PinAPL-Py: A comprehensive web-application for the analysis of CRISPR/Cas9 screens.

Large-scale genetic screens using CRISPR/Cas9 technology have emerged as a major tool for functional genomics. With its increased popularity, experimental biologists frequently acquire large sequencing datasets for which they often do not have an easy analysis option. While a few bioinformatic tools have been developed for this purpose, their utility is still hindered either due to limited functionality or the requirement of bioinformatic expertise. To make sequencing data analysis of CRISPR/Cas9 screens more accessible to a wide range of scientists, we developed a Platform-independent Analysis of Pooled Screens using Python (PinAPL-Py), which is operated as an intuitive web-service. PinAPL-Py implements state-of-the-art tools and statistical models, assembled in a comprehensive workflow covering sequence quality control, automated sgRNA sequence extraction, alignment, sgRNA enrichment/depletion analysis and gene ranking. The workflow is set up to use a variety of popular sgRNA libraries as well as custom libraries that can be easily uploaded. Various analysis options are offered, suitable to analyze a large variety of CRISPR/Cas9 screening experiments. Analysis output includes ranked lists of sgRNAs and genes, and publication-ready plots. PinAPL-Py helps to advance genome-wide screening efforts by combining comprehensive functionality with user-friendly implementation. PinAPL-Py is freely accessible at http://pinapl-py.ucsd.edu with instructions and test datasets

Calixarene-decorated liposomes for intracellular cargo delivery

Amphiphilic calix[4]arenes, functionalized with guanidinium groups, are used to decorate the outer surface of liposomes and significantly improve the cellular uptake of a cargo compared to plain liposomes. The improved uptake is elicited and mediated by the interaction between the cationic polar heads of the macrocycle units embedded in the liposome bilayer and anionic heparan-sulfate proteoglycans surrounding the exterior of cells

Evaporating Black Holes and Entropy

We study the Hawking radiation for the geometry of an evaporating 1+1 dimensional black hole. We compute Bogoliubov coefficients and the stress tensor. We use a recent result of Srednicki to estimate the entropy of entanglement produced in the evaporation process, for the 1+1 dimensional hole and for the 3+1 dimensional hole. It is found that the one space dimensional result of Srednicki is the pertinent one to use, in both cases.Comment: 29 pages, one figure (available from authors), Latex. (Mailer errors removed.

Quantum Gravity and Turning Points in the Semiclassical Approximation

The wavefunctional in quantum gravity gives an amplitude for 3-geometries and matter fields. The four-space is usually recovered in a semiclassical approximation where the gravity variables are taken to oscillate rapidly compared to matter variables; this recovers the Schrodinger evolution for the matter. We examine turning points in the gravity variables where this approximation appears to be troublesome. We investigate the effect of such a turning point on the matter wavefunction, in simple quantum mechanical models and in a closed minisuperspace cosmology. We find that after evolving sufficiently far from the turning point the matter wavefunction recovers to a form close to that predicted by the semiclassical approximation, and we compute the leading correction (from `backreaction') in a simple model. We also show how turning points can appear in the gravitational sector in dilaton gravity. We give some remarks on the behavior of the wavefunctional in the vicinity of turning points in the context of dilaton gravity black holes.Comment: 32 pages, 3 Postscript figures, uses epsf.tex and fps.sty, some discussion, references and Acknowledgements added, version to appear in Phys. Rev.

Multiwaveband Observations of Quasars with Flat Radio Spectra and Strong Millimeter Emission

We present multiwaveband observations of a well selected sample of 28 quasars and two radio galaxies with flat radio spectra and strong millimeter wave emission (referred to here as FSRQ's). The observations include multifrequency VLBI measurements, X-ray observations with ROSAT and submillimeter observations with the JCMT. Particularly interesting among many findings is a correlation between the X-ray to millimeter spectral index and fraction of flux density contained in the VLBI core. This tendency toward higher X-ray fluxes from sources with stronger jet emission implies that the knots in the jet are the prominent source of X-rays.Comment: 38 pages, 17 figures, 12 tables, accepted for publication in Ap J Suppl, May 199

Asymptotic Dirichlet Problem for A-Harmonic Functions on Manifolds with Pinched Curvature

We study the asymptotic Dirichlet problem for -harmonic functions on a Cartan-Hadamard manifold whose radial sectional curvatures outside a compact set satisfy an upper bound and a pointwise pinching condition for some constants epsilon > 0 and C (K) a 1, where P and are any 2-dimensional subspaces of T (x) M containing the (radial) vector acr(x) and r(x) = d(o, x) is the distance to a fixed point o a M. We solve the asymptotic Dirichlet problem with any continuous boundary data . The results apply also to the Laplacian and p-Laplacian, as special cases.Peer reviewe

Coulomb-gas formulation of SU(2) branes and chiral blocks

We construct boundary states in $SU(2)_k$ WZNW models using the bosonized Wakimoto free-field representation and study their properties. We introduce a Fock space representation of Ishibashi states which are coherent states of bosons with zero-mode momenta (boundary Coulomb-gas charges) summed over certain lattices according to Fock space resolution of $SU(2)_k$. The Virasoro invariance of the coherent states leads to families of boundary states including the B-type D-branes found by Maldacena, Moore and Seiberg, as well as the A-type corresponding to trivial current gluing conditions. We then use the Coulomb-gas technique to compute exact correlation functions of WZNW primary fields on the disk topology with A- and B-type Cardy states on the boundary. We check that the obtained chiral blocks for A-branes are solutions of the Knizhnik-Zamolodchikov equations.Comment: 14 pages, 3 figures, revtex4. Essentially the published versio