291 research outputs found
The effect of prolonged simulated non- gravitational environment on mineral balance in the adult male, volume 1 Final report
Effect of prolonged bed rest with simulated weightlessness on mineral balance in male adult - Vol.
Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers
We present a review of the interplay between the evolution of circumstellar
disks and the formation of planets, both from the perspective of theoretical
models and dedicated observations. Based on this, we identify and discuss
fundamental questions concerning the formation and evolution of circumstellar
disks and planets which can be addressed in the near future with optical and
infrared long-baseline interferometers. Furthermore, the importance of
complementary observations with long-baseline (sub)millimeter interferometers
and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics
Review"; The final publication is available at http://www.springerlink.co
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The HOSTS Survey for Exozodiacal Dust: Preliminary results and future prospects
[abridged] The presence of large amounts of dust in the habitable zones of
nearby stars is a significant obstacle for future exo-Earth imaging missions.
We executed an N band nulling interferometric survey to determine the typical
amount of such exozodiacal dust around a sample of nearby main sequence stars.
The majority of our data have been analyzed and we present here an update of
our ongoing work. We find seven new N band excesses in addition to the high
confidence confirmation of three that were previously known. We find the first
detections around Sun-like stars and around stars without previously known
circumstellar dust. Our overall detection rate is 23%. The inferred occurrence
rate is comparable for early type and Sun-like stars, but decreases from 71%
[+11%/-20%] for stars with previously detected mid- to far-infrared excess to
11% [+9%/-4%] for stars without such excess, confirming earlier results at high
confidence. For completed observations on individual stars, our sensitivity is
five to ten times better than previous results. Assuming a lognormal luminosity
function of the dust, we find upper limits on the median dust level around all
stars without previously known mid to far infrared excess of 11.5 zodis at 95%
confidence level. The corresponding upper limit for Sun-like stars is 16 zodis.
An LBTI vetted target list of Sun-like stars for exo-Earth imaging would have a
corresponding limit of 7.5 zodis. We provide important new insights into the
occurrence rate and typical levels of habitable zone dust around main sequence
stars. Exploiting the full range of capabilities of the LBTI provides a
critical opportunity for the detailed characterization of a sample of
exozodiacal dust disks to understand the origin, distribution, and properties
of the dust.GMK is supported by the Royal Society as a Royal Society University Research Fellow. AS is partially supported by funding from the Center for Exoplanets and Habitable Worlds. The Center for Exoplanets and
Habitable Worlds is supported by the Pennsylvania State University, the Eberly College of Science, and the Pennsylvania Space Grant Consortium. JMS is supported by NASA through Hubble Fellowship grant HSTHF2-51398.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555
Measurement of the Z/gamma* + b-jet cross section in pp collisions at 7 TeV
The production of b jets in association with a Z/gamma* boson is studied
using proton-proton collisions delivered by the LHC at a centre-of-mass energy
of 7 TeV and recorded by the CMS detector. The inclusive cross section for
Z/gamma* + b-jet production is measured in a sample corresponding to an
integrated luminosity of 2.2 inverse femtobarns. The Z/gamma* + b-jet cross
section with Z/gamma* to ll (where ll = ee or mu mu) for events with the
invariant mass 60 < M(ll) < 120 GeV, at least one b jet at the hadron level
with pT > 25 GeV and abs(eta) < 2.1, and a separation between the leptons and
the jets of Delta R > 0.5 is found to be 5.84 +/- 0.08 (stat.) +/- 0.72 (syst.)
+(0.25)/-(0.55) (theory) pb. The kinematic properties of the events are also
studied and found to be in agreement with the predictions made by the MadGraph
event generator with the parton shower and the hadronisation performed by
PYTHIA.Comment: Submitted to the Journal of High Energy Physic
Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy
A search for new physics is performed in events with two same-sign isolated
leptons, hadronic jets, and missing transverse energy in the final state. The
analysis is based on a data sample corresponding to an integrated luminosity of
4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of
7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of
140 increase in integrated luminosity over previously published results. The
observed yields agree with the standard model predictions and thus no evidence
for new physics is found. The observations are used to set upper limits on
possible new physics contributions and to constrain supersymmetric models. To
facilitate the interpretation of the data in a broader range of new physics
scenarios, information on the event selection, detector response, and
efficiencies is provided.Comment: Published in Physical Review Letter
Compressed representation of a partially defined integer function over multiple arguments
In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one
The HOSTS Survey for Exozodiacal Dust: Observational Results from the Complete Survey
The Large Binocular Telescope Interferometer (LBTI) enables nulling
interferometric observations across the N band (8 to 13 um) to suppress a
star's bright light and probe for faint circumstellar emission. We present and
statistically analyze the results from the LBTI/HOSTS (Hunt for Observable
Signatures of Terrestrial Systems) survey for exozodiacal dust. By comparing
our measurements to model predictions based on the Solar zodiacal dust in the N
band, we estimate a 1 sigma median sensitivity of 23 zodis for early type stars
and 48 zodis for Sun-like stars, where 1 zodi is the surface density of
habitable zone (HZ) dust in the Solar system. Of the 38 stars observed, 10 show
significant excess. A clear correlation of our detections with the presence of
cold dust in the systems was found, but none with the stellar spectral type or
age. The majority of Sun-like stars have relatively low HZ dust levels
(best-fit median: 3 zodis, 1 sigma upper limit: 9 zodis, 95% confidence: 27
zodis based on our N band measurements), while ~20% are significantly more
dusty. The Solar system's HZ dust content is consistent with being typical. Our
median HZ dust level would not be a major limitation to the direct imaging
search for Earth-like exoplanets, but more precise constraints are still
required, in particular to evaluate the impact of exozodiacal dust for the
spectroscopic characterization of imaged exo-Earth candidates
Insulin Resistance Is Not Conserved in Myotubes Established from Women with PCOS
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among premenopausal women, who often develop insulin resistance. We tested the hypothesis that insulin resistance in skeletal muscle of patients with polycystic ovary syndrome (PCOS) is an intrinsic defect, by investigating the metabolic characteristics and gene expression of in vitro differentiated myotubes established from well characterized PCOS subjects.Using radiotracer techniques, RT-PCR and enzyme kinetic analysis we examined myotubes established from PCOS subjects with or without pioglitazone treatment, versus healthy control subjects who had been extensively metabolically characterized in vivo. Results. Myotubes established from PCOS and matched control subjects comprehensively expressed all insulin-sensitive biomarkers; glucose uptake and oxidation, glycogen synthesis and lipid uptake. There were no significant differences between groups either at baseline or during acute insulin stimulation, although in vivo skeletal muscle was insulin resistant. In particular, we found no evidence for defects in insulin-stimulated glycogen synthase activity between groups. Myotubes established from PCOS patients with or without pioglitazone treatment also showed no significant differences between groups, neither at baseline nor during acute insulin stimulation, although in vivo pioglitazone treatment significantly improved insulin sensitivity. Consistently, the myotube cultures failed to show differences in mRNA levels of genes previously demonstrated to differ in PCOS patients with or without pioglitazone treatment (PLEK, SLC22A16, and TTBK).These results suggest that the mechanisms governing insulin resistance in skeletal muscle of PCOS patients in vivo are not primary, but rather adaptive.ClinicalTrials.gov NCT00145340
What is the future of targeted therapy in rheumatology: biologics or small molecules?
Background: Until late in the 20th century, the therapy of rheumatic diseases relied on the use of drugs that had been developed through empirical approaches without detailed understanding of the molecular mechanisms involved. That approach changed with the introduction of biologic therapeutics at the end of the 20th century and by the recent development of small-molecule inhibitors of intracellular signal transduction pathways. Here we compare and discuss the advantages and disadvantages of those two groups of targeted anti-inflammatory therapeutics.Discussion: TNF-blocking biologic agents were introduced into the therapy of rheumatoid arthritis and other autoimmune and inflammatory diseases in the late 1990s. Further biologic agents targeting cytokine networks or specific lymphocyte subsets have since been added to the armamentarium of anti-rheumatic therapy. During the last few years, another wave of novel discoveries led to the development of a new class of small molecule anti-inflammatory compounds targeting intracellular signal transduction molecules, such as tyrosine kinases. In all those cases, the specific targets of the drugs are well defined and significant knowledge about their role in the disease pathomechanism is available, qualifying them for being targeted therapeutics for inflammatory rheumatic diseases. While both groups of targeted therapeutics offer significant clinical benefit, they clearly differ in several aspects, such as the localization of their targets, their route of administration and target specificity, as well as technical details such as manufacturing procedures and cost basis. In this debate paper, we compare the advantages and disadvantages of the two different approaches, aiming to shed light on the possible future of targeted therapies.Summary: Biologic therapeutics and small-molecule inhibitors both have significant advantages and disadvantages in the therapy of rheumatic diseases. The future of targeted therapies is one of the most exciting questions of current rheumatology research and therapy. © 2014 Mócsai et al.; licensee BioMed Central Ltd
Elucidating the clinical and molecular spectrum of SMARCC2-associated NDD in a cohort of 65 affected individuals
Purpose: Coffin-Siris and Nicolaides-Baraitser syndromes are recognizable neurodevelopmental disorders caused by germline variants in BAF complex subunits. The SMARCC2 BAFopathy was recently reported. Herein, we present clinical and molecular data on a large cohort. Methods: Clinical symptoms for 41 novel and 24 previously published affected individuals were analyzed using the Human Phenotype Ontology. For genotype-phenotype correlations, molecular data were standardized and grouped into non-truncating and likely gene-disrupting (LGD) variants. Missense variant protein expression and BAF-subunit interactions were examined using 3D protein modeling, co-immunoprecipitation, and proximity-ligation assays. Results: Neurodevelopmental delay with intellectual disability, muscular hypotonia, and behavioral disorders were the major manifestations. Clinical hallmarks of BAFopathies were rare. Clinical presentation differed significantly, with LGD variants being predominantly inherited and associated with mildly reduced or normal cognitive development, whereas non-truncating variants were mostly de novo and presented with severe developmental delay. These distinct manifestations and non-truncating variant clustering in functional domains suggest different pathomechanisms. In vitro testing showed decreased protein expression for N-terminal missense variants similar to LGD. Conclusion: This study improved SMARCC2 variant classification and identified discernible SMARCC2-associated phenotypes for LGD and non-truncating variants, which were distinct from other BAFopathies. The pathomechanism of most non-truncating variants has yet to be investigated
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