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In this study, we established consecutive monitoring methods using UAV in pecan orchards of 64 ha each, in San Simon, Arizona, USA. Activity monitoring, tree height map creation and ground surface temperature analysis of trees by UAV with near infrared (NIR)/TIR camera were conducted for pecan orchards in San Simon, Arizona, USA. Using established continuous monitoring methods, the UAV images of a 3-year-old pecan orchard showed circular traces of alfalfa cultivation prior to installation of pivot irrigation that was previously not observed. Tree growth measurements was compared to the trees planted inside and outside of the circle. Growth and tree health activity was found to be better when the trees were outside of the circle. [ABSTRACT FROM AUTHOR]

Donor-derived cell-free DNA (dd-cfDNA) elevation has been shown to correlate with rejection mediated allograft injury, however, the relationship between dd-cfDNA and primary graft dysfunction (PGD) in lung transplantation remains unclear. Measurement of absolute count (AbC) could provide insight into the inconsistent association of cell-free DNA (cfDNA) with PGD. We evaluated the decay of both dd-cfDNA and AbC immediately post-lung transplant. Forty-eight patients with dd-cfDNA levels (%, AlloSure, CareDx) drawn within 1-week post-transplant were included. AbC (copies/mL) was quantified using available biobanked dd-cfDNA samples in 32 of the patients. PGD was graded per ISHLT criteria at 24, 48, and 72 hours (H). When comparing PGD vs no PGD, grades 0 and 1 were compared to grades 2 and 3 at 72H. Median dd-cfDNA across the entire cohort at 24, 48, and 72H were 16.4%, 11.4%, and 8.4%; median AbC across the cohort at the same time points were 8573, 7174, and 4494, respectively. When using 72H PGD grade to classify patients, 33% had no PGD (n = 16), 31% were grade 1 (n = 15), 8% were grade 2 (n = 4), and 27% were grade 3 (n = 13). Neither dd-cfDNA or AbC correlated with PGD grade at 72H (Figure 1). When comparing the average of the first 72H between PGD and no PGD, neither dd-cfDNA (p = 0.90) nor AbC (p = 0.32) were significant. When evaluating the rate of dd-cfDNA decay, there was a non-statistically significant trend towards faster decay with higher PGD grade. These preliminary data show neither dd-cfDNA or AbC measured within the first 3 days post-transplant correlated with PGD grade at 72h, however, there was a trend towards higher decay speed with more severe PGD. As patients with higher PGD grades are more likely to receive extracorporeal mechanical support and renal replacement therapies, the effect of these modalities on cfDNA kinetics should be evaluated. [ABSTRACT FROM AUTHOR]

We have investigated the dielectric and magnetic properties of Eu0.595Y0.405MnO3 without the presence of the 4f magnetic moments of the rare-earth ions and have found two ferroelectric phases with polarization along the a and c axes in a zero magnetic field. A magnetic-field-induced switching from one to the other ferroelectric phase took place in which the direction of ferroelectric polarization changed from the a axis to the c axis by the application of magnetic fields parallel to the a axis. In contrast to the case of TbMnO3, in which the 4f moments of Tb3+ ions play an important role in such a ferroelectric phase switching, the magnetic-field-induced switching between ferroelectric phases in Eu0.595Y0.405MnO3 does not originate from the magnetic transition of the rare-earth 4f moments but from that of the Mn 3d spins. [ABSTRACT FROM AUTHOR]

The HIMAC clinical study has been conducted with a carbon-ion beam since June 1994. Since 2006, as a new treatment research project, NIRS has developed both the accelerator and beam-delivery technologies for the sophisticated heavy-ion radiotherapy, which brings a pencil-beam 3D rescanning technology for both the static and moving-tumor treatments. In this technology, the depth-scanning technique was improved to the full-energy depth scanning by realizing a variable-energy operation of the HIMAC synchrotron itself. At present, a heavy-ion rotating gantry has been developed with the superconducting technology and is in a beam-commissioning stage. As a future plan, we just start a study of a multi-ions irradiation for more sophisticated LET-painting and a design study of a superconducting synchrotron for more compact heavy-ion radiotherapy facility. [ABSTRACT FROM AUTHOR]

We have investigated dielectric properties in Mott insulators GdMnO3 and TbMnO3 under magnetic fields and external quasihydrostatic pressures. In the case of GdMnO3, thermal hysteresis for dielectric constant ε and discontinuous lattice distortion were observed at ferroelectric transition temperature (TC), and ferroelectric spontaneous polarization was suppressed by the application of external pressure. These results indicate that the ferroelectric transition in GdMnO3 is a first-order displacive-type one. On the other hand, the thermal hysteresis and discontinuous lattice striction were not observed at TC in TbMnO3. The peak of ε corresponding to the ferroelectric transition was shifted toward higher temperatures by the application of external pressure in TbMnO3. The ferroelectric transition of TbMnO3 was thought to be a second-order order-disorder-type one. [ABSTRACT FROM AUTHOR]

The endothelial glycocalyx (eGC) is a carbohydrate-rich layer lining the luminal surface of the vascular endothelium. The eGC damage causes endothelial dysfunction, leading to organ dysfunction. Heparanase (HPSE) plays a key role in the dissociation of the eGC in response to cellular stress, but the mechanism of how HPSE regulates eGC degradation and organ dysfunction is not clear. In this study, we aimed to investigate the role of HPSE on the development of ischemia/reperfusion (I/R) injury using a genetic knockout mouse and lung hilar occlusion models. Using B6 wildtype (WT) and HPSE−/− mice, the left lung hilar I/R injury model was established. Left lungs were clamped for an hour followed by reperfusion for 4 hours. We investigated lung quality and eGC status. Data were compared among WT lungs with and without I/R injury and HPSE−/− mice after I/R injury. Left lung function in WT mice was significantly impaired after I/R injury. However, no functional change was found in HPSE−/− lungs after I/R injury compared to WT lungs without I/R. The mRNA expression of proinflammatory cytokines, interleukin-6, and tumor necrosis factor-α were upregulated in lungs after I/R in WT, while no significant upregulation was found in HPSE−/− lungs after I/R injury. Plasma glycosaminoglycans levels increased 6.2-fold in WT (p<0.01) and 1.6-fold in HPSE−/−, compared to baseline normal plasma level. Our data suggest HPSE may facilitate the eGC degradation leading to inflammation and impaired function in the lungs after I/R injury. HPSE may be a therapeutic target to attenuate graft damage in lung transplantation. Further investigation is necessary to better define the interaction between HPSE activity and other I/R-related events. [ABSTRACT FROM AUTHOR]

The authors demonstrate distributed temperature sensing based on slope‐assisted Brillouin optical correlation‐domain reflectometry (BOCDR) with a long measurement range of >10 km. They find that to achieve such a long‐range measurement, a delay line in a reference path needs to be at least four times longer than the sensing fibre. In addition, they show that the use of such a long delay line induces forward‐propagating Brillouin‐scattered light in the reference path, which deteriorates the signal‐to‐noise ratio (SNR) of the system and should be suppressed. Finally, by exploiting a beyond‐nominal‐resolution effect of the slope‐assisted BOCDR, they detect a 3‐m‐long heated section in a 13‐km‐long silica fibre in a distributed manner; the reason for its low SNR is also discussed. [ABSTRACT FROM AUTHOR]

Objective The aim of the study was to examine the early tissue reaction in the tension zone of periodontal ligament (PDL) during orthodontic tooth movement. Design Upper first molars of rats were moved buccally with fixed appliances. The PDL in the tension zone was examined histologically, immunohistochemically and at a molecular level after 24 h, 3 days and 7 days. Results After 24 h of orthodontic force loading, the periodontal space appeared considerably expanded. The periodontal fibers were stretched between the bone and the root. Three days after loading, the expanded periodontal space had slightly narrowed, the periodontal fiber arrangement was relaxed, and the blood vessels did not appear elongated. A considerable layer of osteoid was formed on the bone surface. The total cross-sectional areas of the PDL in experimental groups were significantly larger than control group. The total cross-sectional areas of the blood vessels were not significantly different among the groups. Significantly high expressions of IL-1β and PTX3 were characteristically observed not only in the endothelial cells and cells around the blood vessel, but also in fibroblasts throughout the PDL of the tension zone 24 h after orthodontic force loading. Three and 7 days after loading, these showed tendencies to return to control levels. Conclusions The present results suggest that the early reaction in the tension zone of the PDL during tooth movement consists of two phases: first, inflammation and second, rapid recovery and renovation of the PDL with bone formation. [ABSTRACT FROM AUTHOR]

Rats with dopamine depletion caused by 6-hydroxydopamine (6-OHDA) treatment during adulthood and the neonatal period exhibit akinetic motor activity and spontaneous motor hyperactivity during adolescence, respectively, indicating that the behavioral effects of dopamine depletion depend on the period of lesion development. Dopamine depletion during adulthood induces hyperalgesic response to mechanical, thermal, and/or chemical stimuli, whereas the effects of neonatal dopamine depletion on nociceptive response in adolescent rats are yet to be examined. The latter aspect was addressed in this study, and behavioral responses were examined using von-Frey, tail flick, and formalin tests. The formalin test revealed that rats with neonatal dopamine depletion exhibited a significant increase in nociceptive response during interphase (6–15 min post formalin injection) and phase 2 (16–75 min post formalin injection). This increase in nociceptive response to the formalin injection was not reversed by pretreatment with methamphetamine, which ameliorates motor hyperactivity observed in adolescent rats with neonatal 6-OHDA treatment. The von-Frey filament and tail flick tests failed to reveal significant differences in withdrawal thresholds between neonatal 6-OHDA-treated and vehicle-treated rats. The spinal neuronal response to the formalin injection into the rat hind paw was also examined through immunohistochemical analysis of c-Fos protein. Significantly increased numbers of c-Fos-immunoreactive cells were observed in laminae I–II and V–VI of the ipsilateral spinal cord to the site of the formalin injection in rats with neonatal dopamine depletion compared with vehicle-treated rats. These results suggest that the dopaminergic neural system plays a crucial role in the development of a neural network for tonic pain, including the spinal neural circuit for nociceptive transmission, and that the mechanism underlying hyperalgesia to tonic pain is not always consistent with that of spontaneous motor hyperactivity induced by neonatal dopamine depletion. [ABSTRACT FROM AUTHOR]

Endothelial glycocalyx degradation is known to critically affect graft quality. Glycocalyx protection and preservation during ex vivo lung perfusion (EVLP) may increase conversion to transplant and improve posttransplant outcomes. To date it is unclear the role of routine heparin use on graft protection during current EVLP regardless of blood product use in perfusate. Heparin may protect glycocalyx via inhibiting heparanase activity. In this study, we investigated the effect of heparin on intragraft endothelial protection and graft quality during EVLP. Using a rat EVLP model, 1000U heparin/100mL Steen solution was administered into the perfusate every hour for 4 hours and lung physiologic parameters were monitored. After 4 hours, the perfusate and tissue samples were analyzed for endothelial glycocalyx integrity. Data were compared between lungs with/without heparin treatment. Compared to control tissues, heparin significantly decreased heparanase activity and matrix metalloprotease-9 expression in lung tissue during EVLP. (Figure 1A) We also detected increased levels of syndecan-1 in perfusate during 4h EVLP with heparin. (Figure 1B) Additionally, no significant differences were observed between heparin-treated and control lung tissues regarding gene expression of proinflammatory cytokines, physiological parameters, tissue glycosaminoglycans, and edema development. This study suggests that heparin inhibits heparanase activity in lung tissue during EVLP; however, it may enhance endothelial glycocalyx breakdown. As a result, our findings raise concerns about the use of heparin during EVLP. Alternative treatments aimed at protecting and maintaining graft endothelial cell viability/health during EVLP may result in improved graft preservation and outcomes. [ABSTRACT FROM AUTHOR]

The endothelial glycocalyx (eGC) is a protective layer covering the endothelial surface. Upon the damage to the endothelium, heparanase (HPSE) cleaves heparan sulfate in the eGC and leads to further endothelial dysfunction. We hypothesized that inhibition of HPSE may preserve endothelial glycocalyx and contribute to better organ preservation and improved post lung transplant outcomes. We tested our hypothesis by pre-treating mice with an HPSE inhibitor (heparastatin SF4) using an ischemia-reperfusion (I/R) injury model by total hilar clamping. Mice left lung hilar I/R injury model was used in this study. Before ischemia, PBS (control) or SF4 (40 μM of 50 μl) was administered to the mice intraperitoneally. Left lungs were clamped for an hour followed by reperfusion for 4 hours. Oxygenation, inflammation and eGC related enzyme activities were defined to evaluate organ function. Data were compared among sham, control and SF4 groups. Left lung function measured by PaO2/FiO2 was significantly lower in controls (PBS) compared to SF4 after I/R injury. However, it was not different between SF4 and sham groups (Figure A). The mRNA expressions of proinflammatory cytokines, interleukin-6 and tumor necrosis factor-α, were upregulated in the lung after I/R in control compared to sham but downregulated in SF4 treated lungs (Figure B). HPSE activity in lung tissue after I/R was significantly reduced by SF4 given before ischemia. (p=0.02). In addition, the mRNA level and activity of matrix metalloproteinase (MMP)-2 were also notably decreased in lungs after I/R injury by SF4 treatment compared to control. Significant upregulation of MMP9 proactive form was observed in SF4-treated lungs. HPSE inhibition can attenuate lung injury against I/R by preventing activation of the endothelium and eGC degradation. Protection of eGC may improve graft preservation and post-lung transplant outcomes. [ABSTRACT FROM AUTHOR]

Circulating donor-derived cell-free DNA (dd-cfDNA) levels have been proposed as a potential tool for the diagnosis of graft injury (rejection, infection, ischemia/reperfusion injury). In this study, we prospectively investigated dd-cfDNA plasma levels and their association with severe primary graft dysfunction at 72 hours and acute cellular rejection in the first month after lung transplant. Thirty-five subjects undergoing double lung transplants at our institution between Jun.2020-Oct.2021 were included in this study. Primary Graft Dysfunction (PGD) was graded according to ISHLT criteria. Our protocol includes a surveillance bronchoscopy with transbronchial biopsy at 3 weeks post-transplant. Acute cellular rejection was diagnosed and graded by a pulmonary pathologist after evaluation of histopathology slides. Blood samples were collected at various time points before and after lung transplant. Dd-cfDNA in samples were determined using AlloSure dd-cfDNA test kits (CareDx, Inc.). We observed a rapid increase of dd-cfDNA in blood of recipients after lung transplantation compared to baseline. The levels of dd-cfDNA decreased during the first two weeks (Figure A). The peak was observed within 72 hours after transplantation. The peak values of dd-cfDNA varied among subjects and had no correlation with PGD grade 3 occurrences at 72 hours. (Figure B, p=0.85). We observed an association between levels of dd-cfDNA from blood collected at the time of transbronchial biopsy and the histological diagnosis of ACR at 3 weeks. (Figure C, mean 2.7% versus 1.5%, p=0.015) This preliminary data shows that circulating dd-cfDNA levels are associated with ACR early after transplantation but not with severe PGD at 72hours. Plasma levels of dd-cfDNA may be a less invasive tool to estimate graft rejection after lung transplantation however larger studies are still necessary to better identify thresholds. [ABSTRACT FROM AUTHOR]

The local electronic state at every crystallographically independent molecular site was separately investigated in the organic superconductor α-(BEDT-TTF)2NH4Hg(SCN)4 using site-selective 13C-NMR spectroscopy. The density of states (DOS) at three molecular sites shows independent temperature variation, which is caused by the long-range Coulomb interaction. Comparing the present results with those for a nonsuperconducting counterpart α-(BEDT-TTF)2RbHg(SCN)4, we found that the uniform DOS at two of three independent molecular sites is crucial to induce superconductivity. Taking the site-dependent DOS as a parameter, we constructed a phase diagram for a superconductor with long-range Coulomb interaction, an α-type BEDT-TTF family, and summarized the competition between charge instability and superconductivity. [ABSTRACT FROM AUTHOR]

Abstract: The NIRS has carried out carbon-ion radiotherapy (RT) with HIMAC since 1994. On the basis of their ten-year HIMAC experience, NIRS has developed a standard-type CIRT facility in order to boost availability of carbon-ion RT in Japan. Work has been carried out at its pilot facility at Gunma University since 2010. The current projects of the pilot facility include Saga-HIMAT and i-ROCK, promoted by the Kanagawa prefectural cancer center. Toward the further sophisticated conformal carbon-ion RT with HIMAC, the NIRS has since 2006 been developing new treatment technologies, such as a fast 3D rescanning with a pencil beam and a compact rotating gantry. [Copyright &y& Elsevier]

Abstract: A post linac is being designed for an energy upgrade of a heavy-ion injector. This post linac is to be installed downstream of the formerly developed compact injector, consisting of an Electron-Cyclotron-Resonance Ion-Source (ECRIS), the Radio-Frequency-Quadrupole (RFQ) linac and the Alternating-Phase-Focused Interdigital H-mode Drift-Tube-Linac (APF IH-DTL). It is aimed to increase the output energy of a heavy-ion injector. Carbon ions are initially accelerated with the compact injector to 4MeV/u, and further accelerated with the post linac up to 8MeV/u. The three linacs have the same operating frequency of 200MHz. For beam focusing of the post linac, the APF method is used. Iterative simulations of beam dynamics were performed to determine the optimum array of synchronous phases in each gap. The results of the simulations provided that the calculated efficiency of beam transmission through the post linac is as high as 98.4%. The total length of this APF post linac is estimated to be approximately 3m. A design overview of the injector system including the post linac is presented. [Copyright &y& Elsevier]

We have performed homoepitaxial MBE growth of nitrogen (N) -doped ZnO and studied the postanneal effect on electrical conduction properties. A rapid postanneal after MBE growth is found to enhance the donor-acceptor (D-A) pair emission intensity, converting from n-type (as-grown) to p-type conduction. The p-type ZnO showed extremely high resistivity (>103 Ω cm) at room temperature. Carrier-compensating donor-like defects in N-doped ZnO were traced by using PPC (persistent photocurrent), which is coupled with in situ Hall effect measurements. It is found that highly resistive p-ZnO includes a high density of metastable donor-like defects forming a deep donor band in the midgap region. This midgap donor band plays a role in Fermi-level pinning at around the midgap position, resulting in high resistivity. Based on X-ray photoemission spectroscopy experiments one possible origin of the deep donor band is introduced as nitrogen molecule (N2(o)) defects locating at the O atomic site. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

This retrospective study identified the risk factors for fracture of veneering materials and screw loosening of implant-supported fixed partial dentures in partially edentulous cases. The study group included a total of 182 patients who were installed 219 suprastructures at the Fixed Prosthodontic Clinic of Okayama University Dental Hospital between February 1990 and March 2005 and were subdivided in two subgroups: 120 patients (149 facing suprastructures) were included in the subgroup to investigate the risk factors of fracture of veneering materials, and 81 patients (92 suprastructures) were included in the subgroup to identify the risk factors of abutment screw loosening. Each patient was followed up from the day of suprastructure installation until March, 2005. A Cox proportional hazards regression model was used to identify the risk factors related to technical complications, and eight factors were regarded as candidate risk factors. Screw retention was the significant risk factor for fracture of veneering materials, whereas connection of suprastructures with natural tooth was the significant risk factor for screw loosening. It was suggested that screw retention was a significant risk factor for the fracture of veneering materials, and connection of suprastructures with natural tooth was a significant risk factor for screw loosening. Future studies, involving dynamic factors (e.g. bruxism) as predictors as well, are more helpful to discuss the risk factor of fracture of veneering materials and screw loosening. [ABSTRACT FROM AUTHOR]

Abstract: On the basis of more than 10years of experience with HIMAC, we proposed and designed a new treatment research facility, as an extension of the existing facility, for the further development of radiotherapy with HIMAC. The new facility employs a 3D rescanning technique developed at NIRS. Its building construction was completed in March 2010 and the devices are being installed. A beam commissioning and a pre-clinical study will be initiated from this October. Here, we report recent progress for this new treatment facility project at HIMAC. [Copyright &y& Elsevier]

Abstract: The modifications of direct transition energies by lattice deformations were investigated in β-FeSi2 epitaxial films, polycrystal films and single crystal, systematically. The lattice deformations depending on thermal annealing temperature (T a ) were observed in β-FeSi2 epitaxial films. In photoreflectance (PR) measurements, the direct transition energies of the epitaxial films shifted to lower energies as the T a increased. The polycrystal films did not show the lattice deformation and the shift of direct transition energies. These results show that the direct bandgap is modified by the lattice deformation originating from the lattice mismatch at the hetero-interface of β-FeSi2/Si. [Copyright &y& Elsevier]

Background: Chlorophosphonazo-III (2,7-bis[4-chloro-2-phosphonophenylazo]-1,8-dihydroxy-3,6-naphthalenedisulphonic acid, disodium salt; CPZ-III) reacts with calcium and magnesium in a sample under acidic to neutral conditions. However, the specific method of measuring calcium in serum using CPZ-III has not been established because of the difficulty of avoiding the interaction between CPZ-III and albumin. Methods: In this study, we found that the non-specific reaction between CPZ-III and albumin could be controlled and calcium in serum could be specifically detected using CPZ-III combined with vanadate. On the basis of this finding, we evaluated a novel method of serum calcium determination using CPZ-III. Results: This CPZ-III vanadate method gave linear results from 0 to 7.0 mmol/L. The coefficient of variation was 0.63-0.76%. There was no interference except with Omniscan. There was no change in control performance during 60 d under open-air conditions. The assay results correlated well with those of the Arsenazo-III (2,7-bis(2-arsonophenylazo)-1,8-dihydroxy-3,6-naphthalenedisulphonic acid) method (slope = 1.067; intercept = 20.120; r = 0.989; Sy/x = 0.036 mmol/L), o-cresolphthalein complexone method (slope = 0.911; intercept = 0.186; r = 0.988; Sy/x = 0.035 mmol/L), amylase enzymatic method (slope = 0.981; intercept = 0.072; r = 0.989; Sy/x = 0.036 mmol/L) and inductively coupled plasma emission spectroscopy method (slope = 0.955; intercept = 20.001; r = 0.979; Sy/x = 0.048 mmol/L). Conclusions: These results suggested that the present method has great clinical potential for measuring calcium. [ABSTRACT FROM AUTHOR]

Abstract: Based on more than 10 years of experience with HIMAC, we have proposed a new treatment facility for the further development of therapy with HIMAC. The new facility, as an extension of the existing one, has been designed and the related R&D work has been carried out. The following descriptions give a summary account of the design study and the related R&D work for this new treatment facility at HIMAC. [Copyright &y& Elsevier]

Abstract: New experimental data on the charge-state (q) evolution fractions F q (D) and equilibrium charge-state fractions are presented when 2.65MeV/u C2+, O3+, Ne4+ and Si5+ projectile ions passed through carbon foils with thickness of D =10–200μg/cm2. The equilibrium fractions for Si+C collisions (i.e. for silicon ions colliding with carbon foils) are compared with the data at 4.3 and 6.0MeV/u previously reported, and the observed significant difference is explained by different energy dependencies of the electron-capture and projectile-ionization cross sections. Detailed information about nl-state distribution functions N q (nl) of exit silicon ions is obtained for these three energies by solving linear balance equations for N q (nl) values where n and l are the principal and orbital quantum numbers, respectively, and . The collision cross sections and radiative decay rates as the coefficients of these balance equations are calculated for each ion-beam energy. Based upon the present method, it is found that the fractions of excited Si ions after the carbon foil are about 57%, 33% and 15% at energies of 2.65, 4.3 and 6.0MeV/u, respectively, clearly indicating the significant reduction of the excited-ion component with the collision energy increasing. The calculated equilibrium charge-state fractions for Si ions are in good agreement with available experimental data. [Copyright &y& Elsevier]

Background: It has been reported that nonsteroidal anti-inflammatory drugs may delay the onset of Alzheimer's disease (AD). Since nonsteroidal anti-inflammatory drugs inhibit cyclooxygenase (COX), COX-2, an inducible form of COX, may be involved in the pathology of AD in association with the arachidonic acid cascade. In addition, it has been suggested that alterations in the balance of polyunsaturated fatty acids are associated with brain dysfunctions such as neurodegerative pathologies of the aging brain. Method: To explore COX-2 expression in the hippocampus, we analyzed 45 consecutive autopsy subjects without dementia and 25 AD patients derived from the town of Hisayama, Japan. Results: The neuronal expression of COX-2 in the CA3 subdivision of the hippocampus, subiculum, entorhinal cortex and transentorhinal cortex were consistently observed in both nondemented and AD brains, and COX-2 immunoreactivity correlated with age in nondemented brains. In AD patients, neurons of CA1 exhibited increased COX-2 immunoreactivity which correlated with the severity of AD pathology. This correlation was not apparent in nondemented subjects. Conclusion: These results suggest that COX-2 expression may be differentially regulated among subdivisions of the hippocampus and that elevated COX-2 expression in the CA1 of AD brains may be associated with AD pathology and thus cognitive dysfunction. Copyright (c) 2007 S. Karger AG, Basel. [ABSTRACT FROM AUTHOR]

Leukocyte adhesion to the vascular wall is a critical early step in the pathogenesis of inflammatory diseases and is mediated in part by the leukocyte integrin, VLA4, which binds to endothelial vascular cell adhesion molecule (VCAM) -1. Here, we investigate VLA-4's role in endotoxin-induced uveitis (EIU). At various time points (6-48 h) after EIU induction, the severity of the inflammation was evaluated by quantifying cell and protein content in the aqueous fluid, firm leukocyte adhesion in the retinal vessels, and the number of extravasated leukocytes into the vitreous. Functional activation of VLA-4 in vivo was investigated in our previously introduced autoperfused micro flow chamber assay. Firm adhesion of EIU leukocytes to immobilized VCAM-1 under physiological blood flow conditions was significantly increased compared with normal controls (P<0.05), suggesting an important role for VLA-4 in EIU. VLA-4 blockade in vivo significantly suppressed all uveitis-related inflammatory parameters studied, decreasing the clinical score by 45% (P<0.01 ), protein content in the aqueous fluid by 21% (P<0.01), retinal leukostasis by 68% (P<0.01), and leukocyte accumulation in the vitreous by 75% (P<0.01). Our data provide novel evidence for functional up-regulation of VLA4 during EIU and suggest VLA-4 blockade as a promising therapeutic strategy for treatment of acute inflammatory eye diseases. [ABSTRACT FROM AUTHOR]

Bovine lactoferrin was administered orally, in feed, to six bottlenosed dolphins (Tursiops truncatus) before they were transported for approximately six hours; their stress responses were compared with those of five untreated dolphins. During the journey the dolphins had an increased plasma concentration of cortisol, and lymphopenia, eosinopenia and mild neutrophilia, indicating a stress response. The administration of lactoferrin did not affect the function of the dolphins' polymorphonuclear leucocytes, but affected their leucogram by maintaining the number of circulating eosinophils. [ABSTRACT FROM AUTHOR]

Abstract: In Part 1 [T. Miyoshi, K. Noda, Y. Sato, H. Tawara, I.Yu. Tolstikhina, V.P. Shevelko, Nucl. Instr. and Meth. B, this issue] of our two reports, new experimental data on charge-state evolution F q (D) and equilibrium fractions were presented when 4.3MeV/u projectile ions with the atomic number Z =6–26 pass through carbon. Also, in this paper, a ten-charge-state model for equilibrium fractions expressed in terms of the charge-changing cross sections was suggested. In the present work (Part 2), a new method is suggested to determine the nl-distributions N q (nl) of exit ions with a charge q in the specific nl-states by solving the balance equations with all appropriate effective cross sections as coefficients. The and N q (nl) values are normalized so that and . The efficiency of the present method suggested is illustrated by example of Ar ions colliding with a carbon foil at projectile energy of E =6.0MeV/u. It is found that the exit argon beam comprises about 12% of argon ions in the excited states. This method can be used for evaluation of the excited-ion components in the exit ion beam when the charge equilibrium has been reached. Besides, in this work, extending the method described in [Miyoshi et al., this issue], evaluation of nl-state distributions of exit ions at energies E =4–20MeV/u is performed for the case of Ar+C foil collisions, therefore, allowing to observe the nl-state distributions in a wide energy range. [Copyright &y& Elsevier]

Abstract: New experimental data on charge-state evolution fractions F q (D) and equilibrium charge fractions are presented when 4.3MeV/u projectile ions with an atomic number Z =6–26 passed through carbon foils with thickness of D =10–350μg/cm2. These data are compared with the data at 6.0MeV/u previously reported, and the difference is explained in terms of the energy dependence of the charge-changing cross sections in solid carbon. Using the equations relating the equilibrium fractions with the collision cross sections describing interaction of projectiles with the target atoms, the nl state distributions of exit ions are predicted where n and l are the principal and orbital quantum numbers, respectively. A fitting procedure of getting information about these distributions is described. The influence and importance of the so-called target-density (gas–solid) effects on the collision cross sections for solid targets are also discussed. Using the fitting procedure described in this paper (Part 1), one can obtain information on nl state distributions, which survived after collisions of the projectiles with the target atoms. In the coming second part (Part 2) of our two reports, it will be shown how to estimate the absolute number of exit ions in these nl states. [Copyright &y& Elsevier]

Abstract: Since 1994, the clinical trial for cancer therapy with HIMAC has successfully progressed, and more than 2100 cancer patients have been treated with a carbon beam. Based on the development of the accelerator and irradiation technologies for 10 years, we have designed a new carbon-therapy facility for widespread use in Japan, and key technologies for the new facility have been developed. We describe the conceptual design of the new facility and the status of development for the key technologies. [Copyright &y& Elsevier]

Abstract: In order to define the optical parameters of a slowly extracted beam at the entrance of the extraction channel and to realize optical matching with the beam line, the outgoing separatrix was measured at HIMAC. Modifying the lattice parameters of the ring model according to the measurement result, the simulation result makes it possible to predict the optical parameters at the extraction channel. As a result, it was experimentally verified that optical matching of the slowly extracted beam with the transport line was realized. The measured beam size and dispersion functions were in good agreement with the calculation result at each monitor in the transport line. Particle tracking also predicts the beam profile at each profile monitor in the beam line. Further, a quasi-parallel beam was demonstrated by changing the beam optics in the beam line. [Copyright &y& Elsevier]

Japanese mine safety legislation was enacted in 1949. Improvements in safety and production in the mining industry have been achieved to a large extent under this legislation. However, because of the prescriptive legislation style of mine safety regulations, the degree of safety achieved has not been evaluated from a system performance point of view. Articles of the coalmine safety regulations prescribe detailed technical requirements for coalmine safety. In comparison to performance-based legislation, the prescriptive regulations do not require risk assessment and management. There are few criteria to evaluate safety measures. An investigation of the reliability of the flammable gas measurement system at the Kushiro coalmine has been undertaken. The results demonstrate aspects of implementation of risk management concepts into Japanese mine safety regulations in 2005. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether docetaxel has antitumour activity in patients with advanced or recurrent endometrial carcinoma. Chemotherapy-naïve or previously treated patients (one regimen) with histopathologically documented endometrial carcinoma and Eastern Cooperative Oncology Group performance status 2 entered the study. Docetaxel 70 mg m−2 was administered intravenously on day 1 of a 3-week cycle up to a maximum of six cycles. If patients responded well to docetaxel, additional cycles were administered until progressive disease or unacceptable toxicity occurred. Of 33 patients with a median age of 59 years (range, 39–74 years) who entered the study, 14 patients (42%) had received one prior chemotherapy regimen. In all, 32 patients were evaluable for efficacy, yielding an overall response rate of 31% (95% confidence interval, 16.1–50.0%); complete response and partial response (PR) were 3 and 28%, respectively. Of 13 pretreated patients, three (23%) had a PR. The median duration of response was 1.8 months. The median time to progression was 3.9 months. The predominant toxicity was grade 3–4 neutropenia, occurring in 94% of the patients, although febrile neutropenia arose in 9% of the patients. Oedema was mild and infrequent. Docetaxel has antitumour activity in patients with advanced or recurrent endometrial carcinoma, including those previously treated with chemotherapy; however, the effect was transient and accompanied by pronounced neutropenia in most patients.British Journal of Cancer (2005) 93, 999–1004. doi:10.1038/sj.bjc.6602817 www.bjcancer.com Published online 18 October 2005 [ABSTRACT FROM AUTHOR]

Abstract: In cancer therapy using an ion beam, a scanning irradiation method has been developed in order to realize 3-D conformal irradiation. From studies of the scanning method, it has been required for a medical synchrotron to be capable of controlling the beam intensity during the duration of extraction. For this purpose, a beam-intensity control technique with RF-knockout slow-extraction has been studied and developed at the HIMAC synchrotron. Based on a simple one-dimensional model of extraction, the function of amplitude modulation (AM) for a transverse RF-field was analytically calculated to control the beam current. By cooperating with the feedback system, finally, we could control the beam intensity within a range of one order during a single flattop. We report on a simulation and the experiment result of intensity control for scanning irradiation. [Copyright &y& Elsevier]

Abstract: Toward the study of the free-radicals behavior, we have proposed a production method of a short-pulsed beam, based on a bunch rotation after momentum cooling. The method was experimentally investigated at the HIMAC synchrotron. In the experiment, after the momentum spread was cooled down to around 0.02% at FWHM through electron cooling, an RF-field was non-adiabatically applied. Under an intensity of (3–7)×106 argon-ions and an RF amplitude of 340V, a short-pulsed beam with the duration of 30–35ns at FWHM was obtained after a quarter period of the synchrotron oscillation. [Copyright &y& Elsevier]

Abstract: High-density ion beams obtained by electron cooling will be used for medical and other applications at HIMAC. Cool-stacking injection was carried out with at to increase the intensity to a limit, which was determined by instabilities and by the ion lifetime. The maximum ion stack intensity was , above which fast-ion losses occurred simultaneously with vertical coherent oscillations. The instability depends on the working point, the ion stack density and secondary ions trapped in the cooler. The instability was damped by reducing the stacked ion density with transverse RF-excitation, and/or by clearing the secondary particles. [Copyright &y& Elsevier]

Abstract: We have studied the effect of synchrotron oscillations on the spill ripple in RF-knockout extraction, in order to investigate the ripple component of the synchrotron-oscillation frequency and to suppress this component. By using a simplified model of RF-knockout extraction and the simulation, it was found that the following conditions are essential for suppressing the spill ripple including the component of the synchrotron-oscillation frequency: (1) sufficient amplitude of the synchrotron oscillation and (2) uniform distribution in longitudinal phase-space. In the experiment at the Heavy Ion Medical Accelerator in Chiba (HIMAC) synchrotron, the debunch–recapture was carried out before the extraction to obtain the larger oscillation amplitude and the uniform distribution in the longitudinal phase-space. In this article, the contribution of the synchrotron oscillation to the spill ripple is described in detail. [Copyright &y& Elsevier]

Electron-cooling experiments have been carried out at the HIMAC-synchrotron in order to provide high-quality beams for medical and related research. For investigating the behavior of the free radicals, especially, the beam bunch was compressed by electron cooling with a triangle-wave RF-field. The dependences of the bunch length on the electron energy and the RF voltage were investigated under various intensities of Ar18+ beam. As a result, the bunch length was limited by around 20 ns due to the space-charge effect under an intensity of 1.33×106 ions/bunch and an RF amplitude of 340 V. [Copyright &y& Elsevier]

The time structure of extracted beams has been improved in synchrotron rings with resonant slow-extraction including RF-knockout extraction. In order to control the global spill structure in the RF-knockout slow-extraction method, it is necessary to improve the amplitude modulation (AM) function of the transverse RF-field. For this purpose, a scheme with a simple model of the extraction process has been proposed. Using this simple model, an analysis was carried out for determining the parameter relevant to the diffusion process in the separatrix. With this parameter, the new AM function obtained by the analytical approach could provide a flat spill within ±23% in both a simulation and an experiment at the HIMAC synchrotron. Cooperating with the feedback system, the global spill structure was significantly suppressed to be less than ±5%. [Copyright &y& Elsevier]

A resonant slow-extraction method from synchrotron rings has been successfully developed in order to deliver a beam for a period of over several seconds. In the resonant slow-extraction method, an optimization of the parameters is necessary in order to keep the beam size and position constant during the extraction for sufficient use of the extracted beam. For this purpose, a simple method to measure the outgoing separatrix was proposed and verified at the HIMAC synchrotron. In this method, two tantalum rods each with diameter of 1 mm are used as internal probes located near the extraction channel. By observing the extracted beam under the rods inserted into the ring, the outgoing separatrix can be measured. This technique will significantly contribute to the operation of a synchrotron employing resonant slow-extraction. [Copyright &y& Elsevier]

Electron-capture and -loss processes of fast highly charged ions colliding with residual-gas atoms and molecules in an accelerator are considered. A special attention is paid to the temporal variation of the ion-beam intensity while the ions are accelerated from the initial energy to the final higher energy with a constant acceleration rate. Interactions of C4+, Au53+ and U73+ ions in the MeV/u-energy regime with different residual-gas mixtures and pressures are considered in detail. Based upon the present analysis, the estimated cross sections and lifetimes of ions in the accelerators are favourably compared with the experimentally observed values. [Copyright &y& Elsevier]

Abstract Aims: Isolation and characterization of a transposon mutant of Pseudomonas aeruginosa affecting the uptake of dibenzothiophene (DBT) in n -tetradecane (n -TD). Methods and Results: The dsz desulphurization gene cluster from Rhodococcus erythropolis KA2-5-1 was transferred to the chromosome of P. aeruginosa NCIMB9571 using a transposon vector. A recombinant (named PARM1) was obtained which was able to desulphurize DBT in water, but not in n -TD. Conclusions: PARM1 is a mutant deficient in a DBT transport system operational in n -TD. This transport system is independent of rhamnolipids and of the n -alkane transport system. Significance and Impact of the Study: Pseudomonas aeruginosa NCIMB9571 seems to have a specific system of transporting hydrophobic compounds such as DBT in oil. [ABSTRACT FROM AUTHOR]

An irradiation method for spot scanning has been developed in order to provide accurate irradiation even for an irregular target shape. In spot scanning irradiation, the beam is turned off while the beam position is shifted to the next spot for precise dose management. Recently, the fast beam cut-off method, which can achieve a cut-off time of around 50 μs, was proposed and verified at the Heavy Ion Medical Accelerator in Chiba synchrotron. In order to utilize such a speciality of the technique for spot scanning, the characteristics of fast beam switching were investigated while turning on/off both the transverse and longitudinal RF fields many times during a single flattop. As a result, it was verified that this technique provides more than 50 spots during a single flattop in the synchrotron operation pattern with a cut-off time of 50 μs. With an increase in a switching number, the momentum spread and the size of the extracted beam increase within the allowable range for practical usage. [Copyright &y& Elsevier]

Background: Combination therapy with different classes of antihypertensive drugs often is needed to achieve controlled blood pressure (BP). The combination of an angiotensin II receptor antagonist (AIIA) and a calcium antagonist is a preferred option for reducing uncontrolled BP.Objective: The aim of this study was to assess the clinical efficacy and tolerability of nilvadipine, a dihydropyridine calcium antagonist, in combination with an AIIA.Methods: Patients with essential hypertension whose BP was not controlled by an AIIA alone were eligible for this multicenter, open-label, uncontrolled study. One of 3 AIIAs (candesartan cilexetil, losartan potassium, or valsartan) was given for at least 10 weeks before the addition of nilvadipine (daily dose, 4 or 8 mg orally). This combination therapy was given for 8 weeks. BP and heart rate were measured between 2 and 4 weeks before and 0, 4, and 8 weeks after the start of combination therapy. Adverse events were monitored at each visit.Results: Thirty-one patients (18 women [58.1%], 13 men [41.9%]; mean [SD] age, 58.5 [10.5] years) were enrolled. At weeks 4 and 8 of combination therapy, mean systolic BP (SBP) and diastolic BP (DBP) were significantly decreased (P<0.01) (at week 8, by 22.0 mm Hg and 12.5 mm Hg, respectively). The mean BP-lowering effect did not differ significantly between the 3 AIIAs tested. Pulse pressure also decreased significantly at week 8, by 9.6 mm Hg (P<0.01). The responder rate (ie, the percentage of patients with DBP <90 mm Hg or a decrease in DBP >/= 10 mm Hg) was 72.0% at week 8. Three patients experienced a total of 4 adverse events: mild or severe flushing, mild headache, and mild palpitation. All of these symptoms resolved after nilvadipine treatment was discontinued.Conclusions: Nilvadipine in combination with an AIIA showed good antihypertensive efficacy and was well tolerated in the hypertensive patients in this study. This combination also significantly decreased pulse pressure, suggesting that this combination therapy also may have a beneficial effect in elderly patients with isolated systolic hypertension. [ABSTRACT FROM AUTHOR]

Various electrochemical measurements were performed on titanium with and without culturing murine fibroblasts L929 to characterize the effects of cells on interface electrochemical properties between titanium and cells. Open-circuit potential of titanium decreased with L929 cells, which was caused by the shift of equilibrium potential between cathodic and anodic reactions indicated by the decrease in cathodic current density with L929 cells. In cathodic potential step test, the decrease in current density following to the peak current density was delayed with L929 cells, indicating that diffusivity of molecules and ions decreased with the cells. In addition, alternating current impedance measurement and data approximation to the electrical equivalent circuit model revealed that the circuit element for diffusion resistance of biomolecule adsorption layer increased with L929 cells. Consequently, the effect of cells on the interface property is the retardation of diffusion through the biomolecule adsorption layer due to the increase in biomolecule density with extracellular matrix consisting with proteins and glycosaminoglycans generated by the cells. [Copyright &y& Elsevier]

Two advanced RF-knockout (RF-KO) slow-extraction methods have been developed at HIMAC in order to reduce the spill ripple for accurate heavy-ion cancer therapy: the dual frequency modulation (FM) method and the separated function method. As a result of simulations and experiments, it was verified that the spill ripple could be considerably reduced using these advanced methods, compared with the ordinary RF-KO method. The dual FM method and the separated function method bring about a low spill ripple within standard deviations of around 25% and of 15% during beam extraction within around 2 s, respectively, which are in good agreement with the simulation results. [Copyright &y& Elsevier]

The RF-knockout (RF-KO) slow-extraction method with frequency modulation (FM) and amplitude modulation (AM) has brought high-accuracy irradiation to the treatment of a cancer tumor moving with respiration, because of a quick response to beam start/stop. However, a beam spill extracted from a synchrotron ring through RF-KO slow-extraction has a huge ripple with a frequency of around 1 kHz related to the FM. The spill ripple will disturb the lateral dose distribution in the beam scanning methods. Thus, the source of the spill ripple has been investigated through experiments and simulations. There are two tune regions for the extraction process through the RF-KO method: the extraction region and the diffusion region. The particles in the extraction region can be extracted due to amplitude growth through the transverse RF field, only when its frequency matches with the tune in the extraction region. For a large chromaticity, however, the particles in the extraction region can be extracted through the synchrotron oscillation, even when the frequency does not match with the tune in the extraction region. Thus, the spill structure during one period of the FM strongly depends on the horizontal chromaticity. They are repeated with the repetition frequency of the FM, which is the very source of the spill ripple in the RF-KO method. [Copyright &y& Elsevier]

Background: Nausea and vomiting induced by anticancer drugs cause considerable stress to patients and complicate drug administration and/or cause patients to refuse further courses of therapy. Oral antiemetics, such as ondansetron HCl, were developed to provide a wider selection of drugs to treat chemotherapy-induced nausea and vomiting. Ramosetron HCl oral preparation (intraoral disintegrator) was specially formulated to be taken without water. Studies have shown that ramosetron oral preparation has potent inhibitory effects on cisplatin-induced vomiting.Objective: This multicenter, randomized, parallel-design, double-blind comparative study examined the efficacy, tolerability, and usefulness of ramosetron oral preparation compared with ondansetron HCl oral preparation in inhibiting nausea/vomiting (including retching) induced by the anticancer drug cisplatin.Methods: Japanese inpatients aged >/= 20 years with cancer were eligible. Patients received either a single IV administration or

The interface reactions between materials and tissues must be understood to improve the corrosion resistance in vivo and biocompatibility of the materials. Then, we have developed a new electrolytic cell by which electrochemical measurement can be performed during culturing cells on specimen. Open-circuit potential (Eopen) and AC impedance of commercially pure titanium at Eopen were measured in a cell-culture medium with and without culturing murine fibroblasts L929 and in the medium without proteins. The biomolecule adsorption layer containing proteins and cells was formed on titanium oxide film and worked as a capacitor by preventing the diffusion of molecules. The cell enhanced this prevention. [Copyright &y& Elsevier]

Background: Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. In a phase 2 study of irinotecan plus cisplatin in patients with extensive small-cell lung cancer, there was a high response rate and a promising median survival time.Methods: We conducted a multicenter, randomized, phase 3 study in which we compared irinotecan plus cisplatin with etoposide plus cisplatin in patients with extensive (metastatic) small-cell lung cancer.Results: The planned size of the study population was 230 patients, but enrollment was terminated early because an interim analysis found a statistically significant difference in survival between the patients assigned to receive irinotecan and cisplatin and those assigned to receive etoposide and cisplatin; as a result, only 154 patients were enrolled. The median survival was 12.8 months in the irinotecan-plus-cisplatin group and 9.4 months in the etoposide-plus-cisplatin group (P=0.002 by the unadjusted log-rank test). At two years, the proportion of patients surviving was 19.5 percent in the irinotecan-plus-cisplatin group and 5.2 percent in the etoposide-plus-cisplatin group. Severe or life-threatening myelosuppression was more frequent in the etoposide-plus-cisplatin group than in the irinotecan-plus-cisplatin group, and severe or life-threatening diarrhea was more frequent in the irinotecan-plus-cisplatin group than in the etoposide-plus-cisplatin group.Conclusions: Irinotecan plus cisplatin is an effective treatment for metastatic small-cell lung cancer. [ABSTRACT FROM AUTHOR]

Detection of donor-derived cell-free DNA (dd-cfDNA) in circulating blood of posttransplant recipients is a clinically informative tool to predict acute allograft injury and rejection, although its reliability and feasibility have not been extensively studied in lung transplantation. Here, we present our preliminary data of dd-cfDNA in lung transplant patients during the early posttransplant phase. Eight subjects were included in this study among patients received double lung transplants at our institute between Jun.-Sept. 2020. Re-transplantation cases were excluded per the study protocol. Blood samples were collected at various times from these consented patients before and after transplantation. Dd-cfDNA in obtained blood samples were determined using AlloSure dd-cfDNA test kits (CareDx, Inc). Of the 8 subjects, none developed severe primary graft dysfunction and two patients presented acute cellular rejection (ACR) after lung transplantation. All subjects exhibited increased dd-cfDNA immediately after transplantation with a peak percentage of dd-cfDNA (range 12-27%) within 48h posttransplant. (Figure 1). Over 2 weeks, dd-cfDNA percentage declined with significant variation reaching a similar level of <5%, although patients with severe systemic conditions displayed an overall lower percentage of circulating dd-cfDNA versus recipient derived cfDNA. One patient with early ACR and early spike in donor specific antibodies (DSA) showed a relative slower decline in dd-cfDNA than the ACR alone case. To our knowledge, this is the first report of acute time-dependent changes of dd-cfDNA in patients immediately after lung transplantation. Our preliminary data suggest that recipients' systemic condition may mask the appearance of dd-cfDNA. Additional information regarding circulating whole cfDNA in patients may assist in more accurate detection of dd-cfDNA in the acute phase. [ABSTRACT FROM AUTHOR]