4,464 research outputs found
Patient-derived xenografts and organoids model therapy response in prostate cancer.
Therapy resistance and metastatic processes in prostate cancer (PCa) remain undefined, due to lack of experimental models that mimic different disease stages. We describe an androgen-dependent PCa patient-derived xenograft (PDX) model from treatment-naïve, soft tissue metastasis (PNPCa). RNA and whole-exome sequencing of the PDX tissue and organoids confirmed transcriptomic and genomic similarity to primary tumor. PNPCa harbors BRCA2 and CHD1 somatic mutations, shows an SPOP/FOXA1-like transcriptomic signature and microsatellite instability, which occurs in 3% of advanced PCa and has never been modeled in vivo. Comparison of the treatment-naïve PNPCa with additional metastatic PDXs (BM18, LAPC9), in a medium-throughput organoid screen of FDA-approved compounds, revealed differential drug sensitivities. Multikinase inhibitors (ponatinib, sunitinib, sorafenib) were broadly effective on all PDX- and patient-derived organoids from advanced cases with acquired resistance to standard-of-care compounds. This proof-of-principle study may provide a preclinical tool to screen drug responses to standard-of-care and newly identified, repurposed compounds
A Quasi-Model-Independent Search for New Physics at Large Transverse Momentum
We apply a quasi-model-independent strategy ("Sleuth") to search for new high
p_T physics in approximately 100 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV
collected by the DZero experiment during 1992-1996 at the Fermilab Tevatron.
Over thirty-two e mu X, W+jets-like, Z+jets-like, and 3(lepton/photon)X
exclusive final states are systematically analyzed for hints of physics beyond
the standard model. Simultaneous sensitivity to a variety of models predicting
new phenomena at the electroweak scale is demonstrated by testing the method on
a particular signature in each set of final states. No evidence of new high p_T
physics is observed in the course of this search, and we find that 89% of an
ensemble of hypothetical similar experimental runs would have produced a final
state with a candidate signal more interesting than the most interesting
observed in these data.Comment: 28 pages, 17 figures. Submitted to Physical Review
Search for New Physics in e mu X Data at D0 Using Sleuth: A Quasi-Model-Independent Search Strategy for New Physics
We present a quasi-model-independent search for the physics responsible for
electroweak symmetry breaking. We define final states to be studied, and
construct a rule that identifies a set of relevant variables for any particular
final state. A new algorithm ("Sleuth") searches for regions of excess in those
variables and quantifies the significance of any detected excess. After
demonstrating the sensitivity of the method, we apply it to the semi-inclusive
channel e mu X collected in 108 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV
at the D0 experiment during 1992-1996 at the Fermilab Tevatron. We find no
evidence of new high p_T physics in this sample.Comment: 23 pages, 12 figures. Submitted to Physical Review
Probing BFKL Dynamics in the Dijet Cross Section at Large Rapidity Intervals in ppbar Collisions at sqrt{s}=1800 and 630 GeV
Inclusive dijet production at large pseudorapidity intervals (delta_eta)
between the two jets has been suggested as a regime for observing BFKL
dynamics. We have measured the dijet cross section for large delta_eta in ppbar
collisions at sqrt{s}=1800 and 630 GeV using the DO detector. The partonic
cross section increases strongly with the size of delta_eta. The observed
growth is even stronger than expected on the basis of BFKL resummation in the
leading logarithmic approximation. The growth of the partonic cross section can
be accommodated with an effective BFKL intercept of
a_{BFKL}(20GeV)=1.65+/-0.07.Comment: Published in Physical Review Letter
Ratio of the Isolated Photon Cross Sections at \sqrt{s} = 630 and 1800 GeV
The inclusive cross section for production of isolated photons has been
measured in \pbarp collisions at GeV with the \D0 detector at
the Fermilab Tevatron Collider. The photons span a transverse energy ()
range from 7-49 GeV and have pseudorapidity . This measurement is
combined with to previous \D0 result at GeV to form a ratio
of the cross sections. Comparison of next-to-leading order QCD with the
measured cross section at 630 GeV and ratio of cross sections show satisfactory
agreement in most of the range.Comment: 7 pages. Published in Phys. Rev. Lett. 87, 251805, (2001
A measurement of the W boson mass using large rapidity electrons
We present a measurement of the W boson mass using data collected by the D0
experiment at the Fermilab Tevatron during 1994--1995. We identify W bosons by
their decays to e-nu final states where the electron is detected in a forward
calorimeter. We extract the W boson mass, Mw, by fitting the transverse mass
and transverse electron and neutrino momentum spectra from a sample of 11,089 W
-> e nu decay candidates. We use a sample of 1,687 dielectron events, mostly
due to Z -> ee decays, to constrain our model of the detector response. Using
the forward calorimeter data, we measure Mw = 80.691 +- 0.227 GeV. Combining
the forward calorimeter measurements with our previously published central
calorimeter results, we obtain Mw = 80.482 +- 0.091 GeV
Measurement of the p-pbar -> Wgamma + X cross section at sqrt(s) = 1.96 TeV and WWgamma anomalous coupling limits
The WWgamma triple gauge boson coupling parameters are studied using p-pbar
-> l nu gamma + X (l = e,mu) events at sqrt(s) = 1.96 TeV. The data were
collected with the DO detector from an integrated luminosity of 162 pb^{-1}
delivered by the Fermilab Tevatron Collider. The cross section times branching
fraction for p-pbar -> W(gamma) + X -> l nu gamma + X with E_T^{gamma} > 8 GeV
and Delta R_{l gamma} > 0.7 is 14.8 +/- 1.6 (stat) +/- 1.0 (syst) +/- 1.0 (lum)
pb. The one-dimensional 95% confidence level limits on anomalous couplings are
-0.88 < Delta kappa_{gamma} < 0.96 and -0.20 < lambda_{gamma} < 0.20.Comment: Submitted to Phys. Rev. D Rapid Communication
Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt{s} = 1.96 TeV using Kinematic Characteristics of Lepton + Jets Events
We present a measurement of the top quark pair ttbar production cross section
in ppbar collisions at a center-of-mass energy of 1.96 TeV using 230 pb**{-1}
of data collected by the DO detector at the Fermilab Tevatron Collider. We
select events with one charged lepton (electron or muon), large missing
transverse energy, and at least four jets, and extract the ttbar content of the
sample based on the kinematic characteristics of the events. For a top quark
mass of 175 GeV, we measure sigma(ttbar) = 6.7 {+1.4-1.3} (stat) {+1.6- 1.1}
(syst) +/-0.4 (lumi) pb, in good agreement with the standard model prediction.Comment: submitted to Phys.Rev.Let
Search for Electroweak Production of Single Top Quarks in ppbar Collisions
We present a search for electroweak production of single top quarks in the
electron+jets and muon+jets decay channels. The measurements use ~90 pb^-1 of
data from Run 1 of the Fermilab Tevatron collider, collected at 1.8 TeV with
the DZero detector between 1992 and 1995. We use events that include a tagging
muon, implying the presence of a b jet, to set an upper limit at the 95%
confidence level on the cross section for the s-channel process ppbar->tb+X of
39 pb. The upper limit for the t-channel process ppbar->tqb+X is 58 pb.Comment: 11 pages, 2 figures. This is the published versio
Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt(s)=1.96 TeV using Lepton + Jets Events with Lifetime b-tagging
We present a measurement of the top quark pair () production cross
section () in collisions at TeV
using 230 pb of data collected by the D0 experiment at the Fermilab
Tevatron Collider. We select events with one charged lepton (electron or muon),
missing transverse energy, and jets in the final state. We employ
lifetime-based b-jet identification techniques to further enhance the
purity of the selected sample. For a top quark mass of 175 GeV, we
measure pb, in
agreement with the standard model expectation.Comment: 7 pages, 2 figures, 3 tables Submitted to Phys.Rev.Let
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