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We examine the dynamic relation between credit risk and liquidity in the Italian sovereign bond market during the eurozone crisis and the subsequent European Central Bank (ECB) interventions. Credit risk drives the liquidity of the market. A 10% change in the credit default swap (CDS) spread leads to a 13% change in the bid-ask spread, the relation being stronger when the CDS spread exceeds 500 basis points. The Long-Term Refinancing Operations of the ECB weakened the sensitivity of market makers’ liquidity provision to credit risk, highlighting the importance of funding liquidity measures as determinants of market liquidity.

We investigate the determinants of the term structures of bond yield and market liquidity in the context of the Quantitative Easing (QE) programs implemented by the Bank of Japan. Between 2011 and 2016, we find that Japanese government bonds (JGBs) show an improvement in liquidity through the spotlight effect but also experience a deterioration in liquidity through the scarcity effect. As for the yield, both the spotlight and scarcity effects work in the same direction (i.e., they raise bond prices). Overall, the prices of JGBs rise by reflecting only the strong demand from the QE, despite the deterioration in liquidity.

We show that the European Central Bank’s bond purchases, undertaken in the context of Quantitative Easing, caused significant mispricing between German and Italian government bonds and their respective futures contracts. We document three channels through which the central bank’s bond purchases led to this mispricing: the deterioration of bond market liquidity, the increased bond “specialness” on the repurchase agreement market, and the higher cost of carry. The mispricing we document is the result of two contemporaneous forces: the increased in trading frictions caused by Quantitative Easing, and regulatory capital constraints that imply non-negative required returns on riskless trades.

We investigate the determinants of the term structures of bond yield and market liquidity in the context of the Quantitative Easing (QE) programs implemented by the Bank of Japan. Between 2011 and 2016, we find that Japanese government bonds (JGBs) show an improvement in liquidity through the spotlight effect but also experience a deterioration in liquidity through the scarcity effect. As for the yield, both the spotlight and scarcity effects work in the same direction (i.e., they raise bond prices). Overall, the prices of JGBs rise by reflecting only the strong demand from the QE, despite the deterioration in liquidity.

This paper examines the strategic behavior of High Frequency Traders (HFTs) during the pre-opening phase and the opening auction of the NYSE Euronext Paris exchange. Using data provided by the Base Europeenne de Donnees Financieres a Haute Frequence (BEDOFIH), we find that HFTs actively participate in the pre-opening phase. Contrary to common wisdom, HFTs do not delay their order submission decisions until the very last moment of the pre-opening phase of the trading day. They are able to successfully extract information from the pre-opening order flow, as manifested by the potential profits they make on the positions they take in the opening auction. Furthermore, HFTs make profits on orders submitted in the last second before the opening auction; however, so do slow traders, suggesting that speed is not a necessary condition to make profits in these last second orders. HFTs lead the price discovery process during the pre-opening phase, and neither harm nor improve liquidity provision in the opening auction. Our analysis highlights that HFTs who “come early to the party” enjoy the party (they make profits), however, they also help the other market participants to enjoy the party (they improve market quality) and do not have a privileged entrance to the party (speed advantage is not a necessary condition to make profits).

We study whether the presence of low-latency traders (including high-frequency traders (HFTs)) in the pre-opening period contributes to market quality, defined by price discovery and liquidity provision, in the opening auction. We use a unique dataset from the Tokyo Stock Exchange (TSE) based on server-IDs and find that HFTs dynamically alter their presence in different stocks and on different days. In spite of the lack of immediate execution, about one quarter of HFTs participate in the pre-opening period, and contribute significantly to market quality in the pre-opening period, the opening auction that ensues and the continuous trading period. Their contribution is largely different from that of the other HFTs during the continuous period.

We investigated the cellular function of Msi3p, belonging to the heat shock protein 70 family, in Candida albicans. The mutant strain tetMSI3 was generated, in which MSI3 was controlled by a tetracycline-repressive promoter, because there is evidence to suggest that MSI3 is an essential gene. We controlled the MSI3 expression level by doxycycline (DOX) and compared its phenotype with that of a control strain with the tetracycline-repressive promoter and a wild-type copy MSI3. The results indicated that MSI3 was essential for cell growth. In addition, all the tetMSI3-infected mice survived after DOX administration. Drug susceptibility tests indicated that repression of MSI3 expression resulted in hypersensitivity to fluconazole and conferred fungicidal activity to fluconazole. The expression levels of MSI3 and calcineurin-dependent genes were upregulated in response to fluconazole in the control strain. In tetMSI3, the upregulation of MSI3 was lost, and the expression level of the calcineurin-dependent genes was no longer elevated in response to fluconazole and was not affected by DOX, indicating that the upregulation of MSI3 expression was required for the induction of the calcineurin-dependent gene expression. These data suggest that Msi3p confers fluconazole tolerance by partially influencing the calcineurin signaling pathway and also other tolerance mechanisms.

Farnesyl pyrophosphate (FPP) is utilized for many cellular processes, including the production of dolichols, ubiquinone (CoQ), sterols, farnesylated heme A and prenylated proteins. This lipid synthesized by FPP synthetase (ERG20) becomes attached to target proteins by the prenyltransferases, CDC43/RAM2 and RAM1/RAM2 complexes after the formation of the C15 and C20 units, respectively. Defects in protein prenylation as a result of inhibiting these enzyme complexes lead to pleiotropic effects in all eukaryotes. In this study, using Candida glabrata conditional mutants, the importance of the ERG20 and RAM2 genes for growth using both in vivo and in vitro assays was assessed by placing the RAM2 and ERG20 genes under the control of a regulatable promoter. Repression of RAM2 gene expression revealed growth defects under both conditions. However, repression of ERG20 gene expression did not impair fungal growth in a mouse host, but did result in growth defects on laboratory media. Thus, FPP synthase is not required for survival in an infected mouse, but the RAM2-encoded prenyltransferase was critical for growth under both conditions. This study strongly suggests that inhibitors of prenyltransferase may be promising antifungals.

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the fungus Paracoccidioides brasiliensis (Pb). The cyclosporin A (CsA) is an immunosuppressant drug that inhibits calcineurin and has been described as a potential antifungal drug. The present study investigated the effect of CsA on the immune response, fungal load/antigenemia in experimental murine PCM. It was used four groups of BALB/c mice: (a) infected with 1 x 10⁵ Pb18 yeast cells (Pb), (b) infected and treated with CsA every other day 10 mg/kg of CsA (s.c.) during 30 days (Pb/CsA), (c) treated with CsA (CsA) and (d) no infected/treated (PBS). The immune response was evaluated by lymphocyte proliferation, DTH assays to exoAgs, ELISA for IgG anti-gp43 (specific immune responses) and cytokine serum levels (IFN-γ, TNF-α, IL-4 and IL-10). Fungal load was determined by lung colony-forming units (CFU) counts, lung and liver histopathology analysis and antigenemia determined by inhibition-ELISA. As expected, CsA was able to inhibit the specific cellular and humoral immune response (P < 0.05), with decrease in serum IFN-γ, TNF-α and IL-4 levels (P < 0.05). Cyclosporin A treatment also resulted in significantly decreased lung Pb CFU (P < 0.05) as well as a lower number of yeasts in the lung and liver (P < 0.05) by histopathology. In concordance, the decreased antigenemia was observed in Pb/CsA group (P < 0.05). In conclusion, even with immunosuppressive action, treatment with CsA results in decreased lung fungal load/antigenemia in experimental PCM in BALB/c mice. Further study is required to determine whether this represents less severe disease or protection by CsA.

The Japanese Society for Medical Mycology (JSMM) method used for testing the antifungal susceptibility of yeast, the MIC end point for azole antifungal agents, is currently set at IC(80). It was recently shown, however that there is an inconsistency in the MIC value between the JSMM method and the CLSI M27-A2 (CLSI) method, in which the end- point was to read as IC(50). To resolve this discrepancy and reassess the JSMM method, the MIC for three azoles, fluconazole, itraconazole and voriconazole were compared to 5 strains of each of the following Candida species: C. albicans, C. glabrata, C. tropicalis, C. parapsilosis and C. krusei, for a total of 25 comparisons, using the JSMM method, a modified JSMM method, and the CLSI method. The results showed that when the MIC end- point criterion of the JSMM method was changed from IC(80) to IC(50) (the modified JSMM method) , the MIC value was consistent and compatible with the CLSI method. Finally, it should be emphasized that the JSMM method, using a spectrophotometer for MIC measurement, was superior in both stability and reproducibility, as compared to the CLSI method in which growth was assessed by visual observation.

In vitro comparative evaluations were performed to study the efficacy of combinations of flucytosine and fluconazole in producing a postantifungal effect (PAFE) on Candida albicans. Initial studies were done to determine MIC, FIC (fractional inhibitory concentration) and optimal PAFE parameters. A turbidometric method was used to measure yeast cell growth following exposure to different concentrations of the two drugs for periods of 0.5, 1 or 2 h at temperatures of 30 degrees C and 37 degrees C. The PAFE was determined by the difference in time (h) required for growth of the control and test cultures to reach the 0.5 absorbance level following removal of the drug by dilution. Ten strains of C. albicans were then assayed (30 degrees C; 2 h exposure time) and a synergistic PAFE was evidenced with the two drugs at concentrations well below their individual MICs. PAFEs ranging from 3.8 to 10.5 h, which persisted for 1.2-2.5 h longer than those achieved with either agent separately, were evidenced when flucytosine and fluconazole were combined (flucytosine: fluconazole ratios of 1:16-1:32) at concentrations ranging from 0.024 to 0.098 micrograms ml-1 and 0.78 to 1.56 micrograms ml-1 respectively. The concentrations of each agent required to produce an optimal PAFE varied according to the C. albicans strain being assayed.

Mincle (also called as Clec4e and Clecsf9) is a C-type lectin receptor expressed in activated phagocytes. Recently, we have demonstrated that Mincle is an FcRγ-associated activating receptor that senses damaged cells. To search an exogenous ligand(s), we screened pathogenic fungi using cell line expressing Mincle, FcRγ, and NFAT-GFP reporter. We found that Mincle specifically recognizes theMalasseziaspecies among 50 different fungal species tested.Malasseziais a pathogenic fungus that causes skin diseases, such as tinea versicolor and atopic dermatitis, and fatal sepsis. However, the specific receptor on host cells has not been identified. Mutation of the putative mannose-binding motif within C-type lectin domain of Mincle abrogatedMalasseziarecognition. Analyses of glycoconjugate microarray revealed that Mincle selectively binds to α-mannose but not mannan. Thus, Mincle may recognize specific geometry of α-mannosyl residues onMalasseziaspecies and use this to distinguish them from other fungi.Malasseziaactivated macrophages to produce inflammatory cytokines/chemokines. To elucidate the physiological function of Mincle, Mincle-deficient mice were established.Malassezia-induced cytokine/chemokine production by macrophages from Mincle−/−mice was significantly impaired. In vivo inflammatory responses againstMalasseziawas also impaired in Mincle−/−mice. These results indicate that Mincle is the first specific receptor forMalasseziaspecies to be reported and plays a crucial role in immune responses to this fungus.

The fungus Paracoccidioides brasiliensis is the pathogen of paracoccidioidomycosis (PCM), a systemic mycosis prevalent in Latin America. The loop‐mediated isothermal amplification method (LAMP) was used in this study to detect the presence of P. brasiliensis in sputa samples from patients with chronic PCM, suspected PCM, and a negative control. The target P. brasiliensis gp43 gene was amplified in less than 4 hr in 11 of 18 sputa samples tested. The LAMPmethod had the advantage of speed and simplicity compared with the classic diagnostic methods such as the histopathological test or biological material culture and did not require sophisticated technical apparatus. It would be an important aid in cases where immediate treatment would mean patient survival, especially in immune‐suppressed patients. J. Clin. Lab. Anal. 23:139–143 2009. © 2009 Wiley‐Liss, Inc.

In the pathogenic yeast Candida glabrata , gene targeting to generate knockouts and “knockins” is a potentially powerful method for the analysis of gene function. Its importance increased after the C. glabrata genome sequence project, but progress in the field is hampered by inefficient mechanisms for gene targeting. With the use of 40-bp homologous flanking DNA, no gene targeting was identified. To address this issue, YKU80 was disrupted, leading to an increase in targeting efficiency of 5.1% using 40-bp flanking homologous DNA. To harness the beneficial effects of YKU80 inactivation on gene targeting frequency without incurring any negative effects, such as synthetic sickness or lethality, we developed a new system whereby the expression of YKU80 was restored following a transient knockdown of expression during transformation. Strains used for this new system carried a SAT1 flipper in the YKU80 promoter region, which was used to repress expression during transformation but was spontaneously excised from the locus after the transformation. By using this strain, DNA damage induced by methyl methane sulfonate, H 2 O 2 , UV irradiation, and hydroxyurea before and during gene targeting was evaluated and the mutation rate of URA3 was determined. No significant effects of the SAT1 flipper on these processes have been identified. After the SAT1 flipper is excised, a 34-bp FLP recombination target sequence is left in the promoter region. However, the levels of mRNA transcription were restored and no difference in the survival ratio in vivo compared to that with the YKU80 wild-type strain was identified.

We study whether the presence of low-latency traders (including high-frequency traders (HFTs)) in the pre-opening period contributes to price discovery in the subsequent opening call auction and the continuous trading session. Our analysis evokes shades of the debate on the switch from the current continuous auction in many markets to a periodic auction, affecting the speed advantage of low-latency traders. We empirically investigate these questions using a unique dataset based on server IDs provided by the Tokyo Stock Exchange (TSE), one of the largest stock markets in the world. Our data allow us to develop a more comprehensive classification of traders than in the prior literature, and to investigate the behavior of the different categories of traders, based on their capability for low-latency trading. We find that, perhaps due to the lack of immediate execution, about three quarters of the low-latency traders do not participate in the pre-opening period, but do participate in and dominate the continuous trading session. Furthermore, we find that the larger presence of low-latency traders in the trading of a stock in the pre-opening period as well as in the continuous session improves the price discovery process. Our results suggest that HFTs may not participate in trading in the periodic batch auction because of a lack of immediate execution, and that this large reduction in HFT participation may impede the quality of price discovery.

This paper examines the dynamic relationship between credit risk and liquidity in the sovereign bond market in the context of the European Central Bank (ECB) interventions. Using a comprehensive set of liquidity measures obtained from a detailed, quote-level dataset of the largest interdealer market for Italian government bonds, we show that changes in credit risk, as measured by the Italian sovereign credit default swap (CDS) spread, generally drive the liquidity of the market: a 10% change in the CDS spread leads a 11% change in the bid-ask spread. This relationship is stronger, and the transmission is faster, when the CDS spread is above the 500 basis point threshold, estimated endogenously, and can be ascribed to changes in margins and collateral, as well as clientele effects. Moreover, we show that the Long-Term Refinancing Operations (LTRO) intervention by the ECB weakened the sensitivity of the liquidity provision by the market makers to changes in the Italian government's credit risk. We also document the importance of market-wide and dealer-specific funding liquidity measures in determining the market liquidity for Italian government bonds.

The characteristics of in vitro micafungin (FK463) antifungal activity against six species of dimorphic fungi were investigated in accordance with the NCCLS M27-A microdilution methods. MICs of micafungin, amphotericin B, itraconazole, and fluconazole for Histoplasma capsulatum var. capsulatum , Blastomyces dermatitidis , Paracoccidioides brasiliensis , Penicillium marneffei , and Sporothrix schenckii were determined both for the yeast-like form and mycelial form. Coccidioides immitis was tested only in its mycelial form. We have clearly demonstrated that the in vitro activity of micafungin depends considerably on the growth form of dimorphic fungi. Micafungin exhibited potent activity against the mycelial forms of H. capsulatum , B. dermatitidis , and C. immitis (MIC range, 0.0078 to 0.0625 μg/ml), while it was very weakly active against their yeast-like forms (MIC range, 32 to >64 μg/ml). Micafungin was also more active against the mycelial forms than the yeast-like forms of Paracoccidioides brasiliensis , Penicillium marneffei , and S. schenckii . The MICs of amphotericin B were 2 to 5 dilutions lower for the mycelial forms than for the yeast-like forms of B. dermatitidis and Paracoccidioides brasiliensis . There was no apparent difference in the activity of itraconazole between the two forms. The MICs of fluconazole for the yeast-like forms were generally lower than those for the mycelial forms, and considerably so for B. dermatitidis . These results suggest that the growth form employed in antifungal susceptibility testing of dimorphic fungi can considerably influence the interpretation of results. At present, it cannot be judged whether micafungin has clinical usefulness for dimorphic fungus infections, since for most fungi it remains uncertain which growth form correlates better with therapeutic outcome. However, the results of this study warrant further investigations of micafungin as a therapeutic agent for infections caused by dimorphic fungi.

This is an investigation of the Japanese yen and U.S. dollar interest rate swap markets during 1990–2000. It examines spreads over comparable Treasury yields for different maturities and the transmission of shocks to swap spreads and volatilities from one market to the other. The correlations between yen and dollar interest swap spreads are low, indicating that the credit risk factor is country-specific. Changes in the dollar interest rate swap spreads “Granger-cause” changes in the spreads of yen interest rate swaps for the long (ten-year) maturities. Yen swap spreads are highly correlated with interest rate differentials between the two markets, which influence subsequent movements in yen swap spreads. Transmission of the volatility of swap spreads is strong from the dollar to the yen markets and relatively weak in the other direction. These and other results suggest that specific institutional aspects, such as illiquidity and market frictions, may have affected the yen interest swap market more than the dollar market.

Diazobenzoic acid B (DBB), also known as diazonium blue B or fast blue B, can be used to distinguish basidiomycetous yeasts from ascomycetes. This chemical has long been used for the taxonomic study of yeast species at the phylum level, but the mechanism underlying the DBB staining remains unknown. To identify molecular targets of DBB staining, we isolated Agrobacterium tumefaciens-mediated insertional mutants of Cryptococcus neoformans, a basidiomycetous pathogenic yeast, which were negative to DBB staining. In one of these mutants, we found that the PMT2 gene, encoding a protein-O-mannosyltransferase, was interrupted by a T-DNA insertion. A complete gene knockout of the PMT2 gene revealed that the gene was responsible for DBB staining in C. neoformans, suggesting that one of the targets of Pmt2-mediated glycosylation is responsible for interacting with DBB. We also determined that Cryptococcus gattii, a close relative of C. neoformans, was not stained by DBB when the PMT2 gene was deleted. Our finding suggests that the protein-O-mannosylation by the PMT2 gene product is required for DBB staining in Cryptococcus species in general. We also showed that glycosylation in Cryptococcus by Pmt2 plays important roles in controlling cell size, resistance to high temperature and osmolarity, capsule formation, sexual reproduction, and virulence.

Merton (1987) proposes that an increase in a firm's investor base increases the firm's value. In Japan, companies can reduce their stock's minimum trading unitthe number of shares in a "round lot"-which facilitates trading in the stock by small investors. We find that a reduction in the minimum trading unit greatly increases a firm's base of individual investors and its stock liquidity, and is associated with a significant increase in the stock price. Further, the stock price appreciation is positively related to an increase in the number of shareholders.

Gene deletion in the pathogenic fungus Candida albicans has relied heavily on a URA3 cassette and a recipient delta ura3 strain CAI4. The IRO1 gene adjacent to URA3 was inadvertently deleted during construction of CAI4. We report here that a mutation in IRO1 reduces virulence of C. albicans.

The intestinal resident Candida glabrata opportunistically infects humans. However few genetic factors for adaptation in the intestine are identified in this fungus. Here we describe the C. glabrata CYB2 gene encoding lactate dehydrogenase as an adaptation factor for survival in the intestine. CYB2 was identified as a virulence factor by a silkworm infection study. To determine the function of CYB2, we analysed in vitro phenotypes of the mutant Δcyb2. The Δcyb2 mutant grew well in glucose medium under aerobic and anaerobic conditions, was not supersensitive to nitric oxide which has fungicidal-effect in phagocytes, and had normal levels of general virulence factors protease, lipase and adherence activities. A previous report suggested that Cyb2p is responsible for lactate assimilation. Additionally, it was speculated that lactate assimilation was required for Candida virulence because Candida must synthesize glucose via gluconeogenesis under glucose-limited conditions such as in the host. Indeed, the Δcyb2 mutant could not grow on lactate medium in which lactate is the sole carbon source in the absence of glucose, indicating that Cyb2p plays a role in lactate assimilation. We hypothesized that Cyb2p-mediated lactate assimilation is necessary for proliferation in the intestinal tract, as the intestine is rich in lactate produced by bacteria flora, but not glucose. The Δcyb2 mutant showed 100-fold decreased adaptation and few cells of Saccharomyces cerevisiae can adapt in mouse ceca. Interestingly, C. glabrata could assimilate lactate under hypoxic conditions, dependent on CYB2, but not yeast S. cerevisiae. Because accessible oxygen is limited in the intestine, the ability for lactate assimilation in hypoxic conditions may provide an advantage for a pathogenic yeast. From those results, we conclude that Cyb2p-mediated lactate assimilation is an intestinal adaptation factor of C. glabrata.

We investigate whether increasing the speed of order execution affects investor trading strategy and market liquidity. With the new trading platform Arrowhead, the Tokyo Stock Exchange has eliminated the three-second matching cycle, executes orders immediately, and instantaneously updates the limit order book, rendering computerized trading strategies more powerful. Since Arrowhead’s introduction, there have been an increase in execution frequency and a reduction in trade size, leading to declines in effective spread and increases in adverse selection costs. Among the trade intensity variables we examine, persistency of runs affects adverse selection cost more than share imbalance. High-speed quote revisions contribute to market depth.

The Japanese Society for Medical Mycology (JSMM) method used for testing the antifungal susceptibility of yeast, the MIC end point for azole antifungal agents, is currently set at IC(80). It was recently shown, however that there is an inconsistency in the MIC value between the JSMM method and the CLSI M27-A2 (CLSI) method, in which the end- point was to read as IC(50). To resolve this discrepancy and reassess the JSMM method, the MIC for three azoles, fluconazole, itraconazole and voriconazole were compared to 5 strains of each of the following Candida species: C. albicans, C. glabrata, C. tropicalis, C. parapsilosis and C. krusei, for a total of 25 comparisons, using the JSMM method, a modified JSMM method, and the CLSI method. The results showed that when the MIC end- point criterion of the JSMM method was changed from IC(80) to IC(50) (the modified JSMM method) , the MIC value was consistent and compatible with the CLSI method. Finally, it should be emphasized that the JSMM method, using a spectrophotometer for MIC measurement, was superior in both stability and reproducibility, as compared to the CLSI method in which growth was assessed by visual observation.

We applied multilocus microsatellite typing (MLMT) method to investigate the genetic relation between Cryptococcus neoformans var. grubii clinical and environmental isolates in Sao Paulo, Brazil. This MLMT method includes three functional gene sequences of C. neoformans var. grubii, which are dispersed on three chromosomes. In all, 89 strains (36 clinical and 53 environmental isolates) were analyzed. Of 36 clinical strains, 20 belonged to a major type of MLMT-13 (55.6%). They were mainly isolated from clinical specimens. About 52.8% of strains from the environment belong to a major type of MLMT-36, which are indigenous to environments and which were not isolated from clinical samples. Thus, we recognized two genotypes that distinguish majority of clinical and environmental strains. No differences were found in antifungal susceptibility and capsule size between major environmental and clinical MLMT types.

A firm’s ownership structure influences both its liquidity and value. This paper introduces a new measure of latent investment horizon, a weighted average investment horizon computed from the firm’s ownership structure and the average investment horizon of various investor categories. We find that the latent investment horizon explains differences in liquidity and firm value among firms listed on the Tokyo Stock Exchange. Empirical results indicate that the longer the investment horizon, the lower the firm’s liquidity and value. In addition, concentrated ownerships by foreign (cross-holding) shareholders can lead to superior (inferior) liquidity and corporate governance after accounting for selection bias.

After the rapid progress in therapeutic pharmaceutics against onychomycosis caused by dermatophytes in the 1990s, an optimal therapeutic strategy for individual patients with the onychomycosis has become possible for clinical dermatologists. In this review, we discuss on clinical problems concerning this disease and propose recommendable treatments for each patient with topical and/or systemic use of antifungal agents. Finally, with consideration of already published therapeutic guidelines, we stress the necessity of "order-made" therapy for each patient with his/her medical status and wishes taking into account.

During our studies on toxic substances from clinically isolated Nocarida, a new isolate identified as Nocardia otitidiscaviarum from cutaneous nocardiosis was found to produce a toxic substance called HS-6 that had strong in vitro as well as in vivo toxicity. The mouse intraperitoneal LD50 value was 1.25 mg/kg and the ED50 value for L1210 cultured cells was 0.3 ng/ml. The structure of HS-6 was determined and found to belong to the 16-membered macrocyclic group with a molecular formula of C43H68O12. HS-6 also showed activity against pathogenic fungi such as Cryptococcus neoformans.

(1990). Arbitrage Opportunities in the Japanese Stock and Futures Markets. Financial Analysts Journal: Vol. 46, No. 2, pp. 14-24.

In vitro susceptibilities of ten clinical isolates, including five strains of Cryptococcus neoformans var. grubii and five strains of Aspergillus fumigatus, were determined against nine sulfa drugs using a microdilution method. Among the five tested media, minimum inhibitory concentration (MIC) values were observed only in YNB medium: no detectable level MIC value of less than 125 microg/ml was observed in the four remaining media against Cryptococcus species. Of the nine sulfa drugs, of which sulfaphenazole showed the highest antifungal activity, the MIC values for A. fumigatus and C. neoformans var. grubii were, respectively, 64 microg/ml and 4-8 microg/ml, suggesting high susceptibility of C. neoformans to sulfa drugs.

An important point in the development of an antimicrobial agent is whether its target molecules are essential for growth of the microorganism. From this viewpoint, we focused attention on essential genes as potential targets of antifungal agents in the pathogenic yeast Candida. Here we introduce recent attempts for screening, identification, and characterization of essential genes from a haploid yeast Candida glabrata, using temperature-sensitive mutants. Our experimental results suggesting the essentiality of C. albicans PHO85, the homologue of which is known as a negative regulator of the PHO system and as a non-essential gene in Saccharomyces cerevisiae are also described.

A new thiazolidine-type antibiotic with zinc in its structure, designated transvalencin A, was isolated from Nocardia sp. IFM 10065, a clinical isolate from a patient with actinomycotic mycetoma. The strain was identified as Nocardia transvalensis based on its morphological, phenotypic and phylogenetic characteristics. Transvalencin A showed antimicrobial activity against fungi such as Trichophyton mentagrophytes and Cryptococcus neoformans. The antibiotic is also active against Gram-positive bacteria such as Micrococcus luteus. We observed higher activity for fungi in an acidic medium than in a neutral medium.

Infection is a major cause of morbidity and mortality in bone marrow transplant recipients and in patients with hematological malignancies. The source of infection is almost always endogenous flora or the hospital environment. The present study evaluated bone marrow transplant recipients and patients with hematological malignancies colonized and/or infected with filamentous fungi. During 1 year, environmental air samples were also taken from the bone marrow transplant unit by a modification of gravity air-setting plate (GASP) methodology. Fusarium spp. were the most prevalent genus in the fall and Cladosporium spp. in the winter. Clinically isolated strains grew better at 37 degrees C than environmental strains. According to NCCLS M-38P methods, environmental Aspergillus strains showed higher MICs to miconazol and itraconazol, and clinical Fusarium strains were less susceptible to fluconazole.

When a firm switches its listing venue, there is often a significant increase in the number of shareholders and the trading activities. According to Merton [1987], an increased shareholder base improves diversification of risk, which has a positive impact on the stock price. Amihud and Mendelson [1986] state that improvement in liquidity also has a positive impact on stock price. Most existing research dealt with cases where NASDAQ-listed stocks migrated their listing to the New York Stock Exchange or other exchanges in the U.S.; however, in these cases, it is difficult to extract the pure impact resulted from the increase in the shareholder base because the switching trading mechanisms occur simultaneously. On Japan Securities Dealers Association automated Quotation (JASDAQ) and the Tokyo Stock Exchange (TSE), analyzed in this study, most of stocks are traded under the same order-driven mechanism in either exchanges, and therefore we don't have any effects originated from difference of trading mechanism. This study measured cumulative abnormal returns (CARs) over the period between the listing change announcement date and the actual date of listing migration for stocks that moved from JASDAQ to the TSE from 1999 to 2002. Our findings confirmed a correlation between CARs and the effect of shareholder diversification. However, this relation is seen only in the stocks transferred to TSE Section I; such relation with the effect of shareholder diversification was not really evident for the stocks transferred to TSE Section II. For stocks transferred to TSE Section I, yen-based trading volume increased noticeably following announcement of listing change, suggesting that such a change is an important factor in stimulating trading that is consistent with current understanding. Also, relatively low abnormal returns were observed for stocks stocked by firms that carried out a public offering or secondary distribution concurrently with listing change in order to satisfy the required number of shareholders. This result shows that changes in abnormal returns and volume are not simply a result of the shift of listing from JASDAQ to the TSE, but are also stimulated by both the transfer process itself and post-transfer trading performance. Empirical results of this study regarding the application procedure for listing change show that public offering/secondary distribution immediately before listing change tends to have a negative impact on the stock price and volume. This suggests the need for appropriate consideration of such impact when making an application for listing change without satisfying the required number of shareholders.

A strain of Histoplasma capsulatum var. duboisii (deposited as IFM 50954 in Chiba University) was isolated from the cerebrospinal fluid of a female Ugandan patient infected with HIV. The isolate had in vitro urease activity on Christensen's urea agar slants, although the common belief is that H. capsulatum var. duboisii is urease negative, and is, considered one of the characteristic markers that distinguishes the three varieties of H. capsulatum. Forty H. capsulatum var. capsulatum, five H. capsulatum var. duboisii, and five H. capsulatum var. farciminosum isolates were evaluated for urease activity on Christensen's urea agar slants and for other qualitative and quantitative urease assays of activity. All 50 isolates of H. capsulatum used in this study were positive for urease activity, suggesting that urease activity may be universal characteristic of H. capsulatum. We also compared the urease activity and pathogenicity of seven H. capsulatum isolates that convert into yeast-form cells. Although isolate IFM 50954 showed moderate virulence in mice and moderate urease activity among tested H. capsulatum isolates, there was no correlation between level of urease activity and pathogenicity. In addition, scanning electron microscopy revealed that some microconidia of isolate IFM 50954 formed "double-cell" configurations that were attached to each other by narrow bases.

Bioassay-guided fractionation resulted in the isolation of four antifungal agents from the roots of Cudrania cochinchinensis. Two of these were new compounds, cudraxanthone S [1, 1,3,5,6-tetrahydroxy-2-(1,1-dimethyl-2-propenyl)xanthone] and cudraflavanone B (2, 2',4',5,7-tetrahydroxy-6-prenylflavanone). The remaining two compounds were known compounds, toxyloxanthone C (3) and wighteone (4). Among these compounds, 1, 3, and 4 exhibited antifungal activities against Cryptococcus neoformans, Aspergillusfumigatus, and A. nidulans (MICs = 2-8 microg/mL). Compounds 1 and 3 also showed antifungal activity against Candida glabrata (MICs = 4-8 microg/mL).

Candida dubliniensis is a newly described fungus that is frequently isolated from the oral cavities of HIV-positive patients. Although extensive studies have been performed on the phylogeny of C. dubliniensis, little is known about the pathogenic ecology of this yeast. Here we examined aspects related to C. dubliniensis in comparison with those of C. albicans. When injected intravenously into mice, C. dubliniensis had a higher survival rate than C. albicans. Histopathological analysis disclosed that C. dubliniensis remained mostly in the yeast form in the infected organs, whereas C. albicans changed into the mycelial form. The host inflammatory reaction was aggressive with C. dubliniensis infection and mild with C. albicans infection. Co-culture of the yeasts with human polymorphonuclear leukocytes disclosed that C. dubliniensis is more vulnerable to the fungicidal activity of leukocytes than C. albicans. C. dubliniensis was also more susceptible to the toxic effect of hydrogen peroxide. When cultured in vitro, C. dubliniensis grew more slowly than C. albicans, but the formation of germ tubes was faster. When the fungi were cultured in RPMI 1640, a fetal bovine serum supplement suppressed the growth of C. dubliniensis but enhanced that of C. albicans. These results clearly indicated that C. dubliniensis is less virulence than C. albicans.