Deep Learning (DL) has recently enabled unprecedented advances in one of the grand challenges in computational biology: the half-century-old problem of protein structure prediction. In this paper we ...discuss recent advances, limitations, and future perspectives of DL on five broad areas: protein structure prediction, protein function prediction, genome engineering, systems biology and data integration, and phylogenetic inference. We discuss each application area and cover the main bottlenecks of DL approaches, such as training data, problem scope, and the ability to leverage existing DL architectures in new contexts. To conclude, we provide a summary of the subject-specific and general challenges for DL across the biosciences.
The location of different actin-based structures is largely regulated by Rho GTPases through specific effectors. We use the apical aspect of epithelial cells as a model system to investigate how RhoA ...is locally regulated to contribute to two distinct adjacent actin-based structures. Assembly of the non-muscle myosin-2 filaments in the terminal web is dependent on RhoA activity, and assembly of the microvilli also requires active RhoA for phosphorylation and activation of ezrin. We show that the RhoGAP, ARHGAP18, is localized by binding active microvillar ezrin, and this interaction enhances ARHGAP18's RhoGAP activity. We present a model where ezrin-ARHGAP18 acts as a negative autoregulatory module to locally reduce RhoA activity in microvilli. Consistent with this model, loss of ARHGAP18 results in disruption of the distinction between microvilli and the terminal web including aberrant assembly of myosin-2 filaments forming inside microvilli. Thus, ARHGAP18, through its recruitment and activation by ezrin, fine-tunes the local level of RhoA to allow for the appropriate distribution of actin-based structures between the microvilli and terminal web. As RhoGAPs vastly outnumber Rho GTPases, this may represent a general mechanism whereby individual Rho effectors drive specific actin-based structures.
Extended gas clouds have been previously detected surrounding the brightest known close-in transiting hot Jupiter exoplanets, HD 209458 b and HD 189733 b; we observed the distant but more extreme ...close-in hot Jupiter system, WASP-12, with Hubble Space Telescope (HST). Near-UV (NUV) transits up to three times deeper than the optical transit of WASP-12 b reveal extensive diffuse gas, extending well beyond the Roche lobe. Our spectra reveal significantly enhanced absorption (greater than 3sigma below the median) at ~200 individual wavelengths on each of two HST visits; 65 of these wavelengths are consistent between the two visits, using a strict criterion for velocity matching that excludes matches with velocity shifts exceeding ~20 km s super(-1). Our Visit 2 NUV light curves show evidence for a stellar flare. We show that some of the possible transit detections in resonance lines of rare elements may be due instead to non-resonant transitions in common species. We present optical observations and update the transit ephemeris.
We report the discovery of a transiting planet with an orbital period of 3.05 days orbiting the star TYC 7247-587-1. The star, WASP-41, is a moderately bright G8
V
V
star (
V = 11.6
V
=
11.6
) with a ...metallicity close to solar (Fe/H = -0.08 ± 0.09
Fe
/
H
=
-
0.08
±
0.09
). The star shows evidence of moderate chromospheric activity, both from emission in the cores of the Ca iiH and K ines and photometric variability with a period of 18.4 days and an amplitude of about 1%. We use a new method to show quantitatively that this periodic signal has a low false-alarm probability. The rotation period of the star implies a gyrochronological age for WASP-41 of 1.8 Gyr with an error of about 15%. We have used a combined analysis of the available photometric and spectroscopic data to derive the mass and radius of the planet (0.92 ± 0.06 M
Jup
0.92
±
0.06
M
Jup
,1.20 ± 0.06 R
Jup
1.20
±
0.06
R
Jup
). Further observations of WASP-41 can be used to explore the connections between the properties of hot Jupiter planets and the level of chromospheric activity in their host stars.
NUT midline carcinoma (NMC) is an aggressive type of squamous cell carcinoma that is defined by the presence of BRD-NUT fusion oncogenes, which encode chimeric proteins that block differentiation and ...maintain tumor growth. BRD-NUT oncoproteins contain two bromodomains whose binding to acetylated histones is required for the blockade of differentiation in NMC, but the mechanisms by which BRD-NUT act remain uncertain. Here, we provide evidence that MYC is a key downstream target of BRD4-NUT. Expression profiling of NMCs shows that the set of genes whose expression is maintained by BRD4-NUT is highly enriched for MYC upregulated genes, and MYC and BRD4-NUT protein expression is strongly correlated in primary NMCs. More directly, we find that BRD4-NUT associates with the MYC promoter and is required to maintain MYC expression in NMC cell lines. Moreover, both siRNA knockdown of MYC and a dominant-negative form of MYC, omomyc, induce differentiation of NMC cells. Conversely, differentiation of NMC cells induced by knockdown of BRD4-NUT is abrogated by enforced expression of MYC. Together, these findings suggest that MYC is a downstream target of BRD4-NUT that is required for maintenance of NMC cells in an undifferentiated, proliferative state. Our findings support a model in which dysregulation of MYC by BRD-NUT fusion proteins has a central role in the pathogenesis of NMC.
The WASP Project and the SuperWASP Cameras Pollacco, D. L.; Skillen, I.; Cameron, A. Collier ...
Publications of the Astronomical Society of the Pacific,
10/2006, Letnik:
118, Številka:
848
Journal Article
Recenzirano
Odprti dostop
The SuperWASP cameras are wide‐field imaging systems at the Observatorio del Roque de los Muchachos on the island of La Palma in the Canary Islands, and at the Sutherland Station of the South African ...Astronomical Observatory. Each instrument has a field of view of some 482 deg2with an angular scale of 13
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7 pixel−1, and is capable of delivering photometry with accuracy better than 1% for objects having
\documentclass{aastex} \usepackage{amsbsy} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{bm} \usepackage{mathrsfs} \usepackage{pifont} \usepackage{stmaryrd} \usepackage{textcomp} \usepackage{portland,xspace} \usepackage{amsmath,amsxtra} \usepackageOT2,OT1{fontenc} \newcommand\cyr{ \renewcommand\rmdefault{wncyr} \renewcommand\sfdefault{wncyss} \renewcommand\encodingdefault{OT2} \normalfont \selectfont} \DeclareTextFontCommand{\textcyr}{\cyr} \pagestyle{empty} \DeclareMathSizes{10}{9}{7}{6} \begin{document} \landscape $V\sim 7.0{\mbox{--}} 11.5$ \end{document}
. Lower quality data for objects brighter than
\documentclass{aastex} \usepackage{amsbsy} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{bm} \usepackage{mathrsfs} \usepackage{pifont} \usepackage{stmaryrd} \usepackage{textcomp} \usepackage{portland,xspace} \usepackage{amsmath,amsxtra} \usepackageOT2,OT1{fontenc} \newcommand\cyr{ \renewcommand\rmdefault{wncyr} \renewcommand\sfdefault{wncyss} \renewcommand\encodingdefault{OT2} \normalfont \selectfont} \DeclareTextFontCommand{\textcyr}{\cyr} \pagestyle{empty} \DeclareMathSizes{10}{9}{7}{6} \begin{document} \landscape $V\sim 15.0$ \end{document}
are stored in the project archive. The systems, while designed to monitor fields with high cadence, are capable of surveying the entire visible sky every 40 minutes. Depending on the observational strategy, the data rate can be up to 100 Gbytes per night. We have produced a robust, largely automatic reduction pipeline and advanced archive, which are used to serve the data products to the consortium members. The main science aim of these systems is to search for bright transiting exoplanet systems suitable for spectroscopic follow‐up observations. The first 6 month season of SuperWASP‐North observations produced light curves of ∼6.7 million objects with 12.9 billion data points.
The first WASP public data release Butters, O. W.; West, R. G.; Anderson, D. R. ...
Astronomy and astrophysics (Berlin),
09/2010, Letnik:
520
Journal Article
Recenzirano
Odprti dostop
The WASP (wide angle search for planets) project is an exoplanet transit survey that has been automatically taking wide field images since 2004. Two instruments, one in La Palma and the other in ...South Africa, continually monitor the night sky, building up light curves of millions of unique objects. These light curves are used to search for the characteristics of exoplanetary transits. This first public data release (DR1) of the WASP archive makes available all the light curve data and images from 2004 up to 2008 in both the Northern and Southern hemispheres. A web interface () to the data allows easy access over the Internet. The data set contains 3 631 972 raw images and 17 970 937 light curves. In total the light curves have 119 930 299 362 data points available between them.
Over the past decade, long-duration γ-ray bursts (GRBs)-including the subclass of X-ray flashes (XRFs)-have been revealed to be a rare variety of type Ibc supernova. Although all these events result ...from the death of massive stars, the electromagnetic luminosities of GRBs and XRFs exceed those of ordinary type Ibc supernovae by many orders of magnitude. The essential physical process that causes a dying star to produce a GRB or XRF, and not just a supernova, is still unknown. Here we report radio and X-ray observations of XRF 060218 (associated with supernova SN 2006aj), the second-nearest GRB identified until now. We show that this event is a hundred times less energetic but ten times more common than cosmological GRBs. Moreover, it is distinguished from ordinary type Ibc supernovae by the presence of 1048 erg coupled to mildly relativistic ejecta, along with a central engine (an accretion-fed, rapidly rotating compact source) that produces X-rays for weeks after the explosion. This suggests that the production of relativistic ejecta is the key physical distinction between GRBs or XRFs and ordinary supernovae, while the nature of the central engine (black hole or magnetar) may distinguish typical bursts from low-luminosity, spherical events like XRF 060218.
Despite countless media campaigns, organ donation rates in the United States have remained static while need has risen dramatically. New efforts to increase organ donation through public education ...are necessary to address the waiting list of over 100,000 patients. On May 1, 2012, the online social network, Facebook, altered its platform to allow members to specify “Organ Donor” as part of their profile. Upon such choice, members were offered a link to their state registry to complete an official designation, and their “friends” in the network were made aware of the new status as a donor. Educational links regarding donation were offered to those considering the new organ donor status. On the first day of the Facebook organ donor initiative, there were 13 054 new online registrations, representing a 21.1‐fold increase over the baseline average of 616 registrations. This first‐day effect ranged from 6.9× (Michigan) to 108.9× (Georgia). Registration rates remained elevated in the following 12 days. During the same time period, no increase was seen in registrations from the DMV. Novel applications of social media may prove effective in increasing organ donation rates and likewise might be utilized in other refractory public health problems in which communication and education are essential.
The authors report that an immediate increase in online donation registration was seen around the country following a small change in the platform of a large online social network that allowed for declaration and sharing of one's organ donor status.
Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department ...with septic shock. However, its effectiveness is uncertain.
In this trial conducted at 51 centers (mostly in Australia or New Zealand), we randomly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care. The primary outcome was all-cause mortality within 90 days after randomization.
Of the 1600 enrolled patients, 796 were assigned to the EGDT group and 804 to the usual-care group. Primary outcome data were available for more than 99% of the patients. Patients in the EGDT group received a larger mean (±SD) volume of intravenous fluids in the first 6 hours after randomization than did those in the usual-care group (1964±1415 ml vs. 1713±1401 ml) and were more likely to receive vasopressor infusions (66.6% vs. 57.8%), red-cell transfusions (13.6% vs. 7.0%), and dobutamine (15.4% vs. 2.6%) (P<0.001 for all comparisons). At 90 days after randomization, 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group, for rates of death of 18.6% and 18.8%, respectively (absolute risk difference with EGDT vs. usual care, -0.3 percentage points; 95% confidence interval, -4.1 to 3.6; P=0.90). There was no significant difference in survival time, in-hospital mortality, duration of organ support, or length of hospital stay.
In critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days. (Funded by the National Health and Medical Research Council of Australia and the Alfred Foundation; ARISE ClinicalTrials.gov number, NCT00975793.).
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