606 research outputs found
Type IIA Orientifold Limit of M-Theory on Compact Joyce 8-Manifold of Spin(7)-Holonomy
We show that M-theory compactified on a compact Joyce 8-manifold of
-holonomy, which yields an effective theory in with = 1
supersymmetry, admits at some special points in it moduli space a description
in terms of type IIA theory on an orientifold of compact Joyce 7-manifold of
-holonomy. We find the evidence in favour of this duality by computing the
massless spectra on both M-thory side and type IIA side. For the latter, we
compute the massless spectra by going to the orbifold limit of the Joyce
7-manifold.Comment: 26 pages, 2 eps figures, Latex file, two references and one footnote
added, corrected some typo
<i>In vivo</i> gene silencing following non-invasive siRNA delivery into the skin using a novel topical formulation
AbstractTherapeutics based on short interfering RNAs (siRNAs), which act by inhibiting the expression of target transcripts, represent a novel class of potent and highly specific next-generation treatments for human skin diseases. Unfortunately, the intrinsic barrier properties of the skin combined with the large size and negative charge of siRNAs make epidermal delivery of these macromolecules quite challenging. To help evaluate the in vivo activity of these therapeutics and refine delivery strategies we generated an innovative reporter mouse model that predominantly expresses firefly luciferase (luc2p) in the paw epidermis — the region of murine epidermis that most closely models the tissue architecture of human skin. Combining this animal model with state-of-the-art live animal imaging techniques, we have developed a real-time in vivo analysis work-flow that has allowed us to compare and contrast the efficacies of a wide range nucleic acid-based gene silencing reagents in the skin of live animals. While inhibition was achieved with all of the reagents tested, only the commercially available “self-delivery” modified Accell-siRNAs (Dharmacon) produced potent and sustained in vivo gene silencing. Together, these findings highlight just how informative reliable reporter mouse models can be when assessing novel therapeutics in vivo. Using this work-flow, we developed a novel clinically-relevant topical formulation that facilitates non-invasive epidermal delivery of unmodified and “self-delivery” siRNAs. Remarkably, a sustained >40% luc2p inhibition was observed after two 1-hour treatments with Accell-siRNAs in our topical formulation. Importantly, our ability to successfully deliver siRNA molecules topically brings these novel RNAi-based therapeutics one-step closer to clinical use
Array-based sequencing of filaggrin gene for comprehensive detection of disease-associated variants
The filaggrin gene (FLG) is essential for skin differentiation and epidermal barrier formation. FLG loss-of-function (LoF) variants are associated with ichthyosis vulgaris and the major genetic risk factor for developing atopic dermatitis (AD).1, 2, 3 Genetic stratification of patients with AD according to FLG LoF risk is a common practice for both research and clinical studies; however, few studies comprehensively sequence the entire FLG coding region. Most studies that include FLG genotyping have screened for common predominant LoF variants to report allele frequencies after full Sanger sequencing of a smaller batch of test patient samples or previously published data. This strategy potentially results in underreporting of the genetic contribution especially in ethnicities where FLG LoF variants are highly diverse.4 Distinct LoF variants have been reported for most ethnicities studied to date. For example, 2 predominant sequence variants (p.R501X and c.2282del4) make up approximately 80% of the mutation burden in northern Europeans,5 whereas in East Asian ethnicities, a larger FLG LoF mutation spectrum is found with fewer predominating variants.6, 7 However, routinely Sanger sequencing the entire FLG coding region for large cohorts is not always feasible, although desirable as it is essential to correctly stratify patients. To address this, we developed a robust and cost-effective high-throughput PCR-based method for analyzing the entire coding region of FLG using Fluidigm microfluidics technology and next-generation sequencing (NGS). We have applied this method to fully resequence cohorts of Chinese, Malay, and Indian patients with AD from the Singaporean population.ASTAR (Agency for Sci., Tech. and Research, S’pore)Published versio
Study of the B^0 Semileptonic Decay Spectrum at the Upsilon(4S) Resonance
We have made a first measurement of the lepton momentum spectrum in a sample
of events enriched in neutral B's through a partial reconstruction of B0 -->
D*- l+ nu. This spectrum, measured with 2.38 fb**-1 of data collected at the
Upsilon(4S) resonance by the CLEO II detector, is compared directly to the
inclusive lepton spectrum from all Upsilon(4S) events in the same data set.
These two spectra are consistent with having the same shape above 1.5 GeV/c.
From the two spectra and two other CLEO measurements, we obtain the B0 and B+
semileptonic branching fractions, b0 and b+, their ratio, and the production
ratio f+-/f00 of B+ and B0 pairs at the Upsilon(4S). We report b+/b0=0.950
(+0.117-0.080) +- 0.091, b0 = (10.78 +- 0.60 +- 0.69)%, and b+ = (10.25 +- 0.57
+- 0.65)%. b+/b0 is equivalent to the ratio of charged to neutral B lifetimes,
tau+/tau0.Comment: 14 page, postscript file also available at
http://w4.lns.cornell.edu/public/CLN
Observation of the Charmed Baryon Decays to , , and
We have observed two new decay modes of the charmed baryon into
and using data collected with the
CLEO II detector. We also present the first measurement of the branching
fraction for the previously observed decay mode . The branching fractions for these three modes relative to
are measured to be , , and , respectively.Comment: 12 page uuencoded postscript file, postscript file also available
through http://w4.lns.cornell.edu/public/CLN
Measurement of the diffractive structure function in deep inelastic scattering at HERA
This paper presents an analysis of the inclusive properties of diffractive
deep inelastic scattering events produced in interactions at HERA. The
events are characterised by a rapidity gap between the outgoing proton system
and the remaining hadronic system. Inclusive distributions are presented and
compared with Monte Carlo models for diffractive processes. The data are
consistent with models where the pomeron structure function has a hard and a
soft contribution. The diffractive structure function is measured as a function
of \xpom, the momentum fraction lost by the proton, of , the momentum
fraction of the struck quark with respect to \xpom, and of . The \xpom
dependence is consistent with the form \xpoma where
in all bins of and
. In the measured range, the diffractive structure function
approximately scales with at fixed . In an Ingelman-Schlein type
model, where commonly used pomeron flux factor normalisations are assumed, it
is found that the quarks within the pomeron do not saturate the momentum sum
rule.Comment: 36 pages, latex, 11 figures appended as uuencoded fil
Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set
We report a measurement of the bottom-strange meson mixing phase \beta_s
using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays
in which the quark-flavor content of the bottom-strange meson is identified at
production. This measurement uses the full data set of proton-antiproton
collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment
at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity.
We report confidence regions in the two-dimensional space of \beta_s and the
B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2,
-1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in
agreement with the standard model expectation. Assuming the standard model
value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +-
0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +-
0.009 (syst) ps, which are consistent and competitive with determinations by
other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012
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