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Objective To investigate the effect of PCI on patient-reported outcomes in focal and diffuse coronary artery disease (CAD) as defined by the pullback pressure gradient (PPG). Background Improvements in fractional flow reserve (FFR) following PCI are associated with freedom from angina. CAD patterns influence the FFR change after stenting. Therefore, CAD patterns might be essential to assess the likelihood of PCI success in terms of angina relief. Methods This is a sub-analysis of the TARGET-FFR randomized clinical trial (NCT03259815). The 7-item Seattle Angina Questionnaire (SAQ-7) and EuroQol five-level EQ-5D questionnaire (EQ-5D-5L) were administered at baseline and three months after PCI. The PPG index was calculated from manual pre-PCI FFR pullbacks and the median PPG value was used to define focal and diffuse CAD. Results 103 patients (51 with focal and 52 with diffuse disease) were analyzed. There were no differences in baseline characteristics between patients with focal and diffuse CAD. Patients with focal disease had larger increases in FFR with PCI than those with diffuse disease (0.30±0.14 units vs 0.19±0.12 units, p Conclusion Persistent angina after PCI was almost twice as common in patients with diffuse CAD as defined by the pre-PCI PPG. Patients with focal disease reported greater improvement in angina and quality of life with PCI. The likelihood of successful angina relief from PCI can be predicted by the baseline pattern of CAD. Funding Acknowledgement Type of funding sources: None.

Summary Natural gas dissolved in water (GDW) is a common form of hydrocarbon occurrence in Japan, and gas production from the GDW accounts for 17% (approximately 290 mmscf/day) of total natural gas production in the country. Nakajo field is one of the fields which has long production history from the GDW reservoir. However, as GDW sandstone itself has not been well understood in aspect of the petrophysics and rock physics behaviour, it was a new finding for us that gas-effect and gas-effect-like sonic responses were observed in the GDW sandstone. In this paper, we show result of rock physics modelling, fluid substitutions, synthetic seismogram calculations, wedge modelling and AVO modelling for GDW sandstone. The rock physics modelling results revealed presence of isolated gas in GDW reservoir. Besides, water saturation estimated from rock physics modelling was regarded as useful tool to detect GDW reservoir with gas isolation. An application to seismic data is also encouraged according to synthetic seismogram calculations and AVO modelling. These outcomes allow a better evaluation approach of the surrounding area where future exploration and development potential may exist.

In 2004, we searched for very high energy (VHE) gamma-ray emission from the Galactic Plane using the CANGAROO-III stereoscopic observation system. Two different longitude regions (l = −19°.5 and l = +13°.0) on the Galactic Plane were observed during July and August 2004. We analyzed events that triggered three telescopes aiming to measure the diffuse emission component. No significant signal associated with the Galactic Plane was found from either of the regions. Assuming that the gamma-ray spectrum is described by a single power-law for energies ranging between a few GeV and TeV, lower limits of the power-law spectral indices were found to be 2.2 for both of the regions with a 99.9% confidence level. This result is consistent with the other VHE measurements and constrains a hypothesis in which a very hard (∼2.0) cosmic ray electron spectrum was introduced to explain the EGRET GeV anomaly.

We observed the unidentified TeV gamma-ray source HESS J1804-216 with the CANGAROO-III atmospheric Cerenkov telescopes from May to July in 2006. We detected very high energy gamma rays above 600 GeV at the 10 sigma level in an effective exposure of 76 hr. We obtained a differential flux of (5.0+/-1.5_{stat}+/-1.6_{sys})\times 10^{-12}(E/1 TeV)^{-\alpha} cm^{-2}s^{-1}TeV^{-1} with a photon index \alpha of 2.69 +/- 0.30_{stat} +/- 0.34_{sys}, which is consistent with that of the H.E.S.S. observation in 2004. We also confirm the extended morphology of the source. By combining our result with multi-wavelength observations, we discuss the possible counterparts of HESS J1804-216 and the radiation mechanism based on leptonic and hadronic processes for a supernova remnant and a pulsar wind nebula., Comment: 11 pages, 12 figures, Accepted in ApJ

We have observed the supernova remnant MSH 15-52 (G320.4-1.2), which contains the gamma-ray pulsar PSR B1509-58, using the CANGAROO-III imaging atmospheric Cherenkov telescope array from April to June in 2006. We detected gamma rays above 810 GeV at the 7 sigma level during a total effective exposure of 48.4 hours. We obtained a differential gamma-ray flux at 2.35 TeV of (7.9+/-1.5_{stat}+/-1.7_{sys}) \times 10^{-13} cm^{-2}s^{-1}TeV^{-1} with a photon index of 2.21+/-0.39_{stat}+/-0.40_{sys}, which is compatible with that of the H.E.S.S. observation in 2004. The morphology shows extended emission compared to our Point Spread Function. We consider the plausible origin of the high energy emission based on a multi-wavelength spectral analysis and energetics arguments.

Optical images of SN 1987A show a triple ring structure. The inner (dust) ring has recently increased in brightness and in the number of hot spots suggesting that the supernova shock wave has collided with the dense pre-existing circumstellar medium, a scenario supported by radio and X-ray observations. Such a shocked environment is widely expected to result in the acceleration of charged particles, and the accompanying emission of very high energy gamma-rays. Here, we report the results of observations made in 2004 and 2006 which yield upper limits on the TeV gamma-ray flux, which are compared with a theoretical prediction. In addition, we set upper limits on the TeV flux for four high energy objects which are located within the same field of view of the observation: the super-bubble 30 Dor C, the Crab-like pulsar PSR B0540$-$69, the X-ray binary LMC X-1, and the supernova remnant N157B., Comment: 5 pages, 5 figures, Accepted for publication in ApJ

A strong association between inactive aldehyde dehydrogenase-2 (ALDH2) and risk of esophageal cancer has been demonstrated in East Asian drinkers. An alcohol flushing questionnaire asking about past and current tendency for facial flushing to occur after drinking a glass (≈180 mL) of beer predicts the presence of inactive ALDH2 among Japanese aged 40 years or older with a sensitivity and specificity of approximately 90%. We invented a health-risk appraisal (HRA) model that makes it possible to identify Japanese men who are at high risk for esophageal cancer based on their past and current alcohol flushing tendency, drinking, smoking, and intake of vegetables and fruits. Between 2008 and 2009, 2221 Japanese men aged 50 years or older filled out the HRA questionnaire before undergoing a screening examination by upper gastrointestinal endoscopy at five medical facilities. The endoscopic examination resulted in a diagnosis of esophageal cancer in 19 subjects, and 117 (5.27%) subjects had an HRA score ≥ 11. The proportion of subjects with an HRA score ≥ 11 was higher in the 50-69 age group (6.11-6.88%) than in 70-89 age group (2.84-2.86%). The esophageal cancer detection rate was 4.27% among the subjects with an HRA score ≥ 11 and only 0.67% among the other subjects. Based on a receiver operating characteristic curve analysis, when an HRA score of ≥ 9 was used for subjects aged 50-69 years and of ≥ 8 for those aged 70-89 years as the cutoff value to select individuals with a high risk for esophageal cancer, its sensitivity and false-positive rate was 52.6% and 15.2%, respectively, and the cancer detection rate was 2.91% in the high-risk group, as opposed to 0.48% in the other group. In conclusion, the high detection rates for esophageal cancer in the high-risk groups encouraged screening based on our HRA model in larger Japanese populations.

Abstract 2335 The stepwise lineage-commitment from hematopoietic stem cells (HSCs) in the bone marrow (BM) to T-lymphocyte-restricted progenitors in the thymus represents a paradigm for how distinct stages of lineage restriction from a multipotent to a lineage-restricted progenitor require different extrinsic cues. However, the commitment stage at which progenitors migrate from the BM to the thymus remains unclear. Previous studies demonstrated the existence of adult early thymic progenitors (ETPs) restricted to T lymphocyte and granulocyte-monocyte (GM) fates (Bell and Bhandoola, Nature 2008; Wada et al., Nature 2008). The challenge remains to couple this thymic T–GM restricted progenitor to candidate thymus seeding progenitors (TSPs) identified in the BM, such as common lymphoid progenitors, lymphoid-primed multipotent progenitors (LMPPs) and HSCs, which all also possess B cell potential. Using high resolution FACS and sensitive clonal assays, we have identified the most primitive ETPs in the neonatal thymus and demonstrate at the single cell level that rare Lin−CD4−CD8a−CD25−KIThiFLT3hi ETPs possess combined granulocyte-monocyte (GM), T and B lymphocyte but not megakaryocyte-erythroid (MkE) lineage potentials, identical to closely molecularly related thymus-seeding progenitors in the BM. Moreover, global molecular profiling demonstrates that neonatal Lin−CD4−CD8a−CD25−KIThiFLT3hi ETPs cluster closest to multipotent progenitors in the BM, rather than subsequent (DN1 and DN2) progenitor stages in the thymus. Finally, in support of Lin−CD4−CD8a−CD25−KIThiFLT3hi ETPs with combined T, B and GM lineage potentials, being the most multipotent progenitors in the thymus, phenotypic and functional studies demonstrate that the neonatal thymus is not seeded by HSCs or MPPs with MkE potential. These findings establish for the first time a distinct lineage commitment stage for the transition of T-lineage commitment from the BM to the remote thymus. Disclosures: No relevant conflicts of interest to declare.

The primary photochemical event in rhodopsin is an 11-cis to 11-trans photoisomerization of its retinylidene chromophore to form the primary intermediate photorhodopsin. Earlier picosecond studies have shown that no intermediate is formed when the retinal 11-ene is fixed through a bridging five-membered ring, whereas a photorhodopsin-like intermediate is formed when it is fixed through a flexible seven-membered ring. Results from a rhodopsin analog formed from a retinal with locked 11-ene structure through the more flexible eight-membered ring (Ret8) are described. Incubation of bovine opsin with Ret8 formed two pigments absorbing at 425 nm (P425) and 500 nm (P500). P425, however, is an artifact because it formed from thermally denatured opsin or other proteins and Ret8. Excitation of P500 with a picosecond green pulse led to formation of two intermediates corresponding to photo- and bathorhodopsins. These results demonstrate that an appearance of early intermediates is dependent on the flexibility of the 11-ene and that the photoisomerization of P500 proceeds by stepwise changes of chromophore-protein interaction, which in turn leads to a relaxation of the highly twisted all-trans-retinylidene chromophore in photorhodopsin.

A new finding is reported concerning some structural change in the amorphous state of the polymer which occurs during the so-called induction period before the start of crystallization. Annealing of poly(ethylene terephthalate) (PET) at 115°C, or 40°C above the glass transition temperature, Tg, has been investigated by small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS) techniques. At a very early stage of the induction period the SAXS intensity starts to increase in the range of Q = 0.02–0.04 A −1 , where Q is the length of the scattering vector (Q = 4π sin θ/λ), and continues to increase until the beginning of crystallization. Corresponding to the initation of crystallization, another strong peak, caused by the usual long-period structure, appears in the vicinity of Q = 0.05 A −1 . It is confirmed from the WAXS measurements that no local ordering takes place during the induction period. To clarify the crystallization process, distance distribution analysis is also carried out.

Crystallization processes of poly(ethylene terephthalate) (PET) when annealed at 80°C, or 5°C above the glass transition temperature, Tg, have been investigated by a small-angle X-ray scattering (SAXS) technique. At a very early stage of annealing, a scattering maximum appears at around Q = 0.04 A −1 , where Q is the length of the scattering vector (Q = 4π sin θ/λ). During the so-called induction period of crystallization, this maximum intensity increases with annealing time and the maximum position shifts towards the low Q side. These results confirm the previously reported new finding that the long-range ordered structure is formed in the induction period before crystallization. These ordering processes can be divided into two stages: an early and a late stage. The scattering behaviour in the early stage is in accordance with the prediction of Cahn's linearized theory for spinodal decomposition. The scattering profiles in the late stage can be described in terms of Furukawa's scaling theory for the cluster growth regime. From these experimental results, we conclude that the growth process of the density fluctuation occurs in the induction period and this process is very similar to the spinodal decomposition type of phase separation process. It is considered that after this dense domain grows to a certain size, crystallization begins.

The detection of very high energy gamma‐ray from the direction of the Galactic Center was reported by the CANGAROO‐II and Whipple in 2004. Soon H.E.S.S. detected gamma‐ray above 165 GeV with a quite high significance, of which the photon index was harder than the CANGAROO‐II result. In 2005, MAGIC observation detected a differential gamma‐ray flux consistent with a steady, hard‐slope power law of H.E.S.S. result. We observed the Galactic center in 2005 using CANAROO‐III stereoscopic telescopes and detected the gamma‐ray emission with a significance level of 5.4 sigma above 650 GeV. Its photon spectrum and image were consistent with both H.E.S.S. and MAGIC results.

The gene coding cholesterol oxidase (CHOD) from Brevibacterium sterolicum , which is widely used in clinical analysis, has been selected from pUC19-based gene bank in E.coli MM294 by colony-hybridization using synthetic DNA as probe. The gene was identified to encode the protein having the same amino acid sequence as that determined from amino-acid sequence analysis. The expression of the CHOD gene in E.coli was not observed, probably due to the transcription failure. Attempts are being made to express it in various hosts including Streptomyces lividans , Corynebacterium glutamicum , and B.sterolicum itself.

This concluding chapter is divided into three sections. In the first section, the various types of sojourners are described. The second section introduces some types of Japanese emigrants with a general focus on their social backgrounds in contemporary Japan. Then, in relation to data-analysis, the author explains how the sojourner community is maintained. Then, he concludes with some illustrations that highlight features of the sojourner community, and discusses issues that should be considered in future sociological research. The chapter has continuously confronted the fact that the sojourner concept is associated with temporary residency, and attempted to address some serious conceptual difficulties that have had to be overcome. Japanese immigrants to Australia give evidence of a desire to find a new, probably, transcending way of life.Keywords: Australia; Japanese emigrants; sociological research; sojourner community; sojourner concept; sojourner distinctive features; temporary residency

This chapter discusses study and conceptualisation of Japanese sojourner in Australia. It is divided into three sections: In the first section, some arguments about the concept of the sojourner are given to identify an appropriate sociological meaning for the term. In the second section, basic categories used in this research project are described. Then, in order to introduce the sojourner- and settler-types of foreigners, four basic types of foreigners' settlement will be illustrated by reviewing relevant migration studies. There were a very small number of Japanese settlers who remained permanently; indentured labourers who were basically transients. There are significant numbers of long-term residents who actually live in societies, and should not be classified as settlers in the analysis of global migratory movements.Keywords: Australia; conceptualisation; indentured labourers; Japanese sojourners; long-term residents; migration studies

We develop a readout system dedicated for a hybrid avalanche photo-detector (HAPD). We employ a waveform sampling and digital signal processing (DSP) technique for the system. We fabricate the first prototype of the system. The system is composed of an analog memory cell (AMC) as the waveform sampler and FINENET with field programmable gate arrays (FPGA) to give low power consumption, high resolution, flexible DSP environment and fast output data transfer. A 64-cell AMC is developed and attained a fast sampling speed of 1GHz with the low power consumption of ~72mW. FINENET works with online DSP functionality and achieved the data transfer rate to -1Gbps with SiTCP. We report the performance of the system with HAPD.

This chapter discusses the overall features of Japanese residential patterns in Australia. In particular, through analysing the residential distribution in major Australian cities, with a focus on Melbourne, it highlights findings of author's questionnaire research on demographic information about Japanese residency. To illustrate, occupational profiles derived from Japanese government data are surveyed and their plans and intentions to reside temporarily or permanently in Australia are ascertained. Thereafter, the attitudes of various informants towards naturalisation are also examined. The fieldwork for this research was conducted in Melbourne, so in the context of a generalised summary, why Japanese people came to Australia and their grounds for their residential preference of Melbourne, is explored and explained. Lastly, the chapter presents a more specific sociological analysis of Japanese residency in Melbourne. An overall view of Japanese residency is depicted in the context of population movements among contemporary urbanites.Keywords: Australia; demographic information; Japanese residency; Japanese sojourners; Melbourne; occupational profiles

This chapter attempts to conceptualise a new type of migration in the context of global migration. It focuses on Japanese emigrants in Australia. Since Japanese communities in Australia have been formed by various types of settlers and sojourners, it is essential to describe the grounds for Japanese emigration. Although there are some who change their residency from ‘sojourner’ to ‘settler’, in an analysis of inducement factors for contemporary Japanese emigration, the chapter points to changes in the public consciousness, or perceptions, about their emigration. When we seek to identify sojourners among the data of Australian migration studies, we find two basic types: one is the ‘return migrant’ who had migrated to Australia, but did not become a permanent settler; the other is the long-term temporary resident, including those from expatriate corporate families, overseas students or researchers who do not intend to stay permanently in the host Australian society.Keywords: Australia; global migration; Japanese emigrants; Japanese sojourners; public consciousness

Globalisation in business and human movement involves the emergence of various types of foreign residents, and this brings new types of international schools into existence. This chapter discusses the activities and characteristics of organisations oriented to ethnic Japanese in Melbourne. It illustrates the major features of Japanese schools in Australia, which give evidence of sojourner-oriented characteristics, though the supplementary school has been changing in this regard. To understand the characteristics and activities of Japanese schools in Melbourne, the chapter examines how Japanese schools in Australia compare with similar schools, overseas. Although there are several organisations which involve the Japanese residents, when considering the establishment of Japanese schools overseas, the Japanese Chamber of Commerce and Industries and the Japanese Societies have played vital roles which are explained in the chapter in detail.Keywords: foreign residents; globalisation; Japanese ethnic organisations; Japanese schools; Melbourne; sojourner-oriented characteristics

The first section of this chapter examines the trends in Japanese arrivals in Australia, with special attention to post-Second World War movements. More recent migration movements, related to the significant developments in multi-lateral relationships between the two countries, are described in the second section, the relevance of this research has emerged with the dramatic rise in the number of Japanese settler arrivals since the 1980s. In the third section, a comparison between temporary and permanent status of Japanese residents and an examination of their attitudes towards naturalisation is presented. The last section shows the characteristics of the long-term and permanent movements of Japanese people by analysing their arrivals and departures data. Australia was chosen for Japanese pensioners because there they would relish the environmental and living conditions which they could not enjoy in Japan.Keywords: Australia; Japanese people; pensioner migrants; permanent residents; post-Second World War movements; temporary residents

In this paper, we propose a new model, “Tunneling with Service Discovery”, for accessing local network services from a remote network. The model enables the splicing of local network services from multiple remote networks so that users can transparently access the advertised services as if they were local services. This model consists of splicing networks and relaying services, and is different from the existing remote access technologies such as VPN and SoftEther(Virtual Private Ethernet Environment). In this model, a server makes use of Service Discovery, and dynamically collects and updates the information about available local network services. A client on a remote network talks to the server, obtains the service information, maps these remote services onto its local services, and then, registers the mapped services on its local Service Discovery. Therefore, all hosts on the client’s network are able to use the relayed services as pseudo local services. The model also allows One-way Access, Multi-Network Access and Multi-Stage Access without requiring any network reconfiguration. As an implementation of this model, we have developed “RNSplicer” that splices local network services provided by Multicast DNS (mDNS). RNSplicer works with all types of services provided by Bonjour (Rendezvous), a standard service discovery technology employed by Mac OS X and Darwin.

Vessels of large colonic polyps often cause postpolypectomy hemorrhage. Preligation with endoloop increases the current density and coagulates more at the site of preligation as compared with at the site of polypectomy. Ligation of stalks after polypectomy is very difficult. The Anchor clip keeps the stalk after polypectomy; in addition, the Anchor clip also suppresses the rolling up, which makes it easy to ligate the stalk. The partially placed Anchor clip draws the electrical current, avoiding burn injury around the Endoclips at the site of the polypectomy. The Anchor clip technique allows easy and safe prevention of postpolypectomy hemorrhage. This article is part of an expert video encyclopedia.

This paper proposes possibilistic regression analysis by the identification method of possibility distribution. First we obtain all possible coefficient vectors of linear systems which correspond to different sets of data. After selection of the necessary coefficient vectors, we apply the identification method to the selected coefficient vectors to obtain a possibility distribution of coefficients in a fuzzy linear system. By our proposed approach, the smaller area of possibility distribution can be obtained. This is the characteristic of our proposed regression, compared with the other regression analyses.

The authors present the analysis of a current-mode parallel resonant power converter, and discuss the characteristics of an experimental realization of the converter and the structure of the resonant inductor. Of the several operation modes of the converter, the one most suitable for information processing equipment was identified in terms of the recovery time of the MOSFET's parasitic diode at high frequency. Normalized circuit characteristics were determined. A 5 V, 150 A converter was developed to verify the analysis, and potential problems in the design were identified, of which the loss in the resonant inductor was found to be the most critical. >

This paper presents a novel vector control method for a parallel-connected multiple motor drive system. The proposed control method is based on the stator-flux, and is capable of accurate and responsive torque control even if there are the rotor velocity differences among the motors. To confirm the validity of the proposed control method, the authors compare a simulation result of the proposed control method with that of the conventional V/f control method. The simulation results show that the proposed control method is effective for the step change in load torque, the rotor velocity differences among the motors and the rotor resistance variation. In addition, experiments on the acceleration and deceleration, and the step change in load torque using four test motors yield satisfactory results.

Fluctuations of the neutral point voltage in NPC power converters cause problems such as excessively high voltage applied to their power devices. This paper presents a novel method of controlling the neutral point voltage by adjusting the dead-time that is required to prevent a DC-link short circuit. To analyze the dynamic effects of dead-time, a state-space averaged model for an NPC power converter is derived. This control method is applicable to single-phase NPC power converters, independent of the polarity of power flow, and free from the undesired variation of switching frequency of PWM. Experimental results have revealed satisfactory control performance.

Dyskeratosis congenita (DKC) is a rare inherited disease characterized by reticulated pigmentation of the skin, nail dystrophy and oral leukoplakia. More than 90% of DKC cases are inherited as an X-linked recessive trait. Half the patients develop progressive pancytopenia by the age of 11 yr, and this is the leading cause of death. We experienced a 11-year-old boy with the above symptomatic triad of DKC, complicated by progressive pancytopenia as well as cerebellar ataxia. Genetic analysis of mRNA from his cultured peripheral lymphocytes revealed a missense mutation resulting in substitution of 1,150 C with T in the DKC1 gene. This is identical to the mutation reported by Knight et al. to be prevalent in X-linked cases of DKC (11 out of 21 patients). Existence of the identical mutation in Japan suggests that this mutation has been selected on the basis of not only the DNA structural sequence of dyskerin, but also its biological function. We report the detailed clinical course of this Japanese DKC patient with a mutation in the DKC1 gene, and describe the results of genetic analysis.

Duocarmycins have been reported to derive their potent antitumor activity through a sequence-selective minor groove alkylation of N3 adenine in double-stranded DNA. We have used gel mobility shift assays to detect proteins that bind to DNA treated in vitro with duocarmycin SA and identified a protein, named duocarmycin-DNA adduct recognizing protein (DARP), which binds with increased affinity to duocarmycin-damaged DNA. Examination with partially purified DARP revealed that the protein recognized not only the DNA adduct of structurally related drug, CC-1065, but unexpectedly, the protein also recognized the DNA adduct of another chemotype of minor groove binder, anthramycin. These results demonstrate that DARP recognizes the structural alteration of DNA induced by these potent DNA-alkylating drugs, suggesting the possibility that the protein might modulate the antitumor activity of these drugs.

A 44-year-old woman had been diagnosed with progressive systemic sclerosis (PSS) at the age of 39 years old and mild pancytopenia was noted at that time. At the age of 41 years symptoms of dry mouth appeared. In April 1997, anemia was in progress (Hb 5.8 g/dl) and severe esophageal varices were found by gastrointestinal fiber scope, and massive splenomegaly by abdominal CT. Serological examination was negative for hepatitis virus and for anti-mitochondrial antibody. In addition, Indocyanine Green test was normal and typical findings of liver cirrhosis were not demonstrated by CT scan. Also, the bone marrow result was normal. Therefore hypersplenism with idiopathic portal hypertension (IPH) was suggested and the patient was referred for splenectomy with the aim of improving the pancytopenia. The weight of the spleen was 2100 g and the pressure of the portal vein was measured at 390 mm H2O. The diagnosis of IPH was determined because pathologically there were no findings for liver cirrhosis. After splenectomy, pancytopenia was remarkably improved (Hb 9.6 g/dl). Consequently, this case was diagnosed as IPH complicated with PSS and Sjögren syndrome.

UCN-01 (7-hydroxyl-staurosporine) was originally isolated as a Ca2+- and phospholipid-dependent protein kinase C selective inhibitor and now is being developed as an anticancer agent. Results from our and other laboratories have suggested that UCN-01 induces preferential G1-phase accumulation in several human tumor cell lines tested. To elucidate this mechanism, we examined the effects of UCN-01 on several cell cycle-regulatory proteins critical for G1-S-phase transition in p53-mutated human epidermoid carcinoma A431 cells. After 24 h exposure at around 50% growth-inhibitory concentrations (IC50s), 260 and 520 nM, UCN-01 induced the accumulation of pRb (the dephosphorylated retinoblastoma protein form). The protein expression of cyclin A but not cyclin E was markedly reduced and that of cyclin D1 was partially reduced under the same condition. UCN-01 also showed the concentration-dependent inhibitions of the activity of cyclin-dependent kinase 2 (CDK2) using histone H1 and pRb as substrates in vitro (IC50, 530 and 640 nM, respectively). In addition, CDK2 activities of the cells pretreated with UCN-01 for 24 h at 260 and 520 nM were markedly inhibited, giving IC50s of far less than 260 nM. When the same cell lysates were analyzed by Western blotting for CDK2, the lower band (e.g., active and phosphorylated CDK2) was remarkably reduced, in accordance with the reduced activity. Furthermore, UCN-01 induced the expression of the CDK inhibitor p21 protein and its complex formation with CDK2 after 24 h exposure at 260 and 520 nM, whereas the expression level was very low or undetectable in untreated or DNA-damaged cells. The increase of p21 mRNA levels was also induced under the same condition. UCN-01 further increased luciferase activities in A431 cells transiently transfected with p21 promoter-luciferase reporter plasmid after 24 h exposure at 260 and 520 nM. UCN-01 also increased the expression of the CDK inhibitor p27 protein after 24 h exposure at 260 and 520 nM. These results suggest that G1-phase accumulation induced by UCN-01 is associated with dephosphorylation of Rb and CDK2 proteins as well as induction of CDK inhibitors p21 and p27.