217 research outputs found
Dissecting interferon-induced transcriptional programs in human peripheral blood cells
Interferons are key modulators of the immune system, and are central to the control of many diseases. The response of immune cells to stimuli in complex populations is the product of direct and indirect effects, and of homotypic and heterotypic cell interactions. Dissecting the global transcriptional profiles of immune cell populations may provide insights into this regulatory interplay. The host transcriptional response may also be useful in discriminating between disease states, and in understanding pathophysiology. The transcriptional programs of cell populations in health therefore provide a paradigm for deconvoluting disease-associated gene expression profiles.We used human cDNA microarrays to (1) compare the gene expression programs in human peripheral blood mononuclear cells (PBMCs) elicited by 6 major mediators of the immune response: interferons alpha, beta, omega and gamma, IL12 and TNFalpha; and (2) characterize the transcriptional responses of purified immune cell populations (CD4+ and CD8+ T cells, B cells, NK cells and monocytes) to IFNgamma stimulation. We defined a highly stereotyped response to type I interferons, while responses to IFNgamma and IL12 were largely restricted to a subset of type I interferon-inducible genes. TNFalpha stimulation resulted in a distinct pattern of gene expression. Cell type-specific transcriptional programs were identified, highlighting the pronounced response of monocytes to IFNgamma, and emergent properties associated with IFN-mediated activation of mixed cell populations. This information provides a detailed view of cellular activation by immune mediators, and contributes an interpretive framework for the definition of host immune responses in a variety of disease settings
Characterization of Samples for Optimization of Infrared Stray Light Coatings
NASAâs Stratospheric Observatory for Infrared Astronomy (SOFIA) is a converted 747SP that houses a 2.5 m telescope that observes the sky through an opening in the side of the aircraft. Because it flies at altitudes up to 45,000 feet, SOFIA gets 99.99% transmission in the infrared. Multiple science instruments mount one at a time on the telescope to interpret infrared and visible light from target sources. Ball Infrared Black (BIRB) currently coats everything that the optics sees inside the telescope assembly (TA) cavity in order to eliminate noise from the glow of background sky, aircraft exhaust, and other sources. A reflectometer and emissometer were used to measure and characterize the coatings in terms of their ability to absorb stray light. These measurements were then compared to the BIRB currently used. Though Aeroglaze Z306 showed lower better (lower) reflectance values than Desothane, neither of these coatings showed better reflectance values than the current BIRB. These characterizations help us to determine an improved recipe for TA cavity coating
Turning into frogs: asymmetry in forelimb emergence and escape direction in metamorphosing anurans:Lateralised forelimb emergence and turning
There is considerable debate about the pattern and origin of laterality in forelimb emergence and turning behaviour within amphibians, with the latter being poorly investigated in tadpoles around metamorphic climax. Using 6 species of metamorphosing anurans, we investigated the effect of asymmetrical spiracle location, and disturbance at the time of forelimb emergence, on the pattern of forelimb emergence. Turning behaviour was observed to assess whether motor lateralization occurred in non-neobatrachian anurans and was linked to patterns of forelimb emergence. Biases in forelimb emergence differed among species, supporting the hypothesis that asymmetrical spiracle position results in the same asymmetry in forelimb emergence. However, this pattern only occurred when individuals were undisturbed. Therefore, context at the time of the emergence of the forelimbs may be important, and might explain some discrepancies in the literature. Turning biases, unconnected to forelimb emergence, were found in Pipidae and Bombinatoridae, confirming the basal origin of lateralized behaviour among anurans. Turning direction in our metamorphs differed from the leftward bias commonly observed in tadpoles, but may be analogous to the prevalent right-âhandednessâ among adult anurans. Therefore, the transitions occurring during metamorphosis may affect lateralized behaviour and metamorphosis may be fruitful for understanding the development of lateralization
The Discovery of a Second Field Methane Brown Dwarf from Sloan Digital Sky Survey Commissioning Data
We report the discovery of a second field methane brown dwarf from the
commissioning data of the Sloan Digital Sky Survey (SDSS). The object, SDSS
J134646.45-003150.4 (SDSS 1346-00), was selected because of its very red color
and stellar appearance. Its spectrum between 0.8-2.5 mic is dominated by strong
absorption bands of H_2O and CH_4 and closely mimics those of Gliese 229B and
SDSS 162414.37+002915.6 (SDSS 1624+00), two other known methane brown dwarfs.
SDSS 1346-00 is approximately 1.5 mag fainter than Gliese 229B, suggesting that
it lies about 11 pc from the sun. The ratio of flux at 2.1 mic to that at 1.27
mic is larger for SDSS 1346-00 than for Gliese 229B and SDSS 1624+00, which
suggests that SDSS 1346-00 has a slightly higher effective temperature than the
others. Based on a search area of 130 sq. deg. and a detection limit of z* =
19.8, we estimate a space density of 0.05 pc^-3 for methane brown dwarfs with
T_eff ~ 1000 K in the 40 pc^3 volume of our search. This estimate is based on
small-sample statistics and should be treated with appropriate caution.Comment: 9 pages, 3 figures, AASTeX, to appear in ApJ Letters, authors list
update
Economic immorality and social reformation in English popular preaching, 1585-1625
Popular preachers, often drawing crowds of hundreds, frequently attempted to reform the relationship between rich and poor in Elizabethan and Jacobean England. Rather than accepting economic oppression as part of the divinely-ordained social order, many tried to convince their audiences that the extortions of merchants, landlords and creditors were crimes which should be punished severely by Englandâs earthly authorities. This paper demonstrates how the language of popular homiletics opened up a space for plebeian action with concrete socioeconomic consequences. By analysing the connotative idiom of social complaint found in homilies and other widely-heard sermons, the important but historiographically neglected role of âgodlinessâ in the early modern âmoral economyâ is revealed
ERK and mTORC1 Inhibitors Enhance the Anti-Cancer Capacity of the Octpep-1 Venom-Derived Peptide in Melanoma BRAF(V600E) Mutations
Melanoma is the main cause of skin cancer deaths, with special emphasis in those cases carrying BRAF mutations that trigger the mitogen-activated protein kinases (MAPK) signaling and unrestrained cell proliferation in the absence of mitogens. Current therapies targeting MAPK are hindered by drug resistance and relapse that rely on metabolic rewiring and Akt activation. To identify new drug candidates against melanoma, we investigated the molecular mechanism of action of the Octopus Kaurna-derived peptide, Octpep-1, in human BRAF(V600E) melanoma cells using proteomics and RNAseq coupled with metabolic analysis. Fluorescence microscopy verified that Octpep-1 tagged with fluorescein enters MM96L and NFF cells and distributes preferentially in the perinuclear area of MM96L cells. Proteomics and RNAseq revealed that Octpep-1 targets PI3K/AKT/mTOR signaling in MM96L cells. In addition, Octpep-1 combined with rapamycin (mTORC1 inhibitor) or LY3214996 (ERK1/2 inhibitor) augmented the cytotoxicity against BRAF(V600E) melanoma cells in comparison with the inhibitors or Octpep-1 alone. Octpep-1-treated MM96L cells displayed reduced glycolysis and mitochondrial respiration when combined with LY3214996. Altogether these data support Octpep-1 as an optimal candidate in combination therapies for melanoma BRAF(V600E) mutations
High-Redshift Quasars Found in Sloan Digital Sky Survey Commissioning Data II: The Spring Equatorial Stripe
This is the second paper in a series aimed at finding high-redshift quasars
from five-color (u'g'r'i'z') imaging data taken along the Celestial Equator by
the Sloan Digital Sky Survey (SDSS) during its commissioning phase. In this
paper, we present 22 high-redshift quasars (z>3.6) discovered from ~250 deg^2
of data in the spring Equatorial Stripe, plus photometry for two previously
known high-redshift quasars in the same region of sky. Our success rate of
identifying high-redshift quasars is 68%. Five of the newly discovered quasars
have redshifts higher than 4.6 (z=4.62, 4.69, 4.70, 4.92 and 5.03). All the
quasars have i* < 20.2 with absolute magnitude -28.8 < M_B < -26.1 (h=0.5,
q_0=0.5). Several of the quasars show unusual emission and absorption features
in their spectra, including an object at z=4.62 without detectable emission
lines, and a Broad Absorption Line (BAL) quasar at z=4.92.Comment: 28 pages, AJ in press (Jan 2000), final version with minor changes;
high resolution finding charts available at
http://www.astro.princeton.edu/~fan/paper/qso2.htm
Weak Lensing with SDSS Commissioning Data: The Galaxy-Mass Correlation Function To 1/h Mpc
(abridged) We present measurements of galaxy-galaxy lensing from early
commissioning imaging data from the Sloan Digital Sky Survey (SDSS). We measure
a mean tangential shear around a stacked sample of foreground galaxies in three
bandpasses out to angular radii of 600'', detecting the shear signal at very
high statistical significance. The shear profile is well described by a
power-law. A variety of rigorous tests demonstrate the reality of the
gravitational lensing signal and confirm the uncertainty estimates. We
interpret our results by modeling the mass distributions of the foreground
galaxies as approximately isothermal spheres characterized by a velocity
dispersion and a truncation radius. The velocity dispersion is constrained to
be 150-190 km/s at 95% confidence (145-195 km/s including systematic
uncertainties), consistent with previous determinations but with smaller error
bars. Our detection of shear at large angular radii sets a 95% confidence lower
limit , corresponding to a physical radius of
kpc, implying that galaxy halos extend to very large radii. However, it is
likely that this is being biased high by diffuse matter in the halos of groups
and clusters. We also present a preliminary determination of the galaxy-mass
correlation function finding a correlation length similar to the galaxy
autocorrelation function and consistency with a low matter density universe
with modest bias. The full SDSS will cover an area 44 times larger and provide
spectroscopic redshifts for the foreground galaxies, making it possible to
greatly improve the precision of these constraints, measure additional
parameters such as halo shape, and measure the properties of dark matter halos
separately for many different classes of galaxies.Comment: 28 pages, 11 figures, submitted to A
The Sloan Digital Sky Survey Quasar Catalog I. Early Data Release
We present the first edition of the Sloan Digital Sky Survey (SDSS) Quasar
Catalog. The catalog consists of the 3814 objects (3000 discovered by the SDSS)
in the initial SDSS public data release that have at least one emission line
with a full width at half maximum larger than 1000 km/s, luminosities brighter
than M_i^* = -23, and highly reliable redshifts. The area covered by the
catalog is 494 square degrees; the majority of the objects were found in SDSS
commissioning data using a multicolor selection technique. The quasar redshifts
range from 0.15 to 5.03. For each object the catalog presents positions
accurate to better than 0.2" rms per coordinate, five band (ugriz) CCD-based
photometry with typical accuracy of 0.05 mag, radio and X-ray emission
properties, and information on the morphology and selection method. Calibrated
spectra of all objects in the catalog, covering the wavelength region 3800 to
9200 Angstroms at a spectral resolution of 1800-2100, are also available. Since
the quasars were selected during the commissioning period, a time when the
quasar selection algorithm was undergoing frequent revisions, the sample is not
homogeneous and is not intended for statistical analysis.Comment: 27 pages, 4 figures, 4 tables, accepted by A
An integrated care program to prevent work disability due to chronic low back pain: a process evaluation within a randomized controlled trial
<p>Abstract</p> <p>Background</p> <p>In the past decade, a considerable amount of research has been carried out to evaluate the effectiveness of innovative low back pain (LBP) interventions. Although some interventions proved to be effective, they are not always applied in daily practice. To successfully implement an innovative program it is important to identify barriers and facilitators in order to change practice routine. Because usual care is not directly aimed at return to work (RTW), we evaluated an integrated care program, combining a patient-directed and a workplace-directed intervention provided by a multidisciplinary team, including a clinical occupational physician to reduce occupational disability in chronic LBP patients. The aims of this study were to describe the feasibility of the implementation of the integrated care program, to assess the satisfaction and expectations of the involved stakeholders and to describe the needs for improvement of the program.</p> <p>Methods</p> <p>Eligible for this study were patients who had been on sick leave due to chronic LBP. Data were collected from the patients, their supervisors and the involved health care professionals, by means of questionnaires and structured charts, during 3-month follow-up. Implementation, satisfaction and expectations were investigated.</p> <p>Results</p> <p>Of the 40 patients who were eligible to participate in the integrated care program, 37 patients, their supervisors and the health care professionals actually participated in the intervention. Adherence to the integrated care program was in accordance with the protocol, and the patients, their supervisors and the health care professionals were (very) satisfied with the program. The role of the clinical occupational physician was of additional value in the RTW process. Time-investment was the only barrier for implementation reported by the multidisciplinary team.</p> <p>Conclusion</p> <p>The implementation of this program will not be influenced by any flaws in its application that are related to the program itself, or to the adherence of patients with chronic LBP and their health care professionals.</p> <p>This program is promising in terms of feasibility, satisfaction and compliance of the patients, their supervisors and the health care professionals. Before implementation on a wider scale, the communication and the information technology of the program should be improved.</p> <p>Trials Registration</p> <p>[ISRCTN28478651]</p
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