158 research outputs found
New functional families (FunFams) in CATH to improve the mapping of conserved functional sites to 3D structures.
CATH version 3.5 (Class, Architecture, Topology, Homology, available at http://www.cathdb.info/) contains 173 536 domains, 2626 homologous superfamilies and 1313 fold groups. When focusing on structural genomics (SG) structures, we observe that the number of new folds for CATH v3.5 is slightly less than for previous releases, and this observation suggests that we may now know the majority of folds that are easily accessible to structure determination. We have improved the accuracy of our functional family (FunFams) sub-classification method and the CATH sequence domain search facility has been extended to provide FunFam annotations for each domain. The CATH website has been redesigned. We have improved the display of functional data and of conserved sequence features associated with FunFams within each CATH superfamily
MicroLED biosensor with colloidal quantum dots and smartphone detection
A fluorescence sensor with the capability for spatially multiplexed measurements utilizing smartphone detection is presented. Bioconjugated quantum dots are used as the fluorescent tag and are excited using a blue emitting microLED (µLED). The 1-dimensional GaN µLED array is butt-coupled to one edge of the glass slide to take advantage of total internal reflection fluorescence (TIRF) principles. The bioassays on the top surface of the glass waveguide are excited and the resultant fluorescence is detected with the smartphone. The red, green, and blue channels of the digital image are utilized to spectrally separate the excitation light from the fluorescence for analysis. Using a biotin-functionalized glass slide as proof of principle, we have shown that streptavidin conjugated quantum dots can be detected down to a concentration of 8 nM
CATH: comprehensive structural and functional annotations for genome sequences.
The latest version of the CATH-Gene3D protein structure classification database (4.0, http://www.cathdb.info) provides annotations for over 235,000 protein domain structures and includes 25 million domain predictions. This article provides an update on the major developments in the 2 years since the last publication in this journal including: significant improvements to the predictive power of our functional families (FunFams); the release of our 'current' putative domain assignments (CATH-B); a new, strictly non-redundant data set of CATH domains suitable for homology benchmarking experiments (CATH-40) and a number of improvements to the web pages
The Multi-Object, Fiber-Fed Spectrographs for SDSS and the Baryon Oscillation Spectroscopic Survey
We present the design and performance of the multi-object fiber spectrographs
for the Sloan Digital Sky Survey (SDSS) and their upgrade for the Baryon
Oscillation Spectroscopic Survey (BOSS). Originally commissioned in Fall 1999
on the 2.5-m aperture Sloan Telescope at Apache Point Observatory, the
spectrographs produced more than 1.5 million spectra for the SDSS and SDSS-II
surveys, enabling a wide variety of Galactic and extra-galactic science
including the first observation of baryon acoustic oscillations in 2005. The
spectrographs were upgraded in 2009 and are currently in use for BOSS, the
flagship survey of the third-generation SDSS-III project. BOSS will measure
redshifts of 1.35 million massive galaxies to redshift 0.7 and Lyman-alpha
absorption of 160,000 high redshift quasars over 10,000 square degrees of sky,
making percent level measurements of the absolute cosmic distance scale of the
Universe and placing tight constraints on the equation of state of dark energy.
The twin multi-object fiber spectrographs utilize a simple optical layout
with reflective collimators, gratings, all-refractive cameras, and
state-of-the-art CCD detectors to produce hundreds of spectra simultaneously in
two channels over a bandpass covering the near ultraviolet to the near
infrared, with a resolving power R = \lambda/FWHM ~ 2000. Building on proven
heritage, the spectrographs were upgraded for BOSS with volume-phase
holographic gratings and modern CCD detectors, improving the peak throughput by
nearly a factor of two, extending the bandpass to cover 360 < \lambda < 1000
nm, and increasing the number of fibers from 640 to 1000 per exposure. In this
paper we describe the original SDSS spectrograph design and the upgrades
implemented for BOSS, and document the predicted and measured performances.Comment: 43 pages, 42 figures, revised according to referee report and
accepted by AJ. Provides background for the instrument responsible for SDSS
and BOSS spectra. 4th in a series of survey technical papers released in
Summer 2012, including arXiv:1207.7137 (DR9), arXiv:1207.7326 (Spectral
Classification), and arXiv:1208.0022 (BOSS Overview
The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey : baryon acoustic oscillations in the Data Releases 10 and 11 Galaxy samples
We present a one per cent measurement of the cosmic distance scale from the detections of the baryon acoustic oscillations (BAO) in the clustering of galaxies from the Baryon Oscillation Spectroscopic Survey, which is part of the Sloan Digital Sky Survey III. Our results come from the Data Release 11 (DR11) sample, containing nearly one million galaxies and covering approximately 8500 square degrees and the redshift range 0.2 < z < 0.7. We also compare these results with those from the publicly released DR9 and DR10 samples. Assuming a concordance Λ cold dark matter (ΛCDM) cosmological model, the DR11 sample covers a volume of 13 Gpc3 and is the largest region of the Universe ever surveyed at this density. We measure the correlation function and power spectrum, including density-field reconstruction of the BAO feature. The acoustic features are detected at a significance of over 7σ in both the correlation function and power spectrum. Fitting for the position of the acoustic features measures the distance relative to the sound horizon at the drag epoch, rd, which has a value of rd,fid = 149.28 Mpc in our fiducial cosmology. We find DV = (1264 ± 25 Mpc)(rd/rd,fid) at z = 0.32 and DV = (2056 ± 20 Mpc)(rd/rd,fid) at z = 0.57. At 1.0 per cent, this latter measure is the most precise distance constraint ever obtained from a galaxy survey. Separating the clustering along and transverse to the line of sight yields measurements at z = 0.57 of DA = (1421 ± 20 Mpc)(rd/rd,fid) and H = (96.8 ± 3.4 km s−1 Mpc−1)(rd,fid/rd). Our measurements of the distance scale are in good agreement with previous BAO measurements and with the predictions from cosmic microwave background data for a spatially flat CDM model with a cosmological constant.Publisher PDFPeer reviewe
Targeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia.
Non-genetic drug resistance is increasingly recognised in various cancers. Molecular insights into this process are lacking and it is unknown whether stable non-genetic resistance can be overcome. Using single cell RNA-sequencing of paired drug naïve and resistant AML patient samples and cellular barcoding in a unique mouse model of non-genetic resistance, here we demonstrate that transcriptional plasticity drives stable epigenetic resistance. With a CRISPR-Cas9 screen we identify regulators of enhancer function as important modulators of the resistant cell state. We show that inhibition of Lsd1 (Kdm1a) is able to overcome stable epigenetic resistance by facilitating the binding of the pioneer factor, Pu.1 and cofactor, Irf8, to nucleate new enhancers that regulate the expression of key survival genes. This enhancer switching results in the re-distribution of transcriptional co-activators, including Brd4, and provides the opportunity to disable their activity and overcome epigenetic resistance. Together these findings highlight key principles to help counteract non-genetic drug resistance
Recommended from our members
The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: Baryon Acoustic Oscillations in the Data Release 9 Spectroscopic Galaxy Sample
We present measurements of galaxy clustering from the Baryon Oscillation
Spectroscopic Survey (BOSS), which is part of the Sloan Digital Sky Survey III
(SDSS-III). These use the Data Release 9 (DR9) CMASS sample, which contains
264,283 massive galaxies covering 3275 square degrees with an effective
redshift z=0.57 and redshift range 0.43 < z < 0.7. Assuming a concordance
Lambda-CDM cosmological model, this sample covers an effective volume of 2.2
Gpc^3, and represents the largest sample of the Universe ever surveyed at this
density, n = 3 x 10^-4 h^-3 Mpc^3. We measure the angle-averaged galaxy
correlation function and power spectrum, including density-field reconstruction
of the baryon acoustic oscillation (BAO) feature. The acoustic features are
detected at a significance of 5\sigma in both the correlation function and
power spectrum. Combining with the SDSS-II Luminous Red Galaxy Sample, the
detection significance increases to 6.7\sigma. Fitting for the position of the
acoustic features measures the distance to z=0.57 relative to the sound horizon
DV /rs = 13.67 +/- 0.22 at z=0.57. Assuming a fiducial sound horizon of 153.19
Mpc, which matches cosmic microwave background constraints, this corresponds to
a distance DV(z=0.57) = 2094 +/- 34 Mpc. At 1.7 per cent, this is the most
precise distance constraint ever obtained from a galaxy survey. We place this
result alongside previous BAO measurements in a cosmological distance ladder
and find excellent agreement with the current supernova measurements. We use
these distance measurements to constrain various cosmological models, finding
continuing support for a flat Universe with a cosmological constant.Comment: 33 page
The SDSS-III Baryon Oscillation Spectroscopic Survey: Quasar Target Selection for Data Release Nine
The SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS), a five-year
spectroscopic survey of 10,000 deg^2, achieved first light in late 2009. One of
the key goals of BOSS is to measure the signature of baryon acoustic
oscillations in the distribution of Ly-alpha absorption from the spectra of a
sample of ~150,000 z>2.2 quasars. Along with measuring the angular diameter
distance at z\approx2.5, BOSS will provide the first direct measurement of the
expansion rate of the Universe at z > 2. One of the biggest challenges in
achieving this goal is an efficient target selection algorithm for quasars over
2.2 < z < 3.5, where their colors overlap those of stars. During the first year
of the BOSS survey, quasar target selection methods were developed and tested
to meet the requirement of delivering at least 15 quasars deg^-2 in this
redshift range, out of 40 targets deg^-2. To achieve these surface densities,
the magnitude limit of the quasar targets was set at g <= 22.0 or r<=21.85.
While detection of the BAO signature in the Ly-alpha absorption in quasar
spectra does not require a uniform target selection, many other astrophysical
studies do. We therefore defined a uniformly-selected subsample of 20 targets
deg^-2, for which the selection efficiency is just over 50%. This "CORE"
subsample will be fixed for Years Two through Five of the survey. In this paper
we describe the evolution and implementation of the BOSS quasar target
selection algorithms during the first two years of BOSS operations. We analyze
the spectra obtained during the first year. 11,263 new z>2.2 quasars were
spectroscopically confirmed by BOSS. Our current algorithms select an average
of 15 z > 2.2 quasars deg^-2 from 40 targets deg^-2 using single-epoch SDSS
imaging. Multi-epoch optical data and data at other wavelengths can further
improve the efficiency and completeness of BOSS quasar target selection.
[Abridged]Comment: 33 pages, 26 figures, 12 tables and a whole bunch of quasars.
Submitted to Ap
The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey
The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic
data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data
release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median
z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar
spectra, along with the data presented in previous data releases. These spectra
were obtained with the new BOSS spectrograph and were taken between 2009
December and 2011 July. In addition, the stellar parameters pipeline, which
determines radial velocities, surface temperatures, surface gravities, and
metallicities of stars, has been updated and refined with improvements in
temperature estimates for stars with T_eff<5000 K and in metallicity estimates
for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars
presented in DR8, including stars from SDSS-I and II, as well as those observed
as part of the SDSS-III Sloan Extension for Galactic Understanding and
Exploration-2 (SEGUE-2).
The astrometry error introduced in the DR8 imaging catalogs has been
corrected in the DR9 data products. The next data release for SDSS-III will be
in Summer 2013, which will present the first data from the Apache Point
Observatory Galactic Evolution Experiment (APOGEE) along with another year of
data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at
http://www.sdss3.org/dr
- …