73 research outputs found
Efficacious Intermittent Dosing of a Novel JAK2 Inhibitor in Mouse Models of Polycythemia Vera
A high percentage of patients with the myeloproliferative disorder polycythemia vera (PV) harbor a Val617→Phe activating mutation in the Janus kinase 2 (JAK2) gene, and both cell culture and mouse models have established a functional role for this mutation in the development of this disease. We describe the properties of MRLB-11055, a highly potent inhibitor of both the WT and V617F forms of JAK2, that has therapeutic efficacy in erythropoietin (EPO)-driven and JAK2V617F-driven mouse models of PV. In cultured cells, MRLB-11055 blocked proliferation and induced apoptosis in a manner consistent with JAK2 pathway inhibition. MRLB-11055 effectively prevented EPO-induced STAT5 activation in the peripheral blood of acutely dosed mice, and could prevent EPO-induced splenomegaly and erythrocytosis in chronically dosed mice. In a bone marrow reconstituted JAK2V617F-luciferase murine PV model, MRLB-11055 rapidly reduced the burden of JAK2V617F-expressing cells from both the spleen and the bone marrow. Using real-time in vivo imaging, we examined the kinetics of disease regression and resurgence, enabling the development of an intermittent dosing schedule that achieved significant reductions in both erythroid and myeloid populations with minimal impact on lymphoid cells. Our studies provide a rationale for the use of non-continuous treatment to provide optimal therapy for PV patients
The Magellan-TESS Survey I: Survey Description and Mid-Survey Results
One of the most significant revelations from Kepler is that roughly one-third
of Sun-like stars host planets which orbit their stars within 100 days and are
between the size of Earth and Neptune. How do these super-Earth and sub-Neptune
planets form, what are they made of, and do they represent a continuous
population or naturally divide into separate groups? Measuring their masses and
thus bulk densities can help address these questions of their origin and
composition. To that end, we began the Magellan-TESS Survey (MTS), which uses
Magellan II/PFS to obtain radial velocity (RV) masses of 30 transiting
exoplanets discovered by TESS and develops an analysis framework that connects
observed planet distributions to underlying populations. In the past, RV
measurements of small planets have been challenging to obtain due to the
faintness and low RV semi-amplitudes of most Kepler systems, and challenging to
interpret due to the potential biases in the existing ensemble of small planet
masses from non-algorithmic decisions for target selection and observation
plans. The MTS attempts to minimize these biases by focusing on bright TESS
targets and employing a quantitative selection function and multi-year
observing strategy. In this paper, we (1) describe the motivation and survey
strategy behind the MTS, (2) present our first catalog of planet mass and
density constraints for 25 TESS Objects of Interest (TOIs; 20 in our population
analysis sample, five that are members of the same systems), and (3) employ a
hierarchical Bayesian model to produce preliminary constraints on the
mass-radius (M-R) relation. We find qualitative agreement with prior
mass-radius relations but some quantitative differences (abridged). The the
results of this work can inform more detailed studies of individual systems and
offer a framework that can be applied to future RV surveys with the goal of
population inferences.Comment: 101 pages (39 of main text and references, the rest an appendix of
figures and tables). Submitted to AAS Journal
Two Warm Super-Earths Transiting the Nearby M Dwarf TOI-2095
We report the detection and validation of two planets orbiting TOI-2095 (TIC
235678745). The host star is a 3700K M1V dwarf with a high proper motion. The
star lies at a distance of 42 pc in a sparsely populated portion of the sky and
is bright in the infrared (K=9). With data from 24 Sectors of observation
during TESS's Cycles 2 and 4, TOI-2095 exhibits two sets of transits associated
with super-Earth-sized planets. The planets have orbital periods of 17.7 days
and 28.2 days and radii of 1.30 and 1.39 Earth radii, respectively. Archival
data, preliminary follow-up observations, and vetting analyses support the
planetary interpretation of the detected transit signals. The pair of planets
have estimated equilibrium temperatures of approximately 400 K, with stellar
insolations of 3.23 and 1.73 times that of Earth, placing them in the Venus
zone. The planets also lie in a radius regime signaling the transition between
rock-dominated and volatile-rich compositions. They are thus prime targets for
follow-up mass measurements to better understand the properties of warm,
transition radius planets. The relatively long orbital periods of these two
planets provide crucial data that can help shed light on the processes that
shape the composition of small planets orbiting M dwarfs.Comment: Submitted to AAS Journal
Reaching the boundary between stellar kinematic groups and very wide binaries. The Washington Double Stars with the widest angular separations
Aims. I look for and characterise very wide binaries and multiple systems
with projected physical separations larger than s = 0.1 pc, which is generally
believed to be a sharp upper limit to the distribution of wide binay semimajor
axes. Methods. I investigated in detail 30 Washington Double Stars with angular
separations rho > 1000 arcsec. I discarded 23 of them as probably unbound
systems based on discordant astrometry, photometry, spectral types, and radial
velocities. The remaining seven systems were subject to a comprehensive data
compilation and derivation (multi-wavelength photometry, heliocentric distance,
multiplicity, age, mass, metallicity, membership in young kinematic group).
Results. Of the seven very wide systems, six have projected physical
separations larger than the hypothetical cutoff at s = 0.1 pc; four of them
have separations s > 0.2 pc. Although there are two systems in young kinematic
groups (namely HD 136654 and BD+32 2572 in the Hyades Supercluster, and AU Mic
and AT Mic AB in the beta Pictoris moving group), there is not a clear
prevalence of young systems (tau < 1 Ga) among these very wide binaries.
Finally, I compare the binding energies of the seven systems with those of
other weakly bound systems in the field.Comment: A&A, accepted (this version: as sent to language editor
Italian guidelines for primary headaches: 2012 revised version
The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
The Science Performance of JWST as Characterized in Commissioning
This paper characterizes the actual science performance of the James Webb
Space Telescope (JWST), as determined from the six month commissioning period.
We summarize the performance of the spacecraft, telescope, science instruments,
and ground system, with an emphasis on differences from pre-launch
expectations. Commissioning has made clear that JWST is fully capable of
achieving the discoveries for which it was built. Moreover, almost across the
board, the science performance of JWST is better than expected; in most cases,
JWST will go deeper faster than expected. The telescope and instrument suite
have demonstrated the sensitivity, stability, image quality, and spectral range
that are necessary to transform our understanding of the cosmos through
observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures;
https://iopscience.iop.org/article/10.1088/1538-3873/acb29
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The effect of stellar contamination on low-resolution transmission spectroscopy: needs identified by NASA’s Exoplanet Exploration Program Study Analysis Group 21
Study Analysis Group 21 (SAG21) of NASA’s Exoplanet Exploration Program Analysis Group was organized to study the effect of stellar contamination on space-based transmission spectroscopy, a method for studying exoplanetary atmospheres by measuring the wavelength-dependent radius of a planet as it transits its star. Transmission spectroscopy relies on a precise understanding of the spectrum of the star being occulted. However, stars are not homogeneous, constant light sources but have temporally evolving photospheres and chromospheres with inhomogeneities like spots, faculae, plages, granules, and flares. This SAG brought together an interdisciplinary team of more than 100 scientists, with observers and theorists from the heliophysics, stellar astrophysics, planetary science, and exoplanetary atmosphere research communities, to study the current research needs that can be addressed in this context to make the most of transit studies from current NASA facilities like Hubble Space Telescope and JWST. The analysis produced 14 findings, which fall into three science themes encompassing (i) how the Sun is used as our best laboratory to calibrate our understanding of stellar heterogeneities (‘The Sun as the Stellar Benchmark’), (ii) how stars other than the Sun extend our knowledge of heterogeneities (‘Surface Heterogeneities of Other Stars’), and (iii) how to incorporate information gathered for the Sun and other stars into transit studies (‘Mapping Stellar Knowledge to Transit Studies’). In this invited review, we largely reproduce the final report of SAG21 as a contribution to the peer-reviewed literature
Health beliefs about bottled water: a qualitative study
Abstract Background There has been a consistent rise in bottled water consumption over the last decade. Little is known about the health beliefs held by the general public about bottled water as this issue is not addressed by the existing quantitative literature. The purpose of this study was to improve understanding of the public's health beliefs concerning bottled mineral water, and the extent to which these beliefs and other views they hold, influence drinking habits. Methods A qualitative study using semi-structured interviews, with 23 users of the Munrow Sports Centre on the University of Birmingham campus. Results Health beliefs about bottled water could be classified as general or specific beliefs. Most participants believed that bottled water conferred general health benefits but were unsure as to the nature of these. In terms of specific health beliefs, the idea that the minerals in bottled water conferred a health benefit was the most commonly cited. There were concerns over links between the plastic bottle itself and cancer. Participants believed that bottled water has a detrimental effect on the environment. Convenience, cost and taste were influential factors when making decisions as to whether to buy bottled water; health beliefs were unimportant motivating factors. Conclusion The majority of participants believed that bottled water has some health benefits. However, these beliefs played a minor role in determining bottled water consumption and are unlikely to be helpful in explaining recent trends in bottled water consumption if generalised to the UK population. The health beliefs elicited were supported by scientific evidence to varying extents. Most participants did not feel that bottled water conferred significant, if any, health benefits over tap water.</p
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