108 research outputs found
Inhibition of YAP/TAZ-driven TEAD activity prevents growth of NF2-null schwannoma and meningioma.
Schwannoma tumours typically arise on the 8th cranial nerve and are mostly caused by loss of the tumour suppressor Merlin (NF2). There are no approved chemotherapies for these tumours and the surgical removal of the tumour carries a high risk of damage to the 8th or other close cranial nerve tissue. New treatments for schwannoma and other NF2-null tumours such as meningioma are urgently required. Using a combination of human primary tumour cells and mouse models of schwannoma, we have examined the role of the Hippo signalling pathway in driving tumour cell growth. Using both genetic ablation of the Hippo effectors YAP and TAZ as well as novel TEAD palmitoylation inhibitors, we show that Hippo signalling may be successfully targeted in vitro and in vivo to both block and, remarkably, regress schwannoma tumour growth. In particular, successful use of TEAD palmitoylation inhibitors in a pre-clinical mouse model of schwannoma points to their potential future clinical use. We also identify the cancer stem cell marker aldehyde dehydrogenase 1A1 (ALDH1A1) as a Hippo signalling target, driven by the TAZ protein in human and mouse NF2-null schwannoma cells, as well as in NF2-null meningioma cells, and examine the potential future role of this new target in halting schwannoma and meningioma tumour growth
Implementing Grover Oracles for Quantum Key Search on AES and LowMC
Grover's search algorithm gives a quantum attack against block ciphers by
searching for a key that matches a small number of plaintext-ciphertext pairs.
This attack uses calls to the cipher to search a key space of
size . Previous work in the specific case of AES derived the full gate cost
by analyzing quantum circuits for the cipher, but focused on minimizing the
number of qubits. In contrast, we study the cost of quantum key search attacks
under a depth restriction and introduce techniques that reduce the oracle
depth, even if it requires more qubits. As cases in point, we design quantum
circuits for the block ciphers AES and LowMC. Our circuits give a lower overall
attack cost in both the gate count and depth-times-width cost models. In NIST's
post-quantum cryptography standardization process, security categories are
defined based on the concrete cost of quantum key search against AES. We
present new, lower cost estimates for each category, so our work has immediate
implications for the security assessment of post-quantum cryptography. As part
of this work, we release Q# implementations of the full Grover oracle for
AES-128, -192, -256 and for the three LowMC instantiations used in Picnic,
including unit tests and code to reproduce our quantum resource estimates. To
the best of our knowledge, these are the first two such full implementations
and automatic resource estimations.Comment: 36 pages, 8 figures, 14 table
A novel formulation technology for baculoviruses protects biopesticide from degradation by ultraviolet radiation
Biopesticides are biological pest control agents that are viewed as safer alternatives to the synthetic chemicals that dominate the global insecticide market. A major constraint on the wider adoption of biopesticides is their susceptibility to the ultraviolet (UV: 290–400 nm) radiation in sunlight, which limits their persistence and efficacy. Here, we describe a novel formulation technology for biopesticides in which the active ingredient (baculovirus) is micro-encapsulated in an ENTOSTAT wax combined with a UV absorbant (titanium dioxide, TiO2). Importantly, this capsule protects the sensitive viral DNA from degrading in sunlight, but dissolves in the alkaline insect gut to release the virus, which then infects and kills the pest. We show, using simulated sunlight, in both laboratory bioassays and trials on cabbage and tomato plants, that this can extend the efficacy of the biopesticide well beyond the few hours of existing virus formulations, potentially increasing the spray interval and/or reducing the need for high application rates. The new formulation has a shelf-life at 30 °C of at least 6 months, which is comparable to standard commercial biopesticides and has no phytotoxic effect on the host plants. Taken together, these findings suggest that the new formulation technology could reduce the costs and increase the efficacy of baculovirus biopesticides, with the potential to make them commercially competitive alternatives to synthetic chemicals
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 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
A Measurement of the W Boson Mass
We report a measurement of the W boson mass based on an integrated luminosity
of 82 pb from \ppbar collisions at TeV recorded in
1994--1995 by the \Dzero detector at the Fermilab Tevatron. We identify W
bosons by their decays to and extract the mass by fitting the transverse
mass spectrum from 28,323 W boson candidates. A sample of 3,563 dielectron
events, mostly due to Z to ee decays, constrains models of W boson production
and the detector. We measure \mw=80.44\pm0.10(stat)\pm0.07(syst)~GeV. By
combining this measurement with our result from the 1992--1993 data set, we
obtain \mw=80.43\pm0.11 GeV.Comment: 11 pages, 5 figure
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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