228 research outputs found
Polymerase II Promoter Strength Determines Efficacy of microRNA Adapted shRNAs
Since the discovery of RNAi and microRNAs more than 10 years ago, much research has focused on the development of systems that usurp microRNA pathways to downregulate gene expression in mammalian cells. One of these systems makes use of endogenous microRNA pri-cursors that are expressed from polymerase II promoters where the mature microRNA sequence is replaced by gene specific duplexes that guide RNAi (shRNA-miRs). Although shRNA-miRs are effective in directing target mRNA knockdown and hence reducing protein expression in many cell types, variability of RNAi efficacy in cell lines has been an issue. Here we show that the choice of the polymerase II promoter used to drive shRNA expression is of critical importance to allow effective mRNA target knockdown. We tested the abundance of shRNA-miRs expressed from five different polymerase II promoters in 6 human cell lines and measured their ability to drive target knockdown. We observed a clear positive correlation between promoter strength, siRNA expression levels, and protein target knockdown. Differences in RNAi from the shRNA-miRs expressed from the various promoters were particularly pronounced in immune cells. Our findings have direct implications for the design of shRNA-directed RNAi experiments and the preferred RNAi system to use for each cell type
Toxicity in mice expressing short hairpin RNAs gives new insight into RNAi
Short hairpin RNAs can provide stable gene silencing via RNA interference. Recent studies have shown toxicity in vivo that appears to be related to saturation of the endogenous microRNA pathway. Will these findings limit the therapeutic use of such hairpins
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
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
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
Probing Hard Color-Singlet Exchange in ppbar Collisions at root-s=630 GeV and 1800 GeV
We present results on dijet production via hard color-singlet exchange in
proton-antiproton collisions at root-s = 630 GeV and 1800 GeV using the DZero
detector. The fraction of dijet events produced via color-singlet exchange is
measured as a function of jet transverse energy, separation in pseudorapidity
between the two highest transverse energy jets, and proton-antiproton
center-of-mass energy. The results are consistent with a color-singlet fraction
that increases with an increasing fraction of quark-initiated processes and
inconsistent with two-gluon models for the hard color-singlet.Comment: 16 pages, 6 figure
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