Predicting base editing outcomes using position-specific sequence determinants.

CRISPR/Cas base editors promise nucleotide-level control over DNA sequences, but the determinants of their activity remain incompletely understood. We measured base editing frequencies in two human cell lines for two cytosine and two adenine base editors at ∼14 000 target sequences and find that base editing activity is sequence-biased, with largest effects from nucleotides flanking the target base. Whether a base is edited depends strongly on the combination of its position in the target and the preceding base, acting to widen or narrow the effective editing window. The impact of features on editing rate depends on the position, with sequence bias efficacy mainly influencing bases away from the center of the window. We use these observations to train a machine learning model to predict editing activity per position, with accuracy ranging from 0.49 to 0.72 between editors, and with better generalization across datasets than existing tools. We demonstrate the usefulness of our model by predicting the efficacy of disease mutation correcting guides, and find that most of them suffer from more unwanted editing than pure outcomes. This work unravels the position-specificity of base editing biases and allows more efficient planning of editing campaigns in experimental and therapeutic contexts

Nova Sagittarii 1998 (V4633 Sgr) - a permanent superhump system or an asynchronous polar?

We report the results of observations of V4633 Sgr (Nova Sagittarii 1998) during 1998-2000. Two photometric periodicities were present in the light curve during the three years of observations: a stable one at P=3.014 h, which is probably the orbital period of the underlying binary system, and a second one of lower coherence, approximately 2.5 per cent longer than the former. The latter periodicity may be a permanent superhump, or alternatively, the spin period of the white dwarf in a nearly synchronous magnetic system. A third period, at P=5.06 d, corresponding to the beat between the two periods was probably present in 1999. Our results suggest that a process of mass transfer took place in the binary system since no later than two and a half months after the nova eruption. We derive an interstellar reddening of E(B-V)~0.21 from our spectroscopic measurements and published photometric data, and estimate a distance of d~9 kpc to this nova.Comment: 13 pages, latex, 7 figures, accepted for publication in MNRA

Orientational order in dipolar fluids consisting of nonspherical hard particles

We investigate fluids of dipolar hard particles by a certain variant of density-functional theory. The proper treatment of the long range of the dipolar interactions yields a contribution to the free energy which favors ferromagnetic order. This corrects previous theoretical analyses. We determine phase diagrams for dipolar ellipsoids and spherocylinders as a function of the aspect ratio of the particles and their dipole moment. In the nonpolar limit the results for the phase boundary between the isotropic and nematic phase agree well with simulation data. Adding a longitudinal dipole moment favors the nematic phase. For oblate or slightly elongated particles we find a ferromagnetic liquid phase, which has also been detected in computer simulations of fluids consisting of spherical dipolar particles. The detailed structure of the phase diagram and its evolution upon changing the aspect ratio are discussed in detail.Comment: 35 pages LaTeX with epsf style, 11 figures in eps format, submitted to Phys. Rev.

Gravitational radiation from gamma-ray bursts as observational opportunities for LIGO and VIRGO

Gamma-ray bursts are believed to originate in core-collapse of massive stars. This produces an active nucleus containing a rapidly rotating Kerr black hole surrounded by a uniformly magnetized torus represented by two counter-oriented current rings. We quantify black hole spin-interactions with the torus and charged particles along open magnetic flux-tubes subtended by the event horizon. A major output of Egw=4e53 erg is radiated in gravitational waves of frequency fgw=500 Hz by a quadrupole mass-moment in the torus. Consistent with GRB-SNe, we find (i) Ts=90s (tens of s, Kouveliotou et al. 1993), (ii) aspherical SNe of kinetic energy Esn=2e51 erg (2e51 erg in SN1998bw, Hoeflich et al. 1999) and (iii) GRB-energies Egamma=2e50 erg (3e50erg in Frail et al. 2001). GRB-SNe occur perhaps about once a year within D=100Mpc. Correlating LIGO/Virgo detectors enables searches for nearby events and their spectral closure density 6e-9 around 250Hz in the stochastic background radiation in gravitational waves. At current sensitivity, LIGO-Hanford may place an upper bound around 150MSolar in GRB030329. Detection of Egw thus provides a method for identifying Kerr black holes by calorimetry.Comment: to appear in PRD, 49

HI in the Outskirts of Nearby Galaxies

The HI in disk galaxies frequently extends beyond the optical image, and can trace the dark matter there. I briefly highlight the history of high spatial resolution HI imaging, the contribution it made to the dark matter problem, and the current tension between several dynamical methods to break the disk-halo degeneracy. I then turn to the flaring problem, which could in principle probe the shape of the dark halo. Instead, however, a lot of attention is now devoted to understanding the role of gas accretion via galactic fountains. The current $\rm \Lambda$ cold dark matter theory has problems on galactic scales, such as the core-cusp problem, which can be addressed with HI observations of dwarf galaxies. For a similar range in rotation velocities, galaxies of type Sd have thin disks, while those of type Im are much thicker. After a few comments on modified Newtonian dynamics and on irregular galaxies, I close with statistics on the HI extent of galaxies.Comment: 38 pages, 17 figures, invited review, book chapter in "Outskirts of Galaxies", Eds. J. H. Knapen, J. C. Lee and A. Gil de Paz, Astrophysics and Space Science Library, Springer, in pres

Grain Surface Models and Data for Astrochemistry

AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of ∼25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions

The PHENIX Experiment at RHIC

The physics emphases of the PHENIX collaboration and the design and current status of the PHENIX detector are discussed. The plan of the collaboration for making the most effective use of the available luminosity in the first years of RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program available at http://www.rhic.bnl.gov/phenix

In situ degradability of corn stover and elephant-grass harvested at four stages of maturity

Among tropical forages, corn silage is largely used by farmers trying to explore the maximum genetic potential from the animals. However, other tropical forages, such as elephant-grass (Pennisetum purpureum), are more productive and therefore cheaper to use than corn silage. Our objective was to compare the in situ degradability of elephant-grass with that from corn hybrids, all harvested at four stages of maturity. The experimental design followed a randomized block design with nested subplots. Two corn hybrids: AG5011, ZN8392 were harvested with 25, 30, 35, and 40% dry matter (DM) in the whole plant, and separated in stem + leaf sheath + leaf blade (stover), and cobs. Elephant-grass was harvested with 30, 40, 50 and 60 days after a leveling cut. Dried and ground samples were incubated in nylon bags inside the rumen for 0, 6, 12, 24, 48 and 72 h to estimate the kinetics of ruminal DM and neutral detergent fiber (NDF) degradation. The advance of maturity increased the NDF and acid detergent fiber (ADF) content in elephant-grass, and reduced its DM degradability. However, maturity had little or no effect on fiber content and DM degradability of corn stover. Elephant-grass had a higher NDF degradability than corn stover, and there was no effect of maturity on NDF degradability of either elephant-grass or corn stover. Fiber degradability of elephant-grass was not worse than that of corn stover, and therefore the choice of forage should be made on economical analysis rather than assuming an intrinsic low production potential for elephant-grass based diets.Dentre as forragens, a silagem de milho é amplamente utilizada pelos fazendeiros que visam explorar o máximo do potencial genético dos animais. No entanto, outros volumosos tropicais como o capim-elefante (Pennisetum purpureum) são mais produtivos e, portanto, mais baratos do que a silagem de milho. Nosso objetivo foi comparar a degradabilidade in situ do capim-elefante com a degradabilidade de híbridos de milho, colhidos em quatro estágios de maturidade. O experimento seguiu um delineamento de blocos ao acaso com sub-parcelas. Dois híbridos de milho: AG5011 e ZN8392 foram colhidos com 25, 30, 35 e 40% matéria seca (MS) na planta toda e separados na fração colmo + bainha + folhas e espigas. Capim elefante foi colhido 30, 40, 50 e 60 dias após o corte de nivelamento. As amostras secas e trituradas foram incubadas no rúmen por 0, 6, 12, 24, 48 e 72 h para cálculo da cinética da degradação ruminal da MS e da fibra em detergente neutro (FDN). O avanço da maturidade aumentou os teores de FDN e fibra em detergente ácido (FDA) do capim elefante e reduziu a degradabilidade da MS. Entretanto, a maturidade teve pouco efeito sobre os teores de fibra e a degradabilidade da MS da fração planta dos híbridos de milho. O capim elefante apresentou maior degradabilidade da FDN do que híbridos de milho, e não houve efeito da maturidade sobre a degradabilidade da FDN das duas espécies. A degradabilidade da fibra de capim-elefante não é pior do que a de híbridos de milho e, portanto a escolha da forragem deve ser feita com base em análises econômicas ao invés de assumir um menor potencial de produção em dietas a base de capim elefante

Atmospheric effects on extensive air showers observed with the Surface Detector of the Pierre Auger Observatory

Atmospheric parameters, such as pressure (P), temperature (T) and density, affect the development of extensive air showers initiated by energetic cosmic rays. We have studied the impact of atmospheric variations on extensive air showers by means of the surface detector of the Pierre Auger Observatory. The rate of events shows a ~10% seasonal modulation and ~2% diurnal one. We find that the observed behaviour is explained by a model including the effects associated with the variations of pressure and density. The former affects the longitudinal development of air showers while the latter influences the Moliere radius and hence the lateral distribution of the shower particles. The model is validated with full simulations of extensive air showers using atmospheric profiles measured at the site of the Pierre Auger Observatory.Comment: 24 pages, 9 figures, accepted for publication in Astroparticle Physic

Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter

Data collected by the Pierre Auger Observatory through 31 August 2007 showed evidence for anisotropy in the arrival directions of cosmic rays above the Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{$6\times 10^{19}$eV}. The anisotropy was measured by the fraction of arrival directions that are less than $3.1^\circ$ from the position of an active galactic nucleus within 75 Mpc (using the V\'eron-Cetty and V\'eron $12^{\rm th}$ catalog). An updated measurement of this fraction is reported here using the arrival directions of cosmic rays recorded above the same energy threshold through 31 December 2009. The number of arrival directions has increased from 27 to 69, allowing a more precise measurement. The correlating fraction is $(38^{+7}_{-6})$, compared with $21$ expected for isotropic cosmic rays. This is down from the early estimate of $(69^{+11}_{-13})$. The enlarged set of arrival directions is examined also in relation to other populations of nearby extragalactic objects: galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in hard X-rays by the Swift Burst Alert Telescope. A celestial region around the position of the radiogalaxy Cen A has the largest excess of arrival directions relative to isotropic expectations. The 2-point autocorrelation function is shown for the enlarged set of arrival directions and compared to the isotropic expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201