Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is a high-density lipoprotein-associated protein. However, the tissue source(s) for circulating GPI-PLD and whether serum levels are ...regulated are unknown. Because the diabetic state alters lipoprotein metabolism, and liver and pancreatic islets are possible sources of GPI-PLD, we hypothesized that GPI-PLD levels would be altered in diabetes. GPI-PLD serum activity and liver mRNA were examined in two mouse models of type 1 diabetes, a nonobese diabetic (NOD) mouse model and low-dose streptozotocin-induced diabetes in CD-1 mice. With the onset of hyperglycemia (2- to 5-fold increase over nondiabetic levels), GPI-PLD serum activity and liver mRNA increased 2- to 4-fold in both models. Conversely, islet expression of GPI-PLD was absent as determined by immunofluorescence. Insulin may regulate GPI-PLD expression, because insulin treatment of diabetic NOD mice corrected the hyperglycemia along with reducing serum GPI-PLD activity and liver mRNA. Our data demonstrate that serum GPI-PLD levels are altered in the diabetic state and are consistent with liver as a contributor to circulating GPI-PLD.
Abstract only
Background
The anti–interleukin 13 (IL‐13) monoclonal antibody lebrikizumab improves lung function in patients with moderate‐severe uncontrolled asthma, but its effects on airway ...inflammation and remodeling are unknown. CLAVIER was designed to assess lebrikizumab’s effect on eosinophilic inflammation and remodeling.
Methods
We performed bronchoscopy on patients with uncontrolled asthma before and after 12 weeks of randomised double‐masked treatment with lebrikizumab (n=31) or placebo (n=33). The primary endpoint was relative change in airway subepithelial eosinophils per mm
2
of basement membrane (cells/mm
2
). Pre‐specified secondary and exploratory outcomes included change in IL‐13–associated biomarkers and measures of airway remodeling.
Findings
There was a baseline imbalance in tissue eosinophils and high variability between treatment groups. There was no discernible change in adjusted mean subepithelial eosinophils/mm
2
in response to lebrikizumab (95% CI, −82·5%, 97·5%). As previously observed, FEV
1
increased after lebrikizumab treatment. Moreover, subepithelial collagen thickness decreased 21·5% after lebrikizumab treatment (95% CI, −32·9%, −10·2%), while fractional exhaled nitric oxide,
CCL26
, and
SERPINB2
mRNA expression in bronchial tissues also diminished. Lebrikizumab was well tolerated, with a safety profile consistent with other lebrikizumab asthma studies.
Interpretation
We did not observe reduced tissue eosinophil numbers in association with lebrikizumab treatment. However, in pre‐specified secondary analyses, lebrikizumab treatment was associated with diminished degree of subepithelial fibrosis, a feature of airway remodeling, as well as improved lung function and reduced key pharmacodynamic biomarkers in bronchial tissues. These results reinforce the importance of IL‐13 in airway pathobiology and suggest that neutralization of IL‐13 may reduce asthmatic airway remodeling.
Clinical trial registration
NCT02099656
Support or Funding Information
The study was sponsored by F. Hoffmann‐La Roche Ltd.
The Large Synoptic Survey Telescope (LSST) will be a large, wide-field ground-based system designed to obtain, starting in 2015, multiple images of the sky that is visible from Cerro Pachon in ...Northern Chile. About 90% of the observing time will be devoted to a deep-wide-fast survey mode which will observe a 20,000 deg2 region about 1000 times during the anticipated 10 years of operations (distributed over six bands, ugrizy). Each 30-second long visit will deliver 5s depth for point sources of r~24.5 on average. The co-added map will be about 3 magnitudes deeper, and will include 10 billion galaxies and a similar number of stars. We discuss various measurements that will be automatically performed for these 20 billion sources, and how they can be used for classification and determination of source physical and other properties. We provide a few classification examples based on SDSS data, such as color classification of stars, color-spatial proximity search for wide-angle binary stars, orbital-color classification of asteroid families, and the recognition of main Galaxy components based on the distribution of stars in the position-metallicity-kinematics space. Guided by these examples, we anticipate that two grand classification challenges for LSST will be 1) rapid and robust classification of sources detected in difference images, and 2) simultaneous treatment of diverse astrometric and photometric time series measurements for an unprecedentedly large number of objects.
In the history of astronomy, major advances in our understanding of the Universe have come from dramatic improvements in our ability to accurately measure astronomical quantities. Aided by rapid ...progress in information technology, current sky surveys are changing the way we view and study the Universe. Next- generation surveys will maintain this revolutionary progress. We focus here on the most ambitious survey currently planned in the visible band, the Large Synoptic Survey Telescope (LSST). LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: constraining dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. It will be a large, wide-field ground-based system designed to obtain multiple images covering the sky that is visible from Cerro Pachon in Northern Chile. The current baseline design, with an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg2 field of view, and a 3,200 Megapixel camera, will allow about 10,000 square degrees of sky to be covered using pairs of 15-second exposures in two photometric bands every three nights on average. The system is designed to yield high image quality, as well as superb astrometric and photometric accuracy. The survey area will include 30,000 deg2 with ? < +34.5? , and will be imaged multiple times in six bands, ugrizy, covering the wavelength range 320-1050 nm. About 90% of the observing time will be devoted to a deep- wide-fast survey mode which will observe a 20,000 deg2 region about 1000 times in the six bands during the anticipated 10 years of operation. These data will result in databases including 10 billion galaxies and a similar number of stars, and will serve the majority of science programs. The remaining 10% of the observing time will be allocated to special programs such as Very Deep and Very Fast time domain surveys. We describe how the LSST science drivers led to these choices of system parameters.
U istoriji astronomije, veliki pomaci u nasem razumevanju Vasione cesto su proizilazili iz dramaticnog napretka u mogucnostima preciznog merenja astronomskih velicina. Zahvaljuju i brzom razvoju informacionih tehnologija, savremeni pregledi neba menjaju nacin na koji posmatramo i proucavamo Vasionu. Pregledi neba sledece generacije nastavice ovim putem revolucionarnog napretka. U ovom radu usredsredjujemo se na najambiciozniji planirani projekat pregleda neba u vidljivom delu spektra, Veliki sinopticki teleskop za pregled neba (skr. LSST, od eng. Large Synoptic Survey Telescope). LSST ce imati jedinstvene mogucnosti pregleda u kratkim vremenskim intervalima. Dizajn LSST odredjuju cetiri primarna naucna zadatka: ogranicavanje na parametre vezane za tamnu energiju i tamnu materiju, pravljenje inventara objekata Suncevog sistema, istrazivace kratkotrajnih pojava na nebu u vidljivom delu spektra i mapiranje Mlecnog puta. Teleskop ce predstavljati veliki, zemaljski, sirokougaoni sistem dizajniran za dobijanje visestrukih snimaka koji bi u potpunosti pokrili nebo vidljivo iz mesta Cerro Pachon u severnom Cileu. Aktuelni osnovni dizajn predvidja primarno ogledalo precnika 8.4 m (efektivno 6.5 m), vidno polje od 9.6 kvadratnih stepeni i kameru sa 3200 megapiksela, sto ce omoguciti da se u dve ekspozicije od po 15 sekundi, u dva fotometrijska filtera, za tri noci u proseku, pokrije ukupno 10 000 kvadratnih stepeni neba. Sistem je dizajniran tako da obezbedi visok kvalitet snimaka, kao i izuzetnu astrometrijsku i fotometrijsku tacnost. Pregled ce pokriti ukupnu povrsinu od 30 000 kvadratnih stepeni, u oblasti deklinacija ? < +34.5? , snimaju i vise puta u sest filtera, ugrizy, koji pokrivaju oblasti talasnih duzina od 320-1050 nm. Oko 90% posmatrackog vremena bice iskorisceno za rad u tzv. dubokom-sirokom-brzom modu, pri cemu ce se, tokom predvidjenih 10 godina rada teleskopa, otprilike 1000 puta u sest filtera posmatrati oblast od 20 000 kvadratnih stepeni. Prikupljeni podaci ce biti pohranjeni u bazu koja ce ukljucivati oko 10 milijardi galaksija i priblizno isti broj zvezda, i koja ce sluziti vecini naucnih programa. Preostalih 10% posmatrackog vremena predvidjeno je za posebne programe kao sto su Vrlo Duboki i Vrlo Brzi pregledi. Ovde opisujemo kako se od naucnih zadataka programa LSST doslo do ovih izbora parametara sistema.
The Kepler Mission is a photometric space mission that will continuously observe a single 100 square degree field of view (FOV) of the sky of more than 100,000 stars in the Cygnus-Lyra region for ...four or more years with a precision of 14 parts per million (ppm) for a 6.5 hour integration including shot noise for a twelfth magnitude star. The primary goal of the mission is to detect Earth-size planets in the habitable zone of solar-like stars. In the process, many eclipsing binaries (EB) will also be detected. Prior to launch, the stellar characteristics will have been determined for all the stars in the FOV with K<14.5. As part of the verification process, stars with transits (about 5%) will need to have follow-up radial velocity observations performed to determine the component masses and thereby separate grazing eclipses caused by stellar companions from transits caused by planets. The result will be a rich database on EBs. The community will have access to the archive for uses such as for EB modeling of the high-precision light curves. A guest observer program is also planned for objects not already on the target list.
The Pan-STARRS pathfinding telescope PS1 will begin a major set of surveys starting in 2008, and lasting for 3.5 years. One of these, the PS1 3π Survey, will repeatedly observe the entire sky north ...of −30 degrees, visiting every position 12 times in each of 5 filters. With single-epoch astrometry of 10 milliarcseconds, these observations will yield parallaxes for stars within 100 pc and proper motions out to several hundred pc. The result will be an unprecedented view on nearby stellar populations and insight into the dynamical structure of the local portions of the Galaxy. One exciting science product will be a volume-limited sample of nearby low-mass objects including thousands of L dwarfs, hundreds of T dwarfs, and perhaps even cooler sub-stellar objects. Another project will use proper-motion measurements to improve the membership of nearby star forming regions.
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