2,326 research outputs found
Experimental investigation of a mach 5 isentropic spike inlet at and below design speed
Zero angle of attack performance of isentropic spike inlet designed for maximum external compression at hypersonic spee
Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel
Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al
A variational principle for stationary, axisymmetric solutions of Einstein's equations
Stationary, axisymmetric, vacuum, solutions of Einstein's equations are
obtained as critical points of the total mass among all axisymmetric and
symmetric initial data with fixed angular momentum. In this
variational principle the mass is written as a positive definite integral over
a spacelike hypersurface. It is also proved that if absolute minimum exists
then it is equal to the absolute minimum of the mass among all maximal,
axisymmetric, vacuum, initial data with fixed angular momentum. Arguments are
given to support the conjecture that this minimum exists and is the extreme
Kerr initial data.Comment: 21 page
Lifting the Dusty Veil II: A Large-Scale Study of the Galactic Infrared Extinction Law
We combine near-infrared (2MASS) and mid-infrared (Spitzer-IRAC) photometry
to characterize the IR extinction law (1.2-8 microns) over nearly 150 degrees
of contiguous Milky Way midplane longitude. The relative extinctions in 5
passbands across these wavelength and longitude ranges are derived by
calculating color excess ratios for G and K giant red clump stars in contiguous
midplane regions and deriving the wavelength dependence of extinction in each
one. Strong, monotonic variations in the extinction law shape are found as a
function of angle from the Galactic center, symmetric on either side of it.
These longitudinal variations persist even when dense interstellar regions,
known a priori to have a shallower extinction curve, are removed. The
increasingly steep extinction curves towards the outer Galaxy indicate a steady
decrease in the absolute-to-selective extinction ratio (R_V) and in the mean
dust grain size at greater Galactocentric angles. We note an increasing
strength of the 8 micron extinction inflection at high Galactocentric angles
and, using theoretical dust models, show that this behavior is consistent with
the trend in R_V. Along several lines of sight where the solution is most
feasible, A_lambda/A_Ks as a function of Galactic radius is estimated and shown
to have a Galactic radial dependence. Our analyses suggest that the observed
relationship between extinction curve shape and Galactic longitude is due to an
intrinsic dependence of the extinction law on Galactocentric radius.Comment: Accepted to Ap
NCI-MATCH Arms N & P: Phase II study of PI3K beta inhibitor GSK2636771 in patients (pts) with cancers (ca) with PTEN mutation/deletion (mut/del) or PTEN protein loss
Background: The NCI-MATCH trial is the largest national study (1173 sites) for ptswith relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns tar-geted therapies based on individual tumor molecular alterations detected using theadapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC).We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and Pmay benefit from treatment with the PI3K beta-selective inhibitor GSK2636771.
Methods: Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PS ≤ 1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete loss of cytoplasmic and nuclear PTEN staining on IHC (Arm P), and no other aberrations activating the PI3K/MTOR and MAPK pathways (mut in PIK3CA, PIK3R1, BRAF, KRAS, AKT1, TSC1/2, mTOR, RHEB, NF2, NRAS, HRAS). Pts received GSK2636771 400mg/day (28-days cycles). RECIST 1.1 overall response rate (ORR) was the primary endpoint.
Results: Of 59 enrolled pts, 56 were eligible and received treatment. Of 22 pts with PTEN mut/del (Arm N: 6 uterine, 2 breast, 2 prostate, 2 head/neck ca, 10 other), all are off treatment as of analysis (14 disease progression, 4 for adverse events [AEs], 4 other). One pt (4.5%) with prostate ca (PTEN deletion, MPRSS2-ERG fusion) attained a partial response (-42%). Of 7 (32%) pts with stable disease (SD), 2 had SD \u3e 6 months (uterine leiomyosarcoma; endometrial carcinoma). Of 34 pts with loss of PTEN protein by IHC (Arm P: 7 prostate, 6 breast, 3 squamous anal ca, 2 cholangiocarcinoma, 16 other), all are off treatment as of analysis (26 disease progression, 4 for AE, 4 other). Of 9 (37.5%) pts with SD, 3 had SD \u3e 6 months (prostate cancer; squamous bladder cancer, squamous anal cancer). Median progression-free survival was 1.8 months for both arms. Gr ≥ 3 treatment-related (tr) reversible toxicities were experienced by 30% (7) and 20% (7) of pts in arms N and P, respectively. No tr Gr 5 toxicities were observed in either arm.
Conclusions: Single agent GSK2636771 has very modest activity in ca with PTEN gene mutation/deletion and/or PTEN protein loss
IN-SYNC. V. Stellar kinematics and dynamics in the Orion A Molecular Cloud
The kinematics and dynamics of young stellar populations enable us to test
theories of star formation. With this aim, we continue our analysis of the
SDSS-III/APOGEE IN-SYNC survey, a high resolution near infrared spectroscopic
survey of young clusters. We focus on the Orion A star-forming region, for
which IN-SYNC obtained spectra of stars. In Paper IV we used these
data to study the young stellar population. Here we study the kinematic
properties through radial velocities (). The young stellar population
remains kinematically associated with the molecular gas, following a
gradient along filament. However, near the center
of the region, the distribution is slightly blueshifted and asymmetric;
we suggest that this population, which is older, is slightly in foreground. We
find evidence for kinematic subclustering, detecting statistically significant
groupings of co-located stars with coherent motions. These are mostly in the
lower-density regions of the cloud, while the ONC radial velocities are
smoothly distributed, consistent with it being an older, more dynamically
evolved cluster. The velocity dispersion varies along the filament.
The ONC appears virialized, or just slightly supervirial, consistent with an
old dynamical age. Here there is also some evidence for on-going expansion,
from a --extinction correlation. In the southern filament, is
-- times larger than virial in the L1641N region, where we infer a
superposition along the line of sight of stellar sub-populations, detached from
the gas. On the contrary, decreases towards L1641S, where the
population is again in agreement with a virial state.Comment: 14 pages, 13 figures, ApJ accepte
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