Soft X--Ray Properties of Seyfert Galaxies in the Rosat All--Sky Survey

We present the results of ROSAT All-Sky Survey observations of Seyfert and IR-luminous galaxies from the Extended 12 Micron Galaxy Sample and the optically-selected CfA Sample. Roughly half of the Seyferts (mostly Seyfert 1s) have been fitted to an absorbed power-law model, yielding an average gamma of 2.26+-0.11 for 43 Seyfert 1s and 2.45+-0.18 for 10 Seyfert 2s, with both types having a median value of 2.3. The soft X-ray (SXR) luminosity correlates with the 12um luminosity, with Seyfert 1s having relatively more SXR emission than Seyfert 2s of similar mid-infrared luminosities, by a factor of 1.6+-0.3. Several physical interpretations of these results are discussed, including the standard unified model for Seyfert galaxies. Infrared-luminous non-Seyferts are shown to have similar distributions of SXR luminosity and X-ray-to-IR slope as Seyfert 2s, suggesting that some of them may harbor obscured active nuclei (as has already been shown to be true for several objects) and/or that the soft X-rays from some Seyferts 2s may be non-nuclear. A SXR luminosity function (XLF) is calculated for the 12um sample, which is well described by a single power-law with a slope of -1.75. The normalization of this XLF agrees well with that of a HXR selected sample. Several of our results, related to the XLF and the X-ray-to-IR relation are shown to be consistent with the HXR observations of the 12um sample by Barcons et al.Comment: AASTeX, 40 pages. Text and Table 2 only. PostScript versions of this file, figures, and Table 1, and a latex version of Table 1 are available by ftp://ftp.astro.ucla.edu/pub/rush/papers, get rmfv*. Accepted by ApJ ~1996 May 10. Should be published in late 199

AUTOMATIC GENERATION OF EVENT-RELATED CHECKLISTS

Virtual assistants provide notifications and reminders of upcoming calendar events to users. This disclosure describes the automatic generation of a checklist associated with an upcoming event that is provided to a user. The checklist includes items associated with the event to be carried to the event by the user. The checklist can also include tasks to be performed by the user prior to the event. A machine learned model that is trained to associate event types with items/tasks is utilized to generate the checklist. If the user permits, items mentioned in event related user communications are also included in the checklist. Generated checklists can be shared with other participants. With user permission and express consent, the checklists can be personalized for subsequent use based on user interaction with the checklists

Pharmacological and rAAV gene therapy rescue of visual functions in a blind mouse model of Leber congenital amaurosis

Journal ArticleBACKGROUND: Leber congenital amaurosis (LCA), a heterogeneous early-onset retinal dystrophy, accounts for approximately 15% of inherited congenital blindness. One cause of LCA is loss of the enzyme lecithin:retinol acyl transferase (LRAT), which is required for regeneration of the visual photopigment in the retina. METHODS AND FINDINGS: An animal model of LCA, the Lrat-/- mouse, recapitulates clinical features of the human disease. Here, we report that two interventions--intraocular gene therapy and oral pharmacologic treatment with novel retinoid compounds--each restore retinal function to Lrat-/- mice. Gene therapy using intraocular injection of recombinant adeno-associated virus carrying the Lrat gene successfully restored electroretinographic responses to approximately 50% of wild-type levels (p < 0.05 versus wild-type and knockout controls), and pupillary light responses (PLRs) of Lrat-/- mice increased approximately 2.5 log units (p < 0.05). Pharmacological intervention with orally administered pro-drugs 9-cis-retinyl acetate and 9-cis-retinyl succinate (which chemically bypass the LRAT-catalyzed step in chromophore regeneration) also caused long-lasting restoration of retinal function in LRAT-deficient mice and increased ERG response from approximately 5% of wild-type levels in Lrat-/- mice to approximately 50% of wild-type levels in treated Lrat-/- mice (p < 0.05 versus wild-type and knockout controls). The interventions produced markedly increased levels of visual pigment from undetectable levels to 600 pmoles per eye in retinoid treated mice, and approximately 1,000-fold improvements in PLR and electroretinogram sensitivity. The techniques were complementary when combined. CONCLUSION: Intraocular gene therapy and pharmacologic bypass provide highly effective and complementary means for restoring retinal function in this animal model of human hereditary blindness. These complementary methods offer hope of developing treatment to restore vision in humans with certain forms of hereditary congenital blindness

Lecithin-retinol acyltransferase is essential for accumulation of all-trans-retinyl esters in the eye and in the liver

Journal ArticleLecithin-retinol acyltransferase (LRAT), an enzyme present mainly in the retinal pigmented epithelial cells and liver, converts all-trans-retinol into all-trans-retinyl esters. In the retinal pigmented epithelium, LRAT plays a key role in the retinoid cycle, a two-cell recycling system that replenishes the 11-cis-retinal chromophore of rhodopsin and cone pigments. We disrupted mouse Lrat gene expression by targeted recombination and generated a homozygous Lrat knock-out (Lrat-/-) mouse. Despite the expression of LRAT in multiple tissues, the Lrat-/- mouse develops normally. The histological analysis and electron microscopy of the retina for 6-8-week-old Lrat-/- mice revealed that the rod outer segments are approximately 35% shorter than those of Lrat+/+ mice, whereas other neuronal layers appear normal. Lrat-/- mice have trace levels of all-trans-retinyl esters in the liver, lung, eye, and blood, whereas the circulating all-trans-retinol is reduced only slightly. Scotopic and photopic electroretinograms as well as pupillary constriction analyses revealed that rod and cone visual functions are severely attenuated at an early age. We conclude that Lrat-/- mice may serve as an animal model with early onset severe retinal dystrophy and severe retinyl ester deprivation

Global Regulatory Pathways and Cross-talk Control Pseudomonas aeruginosa Environmental Lifestyle and Virulence Phenotype

Pseudomonas aeruginosa is a metabolically versatile environmental bacterium and an opportunistic human pathogen that relies on numerous signaling pathways to sense, respond, and adapt to fluctuating environmental cues. Although the environmental signals sensed by these pathways are poorly understood, they are largely responsible for determining whether P. aeruginosa adopts a planktonic or sessile lifestyle. These environmental lifestyle extremes parallel the acute and chronic infection phenotypes observed in human disease. In this review, we focus on four major pathways (cAMP/Vfr and c-di-GMP signaling, quorum sensing, and the Gac/Rsm pathway) responsible for sensing and integrating external stimuli into coherent regulatory control at the transcriptional, translational, and post-translational level. A common theme among these pathways is the inverse control of factors involved in promoting motility and acute infection and those associated with biofilm formation and chronic infection. In many instances these regulatory pathways influence one another, forming a complex network allowing P. aeruginosa to assimilate numerous external signals into an integrated regulatory circuit that controls a lifestyle continuum

Use of two-photon lithography with a negative resist and processing to realise cylindrical magnetic nanowires

Cylindrical magnetic nanowires have been shown to exhibit a vast array of fascinating 10 spin textures, including chiral domains, skyrmion tubes and topologically protected domain walls 11 that harbor Bloch points. Here we present a novel methodology that utilizes two-photon 12 lithography in order to realize tailored 3D porous templates upon prefabricated electrodes. 13 Electrochemical deposition is used to fill these porous templates, and reactive ion etching is used to 14 free the encased magnetic nanowires. The nanowires are found to have a diameter of 420nm, length 15 of 2.82m and surface roughness of 7.6nm. Magnetic force microscopy in an externally applied field 16 suggests a complex spiraling magnetization state, which demagnetizes via the production of 17 vortices of alternating chirality. Detailed micro-magnetic simulations confirm such a state and a 18 qualitative agreement is found with respect to the switching of experimental nanowires. 19 Surprisingly, simulations also indicate the presence of a Bloch point as a metastable state during the 20 switching process. Our work provides a new means to realize 3D magnetic nanowires of controlled 21 geometry and calculations suggest a further reduction in diameter to sub-200nm will be possible, 22 providing access to a regime of ultrafast domain wall motion