MODELING OF SPACE-CHARGE-LIMITED CURRENT INJECTION INCORPORATING AN ADVANCED MODEL OF THE POOLE-FRENKEL EFFECT

The current flow due to Space-Charge-Limited (SCL) emission is well known and the associated current-voltage power law relationship can be observed in many materials, particularly in insulators and semiconductors. Under an applied field, the space-charge effect occurs due to the carrier injection, and the resulting current due to the presence of the space-charge effect is referred to as SCL current. In the SCL current theory, the presence of localized traps in a material has a significant effect on the transport of injected carriers; however, in the first order SCL model, the trap barrier height is assumed to be constant for any applied field. According to the theory of the Poole-Frenkel (PF) effect, the barrier height is lowered in the presence of an electric field. The PF effect, which is also a well known conduction mechanism, is the thermal emission of charge carriers from Coulombic traps in the bulk of a material enhanced by an applied field. When an electric field is applied, the potential barrier on one side of the traps is reduced, and due to this barrier lowering, the thermal emission rate of electrons from the traps is increased. Since the presence of traps has a significant effect on the SCL current, the barrier lowering due to the PF effect needs to be incorporated into the SCL model. The incorporation of the PF effect into the SCL model has been accomplished already; however, the classical PF model was used. The classical PF model is based on the Boltzmann approximation for defining the trapped carrier concentration, which fails to predict the saturation of carrier emission once the trap barrier height has been reduced to the ground state. Therefore, the classical PF model leads to erroneous results at high fields, which is where it typically becomes significant. A more physically accurate model, which is referred to as the modern PF model, has been introduced by using the Fermi-Dirac distribution function to define the trapped carrier concentration. The modern PF model can predict PF saturation, and therefore, this model yields more accurate predictions at high fields. In this research, an SCL current model incorporating a modern PF model was derived and analyzed. The SCL model incorporating the classical PF model predicts a current enhancement due to the PF effect; however, it predicts a continuous, gradual increase in the current with voltage for all applied fields, which is unphysical. According to the first order SCL current theory, the SCL current-voltage characteristics shift from the shallow-trap field region to the trap-free-square law region at a transition field. At this transition field, the current increases very sharply for a small change in voltage, which is referred to as the Trap-Filled-Limit (TFL) law. By incorporating the modern PF model, not only does the model predict a higher current level, but the model also predicts a vertical asymptote in the current-voltage characteristics, and this asymptote occurs at the TFL law. A more advanced SCL model was also derived by incorporating the modern PF model and using the exact Poisson equation. The two models discussed above, the SCL models incorporating the classical and modern models of the PF effect, used an approximation in the Poisson equation. By using the exact Poisson equation, instead of the model asymptotically approaching infinity at the TFL law, it predicts a proper transition from the shallow-trap SCL region to the trap-free-square law region. Also, when the PF saturation field is lower than the TFL law, this transition occurs at the PF saturation field instead at the TFL law

Adversarial Example Generation using Evolutionary Multi-objective Optimization

This paper proposes Evolutionary Multi-objective Optimization (EMO)-based Adversarial Example (AE) design method that performs under black-box setting. Previous gradient-based methods produce AEs by changing all pixels of a target image, while previous EC-based method changes small number of pixels to produce AEs. Thanks to EMO's property of population based-search, the proposed method produces various types of AEs involving ones locating between AEs generated by the previous two approaches, which helps to know the characteristics of a target model or to know unknown attack patterns. Experimental results showed the potential of the proposed method, e.g., it can generate robust AEs and, with the aid of DCT-based perturbation pattern generation, AEs for high resolution images

Effects of Small Addition of Ti on Strength and Microstructure of a Cu-Ni-Si Alloy

The effect of addition of 0.04 or 0.2 mass pct Ti on the mechanical properties of a Cu-2.0 mass pct Ni-0.5 mass pct Si alloy has been investigated. The addition of 0.04 mass pct Ti enhances the strength of the Cu-Ni-Si alloy without reducing its electrical conductivity. This increase in strength is caused by the decrease in inter-precipitate spacing of δ-Ni2Si precipitates. The addition of trace Ti reduces the equilibrium concentration of Ni and Si atoms in the alloy bearing the δ precipitates, resulting in an increase in the volume fraction of δ precipitates and decrease in the inter-precipitate spacing. However, the addition of 0.2 mass pct Ti to the Cu-Ni-Si alloy decreases the strength of the alloy. The reduction in strength is attributed to the decrease in the volume fraction of δ precipitates caused by the reduction in Ni and Si atoms in the Cu matrix resulting from the formation of Ni16Si7Ti6 particles. © 2015 The Minerals, Metals & Materials Society and ASM Internationa

Wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase, induces accumulation of DNA double-strand breaks

Wortmannin, a fungal metabolite, is a specific inhibitor of the phosphatidylinositol 3-kinase (PI3K) family, which includes double-stranded DNA dependent protein kinase (DNA-PK) and ataxia telangiectasia mutated kinase (ATM). We investigated the effects of wortmannin on DNA damage in DNA-PK-deficient cells obtained from severe combined immunodeficient mice (SCID cells). Survival of wortmannin-treated cells decreased in a concentration-dependent manner. After treatment with 50 μM wortmannin, survival decreased to 60% of that of untreated cells. We observed that treatment with 20 and 50 μM wortmannin induced DNA damage equivalent to that by 0.37 and 0.69 Gy, respectively, of γ-ray radiation. The accumulation of DNA double-strand breaks (DSBs) in wortmannin-treated SCID cells was assessed using pulsed-field gel electrophoresis. The maximal accumulation was observed 4 h after treatment. Moreover, the presence of DSBs was confirmed by the ability of nuclear extracts from γ-ray-irradiated SCID cells to produce in vitro phosphorylation of histone H2AX. These results suggest that wortmannin induces cellular toxicity by accumulation of spontaneous DSBs through inhibition of ATM

イソプロテレノール誘導肥大心においてNHE-1阻害薬は、ラット左心室の筋スライスのCa2+トランジェントを正常化する

We previously reported that left ventricular (LV) slices from isoproterenol (ISO)-induced hypertrophied rat hearts showed an increase of energy expenditure due to remodeling of Ca2+ handling in excitation–contraction coupling, i.e., suppressed SERCA2a activity and enhanced Na+/Ca2+exchanger-1 (NCX-1) activity. Na+/H+ exchanger-1 (NHE-1) inhibitor (NHEI) has been demonstrated to exert beneficial effects in the development of cardiac remodeling. We hypothesized that a novel NHE-1 selective inhibitor, BIIB723 prevents remodeling of Ca2+ handling in LV slices of ISO-induced hypertrophied rat hearts mediated by inhibiting NCX-1 activity. The significant shortening in duration of multi-cellular Ca2+ transient in ISO group was normalized in ISO + BIIB723 group. The significant increase in amplitude of multi-cellular Ca2+ waves (CaW) generated at high [Ca2+]o of LV slices in ISO group was also normalized in ISO + BIIB723 group. However, the enhanced NCX-1 activity was not antagonized by BIIB723. We recently reported that ISO-induced down-regulation of a Ca2+ handling protein, SERCA2a, was normalized by BIIB723. Therefore, it seems likely that BIIB723 normalized shortened multi-cellular Ca2+ transient duration and increased CaW amplitude in LV slices mediated via normalization of SERCA2a activity. Furthermore, the results presented here suggest the multi-cellular Ca2+ transient duration and CaW amplitude in LV slices might be better indices reflecting SERCA2a activity than SERCA2a protein expression level.博士（医学）・甲618号・平成26年3月17

Mast cells promote the growth of Hodgkin's lymphoma cell tumor by modifying the tumor microenvironment that can be perturbed by bortezomib

名古屋大学Nagoya University博士(医学)Hodgkin's lymphoma is frequently associated with mast cell infiltration that correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear. Here, we report that mast cells promote the growth of Hodgkin's tumor by modifying the tumor microenvironment. A transplantation assay shows that primary murine mast cells accelerate tumor growth by established Hodgkin's cell lines, and promote marked neovascularization and fibrosis. Both mast cells and Hodgkin's cells were sensitive to bortezomib, but mast cells were more resistant to bortezomib. However, bortezomib inhibited degranulation, PGE2-induced rapid release of CCL2, and continuous release of vascular endothelial growth factor-A from mast cells even at the concentration that did not induce cell death. Bortezomib-treated mast cells lost the ability to induce neovasculization and fibrosis, and did not promote the growth of Hodgkin tumor in vivo. These results provide further evidence supporting causal relationships between inflammation and tumor growth, and demonstrate that bortezomib can target the tumor microenvironment.名古屋大学博士学位論文 学位の種類 : 博士(医学)(課程) 学位授与年月日:平成25年3月25日 水野紘樹氏の博士論文として提出されたdoctoral thesi

Comparative study on antioxidative and macrophage-stimulating activities of polyguluronic acid (PG) and polymannuronic acid (PM) prepared from alginate

The antioxidant and macrophage-stimulating activities of polyguluronic acid (PG) and polymannuronic acid (PM) prepared from alginate were examined. A chemiluminescence (CL) method using a luminol analog, L-012, showed that both PM and PG scavenge superoxide produced by hypoxanthine–xanthine oxidase system in a concentration-dependent manner. At 100 μg/ml, PG showed slightly stronger superoxide scavenging activity than PM. In an electron spin resonance (ESR)-spin trapping method in which the Fenton reaction was used as hydroxyl radical generation system, we found that both PM and PG showed potent hydroxyl radical scavenging activity to a similar extent. Because PM and PG showed no chelating activity on Fe2+, it was confirmed that PM and PG can directly scavenge hydroxyl radical. No significant scavenging activity of PM and PG toward hydrogen peroxide was observed. Interestingly, the macrophage-stimulation activity of PG as measured by nitric oxide (NO)-production from mouse macrophage cell line RAW264.7 cells was evidently stronger than that of PM. Our results suggest that RAW264.7 cells might be able to distinguish the conformational differences between PM and PG, and respond differently to them, whereas the effects of such structural differences between PM and PG on the radical scavenging activities may not be so significant

Evaluation of the advantage of surgeons certified by the endoscopic surgical skill qualification system participating in laparoscopic low anterior rectal resection

Background: A technical qualification system was developed in 2004 by the Japan Society for Endoscopic Surgery. An analysis of the EnSSURE study on 3188 stage II–III rectal cancer patients, which was performed by including the participation of qualified surgeons as assistants and advisers without restricting their participation as operators, revealed that the participation of technically qualified surgeons in surgery improved the technical and oncological safety of laparoscopic rectal resection.Aim: This secondary retrospective analysis of the EnSSURE study examined the advantage of qualified surgeons participating in laparoscopic low anterior resection (LAR).Methods: The outcomes of low anterior resection were compared between groups with and without the participation of surgeons qualified by the Endoscopic Surgical Skill Qualification System (Q and non-Q groups, respectively). We used propensity score matching to generate paired cohorts at a one-to-one ratio. The postoperative complication rate, short-term results (hemorrhage volume, operative time, number of dissected lymph nodes, open conversion rate, intraoperative complication rate, and R0 resection rate), and long-term results (disease-free survival rate, local recurrence rate, and overall survival rate) were evaluated.Results: The frequencies of postoperative complications, anastomotic bleeding, and intraperitoneal abscess were significantly lower, the operative time was significantly shorter, the postoperative hospital stay was significantly shorter, and the number of dissected lymph nodes was higher in the Q group. No significant differences were observed in disease-free survival, local recurrence, or overall survival rate rates between the groups.Conclusion: The participation of qualified surgeons in LAR is technically advantageous

Doping Dependence of Upper Critical Field of High-Tc Cuprate Bi2+xSr2−xCaCu2O8+δ Estimated from Irreversibility Field at Zero Temperature

We investigated the temperature (T) dependence of the irreversibility field Hirr(T) in high-critical-temperature cuprate Bi2+xSr2−xCa1−yYyCu2O8+δ (Bi-2212) single crystals over a wide range of hole doping level (p). Hirr(T) was evaluated by measuring the magnetization hysteresis loop. The value of Hirr(T) extrapolated to T = 0 K [Hirr(0)], is either equal to or sets the lower boundary for the upper critical field at T = 0 K [Hc2(0)]. Tc shows a parabolic p-dependence (peak at p = 0.16), whereas μ0Hirr(0) increases monotonically with p by approximately one order of magnitude, from 19 T for the most underdoped sample (p = 0.065, Tc = 24 K) to 209 T for the most overdoped sample (p = 0.200, Tc = 75 K). The present results qualitatively agree with Hc2(0) values evaluated from the specific heat measurements. The observed p-dependence of Hirr(0) in Bi-2212 is distinct from those in YBa2Cu3O7−δ and HgBa2CuO6+δ, in which a pronounced dip structure appears in the underdoped region. Considering that the dip structures observed in these two systems are likely associated with the formation of competing orders (most likely field-induced charge orders), the present results indicate that the influence of the competing order in Bi-2212 is less prominent than that in the other two systems.journal articl