A modular dCas9-SunTag DNMT3A epigenome editing system overcomes pervasive off-target activity of direct fusion dCas9-DNMT3A constructs

Detection of DNA methylation in the genome has been possible for decades; however, the ability to deliberately and specifically manipulate local DNA methylation states in the genome has been extremely limited. Consequently, this has impeded our understanding of the direct effect of DNA methylation on transcriptional regulation and transcription factor binding in the native chromatin context. Thus, highly specific targeted epigenome editing tools are needed to address this. Recent adaptations of genome editing technologies, including fusion of the DNMT3A DNA methyltransferase catalytic domain to catalytically inactive Cas9 (dC9-D3A), have aimed to alter DNA methylation at desired loci. Here, we show that these tools exhibit consistent off-target DNA methylation deposition in the genome, limiting their capabilities to unambiguously assess the functional consequences of DNA methylation. To address this, we developed a modular dCas9-SunTag (dC9Sun-D3A) system that can recruit multiple DNMT3A catalytic domains to a target site for editing DNA methylation. dC9Sun-D3A is tunable, specific, and exhibits much higher induction of DNA methylation at target sites than the dC9-D3A direct fusion protein. Importantly, genome-wide characterization of dC9Sun-D3A binding sites and DNA methylation revealed minimal off-target protein binding and induction of DNA methylation with dC9Sun-D3A, compared to pervasive off-target methylation by dC9-D3A. Furthermore, we used dC9Sun-D3A to demonstrate the binding sensitivity to DNA methylation for CTCF and NRF1 in situ. Overall, this modular dC9Sun-D3A system enables precise DNA methylation deposition with the lowest off-target DNA methylation levels reported to date, allowing accurate functional determination of the role of DNA methylation at single loci.Christian Pflueger, Dennis Tan, Tessa Swain, Trung Nguyen, Jahnvi Pflueger, Christian Nefzger ... et al

WASP-23b: a transiting hot Jupiter around a K dwarf and its Rossiter-McLaughlin effect

We report the discovery of a new transiting planet in the Southern Hemisphere. It has been found by the WASP-south transit survey and confirmed photometrically and spectroscopically by the 1.2m Swiss Euler telescope, LCOGT 2m Faulkes South Telescope, the 60 cm TRAPPIST telescope and the ESO 3.6m telescope. The orbital period of the planet is 2.94 days. We find it is a gas giant with a mass of 0.88 \pm 0.10 Mj and a radius estimated at 0.96 \pm 0.05 Rj . We have also obtained spectra during transit with the HARPS spectrograph and detect the Rossiter-McLaughlin effect despite its small amplitude. Because of the low signal to noise of the effect and of a small impact parameter we cannot place a constraint on the projected spin-orbit angle. We find two confiicting values for the stellar rotation. Our determination, via spectral line broadening gives v sin I = 2.2 \pm 0.3 km/s, while another method, based on the activity level using the index log R'HK, gives an equatorial rotation velocity of only v = 1.35 \pm 0.20 km/s. Using these as priors in our analysis, the planet could either be misaligned or aligned. This should send strong warnings regarding the use of such priors. There is no evidence for eccentricity nor of any radial velocity drift with time.Comment: 13 pages, 8 figures, 7 tables, accepted for publication in A&

Discovery and characterization of WASP-6b, an inflated sub-Jupiter mass planet transiting a solar-type star

We report the discovery of WASP-6b, an inflated sub-Jupiter mass planet transiting every 3.3610060^{\rm + 0.0000022 }_ days a mildly metal-poor solar-type star of magnitude V = 11.9. A combined analysis of the WASP photometry, high-precision followup transit photometry and radial velocities yield a planetary mass M_{\rm p} = 0.503^_ $M_{\rm J}$ and radius R_{\rm p} = 1.224^_ $R_{\rm J}$, resulting in a density $\rho_{\rm p} = 0.27 \pm 0.05$ $\rho_{\rm J}$. The mass and radius for the host star are M_\ast = 0.88^_ $M_\odot$ and R_\ast = 0.870^_ $R_\odot$. The non-zero orbital eccentricity e = 0.054^{\rm +0.018}_ that we measure suggests that the planet underwent a massive tidal heating ~1 Gyr ago that could have contributed to its inflated radius. High-precision radial velocities obtained during a transit allow us to measure a sky-projected angle between the stellar spin and orbital axis \beta = 11^_ deg. In addition to similar published measurements, this result favors a dominant migration mechanism based on tidal interactions with a protoplanetary disk

WASP-42 b and WASP-49 b: two new transiting sub-Jupiters

We report the discovery of two new transiting planets from the WASP survey. WASP-42 b is a 0.500 +/- 0.035 M_jup planet orbiting a K1 star at a separation of 0.0548 +/- 0.0017 AU with a period of 4.9816872 +/- 7.3 x 10^-6 days. The radius of WASP-42 b is 1.080 +/- 0.057 R_jup while its equilibrium temperature is T_eq = 995 +/- 34 K. We detect some evidence for a small but non-zero eccentricity of e=0.060 +/- 0.013. WASP-49 b is a 0.378 +/- 0.027 M_jup planet around an old G6 star. It has a period of 2.7817387 +/- 5.6 x 10^-6 days and a separation of 0.0379 +/- 0.0011 AU. This planet is slightly bloated, having a radius of 1.115 +/- 0.047 R_jup and an equilibrium temperature of T_eq = 1369 +/- 39 K. Both planets have been followed up photometrically, and in total we have obtained 5 full and one partial transit light curves of WASP-42 and 4 full and one partial light curves of WASP-49 using the Euler-Swiss, TRAPPIST and Faulkes South telescopes

Rossiter-McLaughlin Effect Measurements for WASP-16, WASP-25 and WASP-31

We present new measurements of the Rossiter-McLaughlin (RM) effect for three WASP planetary systems, WASP-16, WASP-25 and WASP-31, from a combined analysis of their complete sets of photometric and spectroscopic data. We find a low amplitude RM effect for WASP-16 (Teff = 5700 \pm 150K), suggesting that the star is a slow rotator and thus of an advanced age, and obtain a projected alignment angle of lambda = -4.2 degrees +11.0 -13.9. For WASP-25 (Teff = 5750\pm100K) we detect a projected spin-orbit angle of lambda = 14.6 degrees \pm6.7. WASP-31 (Teff = 6300\pm100K) is found to be well-aligned, with a projected spin-orbit angle of lambda = 2.8degrees \pm3.1. A circular orbit is consistent with the data for all three systems, in agreement with their respective discovery papers. We consider the results for these systems in the context of the ensemble of RM measurements made to date. We find that whilst WASP-16 fits the hypothesis of Winn et al. (2010) that 'cool' stars (Teff < 6250K) are preferentially aligned, WASP-31 has little impact on the proposed trend. We bring the total distribution of the true spin-orbit alignment angle, psi, up to date, noting that recent results have improved the agreement with the theory of Fabrycky & Tremaine (2007) at mid-range angles. We also suggest a new test for judging misalignment using the Bayesian Information Criterion, according to which WASP-25 b's orbit should be considered to be aligned.Comment: 20 pages, 14 tables, 10 figures. Accepted to MNRA

Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

We reconstruct the rare decays $B^+ \to K^+\mu^+\mu^-$, $B^0 \to K^{*}(892)^0\mu^+\mu^-$, and $B^0_s \to \phi(1020)\mu^+\mu^-$ in a data sample corresponding to $4.4 {\rm fb^{-1}}$ collected in $p\bar{p}$ collisions at $\sqrt{s}=1.96 {\rm TeV}$ by the CDF II detector at the Fermilab Tevatron Collider. Using $121 \pm 16$ $B^+ \to K^+\mu^+\mu^-$ and $101 \pm 12$ $B^0 \to K^{*0}\mu^+\mu^-$ decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the $B^+$ and $B^0$ decay modes, and the $K^{*0}$ longitudinal polarization in the $B^0$ decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the $B^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio${\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}$using$27 \pm 6$signal events. This is currently the most rare$B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let

Measurements of the properties of Lambda_c(2595), Lambda_c(2625), Sigma_c(2455), and Sigma_c(2520) baryons

We report measurements of the resonance properties of Lambda_c(2595)+ and Lambda_c(2625)+ baryons in their decays to Lambda_c+ pi+ pi- as well as Sigma_c(2455)++,0 and Sigma_c(2520)++,0 baryons in their decays to Lambda_c+ pi+/- final states. These measurements are performed using data corresponding to 5.2/fb of integrated luminosity from ppbar collisions at sqrt(s) = 1.96 TeV, collected with the CDF II detector at the Fermilab Tevatron. Exploiting the largest available charmed baryon sample, we measure masses and decay widths with uncertainties comparable to the world averages for Sigma_c states, and significantly smaller uncertainties than the world averages for excited Lambda_c+ states.Comment: added one reference and one table, changed order of figures, 17 pages, 15 figure

Search for a New Heavy Gauge Boson Wprime with Electron + missing ET Event Signature in ppbar collisions at sqrt(s)=1.96 TeV

We present a search for a new heavy charged vector boson $W^\prime$ decaying to an electron-neutrino pair in $p\bar{p}$ collisions at a center-of-mass energy of 1.96\unit{TeV}. The data were collected with the CDF II detector and correspond to an integrated luminosity of 5.3\unit{fb}^{-1}. No significant excess above the standard model expectation is observed and we set upper limits on $\sigma\cdot{\cal B}(W^\prime\to e\nu)$. Assuming standard model couplings to fermions and the neutrino from the $W^\prime$ boson decay to be light, we exclude a $W^\prime$ boson with mass less than 1.12\unit{TeV/}c^2 at the 95\unit{%} confidence level.Comment: 7 pages, 2 figures Submitted to PR

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

An Early-Time Infrared and Optical Study of the Type Ia Supernova 1998bu in M96

We present first-season infrared (IR) and optical photometry and spectroscopy of the Type Ia Supernova 1998bu in M96. We also report optical polarimetry of this event. SN1998bu is one of the closest type Ia Supernovae of modern times and the distance of its host galaxy is well-determined. We find that SN1998bu is both photometrically and spectroscopically normal. However, the extinction to this event is unusually high, with Av=1.0 +/-0.11. We find that SN1998bu peaked at an intrinsic Mv=-19.37 +/-0.23. Adopting a distance modulus of 30.25 (Tanvir et al. 1999) and using Phillips et al.'s (1999) relations for the Hubble constant we obtain Ho=70.4 +/-4.3 km/s/Mpc. Combination of our IR photometry with those of Jha et al. (1999) provides one of the most complete early-phase IR light curves for a SN Ia published so far. In particular, SN 1998bu is the first normal SN Ia for which good pre-maximum (in the B band) IR coverage has been obtained. It reveals that the J, H and K light curves peak about 5 days earlier than the flux in the B-band curve.Comment: 22 pages, 9 figues, accepted for publication by MNRA