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MEK inhibitors are among the most successful molecularly targeted agents used as cancer therapeutics. However, to treat cancer more efficiently, resistance to MEK inhibitor-induced cell death must be overcome. Although previous genetic approaches based on comprehensive gene expression analysis or RNAi libraries led to the discovery of factors involved in intrinsic resistance to MEK inhibitors, a feasible combined treatment with the MEK inhibitor has not yet been developed. Here, we show that a chemoproteoinformatics approach identifies ligands overcoming the resistance to cell death induced by MEK inhibition as well as the target molecule conferring this resistance. First, we used natural products, perillyl alcohol and sesaminol, which induced cell death in combination with the MEK inhibitor trametinib, as chemical probes, and identified ribosomal protein S5 (RPS5) as their common target protein. Consistently, trametinib induced cell death in RPS5-depleted cancer cells via upregulation of the apoptotic proteins BIM and PUMA. Using molecular docking and molecular dynamics (MD) simulations, we then screened FDA- and EMA-approved drugs for RPS5-binding ligands and found that acetylsalicylic acid (ASA, also known as aspirin) directly bound to RPS5, resulting in upregulation of BIM and PUMA and induction of cell death in combination with trametinib. Our chemoproteoinformatics approach demonstrates that RPS5 confers resistance to MEK inhibitor-induced cell death, and that aspirin could be repurposed to sensitize cells to MEK inhibition by binding to RPS5.

Anticancer drug delivery by small molecules offers a number of advantages over conventional macromolecular drug delivery systems. We previously developed phenylcyclopropylamine (PCPA)-drug conjugates (PDCs) as small-molecule-based drug delivery vehicles for targeting lysine-specific demethylase 1 (LSD1)-overexpressing cancers. In this study, we applied this PDC strategy to the HDAC-inhibitory anticancer agent vorinostat. Among three synthesized PCPA or arylcyclopropylamine (ACPA)-vorinostat conjugates

Targeting cancer with small molecule prodrugs should help overcome problems associated with conventional cancer-targeting methods. Herein, we focused on lysine-specific demethylase 1 (LSD1) to trigger the controlled release of anticancer drugs in cancer cells, where LSD1 is highly expressed. Conjugates of the LSD1 inhibitor trans-2-phenylcyclopropylamine (PCPA) were used as novel prodrugs to selectively release anticancer drugs by LSD1 inhibition. As PCPA-drug conjugate (PDC) prototypes, we designed PCPA-tamoxifen conjugates 1 a and 1 b, which released 4-hydroxytamoxifen in the presence of LSD1 in vitro. Furthermore, 1 a and 1 b inhibited the growth of breast cancer cells by the simultaneous inhibition of LSD1 and the estrogen receptor without exhibiting cytotoxicity toward normal cells. These results demonstrate that PDCs provide a useful prodrug method that may facilitate the selective release of drugs in cancer cells.

We describe the structure-activity relationship of various arylcyclopropylamines (ACPAs), which are potent LSD1 inhibitors. More than 45 ACPAs were synthesized rapidly by an unconventional method that we have recently developed, consisting of a C-H borylation and cross-coupling sequence starting from cyclopropylamine. We also generated NCD38 derivatives, which are known as LSD1 selective inhibitors, and discovered a more effective inhibitor compared to the original NCD38.

Lysine-specific demethylase 1 (LSD1) is an attractive molecular target for cancer therapy. We have previously reported potent LSD1-selective inhibitors (i.e., NCD18, NCD38, and their analogs) consisting of trans-2-phenylcyclopropylamine (PCPA) or trans-2-arylcyclopropylamine (ACPA) and a lysine moiety that could form a γ-turn structure in the active site of LSD1. Herein we report the design, synthesis and evaluation of γ-turn mimetic compounds for further improvement of LSD1 inhibitory activity and anticancer activity. Among a series of γ-turn mimetic compounds synthesized by a Mitsunobu-reaction-based amination strategy, we identified 1n as a potent and selective LSD1 inhibitor. Compound 1n induced cell cycle arrest and apoptosis through histone methylation in human lung cancer cells. The γ-turn mimetics approach should offer new insights into drug design for LSD1-selective inhibitors.

Hypochlorous acid (HOCl) produced by myeloperoxidase (MPO) of activated neutrophils can react with nucleic acid bases to form chlorinated nucleosides such as 8-chloroguanosine (Cl-Guo). Chlorination is enhanced by nicotine. We investigated the effects of various natural antioxidants including polyphenolic phytochemicals on the formation of Cl-Guo by HOCl in the presence and the absence of nicotine. Polyphenols, including catechins, curcumin, resveratrol, silibinin, and sulfurous compound α-lipoic acid, were found to inhibit both HOCl- and human MPO-induced Cl-Guo formation dose-dependently. Among the test compounds, (-)-epigallocatechin gallate (EGCG) showed the strongest inhibitory effect. Cl-Guo formation, mediated by activated human neutrophils in the presence of nicotine, was inhibited by EGCG, silibinin, and α-lipoic acid. These results suggest that polyphenols and sulfurous compounds have the potential to inhibit the induction of nucleobase damage mediated by chlorination, with possible application to reducing DNA damage associated with inflammation and cigarette-smoke inhalation.

A method that is based on laser-induced fluorescence (LIF) and that involves the use of acetone as a seed can be utilized for measurement of supersonic flows with high temporal and spatial resolutions. In the present study, the feasibility of using this method to measure the number density in supersonic flows at temperatures lower than the atmospheric temperature is investigated. An experiment in which low-temperature conditions are created by supersonic isentropic flows in a convergent–divergent nozzle is carried out. LIF is realized by exciting acetone with the fourth harmonic of a Nd:YAG laser, and the LIF signal is detected by a CCD camera with an image intensifier. In order to theoretically determine the LIF characteristics, a multistep decay model that can be used for temperatures of 300–900 K is extended so that it can be used in the low-temperature regime. The constant included in the model is redetermined by fitting the model to the present experimental data. The LIF calculated by using this extended model is found to agree very well with the experimental data. The model also indicates that the number density measured by the LIF method in the temperature range 170–290 K is insensitive to temperature.

The short chain fatty acid valproic acid (VPA, 2-propylpetanoic acid) is approved for the treatment of epilepsia, bipolar disorders and migraine and clinically used for schizophrenia. In 1999, the first clinical anti-cancer trial using VPA was initiated. Currently, VPA is examined in numerous clinical trials for different leukaemias and solid tumour entities. In addition to clinical assessment, the experimental examination of VPA as anti-cancer drug is ongoing and many questions remain unanswered. Although other mechanisms may also contribute to VPA-induced anti-cancer effects, inhibition of histone deacetylases appears to play a central role. This review focuses on recent developments regarding the anti-cancer activity of VPA.

The three-dimensional flow structure induced by normal shock-wave/boundary-layer interaction in a transonic diffuser is investigated experimentally and computationally. The experiments are done with the wall pressure measurement and oil-flow surface visualization. In the computational work, Reynolds-averaged Navier-Stokes equations are solved numerically with the k-w two-equation turbulence model. The solution reproduces very well the measured streamwise pressure distribution and the vortices observed in the oil-flow visualization. The careful investigation of the calculated flow reveals that the vortices are generated at the foot of the shock wave and bended downstream. It is also found that the boundary layers have a three-dimensional shape downstream of the shock wave. These flow characteristics are explained well with the simple flow model constructed by considering the wave configuration near the diffuser corner.

In this paper, the characteristics of a pressure wave propagating against two parallel subsonic streams in a constant-area straight duct are investigated by one-dimensional analysis, two-dimensional numerical simulation, and experiments. Computations have been carried out by the two-dimensional Euler Equations using the Chakravarthy-Osher-type TVD scheme. Optical observations by the schlieren method as well as wall pressure measurements have been performed to clarify both the structure and the propagation velocity of pressure waves. The results show that the pressure wave propagating against the streams changes into a bifurcated pressure wave and the bifurcation occurs in the low speed streams. It is also found that the propagation velocity of the pressure wave obtained by the analysis and computation agrees well with the present experimental data.

The behavior of two subsonic streams through a single converging nozzle is numerically analyzed from the viewpoint of the choking of the compound nozzle flow. And a new criterion of the compound choking is presented taking the growth of the sonic line extending across the entire exit passage into consideration. The present criterion is compared and discussed with the one based upon the one-dimensional flow model presented by Bernstein et al.

The three-dimensional flow structure induced by normal shock-wave/turbulent boundary-layer interaction in a constant-area rectangular duct is investigated by a laser-induced-fluorescence method. This diagnostic system uses an argon-ion laser as a light source, and the target gas is dry nitrogen with iodine seeded as a fluorescence material. The Mach-number distributions in the duct are obtained from the measured fluorescence intensity, and the threedimensional flow pattern in the expansion region downstream of the initial shock wave is clarified. In addition to this, the region having locally higher Mach number near the duct corners is observed immediately behind the shock wave, and the three-dimensional shape of the boundary layers is found. These flow characteristics are reproduced by solving the Navier‐Stokes equations numerically. The calculated result reveals that the complicated shock-wave configuration is formed at the duct corner because of the interaction of two bifurcated shock waves developed on the two perpendicularly adjacent walls. The simple flow model is also constructed by considering this interaction. This model can explain very well the three-dimensional flow characteristics.

The three-dimensional flow structure induced by normal shock wave/turbulent boundary-layer interaction in a transonic diffuser is investigated by a laser-induced fluorescence method. This diagnostic system uses an argon-ion laser as a light source, and the target gas is dry nitrogen with iodine seeded as a fluorescence material. The three-dimensional Mach number distributions are obtained by the system. Numerical flow simulation is also performed to check the reliability of the measurement and consider the flow field in detail. As a result, the numerical result represents good agreement with the measured flow field, and reveals that two vortices having the direction opposite to each other are generated in the vicinity of the rear leg of the bifurcated shock wave.

To understand choking phenomena of real nozzle flows, an analysis of weak shock waves in duct flows with boundary layers has been carried out by the control volume method where an appropriate mean flow is assumed over a given cross section of the flows. Relations for plane sound waves as the limiting case of the weak shock waves are presented. The criteria for choking and discharge coefficients of convergent nozzles taking account of boundary layers are shown and discussed. As a result, it is found that the ratio of the boundary layer thickness to the duct half-height (or radius in axisymmetric geometries) at the nozzle exit of a convergent nozzle significantly affects choking conditions as well as discharge coefficients.

A tea polyphenol, (−)-epigallocatechin gallate (EGCG), which can scavenge a variety of reactive oxygen species, enhances the yield of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) up to 20-fold in the reaction of 2′-deoxyguanosine with hypochlorous acid (HOCl), compared with the reaction without EGCG. Certain concentrations of EGCG inhibited HOCl-mediated oxidation of 2′-deoxyguanosine to 8-oxo-dG to a limited extent, but efficiently inhibited further oxidation of 8-oxo-dG to spiroiminodihydantoin nucleoside, resulting in the accumulation of 8-oxo-dG in the reaction mixture. Conversely, EGCG inhibited dose-dependently an increase in 8-oxo-dG levels in calf thymus DNA incubated with HOCl. However, addition of HOCl to the DNA preoxidized with an oxidant-generating system (CuCl 2 , ascorbate, H 2 O 2 ), led to the extensive loss of 8-oxo-dG due to its further oxidation. EGCG effectively inhibited this HOCl-mediated loss of 8-oxo-dG in the oxidized DNA, resulting in an apparent increase in 8-oxo-dG levels in the oxidized DNA, compared with the levels found without EGCG. The conversion of 8-oxo-dG into other oxidized lesions will inevitably affect recognition by DNA repair enzymes as well as the rates of mutations and DNA synthesis. Thus, our results suggest that as a biomarker of oxidative DNA damage, not only 8-oxo-dG but also the products of its further oxidation should be analyzed.

Trp53-deficient mice spontaneously develop lymphomas, mainly of thymic origin, although the molecular mechanism remains largely unknown. As several interaction effects between p53 and iNOS have been reported, we hypothesized that iNOS activity in the thymus is causally linked to lymphomagenesis in Trp53-deficient mice. We therefore created mouse strains with different combinations of the Trp53 and iNOS genes. Western blot and histologic analyses showed that the iNOS protein was constitutively expressed in the thymus independently of Trp53 status and its expression was enhanced in Trp53+/- and Trp53-/- mice compared to Trp53+/+ mice. Homozygous disruption of iNOS decreased the incidence of thymic lymphomas by almost 40% (p=0.087) and 90% (p

Three-dimensional unsteady behaviors of a supersonic cavity flow are investigated by the numerical simulation based on the Navier-Stokes equations. The resulting time-dependent solutions are phase-averaged on a dominant frequency. As a result, the standing wave in the cavity and vortex shedding from the leading edge are found to be highly three-dimensional.

The three-dimensional flow structure induced by normal shock wave/turbulent boundary-layer interaction in a constant area rectangular duct is investigated by a laser-induced fluorescence method. This diagnostic system uses an argon-ion laser as a light source, and the target gas is dry nitrogen with iodine seeded as a fluorescence material.The Mach number distributions in the duct are obtained from the measured fluorescence intensity, and the three-dimensional flow pattern in the expansion region downstream of the initial shock wave is clarified. In addition to this, the region having locally higher Mach number at the duct corners is observed just behind the shock wave, and the three-dimensional shape of the boundary layers induced by the shock wave is found. These flow characteristics are explained with the simple flow model constructed by considering the interaction between two bifurcated shock waves developed on the two perpendicularly adjacent walls.

The characteristics of a pressure wave propagating against two parallel subsonic streams in a constant-area straight duct have been investigated experimentally and numerically. Optical observations by the schlieren method as well as wall pressure measurements have been performed to clarify both the structure and the propagation velocity of the pressure wave. Computations have been carried out by two-dimensional Euler equations using the Chakravarthy-Osher-type TVD scheme. The effects of the static pressure ratio across the pressure wave on the propagation velocity are shown and discussed.

An experimental and analytical study has been carried out to obtain the clear understanding of a shock wave transition associated with a steady two-dimensional overexpanded flow. Two-dimensional inviscid theory with respect to a shock wave reflection is used in the present study on the characteristic of shock waves. The results obtained from the flow analysis are compared with those obtained from flow visualizations. It is shown that in the region of regular reflection, the angle of an incident shock wave becomes lower than that calculated by two shock theory with an increment in the ratio p e/p b of the nozzle exit pressure p e to the back pressure p b. It is indicated that the configuration of shock waves in overexpanded jets is influenced by the divergent angle at the nozzle exit. Also it is shown from the flow visualization that a series of shock waves move into the nozzle inside with a decrease in pressure ratio p e/p b, even if the p e/p b is under overexpanded conditions.

The acoustic properties of supersonic jet noise from a convergent-divergent nozzle with a baffle have been studied experimentally over the range of nozzle pressure ratios from 2.0 to 8.0. Acoustic measurements were conducted in a carefully designed anechoic room providing a free-field environment. A new approach for screech noise suppression by a cross-wire is proposed. Schlieren photographs were taken to visualize the shock wave patterns in the supersonic jet with and without the cross-wire. The effects of the baffle and the cross-wire on acoustic properties are discussed. It is shown that the baffle has little effect on the screech frequency for the underexpanded supersonic jet without the cross-wire. Also, the cross-wire introduced in supersonic jets is found to lead to a significant reduction in overall sound pressure level.

Self-excited shock wave oscillation in a two-dimensional transonic diffuser is investigated experimentally and analytically. In theexperiments, the temporal position of a shock wave is recorded by a high-speed charge-coupled device camera combined with a schlieren system, simultaneously measuring the e uctuation of the static pressure on the diffuser wall. The temporal variation of the static pressure is also measured to obtain the propagation of pressure disturbances. The results show that a pressure disturbance is generated near the stem of the shock wave and is convected in the downstream direction. In thedownstream region wheretheboundary layer becomes highly turbulent, another disturbance is generated that propagates upstream and causes the shock wave to oscillate. One-dimensional Euler equations are solved numerically, and the power spectral density distribution of the shock wave oscillation is calculated. The numerical results agree very well with the experiments. It is also shown that the present calculation can explain the shock wave oscillation in the diffusers reported so far.

Multiple shocklets are frequently generated in transonic diffuser flows. The present paper investigates the formation of these shocklets with a high-speed CCD camera combined with the schlieren method. It is observed that compression waves steepen while propagating upstream, and eventually become new shock waves. The ordinary shock wave is found to move upstream beyond the nozzle throat or to disappear while moving downstream depending on the pressure ratio across the nozzle. This phenomenon is also analyzed with the one-dimensional Euler equations by assuming a pressure disturbance given by the sine function at the channel exit. The calculated results are found to reproduce quite well the experimental behavior of the shocklets. The effect of the frequency of disturbance is also studied numerically, and it is shown that the multiple shocklet pattern appears when the amplitude of disturbance is not large and the diverging part of the channel downstream of the ordinary shock wave is long.

Reactive nitrogen species, such as peroxynitrite, nitrogen oxides and nitryl chloride, have been implicated as a cause of diverse pathophysiological conditions, including inflammation, neurodegenerative and cardiovascular diseases and cancer. We previously reported that 8-nitroguanine is formed by reactions of guanine or calf-thymus DNA with peroxynitrite in vitro. In the present study, we have studied the formation of 8-nitroguanosine and 8-oxo-7,8-dihydroguanosine in reactions of calf-liver RNA with various reactive nitrogen species. 8-Nitroguanosine in RNA was found to be much more stable than 8-nitro-2' -deoxyguanosine in DNA, which rapidly depurinates to release 8-nitroguanine. Both 8-nitroguanosine and 8-oxo-7,8-dihydroguanosine were formed in calf-liver RNA following exposure to various reactive nitrogen species, such as synthetic peroxynitrite. They were also formed in RNA by reactive species formed from nitric oxide and superoxide anion generated concomitantly from 3-morpholino-sydnonimine (SIN-1) and those formed with myeloperoxidase or horseradish peroxidase in the presence of nitrite and hydrogen peroxide. 8-Nitroguanosine was detected by HPLC with an electrochemical detector in enzymatic hydrolyzates of RNA isolated from human lung carcinoma cells incubated with synthetic peroxynitrite. Our results indicate that 8-nitroguanosine in cellular RNA could be measured as a marker of damage caused by endogenous reactive nitrogen species in tissues and cells.

Various natural carotenoids, besides β-carotene, were proven to have anticarcinogenic activity, and some of them showed more potent activity than β-carotene. Thus, these carotenoids (α-carotene, lutein, zeaxanthin, lycopene, rbeta β-cryptoxanthin, fucoxanthin, astaxanthin, capsanthin, crocetin and phytoene), as well as β-carotene, may be useful for cancer prevention. In the case of phytoene, the concept of 'bio-chemoprevention', which means biotechnology-assisted method for cancer chemoprevention, may be applicable. In fact, establishment of mammalian cells producing phytoene was succeeded by the introduction of crtB gene, which encodes phytoene synthase, and these cells were proven to acquire the resistance against carcinogenesis. Antioxidative phytoene-containing animal foods may be classified as a novel type of functional food, which has the preventive activity against carcinogenesis, as well as the ability to reduce the accumulation of oxidative damages, which are hazardous for human health.

The choking of dual subsonic streams flowing through a convergent duct in contact has been investigated experimentally and theoretically. The experiment was conducted by using blow-down wind tunnel. The condition, when the dual stream flow choking (compound choking) occurs at the nozzle exit, was explained by one-dimensional analysis of compound sound wave propagation. The experimental results for the condition of compound choking were compared with the prediction from theoretical analysis, and the schlieren optical method using the spark light source has been used to visualize the flowfield.

Hypochlorous acid (HOCl), generated by myeloperoxidase from H(2)O(2) and Cl(-), is a strong chlorinating and oxidizing agent, playing an important role in host defense and inflammatory tissue injury. As several recent studies have shown that various oxidizing agents including peroxynitrite and singlet oxygen react readily with 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) to yield further oxidized products, we have studied the reaction of 8-oxodGuo with reagent HOCl and with a myeloperoxidase-H(2)O(2)-Cl(-) system. When 1 mM 8-oxodGuo was reacted with 0.5 mM HOCl at pH 7.4 and 37 degrees C, two major products were formed. They were identified as the diastereomers of spiroiminodihydantoin deoxyribonucleoside (dSph) on the basis of their identical ESI-MS and UV spectra and HPLC retention times with those of the major reaction products which were reported to be formed in other oxidation systems including potassium monopersulfate plus cobalt (II) chloride, peroxynitrite plus thiol, and type II photosensitization. Under the above reaction conditions, the yield of the diastereomers of dSph was 0.38 mM, with 0.57 mM 8-oxodGuo remaining unreacted. Since the presence of 50% D(2)O, 10 mM sodium azide, or 2% ethanol did not affect the yield of the products, involvement of singlet oxygen and hydroxyl radical in the formation of dSph from 8-oxodGuo with HOCl was ruled out. A 1000-fold excess of dGuo did not inhibit the reaction of 8-oxodGuo with HOCl, indicating that 8-oxodGuo reacts more readily than dGuo with HOCl. dSph was also formed by reaction of 8-oxodGuo with myeloperoxidase in the presence of H(2)O(2) and Cl(-). Our results suggest that formation of dSph from 8-oxodGuo is mediated, possibly via an addition of Cl(+) to, or two-electron oxidation of 8-oxodGuo, with HOCl or the myeloperoxidase-H(2)O(2)-Cl(-) system.

Oral administration of red ginseng extracts (1% in diet for 40 weeks) resulted in the significant suppression of spontaneous liver tumor formation in C3H/He male mice. Average number of tumors per mouse in control group was 1.06, while that in red ginseng extracts-treated group was 0.33 (p

The present paper describes the temperature dependence of the pressure sensitive paints in the pressure range of 1101.3kPa, and the wall temperature range of 263303K. The pressure sensitive paints investigated in the present work are PtOEP, PtTFPP, H2TFPP, H2TCPP, H2TSPP, and H2TTMAPP, and painted on a commercial porous silica thin-layer chromatography (TLC) plate. We estimate the uncertainty of the measured pressure value due to the change in the wall temperature. As a result, the uncertainty of H2TFPP is smaller than 3.5kPa per Kelvin in the present measuring range, and this paint is the most useful paint among the PSPs tested in the present work for measuring the surface pressure of the aerodynamic body on which there are temperature distributions.

The thermal choking phenomenon is of great importance in an inlet isolator in dual-mode ram jet/scramjet combustor. In some cases the choked flow creates a pseudo-shock wave including a shock train in it at the engine inlet and causes large amounts of drag and radically reduces the performance of the engine at high flight Mach numbers. The present paper describes a one-dimensional flow model taking account of the upstream boundary-layer as well as heat addition by using a mass-weighted averaging technique. The simple relationships for the flow field in a constant area duct in which the effect of the upstream boundary-layer is considered but the effect of the wall friction in the duct can be neglected are presented. The results of the calculation such as the maximum heat addition when the thermal choking occurs, the downstream Mach number and the static pressure ratio are presented and examined in detail.

Reactive nitrogen species, including nitrogen oxides (N(2)O(3) and N(2)O(4)), peroxynitrite (ONOO(-)), and nitryl chloride (NO(2)Cl), have been implicated as causes of inflammation and cancer. We studied reactions of secondary amines with peroxynitrite and found that both N-nitrosamines and N-nitramines were formed. Morpholine was more easily nitrosated by peroxynitrite at alkaline pH than at neutral pH, whereas its nitration by peroxynitrite was optimal at pH 8.5. The yield of nitrosomorpholine in this reaction was 3 times higher than that of nitromorpholine at alkaline pH, whereas 2 times more nitromorpholine than nitrosomorpholine was formed at pH

The pressure sensitive paint (PSP) has become a powerful tool for the surface pressure measurements in the windtunnel testing. This diagnostic method, however, is limited to the time-averaged measurements so far, because the temporal behavior of PSP has not been well understood. Present paper describes the experimental investigations on the time response of three pressure sensitive paints, PtOEP, H2TFPP and PtTFPP. The coating on which the PSPs are painted is a commercial porous silica thin-layer chromatography (TLC) plate. The sudden change in pressure is provided by a shock tube, and the luminescence change due to the pressure rise by an incident shock wave is detected by a photomultiplier. The results indicate that the characteristic response time is found to differ among the PSPs tested, and the shortest characteristic time is on the order of ten microseconds. The effect of the sudden change in gas temperature on the luminescence intensity is also investigated by using the contact surface of the shock tube flow, and it is found that the luminescence intensity depends only on the wall temperature and is affected little by the gas temperature.

A method for measuring propagation of disturbance in a high-speed flow has been developed by using a laser induced fluorescence (LIF) technique. A cross correlation function between the time-dependent LIF signal and a pressure sensor signal at a reference point enables to measure a propagation speed of disturbance. Through a bandpass filter, the speed of disturbance with a particular frequency can he obtained. A feature of disturbance propagation can be grasped by drawing maps for the cross-correlation coefficients on a space at successive delay-times and making an animation. The method was applied to a supersonic flow over a rectangular cavity with length to depth ratio of 2, to elucidate feedback mechanisms of self sustaining flow oscillation with several dominant frequencies.

Telomeres, the ends of eukaryotic chromosomes, are essential structures formed by specific protein-DNA complexes that protect chromosomes from degradation and end-to-end fusion. TRF1, a double-stranded telomeric TTAGGG-repeat binding protein, is associated with mammalian telomeres and controls telomere length by inhibiting the action of telomerase. We identified human nucleoside diphosphate kinase nm23-H2 as a human TRF1-interacting protein by yeast two-hybrid screening. In vitro-binding assays using different recombinant nucleoside diphosphate kinases showed that TRF1 predominantly binds the nm23-H2 isoform rather than nm23-H1. Electrophoretic mobility shift analysis revealed that the recombinant nm23-H2 protein can bind the single-stranded telomeric TTAGGG-repeat while it cannot bind the double-stranded telomeric repeat. The synthetic 20 base oligoribonucleotide, which consists of the template sequence CUAACCCUAAC and the adjacent region of the RNA component of human telomerase, was also found to form the complex with the recombinant nm23-H2 protein. Furthermore, the affinity of telomerase for its substrate was increased in vitro by presence of the plentiful nm23-H2 protein. These findings indicate a close relationship between nm23-H2 and human telomeres and suggest a new biological role for nucleoside diphosphate kinase.

The present paper describes the numerical as well as the experimental study on the axisymmetric supersonic jet associated with a sootblower nozzle for boiler cleaning. The Navier-Stokes equations are solved numerically, and the experimental work is also performed with the low-density wind tunnel. Calculations and experiments both cover the region from the nozzle exit to the downstream distance of 20 times the nozzle exit diameter. The effect of the nozzle divergence angle is discussed by comparing the experiments with calculations, and it is pointed out that, even when the expansion ratio across the nozzle is correct, the regular shock-cell structure appears in the jet for the nozzles with finite divergence angles. Also, the present numerical results on the impact pressures along the jet center-line agree favorably well with those reported by the other researchers.

A method for measuring temperature fluctuations in a high-speed flow is developed by the use of a laser-induced fluorescence (LIF) technique. Propagation speed of disturbance can be found by a time lag of cross-correlation functions between the time-dependent LIF signal and a pressure sensor signal at a reference point. The method is applied to a supersonic cavity flow to elucidate the feedback mechanism of self-sustaining flow oscillation.

The influence of bovine lactoferrin (bLF) on colon carcinogenesis was investigated in male F344 rats treated with azoxymethane (AOM). Following three weekly injections of AOM, the animals received 2 or 0.2% bLF for 36 weeks. No effects indicative of toxicity were noted, but significant reduction in both the incidence and number of adenocarcinomas of the large intestine was observed with both doses. Thus, the incidences of adenocarcinomas in the groups receiving 2% and 0.2% bLF were 15% and 25%, respectively, in contrast to the 57.5% control value (P < 0.01 and P < 0.05, respectively). The results indicate that bLF might find application for chemoprevention of colon cancer.

To investigate shock oscillation mechanism in supersonic nozzle, high speed CCD camera is used with schlieren system. Power spectral density distributions of shock displacement and cross-correlation between shock displacement and light intensities at various points are obtained. As a result, it is clarified that shock oscillation mechanism consists of downstream moving large scale turbulent structure generated due to shock motion and disturbance propagating upstream in core flow region.

The laser-induced fluorescence method has offered a powerful diagnostic tool for the measurements of transonic and supersonic flows. The present paper uses a tunable line-narrowed AF excimer laser that lases with the 193.5nm ultra-violet wavelength. This laser is injected into the static gas cell with variable pressure. The gases used are argon for the Rayleigh scattering and oxygen for the Raman scattering and induced fluorescence measurements. The Rayleigh scattering intensity is measured as a function of the cell pressure, and also the spectroscopic characteristics are obtained for the Raman and fluorescence from the oxygen molecules.

A fundamental experiment of the temperature characterisitc of the pressure sensitive paint (PSP) to a continuous change in pressure is performed. As the results, for fixed temperature, as the pressure decreases, the paint's brightness increases and for high temperature the brightness decreases. Also, as temperature increases, relative intensity decreases, and relative sensitivity to pressure changes increases. Furthermore, the characteristic of the response of the PSP to a step change in pressure is presented and the time constant is estimated.

The 3D flow structure induced by a normal shock-wave/boundary-layer interaction in a transonic diffuser is experimentally and computationally investigated. In the diffuser, the shock wave is located in the diverging section. The experiments are done with wall pressure measurements, oil-flow surface visualization, and Mach number measurements with a laser-induced fluorescence (LIF) method. In the computational work, the Reynolds-averaged Navier–Stokes equations are numerically solved with the k-ω two-equation turbulence model. The numerical solution agrees reasonably well with the experiment and clarifies the vortex structure in the interaction zone along with the 3D behavior of the boundary layer downstream of the shock wave. A careful investigation of the calculated flow reveals that the vortices are generated at the foot of the shock wave. It is also found that a complicated wave configuration is formed near the diffuser corner. A flow model is constructed by considering this wave configuration. This model explains the 3D flow characteristics in the transonic diffuser very well.

To investigate the transonic flow in a duct with a cavity, the laser-induced fluorescence (LIF) method is developed. This diagnostic system is based on the argon laser with seeded iodine as fluorescence material, and is applied to the rectangular duct with a cavity. The distributions of temperature and its fluctuation in the cavity are obtained, and the three-dimensional structure of the flow field is clarified.