NHEJ), a major DNA double-strand break (DSB) repair pathway. LKB1 localized to DNA ends upon the generation of micro-irradiation and I-SceI endonuclease-induced DSBs. LKB1 inactivation either by RNA interference or by kinase-dead mutation compromised NHEJ-mediated DNA repair by suppressing the accumulation of BRM, a catalytic subunit of the SWI/SNF complex, at DSB sites, which promotes the recruitment of an essential NHEJ factor, KU70. AMPK2, a major substrate of LKB1 and a histone H2B kinase, was recruited to DSBs in an LKB1-dependent manner. AMPK2 depletion and a mutation of H2B that disrupted the AMPK2 phoshorylation site impaired KU70 and BRM recruitment to DSB sites. LKB1 depletion induced the formation of chromosome breaks and radials. These results suggest that LKB1-AMPK signaling controls NHEJ and contributes to genome stability. [ABSTRACT FROM AUTHOR]

A new real-time radioisotope imaging system (RRIS) to study the kinetics of nutrient uptake and transfer of photosynthetic products in a living plant was developed and evaluated through a test run. C is a common radioisotope of carbon and useful to trace the photosynthetic products as well as a low energy beta emitter. The rationale of this study was to develop a RRIS that has the ability to detect low energy beta emitters, such as C, S, and Ca. To achieve compatibility between the detection of low energy beta emitters and irradiation of the test plant, an intermittent lighting system was added to the RRIS. Furthermore, a commercially available digital camera was added to the RRIS for acquisition of photographic images of the test plants. The capabilities of the new RRIS were evaluated through a test run by using seedlings of rice plants and S-labeled sulfate. It was shown that the new RRIS was able to detect S absorbed by rice plant seedlings, and it was able to acquire photon-counting images and photographic images of the test plants simultaneously. Despite some limitations, the new RRIS provides a means to study the kinetics of elements in plants by utilizing low energy beta emitters. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to develop and validate a bedside test for executive function in patients with idiopathic normal pressure hydrocephalus ( INPH). Materials and Methods Twenty consecutive patients with INPH and 20 patients with Alzheimer's disease ( AD) were enrolled in this study. We developed the counting-backward test for evaluating executive function in patients with INPH. Two indices that are considered to be reflective of the attention deficits and response suppression underlying executive dysfunction in INPH were calculated: the first-error score and the reverse-effect index. Performance on both the counting-backward test and standard neuropsychological tests for executive function was assessed in INPH and AD patients. Results The first-error score, reverse-effect index and the scores from the standard neuropsychological tests for executive function were significantly lower for individuals in the INPH group than in the AD group. The two indices for the counting-backward test in the INPH group were strongly correlated with the total scores for Frontal Assessment Battery and Phonemic Verbal Fluency. The first-error score was also significantly correlated with the error rate of the Stroop colour-word test and the score of the go/no-go test. In addition, we found that the first-error score highly distinguished patients with INPH from those with AD using these tests. Conclusion The counting-backward test is useful for evaluating executive dysfunction in INPH and for differentiating between INPH and AD patients. In particular, the first-error score may reflect deficits in the response suppression related to executive dysfunction in INPH. [ABSTRACT FROM AUTHOR]

It is very important to visualize the process of nutrient absorption and distribution to study the physiological activity of the plant. We developed a real-time radioisotope (RI) imaging system, where RI tracers were applied to the plant sample. This system allowed the quantitative measurement concerning the uptake of nutrients labeled with radioisotopes, such as 45Ca, 35S, 32P and 14C as long as several days. The β-rays emitted from the sample were converted to light by a CsI(Tl) scintillator and were guided to a highly sensitive CCD camera. The scintillator surface was covered with an Al plate to avoid LED light penetration but allow selected β-ray penetration. We employed Lotus japonicus for the plant sample and observed the 32P-phosphate absorption in roots and the accumulation to the aboveground part of the plant. The environment condition of daytime and night was simulated by the ON/OFF of LED timer and the accumulation manner of the 32P-phosphate in roots and leaves during daytime and night was analyzed. The accumulation of 32P-phosphate in leaves was highly dependant on light irradiation and higher when the LEDs was turned on, whereas the absorption of 32P-phosphate in root was higher when the LEDs was turned off. The transfer function concerning the transportation of phosphate within the plant during the developmental stage was obtained from the analysis of P uptake images. We are now trying to get specific moving images of each radioisotope when two kinds of isotopes, such as 32P and 35S, were applied at the same time to the plant, through an image analysis. [ABSTRACT FROM AUTHOR]

The Coulomb dissociation of the proton-rich nuclei 31Cl was studied experimentally using 31Cl beams at 58 MeV/nucleon with a lead target. The relative energy between the reaction products, 30S and proton, was obtained. The first excited state in 31Cl was observed which is relevant to the resonant capture of stellar 30S(p,γ)31Cl reaction. [ABSTRACT FROM AUTHOR]

Cluster structures in the neutron-rich nucleus 12Be were experimentally investigated via α-inelastic scattering. Excited states in the 12Be nucleus were populated by a 12Be(αα') reaction at 60 A MeV in the inverse kinematics, and identified by measuring a 6He+6He and α+8He breakup channels in coincidence. The differential cross section and the angular correlations between the decay particles were obtained for each excitation energy at 10–20 MeV for 6He+6He and at 9–19 MeV for α+8He, respectively, reconstructed by the measured momentum vectors of the two helium isotopes. A multipole decomposition analysis based on the distorted-wave Born approximation was applied for the angular distribution of the inelastic scattering together with the angular correlation between the decay particles with respect to the directions of the incident beam and to the momentum transfer simultaneously. From the decomposed excitation energy spectra for J=0-4, several new excited states were identified. The 0+ excited states were candidates of the band-head of a largely deformed rotational band. The 11.3-MeV 0+ state was found to decay only into the 6He+6He channel. This result support the recent theoretical result by the generalized two-center cluster model. Several negative-parity excited states were observed in the α+8He channel. These excited states possibly forming a negative-parity rotational band, which is very closed to the positive-parity band, can be connected to the existence of the extremely developed cluster structure in 12Be. [ABSTRACT FROM AUTHOR]

Proton inelastic scattering on the neutron-rich nucleus 32Mg has been experimentally studied at Elab = 46.5 MeV/nucleon in inverse kinematics. The energies of excited states in 32Mg were obtained by measuring de-excitation γ rays. Several new states were identified by γ-γ coincidence analysis. Their spins and parities were restricted and the deformation parameters βp,p′ were extracted from the measured angular distribution of the proton inelastic scattering. The present analysis favors 4+ for the spin and parity of the 2321-keV state. [ABSTRACT FROM AUTHOR]

We present the real-time RI imaging and analyzing system to study the kinetics of nutrient uptake manner in a living plant. The system allowed light condition for the up-ground part of the plant and continuous dark condition for the root part, therefore, light/dark cycles was set as 16/8 h. There was 9,000 lx of LED lights in an aluminum container where the plant was set. The container was shielded well so that there was no light leakage to damage highly sensitive CCD camera which detected beta-rays from the sample. With this system, RI imaging was able to perform for 6 days without damaging the activity of the plant. [ABSTRACT FROM AUTHOR]

Aims Interaction of vascular and metabolic factors appears to contribute to the pathogenesis of diabetic neuropathy. The aim of the study was to assess the impact of arterial stiffening and thickness on diabetic neuropathy in Type 2 diabetes. Methods In 294 patients with Type 2 diabetes, neuropathy was assessed by four components: the presence of neuropathic symptoms, the absence of ankle tendon reflexes, perception of vibration scores and heart rate variation. We measured intima-media thickness (IMT) of carotid arteries to assess arterial thickening, and brachial–ankle pulse-wave velocity (PWV) and brachial pulse pressure (PP) which reflect arterial stiffening. Results Diabetic neuropathy, defined as ≥ two of the four components, was significantly associated with age, duration, glycated haemoglobin (HbA1c), systolic blood pressure, diastolic blood pressure, PP, hypertension, retinopathy, urinary albumin excretion rate, nephropathy stages, PWV and IMT. PWV and PP were significantly associated with neuropathy independent of conventional cardiovascular risk factors. Multiple logistic regression analysis revealed that PWV, retinopathy, age, and HbA1c, were significant independent determinants of neuropathy. Conclusions The present cross-sectional study indicates that markers for vascular wall properties such as PWV, IMT and PP are significantly associated with diabetic neuropathy. PWV and PP are significant determinants of neuropathy independent of conventional cardiovascular risk factors. Multifactorial intervention to inhibit progression of the atherosclerotic process may slow progression of neuropathy. [ABSTRACT FROM AUTHOR]

We developed a quantitative, real-time imaging system of labeled compounds in a living plant. The system was composed of CsI scintillator to convert β-rays to visible light and an image intensifier unit (composed of GaAsP semiconductor and MCP; micro channel plate) to detect extremely weak light. When the sensitivity and resolution of the image of our system was compared with that of an imaging plate (IP), the sensitivity of our system (with 20 minutes) was higher than that of an IP, with similar quality to that of an IP. Using this system, the translocation of 32P in a soybean plant tissue was shown in successive images. [ABSTRACT FROM AUTHOR]

The Coulomb dissociation of 27P was studied experimentally using 27P beams at 57MeV/nucleon with a lead target. The E2 gamma decay width of the first excited state in 27P was determined to be (2.8±0.5)×10-5eV. The total ( M1 + E2) gamma decay width of the state, which is of astrophysical interest, is estimated by combining the experimental result and a shell model calculation. The reaction rate of 26Si(p,γ)27P is deduced from the estimated total gamma decay width. The astrophysical implication derived from estimated gamma decay width is discussed. [ABSTRACT FROM AUTHOR]

We propose nonlinear resistance models for bulk resistance of a dielectric layer and contact resistance between a wafer and the dielectric layer used in an equivalent circuit model to predict the clamping or residual clamping pressure in Johnsen-Rahbek-type [A. Johnsen and K. Rahbek, J. Inst. Electr. Eng. 61, 713 (1923)] electrostatic chucks. It is found that the bulk resistance is presumed by a model on the basis of the space-charge-limited current model in insulator. It is also found that the contact resistance is expressed by a superposition of Ohmic resistance in the low-field strength region and a resistance on the basis of field emissions in the high-field strength region. In addition, the gap capacitance is determined based on the probability function of asperity height obtained from a surface roughness profile. The clamping pressure is simulated by calculating a charge stored in the gap, combined with the probability function with circuit simulation. Consequently, the calculation agrees with the measurement within 31% difference. It is also found that the calculation can reproduce the dependency of bulk resistance on the clamping pressure and the time response in residual clamping pressure. [ABSTRACT FROM AUTHOR]

The proton shell structure in neutron-rich fluorine 23F was investigated using the in-beam γ-ray spectroscopy technique via the proton transfer reaction onto the unstable nucleus 22O, in addition to α inelastic scattering on 23F, and the neutron-knockout reaction from 24F. The level and γ-decay scheme in 23F was deduced from de-excitation γ-ray-particle coincidence events. We found that a single-particle state at 4.061MeV has a large contribution from the d shell by the analysis of population strengths and the angular distribution for the state. We reported here the present experiment and the preliminary results. [ABSTRACT FROM AUTHOR]

We measured B( E2;0+g.s. → 2+1) values for the proton-rich 46Cr, 50Fe, and 54Ni nuclides by intermediate-energy Coulomb excitation in order to study the systematic behavior of collectivity in the Z = 20-28 region. The present study completes the B( E2) values for the Tz = ±1 even-even pair nuclei up to Z = 28. The double ratios of proton and neutron matrix elements, (| Mn|/| Mp|)/( N/ Z), have been extracted from the B( E2) values combining with the ones of their mirror nuclei, and compared with theoretical predictions. [ABSTRACT FROM AUTHOR]

The fabrication of heavy-duty printer heads involves a great deal of grinding work. Previously in the printer manufacturing industry, four grinding procedures were manually conducted in four grinding machines, respectively. The productivity of the whole grinding process was low due to the long loading time. Also, the machine floor space occupation was large because of the four separate grinding machines. The manual operation also caused inconsistent quality. This paper reports the system and process development of a highly integrated and automated high-speed grinding system for printer heads. The developed system, which is believed to be the first of its kind, not only produces printer heads of consistently good quality, but also significantly reduces the cycle time and machine floor space occupation. [ABSTRACT FROM AUTHOR]

Discusses surface integrity effects on turned aluminum alloys. Improvement of toughness and resistance to fatigue crack growthby the application of heat treatment; Enhancement of mechanical properties such as high strength/weight ratio, good corrosion resistance, weldability and deformability; Definition of surface integrity.

Even though fluoride toxicity is increasingly being considered to be important, very little information is available on the mechanism of action of fluoride. In the present study, the toxicity of fluoride on human leukemia (HL-60) cells was investigated and the involvement of caspase-3 was also studied. Fluoride induced apoptosis in HL-60 cells in a dose- and time-dependent manner. Annexin staining and DNA ladder formation on agarose gel electrophoresis further revealed that HL-60 cells underwent apoptosis on exposure to 2–5 mM fluoride. Western blotting using polyclonal anti-caspase-3 antibody and mouse anti-human poly(ADP-ribose) polymerase (PARP) monoclonal antibody was performed to investigate caspase-3 and PARP activity. Fluoride led to the activation of caspase-3 which was evident by the loss of the 32 kDa precursor and appearance of the 17 kDa subunit. Furthermore, intact 116 kDa PARP was cleaved by fluoride treatment as shown by the appearance of a cleaved 89 kDa fragment. The results clearly suggest that fluoride causes cell death in HL-60 cells by causing the activation of caspase-3 which in turn cleaves PARP leading to DNA damage and ultimately cell death. [ABSTRACT FROM AUTHOR]