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The Martian atmosphere, which mainly consists of carbon dioxide (CO2), is characterized by extremely low temperatures that cause CO2gas to freeze and dry ice to form. To date, temperatures below the CO2saturation temperature, which can be attributed to the effects of atmospheric waves, have been observed in the polar winter and in the mesosphere. Using data from Mars Global Surveyor (MGS) radio occultation measurements, we investigated the role of large‐scale atmospheric waves including stationary and transient waves at northern high latitudes in winter on CO2supersaturation. A distinct longitudinal dependence of CO2supersaturation was observed at altitudes higher than the pressure level of 200–400 Pa, where a stationary wave with a wave number of 2, whose temperature amplitude had minima at 30–100 Pa, lowered the background temperature to a level close to the CO2saturation temperature. However, the stationary wave alone was not sufficient to cause CO2supersaturation. Additional temperature disturbances caused by transient waves, namely, superposition of both waves, had a significant role in CO2supersaturation. The longitudinal dependence of the occurrence of CO2supersaturation revealed by our study might affect the longitudinal distribution of CO2snowfall and the formation of the seasonal polar ice cap. Using data from MGS radio occultation measurements, we studied the role of stationary and transient waves on CO2supersaturation on MarsWe found a longitudinal dependence of CO2supersaturation above 200–400 Pa, where stationary waves lowered the background temperatureHowever, additional disturbances by transient waves, namely, superposition of both waves, had a significant role in CO2supersaturation

Fluctuations of ozone concentrations with dimensions of a few kilometers (i.e., ozone laminae) are frequently found in ozone‐sounding profiles. We used ozonesonde measurements made at the southern tip of South America to examine the relationship between ozone laminae and atmospheric waves near the edge of the polar vortex and on the leeward side of the Andes Mountains. Laminar structures are formed by vertical and horizontal displacements of isopleths due to gravity waves and by isentropic advection of vortex air filaments with low ozone concentration due to Rossby wave breaking. We extracted components of these ozone fluctuations by applying a high‐pass filter to the observed ozone profiles and normalizing them to background concentrations, which were extracted with a low‐pass filter. Ozone fluctuations due to displacements caused by gravity waves were individually evaluated with experimental data. We assumed that the residuals between the observed and gravity wave‐induced fluctuations were Rossby waves‐induced fluctuations. We found that the gravity wave‐induced variability was larger in the upper troposphere than in the lower stratosphere and was a maximum in winter. Rossby wave‐induced variability showed a distinct seasonal pattern in the lower stratosphere and accounted for a large portion of the observed variability. We also examined the relationship between gravity wave‐induced and Rossby wave‐induced ozone variability and the differences in equivalent latitudes between the sonde positions and the polar vortex edge. We found that variability was larger inside than outside the polar vortex. Ozonesonde data obtained at southern Patagonia were used to quantify the contribution of gravity waves and Rossby waves to ozone laminaeRossby waves played a dominant role in creating ozone laminae, but the role of gravity waves was not negligibleRossby wave‐induced ozone variability was greater inside the polar vortex than outside or near the edge

Aims.Stellar parameters and abundances of Na, Mg, Al, K, Ca, Sr, Ba, and Eu are determined for four very metal-poor (VMP) stars ($-2.15 \ge [$Fe/H$] \ge -2.66$). For two of them, HD 84937 and HD 122563, the fraction of the odd isotopes of Ba derived for the first time.

We have examined the space distribution of IRAS sources in the Galaxy paying attention in particular to the difference between oxygen-rich and carbon stars. The sample consists of about 70 000 sources with good quality photometric data both at 12 and 25 μm. Sample sources are mostly post main sequence stars. Oxygen-rich asymptotic giant branch stars show the highest stellar density at the Galactic center. The density decreases with the increase in the Galactocentric distance. On the other hand, carbon stars show a uniform density distribution within about 3.6 kpc of the Sun. Thus the ratio of carbon stars to oxygen-rich asymptotic giant branch stars increases with the increase in the Galactocentric distance within the range between about 5 and 12 kpc.

This paper presents a method to measure the attention and emotion levels using the near-infrared spectroscopy (NIRS) signals around the prefrontal cortex. The brain blood oxygen concentration over the subjects’ brains is measured by NIRS while they watch the Japanese comic Rakugo and sad videos. The analysis has been done by using the first principal component of measured signals, and the paper proposes the hypothesis to relate the power of the first principal component and its distribution function to the emotion and the attention levels. To verify the hypothesis, an analysis has been performed of experiments in which both normal and dementia subjects watch videos. This paper raises the possibility of diagnosing dementia by measuring levels of emotion and attention.

A comprehensive experimental investigation has been conducted to determine the effective permeability of fluid saturated porous media consisting of small and large spherical particles. Small and large particles were mixed uniformly at a certain mixture ratio so as to form a vertical porous column. Water was drawn from a reservoir to flow through the vertical tube filled with particles of different sizes. The resulting pressure drops between the inlet and outlet sections of the test column were measured at various flow rates to determine the effective permeability. The results were compared with the present theoretical model generalized on the basis of the analysis reported by Liu, Sano and Nakayama for fractured porous media. It has been confirmed that the present mathematical model agrees very well with the experimental data and thus can be used to estimate the permeability of porous media consisting of obstacles of different sizes.

Summary: This study was designed to examine thein vitro metabolism of YM758, a novel cardiovascular agent, and to evaluate its potential to cause drug interactions and induction of CYP isozymes. After incubation with pooled human liver microsomes, YM758 was converted to two major metabolites (AS2036313-00, and YM-394111 or YM-394112). The formation of AS2036313-00, and YM-394111 or YM-394112 were mediated by CYP2D6 and CYP3A4, respectively, which was elucidated by using a bank of human liver microsomes and recombinant CYP enzymes in combination with the utilization of typical substrates and inhibitors. TheK i values of YM758 for midazolam, nifedipine, and metoprolol metabolism ranged from 59 to 340 µM, being much higher than the YM758 concentration in human plasma. The formation of AS2036313-00, and YM-394111 or YM-394112 was inhibited by quinidine and ketoconazole withK i values of 140 and 0.24 µM, respectively, which indicates that YM758 metabolism may be affected by co-administration of strong CYP2D6 and 3A4 inhibitorsin vivo, given the clinical plasma concentrations of quinidine and ketoconazole. After human hepatocytes were exposed to 10 µM YM758, microsomal activity and mRNA level for CYP1A2 were not induced while those for CYP3A4 were slightly induced. The tested concentration was much higher than that in human plasma, which suggests that the induction potential of YM758 is also negligible.

Summary: The pharmacokinetics of YM758, a novelfunny If current channel (If channel) inhibitor, was investigated after single intravenous (i.v.) and oral dosing to rats and dogs, and partially compared with the results in humans by using liver microsomes. After i.v. administration, the plasma YM758 concentrations decreased, with an elimination half-life (t1/2) of 1.14–1.16 h in rats and 1.10–1.30 h in dogs. Total body clearance (CLtot) was 5.71–7.27 and 1.75–1.90 L/h/kg in rats and dogs, respectively which was comparable to the hepatic blood flow rate. In dogs, the pharmacokinetic profiles for i.v. bolus administration and continuous infusion did not differ. After oral administration, the levels of YM758 in rat plasma increased more than dose-proportionally, whereas almost linear pharmacokinetics were observed in dogs. Absolute bioavailability was 7.5%–16.6% in rats and 16.1%–22.0% in dogs. The plasma protein binding saturation of YM758 was observed in dogs and humans; this finding is consistent with the result that the major binding protein of YM758 in plasma is α1-acid glycoprotein (AGP), in particular in humans. The blood-to-plasma partition coefficient values were 1.36–1.42 in rats, 0.95–1.15 in dogs and 0.71–0.85 in humans. The results of the metabolic study on liver microsomes indicated that the non-linear pharmacokinetics of YM758 observed in rats may be partially due to a first-pass effect in the gastrointestinal tract and the liver.

This study examined the contribution made by organic cation transporters (hOCT/rOct) to the saturable component of the renal uptake of 1-methyl-4-phenylpyridinium, tetraethylammonium (TEA), cimetidine and metformin into rOct2-expressing HEK293 cells and rat kidney slices. All the test compounds accumulated in the rat kidney slices in a carrier-mediated manner. The Michaelis–Menten constant (Km) values for saturable uptake of TEA, cimetidine and metformin into rat kidney slices were relatively comparable with those for the rOct2-expressing HEK293 cells. In addition, the relative uptake activity values of TEA, cimetidine and metformin in rat kidney slices were similar to those in rOct2-expressing HEK293 cells. This suggests that the saturable components involved in the renal uptake of TEA, cimetidine and metformin are mediated mainly by rOct2. The saturable uptake profile of cationic compounds into rat kidney can be evaluated in both cDNA-expressing cells and rat kidney slices, as well as the transporter expression pattern. This approach can also be used to estimate the saturable uptake mechanism of cationic compounds into the human kidney when human kidney slices and hOCT2-expressing cells are used.

The correlation between the magnitudes of spin dependent scattering (ΔRA) and impurity polarization was examined in current perpendicular to plane (CPP-) giant magnetoresistance (GMR) films with ultra-thin Cu inserted Fe-Co layers, with changing the chemical compositon of Fe-Co. The enhancing effect of ΔRA by Cu insertion was remarkable for Fe70Co30 layers in which the body centered cubic structure is maintained against Cu insertion and large spin polarization of dissolved Cu is observed via X-ray magnetic circular dichroism. We thus conclude that the enhancement of spin dependent scattering originates from the spin polarized Cu atoms embedded in Fe-Co alloys. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Background:Cementum formation is considered to be a critical event for successful regeneration of periodontal tissues. Cementoblasts share many characteristics with osteoblasts. Prostaglandin E2(PGE2) is an important local factor in bone metabolism. Although the effects of PGE2on osteoblasts are well known, its effects on cementoblasts have not yet been established. We examined the effects of PGE2on proliferation and differentiation in a mouse cementoblast cell line, OCCM‐30 cells. Methods:OCCM‐30 cells were treated with three concentrations of PGE2(10, 100, and 1,000 ng/ml). Cell number, alkaline phosphatase (ALP) activity, and expression for mineralization‐related genes were determined. Osteoprotegerin (OPG) and receptor activator of nuclear factor‐kappa B (NF‐κB) ligand (RANKL) expression were also examined by real‐time polymerase chain reaction (RT‐PCR) and enzyme‐linked immunosorbent assay (ELISA). Results:The addition of PGE2at the highest dose used in this study suppressed cell proliferation of OCCM‐30 cells. The expression of mineralization‐related marker mRNA, such as type 1 collagen, ALP, bone sialoprotein (BSP), and osteocalcin (OCN), was constitutively detected in OCCM‐30 cells. PGE2dose dependently stimulated ALP activity and BSP‐mRNA expression in OCCM‐30 cells at day 3. Transcripts for OPG and RANKL and the protein level of OPG in culture media were upregulated with PGE2stimulation. Conclusion:These results demonstrate that PGE2suppressed cementoblast proliferation but stimulated ALP activity and the BSP‐mRNA level, suggesting a role of PGE2in controlling cementoblast differentiation, and further indicate that PGE2modulates RANKL and OPG expression in cementoblasts; the increase of OPG secreted from cementoblasts with PGE2stimulation may be essential to protect the root surface from resorption.

We present a case of recurrent saddle embolism 6 days and 9 days following corrective osteotomy of the left femur in a 64-year-old man with a history of atrial fibrillation. Although saddle embolism is a relatively rare event, orthopaedic surgeons should be aware of this condition.

Abstract: The distribution and desorption processes of hydrogen and deuterium have been visualized by secondary ion mass spectrometry (SIMS). The present article deals with four principal points: (1) visualizing the hydrogen distribution, (2) visualizing the hydrogen desorption process from each metallurgical microstructure under various holding times at 25 C, (3) visualizing the hydrogen desorption process during heating, and (4) determining the correspondence between desorption profiles and desorption sites. A spheroidal graphite cast iron specimen was prepared for visualizing hydrogen, since it consists of basic microstructures of steels such as ferrite and pearlite. Hydrogen and deuterium were occluded into the cast iron. The amount of hydrogen and the existing states of hydrogen in the cast iron were analyzed by thermal desorption spectrometry (TDS). The TDS analyses show that the hydrogen desorption has two peaks, namely, the low- and high-temperature peaks corresponding to trap activation energies of 21.6 and 105.8 kJ/mol, respectively. The SIMS analyses of the specimen cooled after heating to 100 C, 200 C, and 300 C reveal that the hydrogen desorbs from the ferrite after heating to 100 C, from the pearlite and the interfaces between the ferrite and the graphite after heating to 200 C, and from the pearlite after heating to 300 C. The graphite remains, trapping hydrogen after heating to 300 C. On the basis of TDS and SIMS results, the relationship between the desorption profile and desorption sites was identified; that is, the low-temperature peak corresponds to ferrite, pearlite, and graphite/ferrite interfaces, while the high-temperature peak corresponds to graphite.

The purpose of this retrospective study was to assess regional cerebral blood flow in patients after carbon monoxide intoxication by using brain single photon emission computed tomography and statistical parametric mapping. Eight patients with delayed neuropsychiatric sequelae and ten patients with no neuropsychiatric symptoms after carbon monoxide intoxication were studied with brain single photon emission tomography imaging with 99mTc-hexamethyl-propyleneamine oxime. Forty-four control subjects were also studied. We used the adjusted regional cerebral blood flow images in relative flow distribution (normalization of global cerebral blood flow for each subject to 50 ml.100 g−1.min−1with proportional scaling) to compare these groups with statistical parametric mapping. Using this technique, significantly decreased regional cerebral blood flow was noted extensively in the bilateral frontal lobes as well as the bilateral insula and a part of the right temporal lobe in the patients with delayed neuropsychiatric sequelae as compared with normal volunteers (P< 0.005). In the patients with no neuropsychiatric symptoms, significantly decreased regional blood flow in the bilateral frontal lobes particularly on the left side was detected. There was a significantly decreased regional cerebral blood flow in the right frontal lobe and insula in the patients with delayed neuropsychiatric sequelae as compared to those with no neuropsychiatric sequelae. It is concluded that statistical parametric mapping is a useful technique for highlighting differences in regional cerebral blood flow in patients following carbon monoxide intoxication as compared with normal volunteers. The selectively reduced blood flow noted in this investigation supports the contention that the decrease following carbon monoxide intoxication may be prolonged and further worsen in the frontal lobe. In addition, the present study may help to clarify the characteristics of the pathophysiological alteration underlying delayed neuropsychiatric sequelae.

To discover a highly selective M3 antagonist, a combinatorial library was prepared. The library was designed to identify a novel structural class of M3 antagonists by exploring the spatial arrangement of the pharmacophores in known M3 antagonists. After the evaluation of 1000 library members, a potent M3 antagonist, 14a (Ki = 0.31 nM), with novel structural features was identified. Compound 14a showed high selectivity for M3 receptors over the other muscarinic receptor subtypes (M1/M3 = 380-fold, M2/M3 = 98-fold, M4/M3 = 45-fold, M5/M3 = 120-fold).

Insertion bonding of mild steel and titanium pipes in aluminium castings was performed in two ways; either by holding paired pipe and aluminium cylinder specimens at constant high temperatures, or by pouring molten aluminium into sand moulds containing inserts. The surfaces of the inserts were electroplated using Ag or Au, or spray coated with Al-Si alloy. The bonding was evaluated by shear strength measurements and microstructure observations. To verify the effect of surface coatings, the contact between the molten aluminium and the specimens was observed. At constant high temperatures, coated steels showed good metallurgical bonding when they were maintained for about 200 s in contact with molten aluminium. The time necessary for bonding was shorter with titanium inserts. In bonded specimens, alloyed microstructures were observed at the interfaces. There was no bonding with uncoated specimens. All coatings used were effective when poured, but preheating of the moulds was necessary to allow sufficient solidification time for the melt/insert volume ratios which were 32 and 36. Process analysis by the finite difference method showed that bonding required a period of liquid phase contact of the melt with the inserts. Observation of aluminium droplet contact with the inserts showed that uncoated surfaces of steel and titanium are not wetted by the melt due to stable oxide skins. With Ag electroplating, aluminium droplets can make wet contact with the specimens. The contact angle decreased from about 140° in uncoated specimens to 15°-45° with Ag plating. The plating prevents surface oxidation of the inserts and promotes wet contact when the active aluminium liquid surface is exposed. The Al-Si alloy spray coating has some effect in promoting wettability, but it is inferior to Ag plating.

The presence of a Tumor Necrosis Factor alpha (TNFα)-like molecule has been suggested in fish by biological assays and biological and antigenic cross-reactivities with human TNFα. In the present study, whether rainbow trout macrophages produce TNFα was examined. Murine recombinant TNFα (m-rTNFα) was used as the standard mammalian TNFα. The supernatants were harvested from trout macrophage culture stimulated with lipopolysaccharide (LPS) and then passed through a Polymyxin B column to remove LPS. Results show that trout macrophage culture supernatants exhibit TNF-like activities. The supernatants significantly enhanced neutrophil migration and macrophage respiratory burst activity as assessed by NBT reduction test. The supernatants were also highly cytotoxic to murine L929 cells, which are known to be sensitive to mammalian TNFα. The biological activities of TNF in the trout macrophage culture supernatant was determined as 2·6U ml−1in the presence of actinomycin D. This indicates biological cross-reactivity of trout TNFα-like factor on mammalian cells. Moreover, these activities were inhibited by a rabbit anti-mTNFα antibody. These results suggest that rainbow trout macrophages produce a TNFα-like factor that is similar to the mammalian TNFα in functions.

In the present study, the effect of prostaglandin E2(PGE2) on intercellular adhesion molecule-1 (ICAM-1) expression in human gingival fibroblasts (HGF) stimulated with lipopolysaccharides (LPS) was investigated. LPS were isolated from periodontopathic bacteria, Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) and Porphyromonas gingivalis (P. gingivalis), by the phenol-water method and Escherichia coli (E. coli) LPS was used as a control. PGE2significantly inhibited A. actinomycetemcomitans-, P. gingivalis- and E. coli-LPS-induced ICAM-1 expression. Next, of four PGE2receptor subtypes (EP1, EP2, EP3and EP4), we examined which subtype(s) was involved in inhibition of LPS-elicited ICAM-1 expression by PGE2. Eleven-deoxy-PGE1, a selective EP2/EP4agonist, and butaprost, a selective EP2agonist, attenuated A. actinomycetemcomitans-, P. gingivalis- and E. coli-LPS-elicited ICAM-1 expression, although butaprost was less potent than PGE2and 11-deoxy-PGE1. Sulprostone, an EP1/EP3agonist, and ONO-AP-324, an EP3agonist, was inert to the LPS-elicited ICAM-1 expression. Furthermore, dibutyryl cAMP, a cAMP analogue, and forskolin, an adenylate cyclase activator, downregulated A. actinomycetemcomitans-, P. gingivalis- and E. coli-LPS-elicited ICAM-1 expression in HGF. Our data suggest that PGE2downregulates A. actinomycetemcomitans- and P. gingivalis-LPS-induced ICAM-1 expression in HGF, via EP2/EP4receptors by cAMP-dependent signaling pathways. The cAMP-elevating agents such as EP2/EP4receptor activators may serve to control inflammatory and immune responses in periodontal disease.

The CC chemokines may play an important role in the pathogenesis of chronic inflammatory diseases including rheumatoid arthritis, and their effects are thought to be mediated through CCR1 receptors. Several nonpeptide CCR1 receptor antagonists that showed high affinity for human CCR1 receptors have been identified; however, their effectiveness in animal models of inflammatory diseases has been scarcely demonstrated, probably due to species selectivity of the antagonists. To elucidate the pathophysiological role of CCR1 receptors in murine models of disease, we looked for a potent antagonist for both murine and human CCR1 receptors. Screening of our chemical collection for inhibition of ¹²⁵I-MIP-1α binding to human CCR1 receptors transfected in CHO cells led to the identification of xanthene-9-carboxamide 1a as the lead compound. Derivatization of 1a by quaternarizing the piperidine nitrogen with various alkyl groups and by installing substituents into the xanthene moiety dramatically improved the inhibitory activity against both human and murine CCR1 receptors. As a result, 2q-1 showing IC50 values of 0.9 and 5.8 nM for human and murine CCR1 receptors, respectively, was discovered. This compound is the first murine CCR1 receptor antagonist and may be a useful tool for clarifying the role of CCR1 receptors in murine models of disease.

Abstract: Background. A prospective randomized study was designed to determine whether flutamide (FLU) administered before treatment with a luteinizing hormone-releasing hormone agonist (LH-RHa) prevented prostate-specific antigen (PSA) flare in prostate cancer patients. Methods. Prostate cancer patients were randomized into two groups and received either FLU (n = 11) or no pretreatment (n = 13) for 2 weeks before the initial injection of LH-RHa. LH-RHa (every 4 weeks) and FLU (every day) were administered throughout the period of this study. Blood samples, for the determination of PSA, testosterone (T), and luteinizing hormone levels, were collected before FLU administration, and before and 2, 7, 14, 28, 56, and 84 days after the first administration of LH-RHa. Results. Treatment with FLU prior to LH-RHa induced an early decline in PSA level. The mean PSA level showed no significant secondary rise after LH-RHa administration in those patients with FLU pretreatment. Patients in both groups showed T flare after the first LH-RHa administration. However, the number of patients with PSA flare was significantly lower in patients with prior FLU administration than in those with LH-RHa alone. Conclusion. These results clearly demonstrate that, in patients with prostatic cancer, the administration of FLU for 2 weeks prior to the first LH-RHa administration is effective in preventing PSA flare, as well as in inducing an early decline in PSA levels.

A novel series of (2R)-2-[(1R)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamides was designed and synthesized based on the structure and biological profiles of an active metabolite 2 of our prototype muscarinic M3 receptor selective antagonist 1, to develop a potent, long-acting, orally active M3 antagonist for the treatment of urinary tract disorders, irritable bowel syndrome, and respiratory disorders. Investigation of (2R)-2-[(1R)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamides containing a phenyl or heterocyclic ring as the piperidinyl side chain in place of the 4-methyl-3-pentenyl moiety of 15a revealed that this acid moiety was a versatile template for improving the selectivity for M3 over M2 receptors in comparison with the corresponding cyclopentylphenylacetic acid group. However, since the in vitro metabolic stability of these analogues was insufficient compared with that of 2, further derivatization was performed by introducing an appropriate hydrophilic group into the phenyl or 2-pyridyl ring. Thus, the 1-(6-aminopyridin-2-ylmethyl)piperidine analogue 15y exhibiting 190-fold selectivity for M3 receptors (Ki = 2.8 nM) over M2 receptors (Ki = 530 nM) in a human binding assay and good in vitro metabolic stability in dog and human hepatic microsomes was identified. This compound has excellent oral activity at 4 h after oral dosing (1 mg/kg), inhibiting methacholine-induced bronchoconstriction in dogs, and may be useful in clinical situations in which M3 over M2 selectivity is desirable.

Crystal structures of the α and β modifications of poly(tetramethylene succinate) (PTMS) were analyzed by X-ray diffraction: the β form appeared with an application of stress. These two modifications belonged to the monoclinic system with the space group of P21/n. In both cases, a unit cell included two chemical repeating units. For the α form, the cell dimensions were a=0.523nm,b=0.912nm,c(fiber axis)=1.090nm,and β=123.9°; for the β form, a=0.584nm,b=0.832nm,c(fiber axis)=1.186nm,and β=131.6°. The difference in the fiber periods of the two crystalline forms was attributed mainly to the conformational difference in the tetramethylene unit, i.e. TGTḠTof the α form and TTTTTof the β form. It was also found that in PTMS, the packing coefficient, K, which was defined by the ratio of the intrinsic volume with respect to the true volume of the α form was almost equal to that of the β form. This observation could be contrasted to those obtained in poly(butylene terephthalate) (PBT), where the Kof the α form was considerably greater than that of the β form. The difference between PTMS and PBT was attributed to the difference between the unit cell volumes of the α and β forms of these polymers.

A novel ultrafast optical signal measurement technique is proposed that uses a fast photodetector and electrooptic (EO) sampling. The technique can satisfy three requirements for the measurement: large bandwidth, high sensitivity, and polarization independence. The measurement systems are demonstrated using two kinds of EO sampling configurations. One system uses direct EO sampling. It affords a larger bandwidth. The system can discern 100-Gbits−1 return-to-zero (RZ) optical pulse-pattern signals with an on–off ratio of 22dB. The other system uses a waveguide intensity modulator in EO sampling. It affords higher sesitivity and can measure an 80-Gbits−1 RZ optical eye diagram. It is theoretically expected that the sensitivity of our system is higher than that of the all-optical technique.

The pim-1 oncogene encodes a serine/threonine kinase (Pim-1) involved in the transduction of cytokine-triggered mitogenic signals. Pim-1 is unique in that it closely cooperates with c-Myc not only in oncogenesis, but also in apoptosis induction. However, the molecular basis of Pim-1 function remains poorly understood, largely because the downstream effector molecule(s) for Pim-1 kinase has not been identified. Here we provide several lines of evidence that Cdc25A cell cycle phosphatase, a direct transcriptional target for c-Myc, is a substrate for Pim-1 kinase and functions as an effector for Pim-1. We found that Pim-1 physically interacts with Cdc25A both in vitro and in vivo and phosphorylates Cdc25A. We also observed that Pim-1-mediated phosphorylation of Cdc25A increases its phosphatase activity. In addition, wild-type Pim-1, but not kinase-inactive Pim-1, enhanced Cdc25A-mediated cellular transformation and apoptosis. Our results indicate that Cdc25A might be a key molecule that links Pim-1 and c-Myc and that also ties Pim-1-mediated mitogenic signals to cell cycle machinery.

The expression of c-myc promotes cell proliferation and also sensitizes cells to various extracellular apoptotic stimuli. However, signal pathways regulating the function of Myc proteins during apoptosis are unknown. c-Jun N-terminal kinase (JNK) is activated by various apoptotic stimuli, but neither the target molecule(s) or the action of JNK has been identified in Myc-mediated apoptosis. Here, we found that JNK selectively interacted with, and phosphorylated, c-Myc at Ser-62 and Ser-71 as confirmed with phospho-c-Myc-specific antibodies. Interestingly, dominant negative mutant JNK(APF) impaired the c-Myc-dependent apoptosis, but not mutated c-Myc (S62A/S71A)-dependent apoptosis triggered by UV irradiation. Furthermore, c-Myc (S62A/S71A)-expressing NIH3T3 cells were not sensitized like wild type c-Myc-expressing NIH3T3 cells to JNK-activating apoptotic stimuli, such as UV and Taxol. These results indicate that the JNK pathway is selectively involved in the c-Myc-mediated apoptosis and that the apoptotic function of c-Myc is directly regulated by JNK pathway through phosphorylation at Ser-62 and Ser-71.

In the present study, the effect of prostaglandin E2(PGE2) on intercellular adhesion molecule-1 (ICAM-1) expression in interferon-γ (IFN-γ)-stimulated human gingival fibroblasts (HGF) was investigated. Addition of PGE2to HGF inhibited ICAM-1 expression elicited by IFN-γ. As PGE2elevated intercellular cyclic AMP (cAMP) levels in HGF in a dose-dependent fashion, the effect of dibutyryl cAMP and 8-bromo-cAMP, cAMP analogues, on IFN-γ-elicited ICAM-1 expression was examined. Both the agents downregulated ICAM-1 expression in IFN-γ-stimulated HGF. Next, we examined which subtype(s) of the four PGE2receptor subtypes (EP1, EP2, EP3and EP4) modulated the ICAM-1 expression elicited by IFN-γ, using subtype-specific agonists or antagonists. An EP2/EP4agonist, 11-deoxy-PGE1, attenuated IFN-γ-elicited ICAM-1 expression in a concentration-dependent manner. A specific EP4antagonist, AH-23848B, showed no effect on inhibition of IFN-γ-elicited ICAM-1 expression by PGE2and 11-deoxy-PGE1. Butaprost, an EP2-selective agonist, mimicked inhibition of IFN-γ-elicited ICAM-1 expression by 11-deoxy-PGE1. An EP3agonist, ONO-AP-324, was inert with respect to IFN-γ-elicited ICAM-1 expression. Sulprostone, an EP1/EP3agonist, showed stimulatory effect on ICAM-1 expression elicited by IFN-γ. From these results, we suggest that PGE2downregulates IFN-γ-induced ICAM-1 expression in HGF, primarily via EP2receptors by cAMP-dependent signaling pathways.

The purpose of the present study was to investigate the involvement of cyclooxygease-1 (COX-1) and cyclooxygenase-2 (COX-2) in prostaglandin (PG) production by human periodontal ligament (PDL) fibroblasts stimulated with a proinflammatory cytokine, inerleukin-1β (IL-1β), and to examine the effect of interleukin-4 (IL-4), a Th2 cytokine, and interferon-γ (IFN-γ), a Th1 cytokine, on PG production by the cells. IL-1β-stimulated PDL fibroblasts produced prostaglandin E2(PGE2) in a time-dependent manner. Indomethacin, a non-selective COX-1/COX-2 inhibitor, and NS-398, a selective COX-2 inhibitor, completely inhibited PGE2production by IL-1β-stimulated cells. Northern blot analysis showed that COX-2 mRNA was detected in IL-1β-stimulated PDL cells, although not detected in unstimulated cells, while expression of COX-1 mRNA was in the same extent in both the cells. Dexamethasone inhibited COX-2 mRNA expression, COX activity and PGE2production in IL-1β-stimulated cells. IL-4 and IFN-γ suppressed PGE2production by IL-1β-stimulated PDL fibroblasts, but COX activity enhanced by IL-1β treatment was significantly inhibited by IL-4, not by IFN-γ. Northern blot analysis showed that IL-4 depressed COX-2 mRNA expression with no effect on COX-1 mRNA expression. On the other hand, IFN-γ had no effect on expression of COX-1 and -2 mRNA. These data suggest that COX-2 is primarily responsible for PGE2production by IL-1β-stimulated human PDL fibroblasts and that IL-4 inhibited PGE2production by IL-1β-stimulated PDL fibroblasts through down-regulation of COX-2 expression, while IFN-γ suppressed the PGE2production with no effect on COX-2 expression.

Fine powders of Sm2Fe17Nx were stabilized by microcapsulation with the In and Zn metals produced via photochemical decompositions of In(C2H5)3 and Zn(C2H5)2 under UV light irradiation in an organic solvent to avoid any additional oxidation of them, and after the coating treatment, they still recorded high remanence (Br = ~1.30 T) and coercivity (Hcj = ~0.74 MA m^-1) values to provide maximum energy products of (BH)max = ~279 kJ m^-3 despite the dilution effect by existence of the nonmagnetic In and/or Zn metals used for the protection. The photochemical decomposition of In(C2H5)3 was smoothly performed compared with the case of Zn(C2H5)2, so that a large amount of In metal was deposited on the surface of Sm2Fe17Nx fine particles (~6.5 wt %) to be sufficient for serving as a metal binder for compression-type bonded magnets without any further addition of the same metals with low melting points. The single-layered metal-coated In/Sm2Fe17Nx and double-layered metal-coated In/Zn/Sm2Fe17Nx powders produced the corresponding In metal-bonded Sm2Fe17Nx and Zn/Sm2Fe17Nx magnets, of which the latter ones provided the highest (BH)max value of ~144 kJ m^-3 among a series of metal-bonded Sm2Fe17Nx magnets reported to date.

Abstract: Our purpose was to evaluate diffusion-weighted (DW) echo-planar MRI in differentiating between brain abscess and tumour. We examined two patients with surgically confirmed pyogenic brain abscess and 18 with metastatic brain tumours or high-grade glioma, using a 1.5 T system. The apparent diffusion coefficient (ADC) of each necrotic or solid contrast-enhancing lesion was measured with two different b values (20 and 1200 s/mm2). All capsule-stage brain abscesses (4 lesions) and zones of cerebritis (2 lesions) were identified on high-b-value DWI as markedly high-signal areas of decreased ADC (range, 0.58–0.70 [(10–3 mm2/s; mean, 0.63)]). All cystic or necrotic portions of brain tumours (14 lesions) were identified on high-b-value DWI as low-signal areas of increased ADC (range, 2.20–3.20 [(10–3 mm2/s; mean, 2.70)]). Solid, contrast-enhancing portions of brain tumours (19 lesions) were identified on high-b-value DWI as high-signal areas of sightly decreased or increased ADC (range, 0.77–1.29 [(10–3 mm2/s; mean, 0.94)]). Our preliminary results indicate that DW echo-planar MRI be used for distinguishing between brain abscess and tumour.