A geostationary imaging spectrometer TOMS instrument

One design for a geostationary Total Ozone Mapping Spectrometer (TOMS) with many desirable features is an imaging spectrometer. A preliminary study makes use of a 0.25 m Czerny-Turner spectrometer with which the Earth is imaged on a charge-coupled device (CCD) in dispersed light. The wavelength is determined by a movable grating which can be set arbitrarily by ground control. The signal integration time depends on wavelength but this system allows arbitrary timing by command. Special circumstances such as a requirement to track a low-lying sulfur dioxide cloud or a need to discriminate high level ozone from total ozone at midlatitudes could be obtained by adding a particular wavelength to the normally pre-programmed time sequence. The incident solar irradiance is measured by deploying a diffuser plate in the field of view. Individual detector elements correspond to scene elements in which the several wavelengths are serially sampled and the Earth radiance is compared to the incident sunlight. Thus the problem of uncorrelated drift of multiple detectors is removed

Prolactin prevents hepatocellular carcinoma by restricting innate immune activation of c-Myc in mice

Women are more resistant to hepatocellular carcinoma (HCC) than men despite equal exposure to major risk factors, such as hepatitis B or C virus infection. Female resistance is hormone-dependent, as evidenced by the sharp increase in HCC incidence in postmenopausal women who do not take hormone replacement therapy. In rodent models sex-dimorphic HCC phenotypes are pituitary-dependent, suggesting that sex hormones act via the gonadal-hypophyseal axis. We found that the estrogen-responsive pituitary hormone prolactin (PRL), signaling through hepatocyte-predominant short-form prolactin receptors (PRLR-S), constrained TNF receptor-associated factor (TRAF)-dependent innate immune responses invoked by IL-1β, TNF-α, and LPS/Toll-like receptor 4 (TLR4), but not TRIF-dependent poly(I:C)/TLR3. PRL ubiquitinated and accelerated poststimulatory decay of a “trafasome” comprised of IRAK1, TRAF6, and MAP3K proteins, abrogating downstream activation of c-Myc–interacting pathways, including PI3K/AKT, mTORC1, p38 MAPK, and NF-κB. Consistent with this finding, we documented exaggerated male liver responses to immune stimuli in mice and humans. Tumor promotion through, but regulation above, the level of c-Myc was demonstrated by sex-independent HCC eruption in Alb-Myc transgenic mice. PRL deficiency accelerated liver carcinogenesis in Prl[superscript −/−] mice of both sexes. Conversely, pharmacologic PRL mobilization using the dopamine D2 receptor antagonist domperidone prevented HCC in tumor-prone C3H/HeN males. Viewed together, our results demonstrate that PRL constrains tumor-promoting liver inflammation by inhibiting MAP3K-dependent activation of c-Myc at the level of the trafasome. PRL-targeted therapy may hold promise for reducing the burden of liver cancer in high-risk men and women.National Institutes of Health (U.S.) (Grant CA067529

Insulin Resistance and Metabolic Hepatocarcinogenesis with Parent-of-Origin Effects in A×B Mice

Insulin resistance is a defining feature of metabolic syndrome and type 2 diabetes mellitus but also may occur independently of these conditions. Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of these disorders, increases the risk of hepatocellular carcinoma (HCC). However, mechanisms linking hyperinsulinemia to NAFLD and HCC require clarification. We describe a novel model of primary insulin resistance and HCC with strong parent-of-origin effects. Male AB6F1 (A/JCr dam × C57BL/6 sire) but not B6AF1 (B6 dam × A/J sire) mice developed spontaneous insulin resistance, NAFLD, and HCC without obesity or diabetes. A survey of mitochondrial, imprinted, and sex-linked traits revealed modest associations with X-linked genes. However, a diet-induced obesity study, including B6.A chromosome substitution–strain (consomic) mice, showed no segregation by sex chromosome. Thus, parent-of-origin effects were specified within the autosomal genome. Next, we interrogated mechanisms of insulin-associated hepatocarcinogenesis. Steatotic hepatocytes exhibited adipogenic transition characterized by vacuolar metaplasia and up-regulation of vimentin, adipsin, fatty acid translocase (CD36), peroxisome proliferator–activated receptor-γ, and related products. This profile was largely recapitulated in insulin-supplemented primary mouse hepatocyte cultures. Importantly, pyruvate kinase M2, a fetal anabolic enzyme implicated in the Warburg effect, was activated by insulin in vivo and in vitro. Thus, our study reveals parent-of-origin effects in heritable insulin resistance, implicating adipogenic transition with acquired anabolic metabolism in the progression from NAFLD to HCC.National Institutes of Health (U.S.) (NIH grant AA016563)National Institutes of Health (U.S.) (NIH grant CA067529)National Institutes of Health (U.S.) (NIH grant P01CA0267)National Institutes of Health (U.S.) (NIH grant P30ES02109)National Institutes of Health (U.S.) (NIH grant RR007036)National Institutes of Health (U.S.) (NIH grant CA158661)National Institutes of Health (U.S.) (NIH grant CA016086

Overexpression of glycine-extended gastrin inhibits parietal cell loss and atrophy in the mouse stomach

Recently we have reported synergistic effects between glycine-extended gastrin (G-gly) and amidated gastrin-17 on acid secretion in short-term infusion studies. In the present study, we examined the long-term effect of G-gly on the atrophy-promoting effects of amidated gastrin in the mouse stomach with or without Helicobacter infection. Transgenic mice overexpressing amidated gastrin (INS-GAS mice), G-gly (MTI/G-gly mice), and both peptides (INS-GAS/G-gly mice) were used for assessment of acid secretion and ulcer susceptibility and histologic examination and scoring of preneoplastic lesions in response to the 3 and 6 months Helicobacter felis (H. felis) infection. We found that MTI/G-gly mice had normal gastric histology and acid secretion. Double transgenic (INS-GAS/G-gly) mice showed 2-fold increases in acid secretion compared with INS-GAS mice. Acute peptic ulcers after pyloric ligation were noted in 50% of the INS-GAS/G-gly mice but in none of the INS-GAS mice at 6 months of age. Whereas male INS-GAS mice had a \u3e50% decrease in the numbers of parietal cell and enterochromaffin-like cell at 6 months of age, the male double transgenic mice had no such decrease. Overexpression of G-gly reduced the scores of preneoplasia in the stomach; however, it did not prevent the development of amidated gastrin-dependent gastric cancer in both H. felis-infected mice and uninfected mice. We conclude that G-gly synergizes with amidated gastrin to stimulate acid secretion and inhibits parietal cell loss in INS-GAS/G-gly mice. The overexpression of G-gly seems to increase the susceptibility to peptic ulcer disease and delay the development of Helicobacter-mediated gastric preneoplasia in this model

Limits from the Hubble Space Telescope on a Point Source in SN 1987A

We observed supernova 1987A (SN 1987A) with the Space Telescope Imaging Spectrograph (STIS) on the Hubble Space Telescope (HST) in 1999 September, and again with the Advanced Camera for Surveys (ACS) on the HST in 2003 November. No point source is observed in the remnant. We obtain a limiting flux of F_opt < 1.6 x 10^{-14} ergs/s/cm^2 in the wavelength range 2900-9650 Angstroms for any continuum emitter at the center of the supernova remnant (SNR). It is likely that the SNR contains opaque dust that absorbs UV and optical emission, resulting in an attenuation of ~35% due to dust absorption in the SNR. Taking into account dust absorption in the remnant, we find a limit of L_opt < 8 x 10^{33} ergs/s. We compare this upper bound with empirical evidence from point sources in other supernova remnants, and with theoretical models for possible compact sources. Bright young pulsars such as Kes 75 or the Crab pulsar are excluded by optical and X-ray limits on SN 1987A. Of the young pulsars known to be associated with SNRs, those with ages < 5000 years are all too bright in X-rays to be compatible with the limits on SN 1987A. Examining theoretical models for accretion onto a compact object, we find that spherical accretion onto a neutron star is firmly ruled out, and that spherical accretion onto a black hole is possible only if there is a larger amount of dust absorption in the remnant than predicted. In the case of thin-disk accretion, our flux limit requires a small disk, no larger than 10^{10} cm, with an accretion rate no more than 0.3 times the Eddington accretion rate. Possible ways to hide a surviving compact object include the removal of all surrounding material at early times by a photon-driven wind, a small accretion disk, or very high levels of dust absorption in the remnant.Comment: 40 pages, 5 figures. AAStex. Accepted, ApJ 04/28/200

Lunar Outgassing, Transient Phenomena and The Return to The Moon, I: Existing Data

Herein the transient lunar phenomena (TLP) report database is subjected to a discriminating statistical filter robust against sites of spurious reports, and produces a restricted sample that may be largely reliable. This subset is highly correlated geographically with the catalog of outgassing events seen by the Apollo 15, 16 and Lunar Prospector alpha-particle spectrometers for episodic Rn-222 gas release. Both this robust TLP sample and even the larger, unfiltered sample are highly correlated with the boundary between mare and highlands, as are both deep and shallow moonquakes, as well as Po-210, a long-lived product of Rn-222 decay and a further tracer of outgassing. This offers another significant correlation relating TLPs and outgassing, and may tie some of this activity to sagging mare basalt plains (perhaps mascons). Additionally, low-level but likely significant TLP activity is connected to recent, major impact craters (while moonquakes are not), which may indicate the effects of cracks caused by the impacts, or perhaps avalanches, allowing release of gas. The majority of TLP (and Rn-222) activity, however, is confined to one site that produced much of the basalt in the Procellarum Terrane, and it seems plausible that this TLP activity may be tied to residual outgassing from the formerly largest volcanic ffusion sites from the deep lunar interior. With the coming in the next few years of robotic spacecraft followed by human exploration, the study of TLPs and outgassing is both promising and imperiled. We will have an unprecedented pportunity to study lunar outgassing, but will also deal with a greater burden of anthropogenic lunar gas than ever produced. There is a pressing need to study lunar atmosphere and its sources while still pristine. [Abstract abridged.]Comment: 35 pages, 3 figures, submitted to Icarus. Other papers in series found at http://www.astro.columbia.edu/~arlin/TLP

The DNA damage checkpoint protein ATM promotes hepatocellular apoptosis and fibrosis in a mouse model of non-alcoholic fatty liver disease

Steatoapoptosis is a hallmark of non-alcoholic fatty liver disease (NAFLD) and is an important factor in liver disease progression. We hypothesized that increased reactive oxygen species resulting from excess dietary fat contribute to liver disease by causing DNA damage and apoptotic cell death, and tested this by investigating the effects of feeding mice high fat or standard diets for 8 weeks. High fat diet feeding resulted in increased hepatic H2O2, superoxide production, and expression of oxidative stress response genes, confirming that the high fat diet induced hepatic oxidative stress. High fat diet feeding also increased hepatic steatosis, hepatitis and DNA damage as exemplified by an increase in the percentage of 8-hydroxyguanosine (8-OHG) positive hepatocytes in high fat diet fed mice. Consistent with reports that the DNA damage checkpoint kinase Ataxia Telangiectasia Mutated (ATM) is activated by oxidative stress, ATM phosphorylation was induced in the livers of wild type mice following high fat diet feeding. We therefore examined the effects of high fat diet feeding in Atm-deficient mice. The prevalence of apoptosis and expression of the pro-apoptotic factor PUMA were significantly reduced in Atm-deficient mice fed the high fat diet when compared with wild type controls. Furthermore, high fat diet fed Atm−/− mice had significantly less hepatic fibrosis than Atm+/+ or Atm+/− mice fed the same diet. Together, these data demonstrate a prominent role for the ATM pathway in the response to hepatic fat accumulation and link ATM activation to fatty liver-induced steatoapoptosis and fibrosis, key features of NAFLD progression

Average Properties of a Large Sample of z_abs ~ z_em associated Mg II Absorption Line Systems

We have studied a sample of 415 associated (z_ab z_em; relative velocity with respect to QSO <3000km/s) Mg II absorption systems with 1.0<=z_ab<=1.86, in the spectra of SDSS DR3 QSOs, to determine the dust content and ionization state in the absorbers. We studied the dependence of these properties on the properties of the QSOs and also, compared the properties with those of a similarly selected sample of 809 intervening systems (apparent relative velocity with respect to the QSO of >3000km/s), so as to understand their origin. From the analysis of the composite spectra, as well as from the comparison of measured equivalent widths in individual spectra, we conclude that the associated Mg II absorbers have higher apparent ionization, measured by the strength of the C IV absorption lines compared to the Mg II absorption lines, than the intervening absorbers. The ionization so measured appears to be related to apparent ejection velocity, being lower as the apparent ejection velocity is more and more positive. There is clear evidence, from the composite spectra, for SMC like dust attenuation in these systems; the 2175AA absorption feature is not present. The extinction is almost twice that observed in the similarly selected sample of intervening systems. We reconfirm that QSOs with non-zero FIRST radio flux are intrinsically redder than the QSOs with no detection in the FIRST survey. The incidence of associated Mg II systems in QSOs with non-zero FIRST radio flux is 1.7 times that in the QSOs with no detection in the FIRST survey. The associated absorbers in radio-detected QSOs which comprise about 12% of our sample, cause 3 times more reddening than the associated absorbers in radio-undetected QSOs. This excess reddening possibly suggests an intrinsic nature for the associated absorbers in radio-detected QSOs.Comment: Accepted for publication in Ap

Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice

Antibiotic exposure in children has been associated with the risk of Inflammatory Bowel Disease (IBD). Since antibiotic use in children or in their pregnant mother can affect how the intestinal microbiome develops, we asked whether the transfer of an antibiotic-perturbed microbiota from mothers to their children could affect their risk of developing IBD. Here we demonstrate that germ-free adult pregnant mice inoculated with a gut microbial community shaped by antibiotic exposure transmitted their perturbed microbiota to their offspring with high fidelity. Without any direct or continued exposure to antibiotics, this dysbiotic microbiota in the offspring remained distinct from controls for at least 21 weeks. By using both IL-10-deficient and wild type mothers, we showed that both inoculum and genotype shape the microbiota populations in the offspring. Since IL10−/− mice are genetically susceptible to colitis, we could assess the risk due to maternal transmission of an antibiotic-perturbed microbiota. We found that the IL10−/− offspring that had received the perturbed gut microbiota developed markedly increased colitis. Taken together, our findings indicate that antibiotic exposure shaping the maternal gut microbiota has effects that extend to their offspring with both ecological and long-term disease consequences

Optical Light Curves of the Type Ia Supernovae 1990N and 1991T

We present UBVRI light curves for the bright Type Ia supernovae SN 1990N in NGC 4639 and SN 1991T in NGC 4527 based on photometry gathered in the course of the Calan/Tololo supernova program. Both objects have well-sampled light curves starting several days before maximum light and spanning well through the exponential tail. These data supercede the preliminary photometry published by Leibundgut et al (1991) and Phillips et al (1992). The host galaxies for these supernovae have (or will have) accurate distances based on the Cepheid period-luminosity relationship. The photometric data in this paper provide template curves for the study of general population of Type Ia supernova and accurate photometric indices needed for the Cepheid-supernova distance scale.Comment: AAS LaTeX, 30 pages, 10 figures, to appear in the Jan 1998 Astronomical Journal. Figs 1 and 2 (finding charts) not include