396 research outputs found
Characterization of Overlap in Observational Studies
Overlap between treatment groups is required for non-parametric estimation of
causal effects. If a subgroup of subjects always receives the same
intervention, we cannot estimate the effect of intervention changes on that
subgroup without further assumptions. When overlap does not hold globally,
characterizing local regions of overlap can inform the relevance of causal
conclusions for new subjects, and can help guide additional data collection. To
have impact, these descriptions must be interpretable for downstream users who
are not machine learning experts, such as policy makers. We formalize overlap
estimation as a problem of finding minimum volume sets subject to coverage
constraints and reduce this problem to binary classification with Boolean rule
classifiers. We then generalize this method to estimate overlap in off-policy
policy evaluation. In several real-world applications, we demonstrate that
these rules have comparable accuracy to black-box estimators and provide
intuitive and informative explanations that can inform policy making.Comment: To appear at AISTATS 202
Prevalence of Escherichia coli O157:H7 in cow-calf herds in Kansas
Fecal samples from cows and calves and samples of water sources were collected monthly for 8 months from 10 Kansas cow-calf farms to determine the prevalence of E. coli O157:H7. The bacterium was found in 8% of fecal samples from cows that were within 24 hours of calving, 1.4% of fecal samples from cows which were not within 24 hours of calving, 1.4% of calf fecal samples, and 1.5% of water samples. E. coli O157:H7 was identified from at least one sample on all farms
KELT-11b: A Highly Inflated Sub-Saturn Exoplanet Transiting the V=8 Subgiant HD 93396
We report the discovery of a transiting exoplanet, KELT-11b, orbiting the
bright () subgiant HD 93396. A global analysis of the system shows that
the host star is an evolved subgiant star with K,
, , log , and [Fe/H].
The planet is a low-mass gas giant in a day orbit,
with , , g cm, surface gravity log , and equilibrium temperature K. KELT-11 is the brightest known transiting exoplanet host
in the southern hemisphere by more than a magnitude, and is the 6th brightest
transit host to date. The planet is one of the most inflated planets known,
with an exceptionally large atmospheric scale height (2763 km), and an
associated size of the expected atmospheric transmission signal of 5.6%. These
attributes make the KELT-11 system a valuable target for follow-up and
atmospheric characterization, and it promises to become one of the benchmark
systems for the study of inflated exoplanets.Comment: 15 pages, Submitted to AAS Journal
The CEA/CD3-Bispecific Antibody MEDI-565 (MT111) Binds a Nonlinear Epitope in the Full-Length but Not a Short Splice Variant of CEA
MEDI-565 (also known as MT111) is a bispecific T-cell engager (BiTE®) antibody in development for the treatment of patients with cancers expressing carcinoembryonic antigen (CEA). MEDI-565 binds CEA on cancer cells and CD3 on T cells to induce T-cell mediated killing of cancer cells. To understand the molecular basis of human CEA recognition by MEDI-565 and how polymorphisms and spliced forms of CEA may affect MEDI-565 activity, we mapped the epitope of MEDI-565 on CEA using mutagenesis and homology modeling approaches. We found that MEDI-565 recognized a conformational epitope in the A2 domain comprised of amino acids 326–349 and 388–410, with critical residues F326, T328, N333, V388, G389, P390, E392, I408, and N410. Two non-synonymous single-nucleotide polymorphisms (SNPs) (rs10407503, rs7249230) were identified in the epitope region, but they are found at low homozygosity rates. Searching the National Center for Biotechnology Information GenBank® database, we further identified a single, previously uncharacterized mRNA splice variant of CEA that lacks a portion of the N-terminal domain, the A1 and B1 domains, and a large portion of the A2 domain. Real-time quantitative polymerase chain reaction analysis of multiple cancers showed widespread expression of full-length CEA in these tumors, with less frequent but concordant expression of the CEA splice variant. Because the epitope was largely absent from the CEA splice variant, MEDI-565 did not bind or mediate T-cell killing of cells solely expressing this form of CEA. In addition, the splice variant did not interfere with MEDI-565 binding or activity when co-expressed with full-length CEA. Thus MEDI-565 may broadly target CEA-positive tumors without regard for expression of the short splice variant of CEA. Together our data suggest that MEDI-565 activity will neither be impacted by SNPs nor by a splice variant of CEA
KELT-8b: A highly inflated transiting hot Jupiter and a new technique for extracting high-precision radial velocities from noisy spectra
We announce the discovery of a highly inflated transiting hot Jupiter
discovered by the KELT-North survey. A global analysis including constraints
from isochrones indicates that the V = 10.8 host star (HD 343246) is a mildly
evolved, G dwarf with K, , , an inferred mass
M, and radius
R. The planetary companion has mass , radius
, surface gravity , and density
g cm. The planet is on a roughly
circular orbit with semimajor axis AU and
eccentricity . The best-fit linear ephemeris is
BJD and
days. This planet is one of the most inflated of all known transiting
exoplanets, making it one of the few members of a class of extremely low
density, highly-irradiated gas giants. The low stellar and large
implied radius are supported by stellar density constraints from follow-up
light curves, plus an evolutionary and space motion analysis. We also develop a
new technique to extract high precision radial velocities from noisy spectra
that reduces the observing time needed to confirm transiting planet candidates.
This planet boasts deep transits of a bright star, a large inferred atmospheric
scale height, and a high equilibrium temperature of
K, assuming zero albedo and perfect heat redistribution, making it one of the
best targets for future atmospheric characterization studies.Comment: Submitted to ApJ, feedback is welcom
KELT-10b: The First Transiting Exoplanet from the KELT-South Survey -- A Hot Sub-Jupiter Transiting a V = 10.7 Early G-Star
We report the discovery of KELT-10b, the first transiting exoplanet
discovered using the KELT-South telescope. KELT-10b is a highly inflated
sub-Jupiter mass planet transiting a relatively bright star (TYC
8378-64-1), with T = K, =
and [Fe/H] = , an inferred mass
M = M and radius R =
R. The planet has a radius R =
R and mass M =
M. The planet has an eccentricity consistent with zero and a semi-major
axis = AU. The best fitting linear
ephemeris is = 2457066.720450.00027 BJD and P =
4.16627390.0000063 days. This planet joins a group of highly inflated
transiting exoplanets with a radius much larger and a mass much less than those
of Jupiter. The planet, which boasts deep transits of 1.4%, has a relatively
high equilibrium temperature of T = K, assuming zero
albedo and perfect heat redistribution. KELT-10b receives an estimated
insolation of 10 erg s cm,
which places it far above the insolation threshold above which hot Jupiters
exhibit increasing amounts of radius inflation. Evolutionary analysis of the
host star suggests that KELT-10b is unlikely to survive beyond the current
subgiant phase, due to a concomitant in-spiral of the planet over the next
1 Gyr. The planet transits a relatively bright star and exhibits the
third largest transit depth of all transiting exoplanets with V 11 in the
southern hemisphere, making it a promising candidate for future atmospheric
characterization studies.Comment: 20 pages, 13 figures, 7 tables, accepted for publication in MNRA
Potent Immune Modulation by MEDI6383, an Engineered Human OX40 Ligand IgG4P Fc Fusion Protein.
Ligation of OX40 (CD134, TNFRSF4) on activated T cells by its natural ligand (OX40L, CD252, TNFSF4) enhances cellular survival, proliferation, and effector functions such as cytokine release and cellular cytotoxicity. We engineered a recombinant human OX40L IgG4P Fc fusion protein termed MEDI6383 that assembles into a hexameric structure and exerts potent agonist activity following engagement of OX40. MEDI6383 displayed solution-phase agonist activity that was enhanced when the fusion protein was clustered by Fc gamma receptors (FcγRs) on the surface of adjacent cells. The resulting costimulation of OX40 on T cells induced NFκB promoter activity in OX40-expressing T cells and induced Th1-type cytokine production, proliferation, and resistance to regulatory T cell (Treg)-mediated suppression. MEDI6383 enhanced the cytolytic activity of tumor-reactive T cells and reduced tumor growth in the context of an alloreactive human T cell:tumor cell admix model in immunocompromised mice. Consistent with the role of OX40 costimulation in the expansion of memory T cells, MEDI6383 administered to healthy nonhuman primates elicited peripheral blood CD4 and CD8 central and effector memory T-cell proliferation as well as B-cell proliferation. Together, these results suggest that OX40 agonism has the potential to enhance antitumor immunity in human malignancies
KELT-7b: A hot Jupiter transiting a bright V=8.54 rapidly rotating F-star
We report the discovery of KELT-7b, a transiting hot Jupiter with a mass of
MJ, radius of RJ, and an orbital
period of days. The bright host star (HD33643;
KELT-7) is an F-star with , Teff K, [Fe/H]
, and . It has a mass of
Msun, a radius of Rsun, and
is the fifth most massive, fifth hottest, and the ninth brightest star known to
host a transiting planet. It is also the brightest star around which KELT has
discovered a transiting planet. Thus, KELT-7b is an ideal target for detailed
characterization given its relatively low surface gravity, high equilibrium
temperature, and bright host star. The rapid rotation of the star (
km/s) results in a Rossiter-McLaughlin effect with an unusually large amplitude
of several hundred m/s. We find that the orbit normal of the planet is likely
to be well-aligned with the stellar spin axis, with a projected spin-orbit
alignment of degrees. This is currently the second most
rapidly rotating star to have a reflex signal (and thus mass determination) due
to a planetary companion measured.Comment: Accepted to The Astronomical Journa
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