New opportunities for the synthesis of quinoxaline-substituted heterocyclic and aryl moieties

6.7-Difluoroquinoxaline (I) reacted with dimedone, indandione, and 3-methyl-1-phenylpyrazol-5-one in DMSO solution in the presence of acid to form mono-substituted products IIa - c. Heating I with resorcinol in EtOH in the presence of acid gave resorcinol derivative IId. 6.7-Difluoroquinoxaline in the presence of base reacted with 3-methyl-1-phenylmethylpyrazol-5-one to form dipyrazolylmethane III and tetrapyrazolylethane derivative IV. Heating products IIa - c with N-methylpiperazine produced 7-methylpiperazine derivatives Va - c of 2-substituted quinoxalines. © 2013 Springer Science+Business Media New York

Masses, radii, and orbits of small Kepler planets : The transition from gaseous to rocky planets

We report on the masses, sizes, and orbits of the planets orbiting 22 Kepler stars. There are 49 planet candidates around these stars, including 42 detected through transits and 7 revealed by precise Doppler measurements of the host stars. Based on an analysis of the Kepler brightness measurements, along with high-resolution imaging and spectroscopy, Doppler spectroscopy, and (for 11 stars) asteroseismology, we establish low false-positive probabilities (FPPs) for all of the transiting planets (41 of 42 have an FPP under 1%), and we constrain their sizes and masses. Most of the transiting planets are smaller than three times the size of Earth. For 16 planets, the Doppler signal was securely detected, providing a direct measurement of the planet's mass. For the other 26 planets we provide either marginal mass measurements or upper limits to their masses and densities; in many cases we can rule out a rocky composition. We identify six planets with densities above 5 g cm-3, suggesting a mostly rocky interior for them. Indeed, the only planets that are compatible with a purely rocky composition are smaller than 2 R ⊕. Larger planets evidently contain a larger fraction of low-density material (H, He, and H2O).Peer reviewedFinal Accepted Versio

Oxygen in the Very Early Galaxy

Oxygen abundances in a sample of ultra-metal-poor subdwarfs have been derived from measurements of the oxygen triplet at 7771--5 A and OH lines in the near UV performed in high-resolution and high signal-to-noise spectra obtained with WHT/UES, KeckI/HIRES, and VLT/UVES. Our Fe abundances were derived in LTE and then corrected for NLTE effects following Thevenin and Idiart (1999). The new oxygen abundances confirm previous findings for a progressive linear rise in the oxygen-to-iron ratio with a slope -0.33+-0.02 from solar metallicity to [Fe/H] -3. A slightly higher slope would be obtained if the Fe NLTE corrections were not considered. Below [Fe/H]= -2.5 our stars show [O/Fe] ratios as high as ~ 1.17 (G64-12), which can be interpreted as evidence for oxygen overproduction in the very early epoch of the formation of the halo, possibly associated with supernova events with very massive progenitor stars. We show that the arguments against this linear trend given by Fulbright and Kraft (1999), based on the LTE Fe analysis of two metal-poor stars cannot be sustained when an NLTE analysis is performed. Using 1-D models our analysis of three oxygen indicators available for BD +23 3130 gives consistent abundances within 0.16 dex and average [O/Fe] ratio of 0.91.Comment: 45 pages, 11 figures, accepted for publication in The Astrophysical Journa

Masses, radii, and orbits of small Kepler planets: the transition from gaseous to rocky planets

We report on the masses, sizes, and orbits of the planets orbiting 22 Kepler stars. There are 49 planet candidates around these stars, including 42 detected through transits and 7 revealed by precise Doppler measurements of the host stars. Based on an analysis of the Kepler brightness measurements, along with high-resolution imaging and spectroscopy, Doppler spectroscopy, and (for 11 stars) asteroseismology, we establish low false-positive probabilities (FPPs) for all of the transiting planets (41 of 42 have an FPP under 1%), and we constrain their sizes and masses. Most of the transiting planets are smaller than three times the size of Earth. For 16 planets, the Doppler signal was securely detected, providing a direct measurement of the planet's mass. For the other 26 planets we provide either marginal mass measurements or upper limits to their masses and densities; in many cases we can rule out a rocky composition. We identify six planets with densities above 5 g cm-3, suggesting a mostly rocky interior for them. Indeed, the only planets that are compatible with a purely rocky composition are smaller than 2 R ⊕. Larger planets evidently contain a larger fraction of low-density material (H, He, and H2O)

Multiple Regulatory Layers of SREBP1/2 by SIRT6

The NAD+-dependent protein deacetylase SIRT6 regulates genome stability, cancer, and lifespan. Mice overexpressing SIRT6 (MOSES) have lower low-density lipoprotein cholesterol levels and are protected against the physiological damage of obesity. Here, we examined the role of SIRT6 in cholesterol regulation via the lipogenic transcription factors SREBP1 and SREBP2, and AMP-activated protein kinase (AMPK). We show that SIRT6 represses SREBP1 and SREBP2 by at least three mechanisms. First, SIRT6 represses the transcription levels of SREBP1/SREBP2 and that of their target genes. Second, SIRT6 inhibits the cleavage of SREBP1/SREBP2 into their active forms. Third, SIRT6 activates AMPK by increasing the AMP/ATP ratio, which promotes phosphorylation and inhibition of SREBP1 by AMPK. Reciprocally, the expression of miR33a and miR33b from the introns of SREBP2 and SREBP1, respectively, represses SIRT6 levels. Together, these findings explain the mechanism underlying the improved cholesterol homeostasis in MOSES mice, revealing a relationship between fat metabolism and longevity

External Ba2+ Block of Human Kv1.5 at Neutral and Acidic pH: Evidence for Ho+-Induced Constriction of the Outer Pore Mouth at Rest

Previous studies have shown that low pHo accelerates depolarization-induced inactivation and decreases the macroscopic conductance by reducing channel availability. To test the hypothesis that outer pore constriction underlies the decreased conductance at low pHo, external Ba2+ was used to examine the accessibility of the channel pore at rest under neutral and acidic conditions. At pHo 7.4, Ba2+ block of closed channels follows a monoexponential time course and involves a low-affinity superficial site (KD ≅ 1 mM, −80 mV, 0 mM \documentclass[10pt]{article} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{pmc} \usepackage[Euler]{upgreek} \pagestyle{empty} \oddsidemargin -1.0in \begin{document} \begin{equation*}{\mathrm{K}}_{{\mathrm{o}}}^{+}\end{equation*}\end{document}) and a high-affinity site (KD ≅ 4 μM) deeper in the pore. Depolarization promotes Ba2+ dissociation and an analytical model incorporating state-dependent changes of Ba2+ affinity is presented that replicates the frequency dependence of the time course and the extent of block. Open-channel block by Ba2+ is weak. At pHo 5.5, both the access to and exit from the deep site is inhibited. These results are consistent with a low-pHo-induced conformational change in the outer pore that prevents Ba2+ binding at rest or unbinding during depolarization. If a pore constriction is involved, similar to that proposed to occur during P/C-type inactivation, this would imply that closed-state inactivation in Kv1.5 occurs under acidic conditions