Efficient generation of highly squeezed light and second harmonic wave with periodically poled MgO:LiNbO_3

We report on effective generation of continuous-wave squeezed light and second harmonics with a periodically poled MgO:LiNbO$_{\mathrm{3}}$ (PPMgLN) crystal which enables us to utilize the large nonlinear optical coefficient $d_{\mathrm{33}}$. We achieved the squeezing level of $-7.60 \pm 0.15$dB at 860 nm by utilizing a subthreshol optical parametric oscillator with a PPMgLN crystal. We also generated 400 mW of second harmonics at 430 nm from 570 mW of fundamental waves with 70% of conversion efficiency by using a PPMgLN crystal inside an external cavity.Comment: 4 pages, 3 figure

ALMA Detection of 321 GHz water maser emission in the radio galaxy NGC 1052

The Atacama Large Millimeter/submillimeter Array (ALMA) serendipitously detected H$_2$O $J_{Ka, Kc} = 10_{2,9} - 9_{3,6}$ emission at 321 GHz in NGC 1052. This is the first submillimeter maser detection in a radio galaxy and the most luminous 321-GHz H$_2$O maser known to date with the isotropic luminosity of 1090 $L_{\odot}$. The line profile consists of a broad velocity component with FWHM $= 208 \pm 12$ km s$^{-1}$ straddling the systemic velocity and a narrow component with FWHM $= 44 \pm 3$ km s$^{-1}$ blueshifted by 160 km s$^{-1}$. The profile is significantly different from the known 22-GHz $6_{1,6} - 5_{2,3}$ maser which shows a broad profile redshifted by 193 km s$^{-1}$. The submillimeter maser is spatially unresolved with a synthesized beam of $0^{\prime \prime}.68 \times 0^{\prime \prime}.56$ and coincides with the continuum core position within 12 pc. These results indicate amplification of the continuum emission through high-temperature ($>1000$ K) and dense ($n({\rm H}_2{\rm O}) > 10^4$ cm$^{-3}$) molecular gas in front of the coreComment: 3 figures, Accepted for publication in Publications of Astronomical Society of Japa

Absorption, Metabolism, and Excretion of [ 14 C]Imidafenacin, a New Compound for Treatment of Overactive Bladder, After Oral Administration to Healthy Male Subjects

ABSTRACT: The absorption, metabolism, and excretion of imidafenacin [KRP-197/ONO-8025, 4-(2-methyl-1H-imidazol-1-yl)-2,2-diphenylbutanamide], a new antimuscarinic drug developed for treatment of overactive bladder, were assessed in six healthy male subjects after a single oral administration of 0.25 mg of [ 14 C]imidafenacin (approximately 46 Ci). The highest radioactivity in the plasma was observed at 1.5 h after administration. The apparent terminal elimination half-life of the total radioactivity was 72 h. Approximately 65.6 and 29.4% of the administered radioactivity were recovered in the urine and feces, respectively, within 192 h after administration. The metabolite profiling by high-performance liquid chromatography-radiodetector and liquid chromatography/tandem mass spectrometry demonstrated that the main component of radioactivity was unchanged imidafenacin in the 2-h plasma. The N-glucuronide conjugate (M-9) was found as the major metabolite and the oxidized form of the 2-methylimidazole moiety (M-2) and the ringcleavage form (M-4) were detected as the minor metabolites in the 2-h plasma, but M-4 was found to be the main component in the 12-h plasma. Unchanged imidafenacin, M-9, M-2, and other oxidized metabolites were excreted in the urine, but the unchanged imidafenacin and M-9 were not found in the feces. Two unique metabolites were found in the urine and feces, which were identified as the interchangeable cis-and trans-isomers of 4,5-dihydrodiol forms of the 2-methylimidazole moiety. These findings indicate that imidafenacin is rapidly and well absorbed (at least 65% of dose recovered in urine) after oral administration, circulates in human plasma as the unchanged form, its glucuronide, and other metabolites, and is then excreted in urine and feces as the oxidized metabolites of 2-methylimidazole moiety. Imidafenacin [KRP-197/ONO-8025, 4-(2-methyl-1H-imidazol-1-yl)-2,2-diphenylbutanamide] In the pharmacokinetic assays in the preclinical toxicology studies, imidafenacin was absorbed rapidly with absolute bioavailability of 5.6% in rats and 36.1% in dogs after oral administration (Masuda et al., unpublished observations). Orally administered [ 14 C]imidafenacin was excreted as many metabolites in the feces, and the total recovery in the urine and feces were more than 95% of the administered dose in rats and dogs (Sato et al., unpublished observations). In phase I clinical trials, the plasma concentration and urinary excretion of imidafenacin increased dose dependently in the range from 0.025 to 0.5 mg of single oral dose, and the apparent elimination half-life ranged from 2.6 to 3.0 h Article, publication date, and citation information can be found a

Different Effects of Palmitoyl-L-carnitine and Palmitoyl-CoA on Mitochondrial Function in Rat Ventricular Myocytes

Although mitochondrial oxidative catabolism of fatty acid (FA) is a major energy source for the adult mammalian heart, cardiac lipotoxity resulting from elevated serum FA and enhanced FA use has been implicated in the pathogenesis of heart failure. To investigate the effects of the intermediates of FA metabolism, palmitoyl-L-carnitine (Pal-car) and palmitoyl-CoA (Pal-CoA), on mitochondrial function, we measured membrane potential(Δψm), opening of the mitochondrial permeability transition pore (mPTP) and the production of reactive oxygen species (ROS) in saponin-treated rat ventricular myocytes with a laser scanning confocal microscope. Our results revealed that: 1) lower concentrations of Pal-car (1 and 5μM) caused a slight hyperpolarization of Δψm (TMRE intensity increased to 115.5 ± 5.4 % and 110.7±1.6 % of the baseline, respectively. p<0.05) but did not open mPTP, 2) a higher concentration of Pal-car (10μM) depolarized Δψm (TMRE intensity decreased to 61.9 ± 12.2 % of the baseline, p<0.01) and opened mPTP (calcein intensity decreased to 70.7 ± 2.8% of the baseline, p<0.01), 3) Pal-CoA depolarized Δψm without opening mPTP, and 4) only the higher concentration of Pal-car (10μM) increased ROS generation (DCF intensity increased to 3.4 ± 0.3 fold of the baseline). We concluded that excessive exogenous intermediates of long chain saturated FA may disturb mitochondrial function in different ways between Pal-car and Pal-CoA. The distinct mechanisms of the deteriorating effects of long chain FA on mitochondrial function are important for our understanding of the development of cardiac diseases in systemic metabolic disorders.浜松医科大学学位論文　医博第517号(平成２０年１０月１７日

Genomic organization and promoter function of the mouse uncoupling protein 2 (UCP2) gene1The nucleotide sequences reported in this paper will appear in the DDBJ, and GenBank/EMBL Data Bank with accession number AB012159.1

AbstractWe cloned and characterized the mouse uncoupling protein 2 (UCP2) gene and its promoter region. The gene spans approximately 6.3 kb and contains eight exons and seven introns. Two short exons are located in the 5′ untranslated region, and each of the remaining exons encodes one of the transmembrane domains. 3′-RACE analysis showed that a polyadenylation signal 257 bp downstream from the stop codon was functional. Primer extension analysis indicated a single transcriptional start site 369 bp upstream from the translational start site. The promoter region lacks both TATA and CAAT boxes but is GC-rich. A construct containing 1250 bp of the promoter region showed significant activity in all 6 cell lines examined, and the region between −160 and −678 bp exhibited strong positive regulatory activity. These features of the UCP2 gene are different from those of the UCP1 gene and may contribute to its ubiquitous expression

Nilvadipine attenuates ischemic degradation of gerbil brain cytoskeletal proteins. Stroke

A ccumulating evidence shows that calcium L \ channel blockers have protective effects J. \ , against cerebral ischemia, 1 and this protection has been attributed not only to the vascular effects of these drugs 2 but also to their direct effects on nervous tissue. 3 Nilvadipine, 4 a new dihydropyridine-derived calcium channel blocker, possesses advantages over known blockers in having a selective relaxant effect on the basilar artery and prolonged facilitation of blood flow. A previous study has shown that nilvadipine was effective in reducing ischemia in models of chronic coronary artery occlusion in dogs