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In this paper, we propose a simulation framework to assess systemic risk in over-the-counter derivatives markets. We incorporate credit valuation adjustment (CVA), a mark-to-market estimate of counterparty credit risk booked on a bank’s balance sheet, into an otherwise standard structural model of credit risk. In this model, banks optimally hedge CVA by trading a credit default swap (CDS). The model aims to capture a possible adverse effect called “CDS–CVA feedback loop” from CVA hedging, which could increase CDS spreads due to a lack of liquidity in CDS markets and even further increase CVA because CVA is valued using the default probability extracted from CDS spreads. In order to measure systemic counterparty credit risk, we aggregate CVA across banks and examine how the distribution of systemic counterparty credit risk changes depending on underlying model parameters. We document that the tail risk of CVA increases nonlinearly when the liquidity of CDS markets declines. As an extension, we also model cost of posting collateral and discuss the trade-off between reducing systemic counterparty credit risk, stability of CDS markets and collateral cost.

The rising of thin-film-based plasmonic electro-optic (EO) devices triggers considerable exploitation of ferroelectric oxide thin films with large EO response. In this study, epitaxial (001)-orientated Ni-doped K(Ta0.6Nb0.4)O3 (KTN) films were fabricated on SrRuO3/SrTiO3 substrates via pulsed laser deposition. In comparison with a pure KTN film, a larger withstand electric field was achieved by Ni doping. The EO measurements revealed that the doping of Ni ions induced a decrease in the effective EO coefficient. Instead, the variation of refractive index by the applicable maximum electric field was increased due to the increment of withstand electric field, particularly for the case of 2% Ni dopant.

With the recent rise of HTTPS adoption on the Web, attackers have begun "HTTPSifying" phishing websites. HTTPSifying a phishing website has the advantage of making the website appear legitimate and evading conventional detection methods that leverage URLs or web contents in the network. Further, adopting HTTPS could also contribute to generating intrinsic footprints and provide defenders with a great opportunity to monitor and detect websites, including phishing sites, as they would need to obtain a public-key certificate issued for the preparation of the websites. The potential benefits of certificate-based detection include (1) the comprehensive monitoring of all HTTPSified websites by using certificates immediately after their issuance, even if the attacker utilizes dynamic DNS (DDNS) or hosting services; this could be overlooked with the conventional domain-registration-based approaches; and (2) to detect phishing websites before they are published on the Internet. Accordingly, we address the following research question: How can we make use of the footprints of TLS certificates to defend against phishing attacks? For this, we collected a large set of TLS certificates corresponding to phishing websites from Certificate Transparency (CT) logs and extensively analyzed these TLS certificates. We demonstrated that a template of common names, which are equivalent to the fully qualified domain names, obtained through the clustering analysis of the certificates can be used for the following promising applications: (1) The discovery of previously unknown phishing websites with low false positives and (2) understanding the infrastructure used to generate the phishing websites. We use our findings on the abuse of free certificate authorities (CAs) for operating HTTPSified phishing websites to discuss possible solutions against such abuse and provide a recommendation to the CAs.

In this paper, I investigate how the relationship between safe haven assets and the US stock market has changed since the global financial crisis. To do so, I propose a new concept of bear-market correlation which allows us to see the effectiveness of the safe haven asset as a hedge and portfolio diversification tool. I compute the bear-market correlation of five safe haven assets during two sample periods, pre-financial crisis (1995–2009) and post-financial crisis (2010–2018). My findings are as follows: First, I find that the empirical bear-market correlations are not explained by multivariate normal and t-distributions. Second, I document that the bear-market correlations of both the Japanese yen and gold show notable changes after the crisis. Third, I estimate a multivariate normal mixture, a multivariate t-distribution mixture, and a generalized dynamic conditional correlation model. I document that these mixture models outperform the dynamic conditional correlation model in most cases. Finally, I discuss the economic impact of failing to capture the bear-market correlation for portfolio optimization.

The clinical efficacy of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been demonstrated in ALK fusion-positive non-small cell lung cancer (NSCLC); however, brain metastases are frequent sites of initial failure in patients due to poor penetration of the central nervous system by crizotinib. Here, we examined the efficacy of a selective ALK inhibitor alectinib/CH5424802 in preclinical models of intracranial tumors.We established intracranial tumor implantation mouse models of EML4-ALK-positive NSCLC NCI-H2228 and examined the antitumor activity of alectinib in this model. Plasma distribution and brain distribution of alectinib were examined by quantitative whole-body autoradiography administrating a single oral dose of (14)C-labeled alectinib to rats. The drug permeability of alectinib was evaluated in Caco-2 cell.Alectinib resulted in regression of NCI-H2228 tumor in mouse brain and provided a survival benefit. In a pharmacokinetic study using rats, alectinib showed a high brain-to-plasma ratio, and in an in vitro drug permeability study using Caco-2 cells, alectinib was not transported by P-glycoprotein efflux transporter that is a key factor in blood-brain barrier penetration.We established intracranial tumor implantation models of EML4-ALK-positive NSCLC. Alectinib showed potent efficacy against intracranial EML4-ALK-positive tumor. These results demonstrated that alectinib might provide therapeutic opportunities for crizotinib-treated patients with brain metastases.

The reclaimed wastewater quality in 34 treatment facilities of combined household wastewater for individual houses were investigated in the rural area in Ehime Prefecture, in Japan. The results showed that saline concentrations in the reclaimed wastewater were varied in each facility. Temporal and seasonal variations of the concentrations will be relatively small. Under the reclaimed wastewater reuse for gardens, the risks of Ca2+, Mg2+, Cl-, SO42- for plant growth will be low. However, the risk of high concentration of EC, Na+, K+ can lead some problem for plant growth or soil permeability. We should respond appropriately to the risks.

The reclaimed wastewater quality in 34 treatment facilities of combined household wastewater for individual houses were investigated in the rural area in Ehime Prefecture, in Japan. The mean concentrations of Cd, Cr, Pb, Ni, Cu, Zn, Fe, Mn were

The reclaimed wastewater quality in 39 treatment facilities of combined household wastewater for individual houses were investigated in the rural area in Ehime Prefecture, in Japan. The mean values of SS·BOD·COD·T-P·T-N were 8.70mg·L-1, 12.0mg·L-1, 25.3mg·L-1, 3.69mg·L-1, 23.6mg·L-1, respectively. The SS·BOD·T-N concentrations decreased when the return flow devices were continuously operated. The COD·T-N concentrations decreased when it was shorter period since the cleaning, including back washing and sludge carry out. Based on the results, the availability, limitation and the key of the better management practices of the treatment systems to the water quality conservation in Japanese rural area were also discussed.

Our previous studies showed that the mRNA level of human organic anion transporter (hOAT) 3 in the kidney was correlated with the rate of elimination of an anionic antibiotic cefazolin. However, the correlation coefficient was not so high. In the present study, therefore, we enrolled more patients to examine whether additional factors were responsible for the correlation. hOAT mRNA levels in renal biopsy specimens were quantified using the real-time polymerase chain reaction method. The elimination rates for the free fraction of cefazolin were determined in patients with various renal diseases. In the present study, the coefficient of correlation between the hOAT3 mRNA level and the elimination rates for the free fraction of cefazolin was not so high in the patients overall as in our previous study (r = 0.536). However, following the classification of renal diseases, a better correlation was obtained in patients with mesangial proliferative glomerulonephritis (r = 0.723). In contrast, multiple regression analyses including gender, age, and liver function did not result in any improvements in the correlation coefficients. These results suggest that the hOAT3 mRNA level is a significant marker of pharmacokinetics with which to predict the rate of elimination of cefazolin in patients with mesangial proliferative glomerulonephritis.

In this paper, we propose a simulation framework to assess the risk of financial contagion in over-the-counter (OTC) derivatives markets. We incorporate Credit Valuation Adjustment (CVA), a mark-to-market estimate of counterparty credit risk booked in a bank's balance sheet, into a model of interbank network. In this simulation framework, a bank can make a margin call and purchase protection in credit default swap (CDS) markets in order to reduce CVA. We also model the adverse market impacts in CDS markets where the bank's CVA hedging increases CDS spreads due to the lack of liquidity. A financial shock propagates through the interbank linkage of CVA and banks' CDS markets. Utilizing this simulation framework, we study the impact of four different shocks on the financial soundness of banks in the OTC derivatives markets: a large loss from a credit portfolio, a large loss from a derivative trade, a market-wide haircut rate change and a downgrade trigger. We also analyze whether and to what extent the introduction of central clearing party (CCP) attenuates the negative effect of CVA hedging on the financial stability. Our simulation results highlights the importance of understanding collateral management at bank level to assess a potential contagious risk in the OTC derivatives markets.

A phase-separated monolayer of a binary mixture of pyrene-labeled poly(isobutyl methacrylate) (PiBMA-Py) and perylene-labeled poly(octadecyl methacrylate) (PODMA-Pe) was investigated by the fluorescence scanning near-field optical microscope (SNOM), which provided optical images of samples with a high resolution beyond the diffraction limit, by using evanescent field from an aperture smaller than the wavelength of light. Each phase of the PiBMA-Py/PODMA-Pe was selectively imaged as a bright area by choosing the excitation wavelength (325- or 442-nm line of a He−Cd laser). The fluorescence SNOM enabled mapping of the excitation energy transfer efficiency on the monolayer plane. The energy transfer measurement revealed that the phase separation of the PiBMA-Py/PODMA-Pe blend at the air/water interface was almost completed by annealing for 60 min at 40 °C and the phase boundary had a width of a few hundred nanometers.

ポリイソブチルメタクリレート (PiBMA) とポリオクタデシルメタクリレート (PODMA) が形成する混合単分子膜の相分離構造をBrewster角顕微鏡 (BAM), 原子間力顕微鏡 (AFM) を用いて観察した. 下層水温20℃で混合単分子膜を作製すると, PODMAの結晶性のため, 展開時の相分離構造が微小な網目構造として保持されることがわかった. また, 40℃でアニーリングを行うことによって, PODMAが融解して相分離が進行し, 二次元平面内で完全に分離したドメイン構造をとることがわかった.

The influence of variations in the availability of soil moisture, with or without mulches, on the evapotranspiration (ET), yield and water use efficiency (WUE) was investigated using wheat as a test crop, growing in Wagnar pots (1/2000a). Three soil moisture conditions as pF1.8, pF2.5 and pF 1.8-2.8 with no or straw or vinyl mulch was imposed on the wheat, variety Omase. Seasonal total and mean ET varied among the soil moisture conditions and mulch types. The highest ET was observed at pF1.8-2.8 without mulch. Mulch efficiently conserved moisture suppressing soil evaporation. ET increased from the tillering to the panicle initiation stages, remained similar till the dough stage and decreased up to maturity. Eliminating the influences of meteorological factors, the ET/Epan ratio was calculated and showed that the ratio increased from tillering to panicle initiation and decreased gradually in the following stages. Continuous wet conditions with excess moisture at pF1.8 hampered root growth, affected crop performance and resulted in a reduced ET, yield, harvest index (HI) and WUE. At pF1.8 and pF2.5 more grains per panicle and bolder grains contributed to the relatively higher grain yield with straw mulch while at pF1.8-2.8 bolder grains contributed to the highest grain yield under the no mulch condition. Dry matter yield (DMY) reduced under the dry condition at pF 2.5 compared to the standard condition (pF 1.8-2.8). Use of mulch decreased DMY under dry condition at pF 2.5 relative to the ideal irrigation condition, but increased the WUE reducing ET. HI decreased under wet or dry conditions but use of mulch improved the HI. However, the continuous wet conditions reduced the effectiveness of moisture and at pF 1.8-2.8 with or without mulches were conducive for increased WUE. These results may be useful for the appropriate husbandry of the limited soil moisture, where soil moisture is the principal source of water for cropping in the water shortage areas.

Rehypothecation is the practice where a derivatives dealer reuses collateral posted from its end user in over-the-counter (OTC) derivatives markets. Although rehypothecation benefits the end user through cost reduction of derivative trades, it also creates additional counterparty credit risk since the end user may not receive the collateral back when the dealer suddenly defaults. To evaluate the benefits and risks of rehypothecation, we propose a derivative pricing framework with bilateral counterparty credit risk that determines the amount of rehypothecable collateral. We also model the realistic features of derivative trades: two different types of collateral, the time delay of collateral posting and the rating-dependent collateral agreement. We apply our pricing framework to cross currency swaps and investigate the impact of rehypothecation on the swap spreads.

L-Leucyl-L-leucine methyl esters (LeuLeuOMe) is a lysosomotropic agent that induces apoptosis of certain immune cells. Glucose-carrying 2-nitrobenzyl (2-NB) and 2-nitrophenethyl (2-NPE) caged LeuLeuOMe, 1a and b, were synthesized and their photochemical and immunological properties were studied. Caged glycine methyl esters (GlyOMe), 2a,b, were also prepared to examine the cytotoxic activity of the photolytic byproducts from 1a,b. All the caged compounds were soluble in PBS containing 1% DMSO more than 400 microM, and efficiently released the substrates upon irradiation at 350 nm. While both 1a and 1b were not toxic to HL60 cells, 1b released LeuLeuOMe more quickly and induced apoptosis of HL60 cells far more efficiently than 1a. Although GlyOMe was not cytotoxic, 2a and b were slightly toxic before and after irradiation almost to the similar extent. Therefore, the photolytic products from the caging groups appear to be not toxic to the cells, and the apoptosis inducing activity of 1a and b may be for the most part due to LeuLeuOMe.

This paper investigates when and how the US dollar shortage problem evolved into the full crisis during the financial turmoil that started in the summer of 2007, using cross-currency swap prices between three European currencies (EUR, GBP, and CHF) and USD. We employ the dynamic global (latent) factor model with regime-switching beta coefficients proposed by Kim (1994). The main findings are as follows. The global factor exists and there are 2 (high and low) distinctive regimes for beta coefficients of each observable price with respect to the global factor. The crisis indicators such as US and European financial credit spreads and TED spread have significant predictive power for regime-switching from and to the high-beta crisis regime. The 1-year market first entered the crisis regime soon after the onset of the subprime problem in August 2007, and has stayed in the crisis regime since early March, 2008. The 5-year market shows more gradual and delayed movements of both the global factor and the crisis regime probability, entering the crisis regime just after the collapse of Bear Sterns in mid-March, 2008.

This paper analyzes the Japanese government bond (JGB) yield curve using the Black-Gorovoi-Linetsky (BGL) model of interest rates as options with a view to monitoring the JGB market expectations about the Bank of Japan's (BOJ) zero interest rate policy (ZIRP). Main findings are as follows. First, overall fitting performance of the BGL model is much better than that of the original Vasicek model in our sample period from the start of the quantitative monetary easing policy on March 19, 2001 through the end of the ZIRP on July 14, 2006. Second, the shadow interest rate is estimated to be negative throughout the period and rise toward zero quite recently. Third, the first hitting time until the negative shadow interest rate first hits zero shows a very good performance in predicting the ending time of the ZIRP with an error of only about one month. Fourth, the estimated probability density function of the first hitting time shows that the JGB market expectations rapidly converge to the mode value as the ending time of the ZIRP approaches.

To elucidate the catalytic mechanism of the esterase-like activity of serum albumin (SA), the reactivity of SA from six species was investigated using p-nitrophenyl esters as model substrates.The effect of pH and the energetic and thermodynamic profiles of SA were determined for all species for p-nitrophenyl acetate (PNPA). Then, kinetic and thermodynamic studies using a series of p- and o-nitrophenyl esters with different side chains and human SA (HSA) were carried out. The influence of deuterium oxide was also evaluated. Finally, the information gained was used to construct a computer model of the structural chemistry of the reaction.The pH profiles suggest that the nucleophilic character of the catalytic residue (Tyr-411 in the case of HSA) is essential for activity. This kcat-dependent activity was found to increase with a decrease in the activation free energy change (deltaG). Hence, the magnitude of deltaG, which is dependent on activation entropy change (deltaS), as calculated from the thermodynamic analysis, can be regarded as an indicator of hydrolytic activity. It indicates that p-nitrophenyl propionate (PNPP) is the best substrate by evaluating the reactions of nitrophenyl esters with HSA. The findings here indicate that deuterium oxide has no significant effect on the rate of hydrolysis of PNPA by HSA.The results are consistent with a scenario in which HSA becomes acylated due to a nucleophilic attack by Tyr-411 on the substrate and then is deacylated by general acid or base catalysis with the participation of water.

Because the urinary excretion of drugs is often decreased in renal diseases, dosage regimens are adjusted to avoid adverse drug reactions. The aim of present study was to clarify the alteration in the levels of renal drug transporters and their correlation with the urinary drug excretion in renal diseases patients.We quantified the mRNA levels of human organic anion transporters (hOATs) by real-time polymerase chain reaction and examined the excretion of the anionic drug, cefazolin, in renal disease patients. Moreover, transport of cefazolin by hOAT1 and hOAT3 were examined using HEK293 transfectants.Among four hOATs, the level of hOAT1 mRNA was significantly lower in the kidney of patients with renal diseases than in the normal controls. The elimination constant of cefazolin showed a significant correlation with the values of phenolsulfonphthalein test and mRNA levels of hOAT3. The uptake study using HEK293 transfectants revealed that cefazolin and phenolsulfonphthalein were transported by hOAT3.These results suggest that hOAT3 plays an important role for anionic drug secretion in patients with renal diseases and that the expression levels of drug transporters may be related to the alteration of renal drug secretion.

Renal excretion of organic anions and cations is mediated by the organic ion transporter family (SLC22A). In this study, the mRNA levels of the organic ion transporters were quantified by real-time PCR in normal parts of renal tissues from seven nephrectomized patients with renal cell carcinoma, and the distributions and localization of human (h)OAT1, hOAT3, and hOCT2 proteins were investigated by immunohistochemical analyses in the human kidney. The expression level of hOAT3 mRNA was the highest among the organic ion transporter family, followed by that of hOAT1 mRNA. The hOCT2 mRNA level was the highest in the human OCT family, and the level of hOCTN2 mRNA was higher than that of hOCTN1. hOCT1 mRNA showed the lowest level of expression in organic ion transporter family. hOAT1, hOAT3, and hOCT2 proteins were detected in crude membranes from the kidney of all patients by Western blot analyses, whereas hOCT1 protein could not be detected. Immunohistochemical analyses showed that both hOAT1 and hOAT3 were localized to the basolateral membrane of the proximal tubules in the cortex, and hOCT2 was localized to the basolateral membrane of the proximal tubules in both the cortex and medullary ray. Immunohistochemical analyses of serial sections indicated that hOAT1, hOAT3, and hOCT2 were coexpressed in a portion of the proximal tubules. These results suggest that hOAT1, hOAT3, and hOCT2 play predominant roles in the transport of organic ions across the basolateral membrane of human proximal tubules.

L-Leucyl-L-leucine methyl esters (LeuLeuOMe) is a lysosomotropic agent that induces apoptosis of certain immune cells. Glucose-carrying 2-nitrobenzyl (2-NB) and 2-nitrophenethyl (2-NPE) caged LeuLeuOMe, 1a and b, were synthesized and their photochemical and immunological properties were studied. Caged glycine methyl esters (GlyOMe), 2a,b, were also prepared to examine the cytotoxic activity of the photolytic byproducts from 1a,b. All the caged compounds were soluble in PBS containing 1% DMSO more than 400 microM, and efficiently released the substrates upon irradiation at 350 nm. While both 1a and 1b were not toxic to HL60 cells, 1b released LeuLeuOMe more quickly and induced apoptosis of HL60 cells far more efficiently than 1a. Although GlyOMe was not cytotoxic, 2a and b were slightly toxic before and after irradiation almost to the similar extent. Therefore, the photolytic products from the caging groups appear to be not toxic to the cells, and the apoptosis inducing activity of 1a and b may be for the most part due to LeuLeuOMe.

l-Leucyl l-leucine methyl ester (LeuLeuOMe) is a lysosomotropic agent which is converted to a membranolytic compound by dipeptidyl peptidase I and kills human leukocytes such as CD8+ T cells and monocytes but not B cells. The reagent has also been used in mice on the assumption that the cell-type specificity to murine leukocytes is the same as that to human leukocytes. During study on the effect of LeuLeuOMe on antigen-driven IL-2 production using murine splenocytes as antigen-presenting cells, however, we noticed that murine B cells were sensitive to LeuLeuOMe. We therefore examined the cell-type specificity using murine splenocytes and peritoneal macrophages. Flow cytometric analysis revealed that the most sensitive cells to LeuLeuOMe were CD8+ cells and that CD19+ cells (B cells) were as sensitive as CD3+ cells (T cells). Murine splenic B cells, which were either positively or negatively sorted with a cell sorter, were also sensitive to LeuLeuOMe, whereas human peripheral blood B cells, which were positively sorted, were not. Peritoneal macrophages were the most insensitive to LeuLeuOMe. Thus, this study demonstrated that the cell-type specificity to murine leukocytes is different from that to human leukocytes.

With respect to the printability of paper, several problems of color were investigated.Summary was as follows.(1) Max., min., and average qualities of each grade of printing Papers in Japan.(2) Inter relation of each other properties of paper testing figures of the middle class printing Paper.(3) Spectral reflect curve of the typical papers and pulps.(4) Effect of dyes on the paper color.(5) Effect of the kinds of color inks and paper qualities on the printing coloring effect.(6) Relation between paper testing values and theprinting coloring effect.Coloring effect was measured by means of comparing the spectral reHect curve of test sample with that of standard sheet printed under the standard condition.Calculation of the relation between A and B was done as follows.pA→B=SA (B) -a-1/b-1SC (B) /ST (B) -a (r-1) /b (r-1) SM (B)

The photo and reverse thermal cis–trans-isomerisation of the title compound in chloroform has been investigated kinetically, giving the rate constants and thermodynamic parameters of the thermal isomerisation and confirming the mechanism of the isomerisation.