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

Increased IP-10 production by blood–nerve barrier in multifocal acquired demyelinating sensory and motor neuropathy and multifocal motor neuropathy

Objective Dysfunction of the blood–nerve barrier (BNB) plays important roles in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). The aim of the present study was to identify the candidate cytokines/chemokines that cause the breakdown of the BNB using sera from patients with CIDP and MMN. Methods We determined the levels of 27 cytokines and chemokines in human peripheral nerve microvascular endothelial cells (PnMECs) after exposure to sera obtained from patients with CIDP variants (typical CIDP and multifocal acquired demyelinating sensory and motor neuropathy [MADSAM]), MMN and amyotrophic lateral sclerosis (ALS), and healthy controls (HC), using a multiplexed fluorescent bead-based immunoassay system. Results The induced protein (IP)10 level in the cells in both the MADSAM and MMN groups was markedly increased in comparison with the typical CIDP, ALS and HC groups. The other cytokines, including granulocyte colony-stimulating factor, vascular endothelial growth factor (VEGF) and interleukin-7, were also significantly upregulated in the MADSAM group. The increase of IP-10 produced by PnMECs was correlated with the presence of conduction block in both the MADSAM and MMN groups. Conclusion The autocrine secretion of IP-10 induced by patient sera in PnMECs was markedly upregulated in both the MADSAM and MMN groups. The overproduction of IP-10 by PnMECs leads to the focal breakdown of the BNB and may help to mediate the transfer of pathogenic T cells across the BNB, thereby resulting in the appearance of conduction block in electrophysiological studies of patients with MADSAM and MMN

Violation of Kohler's Rule in the Magnetoresistance near the Lower Charge-Density-Wave Instability in NbSe 3

This paper reports the measurements of resistance (R) and magnetoresistance of NbSe 3 near the critical pressure (P c ¼ 7:5 kbar), where the lower charge-density-wave (CDW) phase is on the verge of destruction. For P ¼ 7:6 kbar, the temperature dependence of dR=dT exhibits a weak anomaly at T Ã ¼ 15 K and the superconducting transition is observed at T c ¼ 2:8 K. From the observation of a large magnetoresistance due to an imperfect nesting of Fermi surface, we show that the weak anomaly is closely related to the lower CDW phase. Moreover, an excess conductance and violation of Kohler's rule are found below $T Ã . The origins of the excess conductance and the violation of Kohler's rule are discussed in terms of charge fluctuation associated with the lower CDW state

Progress in the beginning stage of new reclamation work in early 19th-century Kashobara, in the southern part of Saijo Basin, Higashi-Hiroshima City, southwestern Japan: Analysis of “Kokugunshi-goyo-kakiagecho, Kamo-gun Kashobara”

本稿は，「国郡志御用書上帳　賀茂郡柏原　ひかへ」の分析を通して，19世紀初頭の東広島市西条盆地南部，柏原における新田開発初期の進捗過程の詳細を明らかにすることを目的とする。本史料は，1825（文政8）年に広島藩の地誌書として完成した『芸藩通誌』の編纂材料として，領内各郡村から藩へ提出された調査報告書である。開発の特徴として，1）入植を伴う新田開発は，広島藩からの指示によって始まったが，水利施設の増築という入植者からの要望が，割庄屋を通して藩へ申し入れられ，それが叶えられていること，2）入植者を増やす方策として，藩が入植者を経済的に支援し，年貢の免除や軽減を認めていることなど，入植者に配慮した藩の手厚い対応が垣間見られた。また，本稿では，水利施設に関する記載内容の合理的な解釈を，絵図や現実の地形条件に基づいて行った。文献史料と絵図・地形図などを組み合わせて活用する方法をとることで，当時の様子を精緻に再現できたところに，分野横断型の研究手法の意義を見出すことができた。We discuss progress during the beginning stage of new reclamation work in early 19th-century Kashobara, in the southern part of Saijo Basin, Higashi-Hiroshima City, through interpretation of the historical document “Kokugunshigoyo-kakiagecho, Kamo-gun Kashobara.” The document is a copy of a report wherein county leaders (Warijoya) wrote geographical descriptions of each village in their county as of the early 19th century, at the order of the Hiroshima Domain; then, in 1825, the Domain compiled the reports as a book entitled “Geihantushi.” This study highlights that 1) the Domain ordered local villagers to engage in reclamation work in local neighborhoods, while villagers demanded through the county leaders that the Domain build irrigation facilities for growing rice (such as ponds and canals), which the Domain agreed to and provided financial support for; and 2) the Domain further supported poor newcomers by reducing their taxes. This case reveals that the Domain treated the local people in the county with kindness, whereas many other Domains were well-known to have ruled farmers heavy-handedly. Although it is difficult to understand some complicated descriptions in the document, such as concerning embankments of the irrigation ponds, we can arrive at reasonable reconstructions by interpreting old drawings and considering the actual topography. This research is a good example of the advantages of cross-disciplinary methods

A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease

Background: Kawasaki disease (KD) is a systemic vasculitis which may be associated with coronary artery aneurysms. A notable risk factor for the development of coronary artery aneurysms is resistance to intravenous immunoglobulin (IVIG) therapy, which comprises standard treatment for the acute phase of KD. The cause of IVIG resistance in KD is largely unknown; however, the contribution of genetic factors, especially variants in immune-related genes, has been suspected. Methods: To explore genetic variants related to IVIG-unresponsiveness, we designated KD patients who did not respond to both first and second courses of IVIG therapy as IVIG-unresponsive patients. Using genomic DNA from 30 IVIG-unresponsive KD patients, we performed pooled genome sequencing targeting 39 immune-related cytokine receptor genes. Results: The single nucleotide variant (SNV), rs563535954 (located in the IL4R locus), was concentrated in IVIG-unresponsive KD patients. Individual genotyping showed that the minor allele of rs563535954 was present in 4/33 patients with IVIG-unresponsive KD, compared with 20/1063 individuals in the Japanese genome variation database (odds ratio = 7.19, 95% confidence interval 2.43-21.47). Furthermore, the minor allele of rs563535954 was absent in 42 KD patients who responded to IVIG treatment (P = 0.0337), indicating that a low-frequency variant, rs563535954, is associated with IVIG-unresponsiveness in KD patients. Although rs563535954 is located in the 3'-untranslated region of IL4R, there was no alternation in IL4R expression associated with the mior allele of rs563535954. However, IVIG-unresponsive patients that exhibited the minor allele of rs563535954 tended to be classified into the low-risk group (based on previously reported risk scores) for prediction of IVIG-resistance. Therefore, IVIG-unresponsiveness associated with the minor allele of rs563535954 might differ from IVIG-unresponsiveness associated with previous risk factors used to evaluate IVIG-unresponsiveness in KD. Conclusion: These findings suggest that the SNV rs563535954 could serve as a predictive indicator of IVIG-unresponsiveness, thereby improving the sensitivity of risk scoring systems, and may aid in prevention of coronary artery lesions in KD patients.ArticlePEDIATRIC RHEUMATOLOGY.17:34(2019)journal articl

The clinical utility of a one-shot energy subtraction method for thoracic spine radiography

Background: The interpretation of thoracic spine X-rays is difficult because these images cannot clearly visualize the thoracic spine because of the overlap with soft tissues, such as the heart and pulmonary blood vessels. Thus, to improve the clarity of thoracic spine radiographs using existing radiograph equipment, we have investigated a one-shot energy subtraction method to visualize thoracic spine radiographs. Our objective was to evaluate whether the thoracic spine radiographs generated using this method could visualize the spine more clearly than the corresponding original thoracic spine radiographs. Methods: This study included 29 patients who underwent thoracic spine radiographs. We used a one-shot energy subtraction method to improve the clarity of thoracic spine radiographs. Image definition was evaluated using vertebrae sampled from each region of the thoracic spine. Specifically, these were: Th1, Th5, Th9, and Th12. Image definition was assessed using a three-point grading system. The conventional and processed computed radiographs (both frontal and lateral views) of all 29 study patients were evaluated by 5 spine surgeons. Results: In all thoracic regions on both frontal and lateral views, the processed images showed statistically significantly better clarity than the corresponding conventional images, especially at all sampling sites on the frontal view and T5 and 9 on the lateral view. Conclusions: Thoracic spine radiographs generated using this method visualized the spine more clearly than the corresponding original thoracic spine radiographs. The greatest advantages of this image processing technique were its ability to clearly depict the whole thoracic spine on frontal views and the middle thoracic spine on lateral views. © 2012 The Japanese Orthopaedic Association