Functional rescue of dystrophin deficiency in mice caused by frameshift mutations using Campylobacter jejuni Cas9

Duchenne muscular dystrophy (DMD) is a fatal, X-linked muscle wasting disease caused by mutations in the DMD gene. In 51% of DMD cases, a reading frame is disrupted because of deletion of several exons. Here, we show that CjCas9 derived from Campylobacter jejuni can be used as a gene editing tool to correct an out-of-frame Dmd exon in Dmd knockout mice. Herein, we used Cas9 derived from S. pyogenes to generate Dmd knockout (KO) mice with a frameshift mutation in Dmd gene. Then, we expressed CjCas9, its single-guide RNA, and the eGFP gene in the tibialis anterior muscle of the Dmd KO mice using an all-in-one adeno-associated virus (AAV) vector. CjCas9 cleaved the target site in the Dmd gene efficiently in vivo and induced small insertions or deletions at the target site. This treatment resulted in conversion of the disrupted Dmd reading frame from out-of-frame to in-frame, leading to the expression of dystrophin in the sarcolemma. Importantly, muscle strength was enhanced in the CjCas9-treated muscles, without off-target mutations, indicating high efficiency and specificity of CjCas9. This work suggests that in vivo DMD frame correction, mediated by CjCas9 has great potential for the treatment of DMD and other neuromuscular diseases

Star Forming Dense Cloud Cores in the TeV {\gamma}-ray SNR RX J1713.7-3946

RX J1713.7-3946 is one of the TeV {\gamma}-ray supernova remnants (SNRs) emitting synchrotron X rays. The SNR is associated with molecular gas located at ~1 kpc. We made new molecular observations toward the dense cloud cores, peaks A, C and D, in the SNR in the 12CO(J=2-1) and 13CO(J=2-1) transitions at angular resolution of 90". The most intense core in 13CO, peak C, was also mapped in the 12CO(J=4-3) transition at angular resolution of 38". Peak C shows strong signs of active star formation including bipolar outflow and a far-infrared protostellar source and has a steep gradient with a r^{-2.2$\pm$0.4} variation in the average density within radius r. Peak C and the other dense cloud cores are rim-brightened in synchrotron X rays, suggesting that the dense cloud cores are embedded within or on the outer boundary of the SNR shell. This confirms the earlier suggestion that the X rays are physically associated with the molecular gas (Fukui et al. 2003). We present a scenario where the densest molecular core, peak C, survived against the blast wave and is now embedded within the SNR. Numerical simulations of the shock-cloud interaction indicate that a dense clump can indeed survive shock erosion, since shock propagation speed is stalled in the dense clump. Additionally, the shock-cloud interaction induces turbulence and magnetic field amplification around the dense clump that may facilitate particle acceleration in the lower-density inter-clump space leading to the enhanced synchrotron X rays around dense cores.Comment: 22 pages, 7 figures, to accepted in The Astrophysical Journal. A full color version with higher resolution figures is available at http://www.a.phys.nagoya-u.ac.jp/~sano/ApJ10/ms_sano.pd

Reaction-diffusion dynamics: confrontation between theory and experiment in a microfluidic reactor

We confront, quantitatively, the theoretical description of the reaction-diffusion of a second order reaction to experiment. The reaction at work is \ca/CaGreen, and the reactor is a T-shaped microchannel, 10 $\mu$m deep, 200 $\mu$m wide, and 2 cm long. The experimental measurements are compared with the two-dimensional numerical simulation of the reaction-diffusion equations. We find good agreement between theory and experiment. From this study, one may propose a method of measurement of various quantities, such as the kinetic rate of the reaction, in conditions yet inaccessible to conventional methods

Structure and peculiarities of the (8 x n)-type Si(001) surface prepared in a molecular-beam epitaxy chamber: a scanning tunneling microscopy study

A clean Si(001) surface thermally purified in an ultrahigh vacuum molecular-beam epitaxy chamber has been investigated by means of scanning tunneling microscopy. The morphological peculiarities of the Si(001) surface have been explored in detail. The classification of the surface structure elements has been carried out, the dimensions of the elements have been measured, and the relative heights of the surface relief have been determined. A reconstruction of the Si(001) surface prepared in the molecular-beam epitaxy chamber has been found to be (8 x n). A model of the Si(001)-(8 x n) surface structure is proposed.Comment: 4 pages, 8 figures. Complete versio

Discovery of a Quadruple Lens in CANDELS with a Record Lens Redshift z=1.53

Using spectroscopy from the Large Binocular Telescope and imaging from the Hubble Space Telescope we discovered the first strong galaxy lens at z(lens)>1. The lens has a secure photometric redshift of z=1.53+/-0.09 and the source is spectroscopically confirmed at z=3.417. The Einstein radius (0.35"; 3.0 kpc) encloses 7.6 x 10^10 Msol, with an upper limit on the dark matter fraction of 60%. The highly magnified (40x) source galaxy has a very small stellar mass (~10^8 Msol) and shows an extremely strong [OIII]_5007A emission line (EW_0 ~ 1000A) bolstering the evidence that intense starbursts among very low-mass galaxies are common at high redshift.Comment: accepted for publication in ApJ Letter

The Role of Bulge Formation in the Homogenization of Stellar Populations at z∼2z\sim2 as revealed by Internal Color Dispersion in CANDELS

We use data from the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey to study how the spatial variation in the stellar populations of galaxies relate to the formation of galaxies at $1.5 < z < 3.5$. We use the Internal Color Dispersion (ICD), measured between the rest-frame UV and optical bands, which is sensitive to age (and dust attenuation) variations in stellar populations. The ICD shows a relation with the stellar masses and morphologies of the galaxies. Galaxies with the largest variation in their stellar populations as evidenced by high ICD have disk-dominated morphologies (with S\'{e}rsic indexes $< 2$) and stellar masses between $10 < \mathrm{Log~M/ M_\odot}< 11$. There is a marked decrease in the ICD as the stellar mass and/or the S\'ersic index increases. By studying the relations between the ICD and other galaxy properties including sizes, total colors, star-formation rate, and dust attenuation, we conclude that the largest variations in stellar populations occur in galaxies where the light from newly, high star-forming clumps contrasts older stellar disk populations. This phase reaches a peak for galaxies only with a specific stellar mass range, $10 < \mathrm{Log~M/ M_\odot} < 11$, and prior to the formation of a substantial bulge/spheroid. In contrast, galaxies at higher or lower stellar masses, and/or higher S\'{e}rsic index ($n > 2$) show reduced ICD values, implying a greater homogeneity of their stellar populations. This indicates that if a galaxy is to have both a quiescent bulge along with a star forming disk, typical of Hubble Sequence galaxies, this is most common for stellar masses $10 < \mathrm{Log~M/M_\odot} < 11$ and when the bulge component remains relatively small ($n<2$).Comment: 15 pages, 14 figure

Constraining The Assembly Of Normal And Compact Passively Evolving Galaxies From Redshift z=3 To The Present With CANDELS

We study the evolution of the number density, as a function of the size, of passive early-type galaxies with a wide range of stellar masses 10^10<M*/Msun<10^11.5) from z~3 to z~1, exploiting the unique dataset available in the GOODS-South field, including the recently obtained WFC3 images as a part of the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS). In particular, we select a sample of 107 massive (M*>10^10 M_sun), passive (SSFR<10^-2 Gyr^-1) and morphologically spheroidal galaxies at 1.2<z<3, taking advantage of the panchromatic dataset available for GOODS, including VLT, CFHT, Spitzer, Chandra and HST ACS+WFC3 data. We find that at 1<z<3 the passively evolving early-type galaxies are the reddest and most massive objects in the Universe, and we prove that a correlation between mass, morphology, color and star-formation activity is already in place at that epoch. We measure a significant evolution in the mass-size relation of passive early-type galaxies (ETGs) from z~3 to z~1, with galaxies growing on average by a factor of 2 in size in a 3 Gyr timescale only. We witness also an increase in the number density of passive ETGs of 50 times over the same time interval. We find that the first ETGs to form at z>2 are all compact or ultra-compact, while normal sized ETGs (meaning ETGs with sizes comparable to those of local counterparts of the same mass) are the most common ETGs only at z<1. The increase of the average size of ETGs at 0<z<1 is primarily driven by the appearance of new large ETGs rather than by the size increase of individual galaxies.Comment: 9 pages, 5 figures, submitted to Ap

Enlarged symmetry algebras of spin chains, loop models, and S-matrices

The symmetry algebras of certain families of quantum spin chains are considered in detail. The simplest examples possess m states per site (m\geq2), with nearest-neighbor interactions with U(m) symmetry, under which the sites transform alternately along the chain in the fundamental m and its conjugate representation \bar{m}. We find that these spin chains, even with {\em arbitrary} coefficients of these interactions, have a symmetry algebra A_m much larger than U(m), which implies that the energy eigenstates fall into sectors that for open chains (i.e., free boundary conditions) can be labeled by j=0, 1, >..., L, for the 2L-site chain, such that the degeneracies of all eigenvalues in the jth sector are generically the same and increase rapidly with j. For large j, these degeneracies are much larger than those that would be expected from the U(m) symmetry alone. The enlarged symmetry algebra A_m(2L) consists of operators that commute in this space of states with the Temperley-Lieb algebra that is generated by the set of nearest-neighbor interaction terms; A_m(2L) is not a Yangian. There are similar results for supersymmetric chains with gl(m+n|n) symmetry of nearest-neighbor interactions, and a richer representation structure for closed chains (i.e., periodic boundary conditions). The symmetries also apply to the loop models that can be obtained from the spin chains in a spacetime or transfer matrix picture. In the loop language, the symmetries arise because the loops cannot cross. We further define tensor products of representations (for the open chains) by joining chains end to end. The fusion rules for decomposing the tensor product of representations labeled j_1 and j_2 take the same form as the Clebsch-Gordan series for SU(2). This and other structures turn the symmetry algebra \cA_m into a ribbon Hopf algebra, and we show that this is ``Morita equivalent'' to the quantum group U_q(sl_2) for m=q+q^{-1}. The open-chain results are extended to the cases |m|< 2 for which the algebras are no longer semisimple; these possess continuum limits that are critical (conformal) field theories, or massive perturbations thereof. Such models, for open and closed boundary conditions, arise in connection with disordered fermions, percolation, and polymers (self-avoiding walks), and certain non-linear sigma models, all in two dimensions. A product operation is defined in a related way for the Temperley-Lieb representations also, and the fusion rules for this are related to those for A_m or U_q(sl_2) representations; this is useful for the continuum limits also, as we discuss in a companion paper

The DEEP2 Galaxy Redshift Survey: The Evolution of Void Statistics from z~1 to z~0

We present measurements of the void probability function (VPF) at z~1 using data from the DEEP2 Redshift Survey and its evolution to z~0 using data from the Sloan Digital Sky Survey (SDSS). We measure the VPF as a function of galaxy color and luminosity in both surveys and find that it mimics trends displayed in the two-point correlation function, $\xi$; namely that samples of brighter, red galaxies have larger voids (i.e. are more strongly clustered) than fainter, blue galaxies. We also clearly detect evolution in the VPF with cosmic time, with voids being larger in comoving units at z~0. We find that the reduced VPF matches the predictions of a `negative binomial' model for galaxies of all colors, luminosities, and redshifts studied. This model lacks a physical motivation, but produces a simple analytic prediction for sources of any number density and integrated two-point correlation function, \bar{\xi}. This implies that differences in the VPF across different galaxy populations are consistent with being due entirely to differences in the population number density and \bar{\xi}. The robust result that all galaxy populations follow the negative binomial model appears to be due to primarily to the clustering of dark matter halos. The reduced VPF is insensitive to changes in the parameters of the halo occupation distribution, in the sense that halo models with the same \bar{\xi} will produce the same VPF. For the wide range of galaxies studied, the VPF therefore does not appear to provide useful constraints on galaxy evolution models that cannot be gleaned from studies of \bar{\xi} alone. (abridged)Comment: 17 pages, 15 figures, ApJ accepte