469 research outputs found
Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.
We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies
Predicting Quantitative Genetic Interactions by Means of Sequential Matrix Approximation
Despite the emerging experimental techniques for perturbing multiple genes and measuring their quantitative phenotypic effects, genetic interactions have remained extremely difficult to predict on a large scale. Using a recent high-resolution screen of genetic interactions in yeast as a case study, we investigated whether the extraction of pertinent information encoded in the quantitative phenotypic measurements could be improved by computational means. By taking advantage of the observation that most gene pairs in the genetic interaction screens have no significant interactions with each other, we developed a sequential approximation procedure which ranks the mutation pairs in order of evidence for a genetic interaction. The sequential approximations can efficiently remove background variation in the double-mutation screens and give increasingly accurate estimates of the single-mutant fitness measurements. Interestingly, these estimates not only provide predictions for genetic interactions which are consistent with those obtained using the measured fitness, but they can even significantly improve the accuracy with which one can distinguish functionally-related gene pairs from the non-interacting pairs. The computational approach, in general, enables an efficient exploration and classification of genetic interactions in other studies and systems as well
Partition functions of higher spin black holes and their CFT duals
We find black hole solutions of D=3 higher-spin gravity in the hs[\lambda] +
hs[\lambda] Chern-Simons formulation. These solutions have a spin-3 chemical
potential, and carry nonzero values for an infinite number of charges of the
asymptotic W_{\infty}[\lambda] symmetry. Applying a previously developed set of
rules for ensuring smooth solutions, we compute the black hole partition
function perturbatively in the chemical potential. At \lambda =0, 1 we compare
our result against boundary CFT computations involving free bosons and
fermions, and find perfect agreement. For generic \lambda\ we expect that our
gravity result will match the partition function of the coset CFTs conjectured
by Gaberdiel and Gopakumar to be dual to these bulk theories.Comment: 28 pages; v2, added re
Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV
We present limits on anomalous WWZ and WW-gamma couplings from a search for
WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p
-> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron
Collider during the 1992-1995 run. The data sample corresponds to an integrated
luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling
parameters, the 95% CL limits on the CP-conserving couplings are
-0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a
form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also
presented.Comment: 11 pages, 2 figures, 2 table
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
Search For Heavy Pointlike Dirac Monopoles
We have searched for central production of a pair of photons with high
transverse energies in collisions at TeV using of data collected with the D\O detector at the Fermilab Tevatron in
1994--1996. If they exist, virtual heavy pointlike Dirac monopoles could
rescatter pairs of nearly real photons into this final state via a box diagram.
We observe no excess of events above background, and set lower 95% C.L. limits
of on the mass of a spin 0, 1/2, or 1 Dirac
monopole.Comment: 12 pages, 4 figure
The Dijet Mass Spectrum and a Search for Quark Compositeness in bar{p}p Collisions at sqrt{s} = 1.8 TeV
Using the DZero detector at the 1.8 TeV pbarp Fermilab Tevatron collider, we
have measured the inclusive dijet mass spectrum in the central pseudorapidity
region |eta_jet| < 1.0 for dijet masses greater than 200 Gev/c^2. We have also
measured the ratio of spectra sigma(|eta_jet| < 0.5)/sigma(0.5 < |eta_jet| <
1.0). The order alpha_s^3 QCD predictions are in good agreement with the data
and we rule out models of quark compositeness with a contact interaction scale
< 2.4 TeV at the 95% confidence level.Comment: 11 pages, 4 figures, 2 tables, submitted to Phys. Rev. Let
Search for High Mass Photon Pairs in p-pbar --> gamma-gamma-jet-jet Events at sqrt(s)=1.8 TeV
A search has been carried out for events in the channel p-barp --> gamma
gamma jet jet. Such a signature can characterize the production of a
non-standard Higgs boson together with a W or Z boson. We refer to this
non-standard Higgs, having standard model couplings to vector bosons but no
coupling to fermions, as a "bosonic Higgs." With the requirement of two high
transverse energy photons and two jets, the diphoton mass (m(gamma gamma))
distribution is consistent with expected background. A 90(95)% C.L. upper limit
on the cross section as a function of mass is calculated, ranging from
0.60(0.80) pb for m(gamma gamma) = 65 GeV/c^2 to 0.26(0.34) pb for m(gamma
gamma) = 150 GeV/c^2, corresponding to a 95% C.L. lower limit on the mass of a
bosonic Higgs of 78.5 GeV/c^2.Comment: 9 pages, 3 figures. Replacement has new H->gamma gamma branching
ratios and corresponding new mass limit
Zgamma Production in pbarp Collisions at sqrt(s)=1.8 TeV and Limits on Anomalous ZZgamma and Zgammagamma Couplings
We present a study of Z +gamma + X production in p-bar p collisions at
sqrt{S}=1.8 TeV from 97 (87) pb^{-1} of data collected in the eegamma
(mumugamma) decay channel with the D0 detector at Fermilab. The event yield and
kinematic characteristics are consistent with the Standard Model predictions.
We obtain limits on anomalous ZZgamma and Zgammagamma couplings for form factor
scales Lambda = 500 GeV and Lambda = 750 GeV. Combining this analysis with our
previous results yields 95% CL limits |h{Z}_{30}| < 0.36, |h{Z}_{40}| < 0.05,
|h{gamma}_{30}| < 0.37, and |h{gamma}_{40}| < 0.05 for a form factor scale
Lambda=750 GeV.Comment: 17 Pages including 2 Figures. Submitted to PR
Packages of Care for Epilepsy in Low- and Middle-Income Countries
In the second in a series of six articles on packages of care for mental health disorders in low- and middle-income countries, Caroline Mbuba and Charles Newton discuss treatment for epilepsy
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