999 research outputs found
Resistance to antiangiogenic therapies by metabolic symbiosis in renal cell carcinoma PDX models and patients
Antiangiogenic drugs are used clinically for treatment of renal cell carcinoma (RCC) as a standard first-line treatment. Nevertheless, these agents primarily serve to stabilize disease, and resistance eventually develops concomitant with progression. Here, we implicate metabolic symbiosis between tumor cells distal and proximal to remaining vessels as a mechanism of resistance to antiangiogenic therapies in patient-derived RCC orthoxenograft (PDX) models and in clinical samples. This metabolic patterning is regulated by the mTOR pathway, and its inhibition effectively blocks metabolic symbiosis in PDX models. Clinically, patients treated with antiangiogenics consistently present with histologic signatures of metabolic symbiosis that are exacerbated in resistant tumors. Furthermore, the mTOR pathway is also associated in clinical samples, and its inhibition eliminates symbiotic patterning in patient samples. Overall, these data support a mechanism of resistance to antiangiogenics involving metabolic compartmentalization of tumor cells that can be inhibited by mTOR-targeted drugs
Risk Factors and Outcomes for Late Presentation for HIV-Positive Persons in Europe: Results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE).
Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality
A search for point sources of EeV photons
Measurements of air showers made using the hybrid technique developed with
the fluorescence and surface detectors of the Pierre Auger Observatory allow a
sensitive search for point sources of EeV photons anywhere in the exposed sky.
A multivariate analysis reduces the background of hadronic cosmic rays. The
search is sensitive to a declination band from -85{\deg} to +20{\deg}, in an
energy range from 10^17.3 eV to 10^18.5 eV. No photon point source has been
detected. An upper limit on the photon flux has been derived for every
direction. The mean value of the energy flux limit that results from this,
assuming a photon spectral index of -2, is 0.06 eV cm^-2 s^-1, and no celestial
direction exceeds 0.25 eV cm^-2 s^-1. These upper limits constrain scenarios in
which EeV cosmic ray protons are emitted by non-transient sources in the
Galaxy.Comment: 28 pages, 10 figures, accepted for publication in The Astrophysical
Journa
Reconstruction of inclined air showers detected with the Pierre Auger Observatory
We describe the method devised to reconstruct inclined cosmic-ray air showers
with zenith angles greater than detected with the surface array of
the Pierre Auger Observatory. The measured signals at the ground level are
fitted to muon density distributions predicted with atmospheric cascade models
to obtain the relative shower size as an overall normalization parameter. The
method is evaluated using simulated showers to test its performance. The energy
of the cosmic rays is calibrated using a sub-sample of events reconstructed
with both the fluorescence and surface array techniques. The reconstruction
method described here provides the basis of complementary analyses including an
independent measurement of the energy spectrum of ultra-high energy cosmic rays
using very inclined events collected by the Pierre Auger Observatory.Comment: 27 pages, 19 figures, accepted for publication in Journal of
Cosmology and Astroparticle Physics (JCAP
Highlights from the Pierre Auger Observatory
The Pierre Auger Observatory is the world's largest cosmic ray observatory.
Our current exposure reaches nearly 40,000 km str and provides us with an
unprecedented quality data set. The performance and stability of the detectors
and their enhancements are described. Data analyses have led to a number of
major breakthroughs. Among these we discuss the energy spectrum and the
searches for large-scale anisotropies. We present analyses of our X
data and show how it can be interpreted in terms of mass composition. We also
describe some new analyses that extract mass sensitive parameters from the 100%
duty cycle SD data. A coherent interpretation of all these recent results opens
new directions. The consequences regarding the cosmic ray composition and the
properties of UHECR sources are briefly discussed.Comment: 9 pages, 12 figures, talk given at the 33rd International Cosmic Ray
Conference, Rio de Janeiro 201
Operations of and Future Plans for the Pierre Auger Observatory
Technical reports on operations and features of the Pierre Auger Observatory,
including ongoing and planned enhancements and the status of the future
northern hemisphere portion of the Observatory. Contributions to the 31st
International Cosmic Ray Conference, Lodz, Poland, July 2009.Comment: Contributions to the 31st ICRC, Lodz, Poland, July 200
The Pierre Auger Observatory III: Other Astrophysical Observations
Astrophysical observations of ultra-high-energy cosmic rays with the Pierre
Auger ObservatoryComment: Contributions to the 32nd International Cosmic Ray Conference,
Beijing, China, August 201
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