Potent CRISPR-Cas9 inhibitors from Staphylococcus genomes.

Anti-CRISPRs (Acrs) are small proteins that inhibit the RNA-guided DNA targeting activity of CRISPR-Cas enzymes. Encoded by bacteriophage and phage-derived bacterial genes, Acrs prevent CRISPR-mediated inhibition of phage infection and can also block CRISPR-Cas-mediated genome editing in eukaryotic cells. To identify Acrs capable of inhibiting Staphylococcus aureus Cas9 (SauCas9), an alternative to the most commonly used genome editing protein Streptococcus pyogenes Cas9 (SpyCas9), we used both self-targeting CRISPR screening and guilt-by-association genomic search strategies. Here we describe three potent inhibitors of SauCas9 that we name AcrIIA13, AcrIIA14, and AcrIIA15. These inhibitors share a conserved N-terminal sequence that is dispensable for DNA cleavage inhibition and have divergent C termini that are required in each case for inhibition of SauCas9-catalyzed DNA cleavage. In human cells, we observe robust inhibition of SauCas9-induced genome editing by AcrIIA13 and moderate inhibition by AcrIIA14 and AcrIIA15. We also find that the conserved N-terminal domain of AcrIIA13-AcrIIA15 binds to an inverted repeat sequence in the promoter of these Acr genes, consistent with its predicted helix-turn-helix DNA binding structure. These data demonstrate an effective strategy for Acr discovery and establish AcrIIA13-AcrIIA15 as unique bifunctional inhibitors of SauCas9

Janus face aspect of all-cis 1,2,3,4,5,6-hexafluorocyclohexane dictates remarkable anion and cation interactions in the gas phase

The authors acknowledge support in the form of NSERC (Canada) Discovery Grants to EF, WSH, and TBM and an EPSRC (UK) responsive mode grant to DO’H and NSK is gratefully acknowledged.Experiments have been carried out in which electrospray ionization has been used to generate ionic complexes of all-cis 1,2,3,4,5,6 hexafluorocyclohexane. These complexes were subsequently mass isolated in a quadrupole ion trap mass spectrometer and then irradiated by the tunable infrared output of a free electron laser in the 800-1600 cm−1 range. From the frequency dependence of the fragmentation of the complexes, vibrational signatures of the complexes were obtained. Computational work carried out in parallel reveals that the complexes formed are very strongly bound and are among the most strongly bound complexes of Na+ and Cl− ever observed with molecular species. The dipole moment calculated for the heaxafluorocyclohexane is very large (~7 D) and it appears that the bonding in each of the complexes has a significant electrostatic contribution.PostprintPeer reviewe

Photometric Selection of Emission Line Galaxies, Clustering Analysis and a Search for the ISW effect

We investigate the use of simple colour cuts applied to the SDSS optical imaging to perform photometric selections of emission line galaxies out to z<1. From colour-cuts using the SDSS g, r and i bands, we obtain mean photometric redshifts of z=0.32+-0.08, z=0.44+-0.12 and z=0.65+-0.21. We further calibrate our high redshift selection using spectroscopic observations with the AAOmega spectrograph on the 4m Anglo-Australian Telescope (AAT), observing ~50-200 galaxy candidates in 4 separate fields. With just 1-hour of integration time and with seeing of ~1.6", we successfully determined redshifts for ~65% of the targeted candidates. We calculate the angular correlation functions of the samples and find correlation lengths of r0=2.64 h-1 Mpc, r0=3.62 h-1 Mpc and r0=5.88 h-1 Mpc for the low, mid and high redshift samples respectively. Comparing these results with predicted dark matter clustering, we estimate the bias parameter for each sample to be b=0.70, b=0.92 and b=1.46. We calculate the 2-point redshift-space correlation function at z~0.6 and find a clustering amplitude of s0=6.4 h-1 Mpc. Finally, we use our photometric sample to search for the Integrated Sachs-Wolfe signal in the WMAP 5yr data. We cross-correlate our three redshift samples with the WMAP W, V, Q and K bands and find an overall trend for a positive signal similar to that expected from models. However, the signal in each is relatively weak. Combining all three galaxy samples we find a signal of wTg(<100')=0.20+-0.12 microK in the WMAP W-band, a significance of 1.7sigma.Comment: 14 pages, 17 figures, submitted to MNRA

Organic carbon accumulation in British saltmarshes

Funding: This research was financially supported by the Natural Environment Research Council funded Carbon Storage in Intertidal Environments (C-SIDE) project (grant NE/R010846/1) with additional support from the Scottish Blue Forum. Radiocarbon dating was supported by the National Environment Isotope Facility Radiocarbon (Environment) Laboratory (allocation 2351.0321).Saltmarshes are a crucial component of the coastal carbon (C) system and provide a natural climate regulation service through the accumulation and long-term storage of organic carbon (OC) in their soils. These coastal ecosystems are under growing pressure from a changing climate and increasing anthropogenic disturbance. To manage and protect these ecosystems for C and to allow their inclusion in emissions and natural-capital accounting, as well as carbon markets, accurate and reliable estimates of OC accumulation are required. However, globally, such data are rare or of varying quality. Here, we quantify sedimentation rates and OC densities for 21 saltmarshes in Great Britain (GB). We estimate that, on average, saltmarshes accumulate OC at a rate of 110.88 ± 43.12 g C m-2 yr-1. This is considerably less than widely applied global saltmarsh averages. It is therefore highly likely that the contribution of northern European saltmarshes to global saltmarsh OC accumulation has been significantly overestimated. Taking account of the climatic, geomorphological, oceanographic, and ecological characteristics of all GB saltmarshes and the areal extent of different saltmarsh zones, we estimate that the 451.65 km2 of GB saltmarsh accumulates 46,563 ± 4,353 tonnes of OC annually. These low OC accumulation rates underline the importance of the 5.20 ± 0.65 million tonnes of OC already stored in these vulnerable coastal ecosystems. Going forward the protection and preservation of the existing stores of OC in GB saltmarshes must be a priority for the UK as this will provide climate benefits through avoided emissions several times more significant than the annual accumulation of OC in these ecosystems.Peer reviewe

Identifications of FIRST radio sources in the NOAO Deep-Wide Field Survey

In this paper we present the results of an optical and near infrared identification of 514 radio sources from the FIRST survey (Faint Images of the Radio Sky Survey at Twenty centimeters) with a flux-density limit of 1 mJy in the NOAO Deep-Wide Field Survey (NDWFS) Bootes field. Using optical (Bw, R, I) and K band data with approximate limits of Bw ~ 25.5mag, R ~ 25.8 mag, I ~25.5 mag and K~19.4 mag, optical counterparts have been identified for 378 of 514 FIRST radio sources. This corresponds to an identification rate of 34% in four bands (BwRIK), 60% in optical bands (BwRI) and 74% in I band. Photometric redshifts for these sources have been computed using the hyperz code. The inclusion of quasar template spectra in hyperz is investigated. We note that the photometric data are, in many cases, best matched to templates with very short star-formation timescales and the inferred ages of identified galaxies depend strongly on the assumptions about the star-formation timescale. The redshifts obtained are fairly consistent with those expected from the K-z relation for brighter radio sources but there is more scatter in the K-z diagram at z<1.Comment: 9 pages, 7 figures. Accepted for publication in Astronomische Nachrichten; will appear in the issue 5/32

Probing the neutrino mass hierarchy with CMB weak lensing

We forecast constraints on cosmological parameters with primary CMB anisotropy information and weak lensing reconstruction with a future post-Planck CMB experiment, the Cosmic Origins Explorer (COrE), using oscillation data on the neutrino mass splittings as prior information. Our MCMC simulations in flat models with a non-evolving equation-of-state of dark energy w give typical 68% upper bounds on the total neutrino mass of 0.136 eV and 0.098 eV for the inverted and normal hierarchies respectively, assuming the total summed mass is close to the minimum allowed by the oscillation data for the respective hierarchies (0.10 eV and 0.06 eV). Including information from future baryon acoustic oscillation measurements with the complete BOSS, Type 1a supernovae distance moduli from WFIRST, and a realistic prior on the Hubble constant, these upper limits shrink to 0.118 eV and 0.080 eV for the inverted and normal hierarchies, respectively. Addition of these distance priors also yields percent-level constraints on w. We find tension between our MCMC results and the results of a Fisher matrix analysis, most likely due to a strong geometric degeneracy between the total neutrino mass, the Hubble constant, and w in the unlensed CMB power spectra. If the minimal-mass, normal hierarchy were realised in nature, the inverted hierarchy should be disfavoured by the full data combination at typically greater than the 2-sigma level. For the minimal-mass inverted hierarchy, we compute the Bayes' factor between the two hierarchies for various combinations of our forecast datasets, and find that the future probes considered here should be able to provide `strong' evidence (odds ratio 12:1) for the inverted hierarchy. Finally, we consider potential biases of the other cosmological parameters from assuming the wrong hierarchy and find that all biases on the parameters are below their 1-sigma marginalised errors.Comment: 16 pages, 13 figures; minor changes to match the published version, references adde

Two 100 Mpc-scale structures in the 3-D distribution of radio galaxies and their implications

We present unequivocal evidence for a huge (~80 x 100 x 100 Mpc^3) super-structure at redshift z=0.27 in the 3-D distribution of radio galaxies from the TONS08 sample, confirming tentative evidence for such a structure from the 7C redshift survey (7CRS). A second, newly discovered super-structure is also less securely found at redshift 0.35 (of dimensions ~100 x 100 x 100 Mpc^3). We present full observational details on the TONS08 sample which was constructed to probe structures in the redshift range 0 < z < 0.5 by matching NVSS sources with objects in APM catalogues to obtain a sample of optically bright (E ~ R 3 mJy) radio galaxies in the same 25 deg^2 area as part-II of the 7CRS. Out of the total sample size of 84 radio galaxies, at least 25 are associated with the two ~100 Mpc-scale super-structures. We use quasi-linear structure formation theory to estimate the number of such structures expected in the TONS08 volume if the canonical value for radio galaxy bias is assumed. Under this assumption, the structures represent ~ 4-5 sigma peaks in the primordial density field and their expected number is low (~10^-2 - 10^-4). Fortunately, there are several plausible explanations (many of which are testable) for these low probabilities in the form of potential mechanisms for boosting the bias on large scales. These include: the association of radio galaxies with highly biased rich clusters in super-structures, enhanced triggering by group/group mergers, and enhanced triggering and/or redshift space distortion in collapsing systems as the growth of super-structures moves into the non-linear regime (abridged).Comment: Accepted for publication in MNRAS. 26 pages,16 figures. spectra can be found in: http://www-astro.physics.ox.ac.uk/~brand/08_paper.ps.g

Furthering alternative cultures of valuation in higher education research

The value of higher education is often implicit or assumed in educational research. The underlying and antecedent premises that shape and influence debates about value remain unchallenged which perpetuates the dominant, but limiting, terms of the debate and fosters reductionism. I proceed on the premise that analyses of value are not self–supporting or self-referential but are embedded within prevailing cultures of valuation. I contend that challenging, and providing alternatives to, dominant narratives of higher education requires an appreciation of those cultures. I therefore highlight some of the existing cultures of valuation and their influence. I then propose Sayer’s concept of lay normativity as a culture of valuation and discuss how it translates into the practices of research into higher education, specifically the practice of analysis. I animate the discussion by detecting the presence of lay normativity in the evaluative space of the capability approach

The Strategies to Reduce Injuries and Develop Confidence in Elders Intervention: Falls Risk Factor Assessment and Management, Patient Engagement, and Nurse Co‐management

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141587/1/jgs15121.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141587/2/jgs15121_am.pd

The Atacama Cosmology Telescope: Two-Season ACTPol Lensing Power Spectrum

We report a measurement of the power spectrum of cosmic microwave background (CMB) lensing from two seasons of Atacama Cosmology Telescope Polarimeter (ACTPol) CMB data. The CMB lensing power spectrum is extracted from both temperature and polarization data using quadratic estimators. We obtain results that are consistent with the expectation from the best-fit Planck LCDM model over a range of multipoles L=80-2100, with an amplitude of lensing A_lens = 1.06 +/- 0.15 (stat.) +/- 0.06 (sys.) relative to Planck. Our measurement of the CMB lensing power spectrum gives sigma_8 Omega_m^0.25 = 0.643 +/- 0.054; including baryon acoustic oscillation scale data, we constrain the amplitude of density fluctuations to be sigma_8 = 0.831 +/- 0.053. We also update constraints on the neutrino mass sum. We verify our lensing measurement with a number of null tests and systematic checks, finding no evidence of significant systematic errors. This measurement relies on a small fraction of the ACTPol data already taken; more precise lensing results can therefore be expected from the full ACTPol dataset.Comment: 17 pages, 11 figures, to be submitted to Physical Review