SUMO-targeted ubiquitin ligase (STUbL) Slx5 regulates proteolysis of centromeric histone H3 variant Cse4 and prevents its mislocalization to euchromatin

Centromeric histone H3, CENP-ACse4, is essential for faithful chromosome segregation. Stringent regulation of cellular levels of CENP-ACse4 restricts its localization to centromeres. Mislocalization of CENP-ACse4 is associated with aneuploidy in yeast and flies and tumorigenesis in human cells; thus defining pathways that regulate CENP-A levels is critical for understanding how mislocalization of CENP-A contributes to aneuploidy in human cancers. Previous work in budding yeast shows that ubiquitination of overexpressed Cse4 by Psh1, an E3 ligase, partially contributes to proteolysis of Cse4. Here we provide the first evidence that Cse4 is sumoylated by E3 ligases Siz1 and Siz2 in vivo and in vitro. Ubiquitination of Cse4 by the small ubiquitin-related modifier (SUMO)-targeted ubiquitin ligase (STUbL) Slx5 plays a critical role in proteolysis of Cse4 and prevents mislocalization of Cse4 to euchromatin under normal physiological conditions. Accumulation of sumoylated Cse4 species and increased stability of Cse4 in slx5∆ strains suggest that sumoylation precedes ubiquitin-mediated proteolysis of Cse4. Slx5-mediated Cse4 proteolysis is independent of Psh1, since slx5∆ psh1∆ strains exhibit higher levels of Cse4 stability and mislocalization than either slx5∆ or psh1∆ strains. Our results demonstrate a role for Slx5 in ubiquitin-mediated proteolysis of Cse4 to prevent its mislocalization and maintain genome stability

Concert recording 2013-03-31b

[Track 01]. Sweet Georgie fame / Blossom Dearie -- [Track 02]. Joy spring / Clifford Brown -- [Track 03]. Summer samba / Marcos Valle -- [Track 04]. Rhythm\u27ning / Thelonious Monk -- [Track 05]. One note samba / Antonio Carlos Jobim -- [Track 06]. In a sentimental mood / Duke Ellington -- [Track 07]. Recordame / Joe Henderson -- [Track 08]. Full house / Wes Montgomery -- [Track 09]. Cats and kittens / Peter Erskine -- [Track 10]. Primal prayer / Dan Haerle -- [Track 11]. Cookin\u27 Boox / Detroit Jackson

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

The LSST Dark Energy Science Collaboration (DESC) Science Requirements Document

The Large Synoptic Survey Telescope (LSST) Dark Energy Science Collaboration (DESC) will use five cosmological probes: galaxy clusters, large scale structure, supernovae, strong lensing, and weak lensing. This Science Requirements Document (SRD) quantifies the expected dark energy constraining power of these probes individually and together, with conservative assumptions about analysis methodology and follow-up observational resources based on our current understanding and the expected evolution within the field in the coming years. We then define requirements on analysis pipelines that will enable us to achieve our goal of carrying out a dark energy analysis consistent with the Dark Energy Task Force definition of a Stage IV dark energy experiment. This is achieved through a forecasting process that incorporates the flowdown to detailed requirements on multiple sources of systematic uncertainty. Future versions of this document will include evolution in our software capabilities and analysis plans along with updates to the LSST survey strategy.Comment: 32 pages + 60 pages of appendices. This is v1 of the DESC SRD, an internal collaboration document that is being made public and is not planned for submission to a journal. Data products for reproducing key plots are available at the LSST DESC Zenodo community, https://zenodo.org/communities/lsst-desc; see "Executive Summary and User Guide" for instructions on how to use and cite those product

Discovery of an Unusual Optical Transient with the Hubble Space Telescope

We present observations of SCP 06F6, an unusual optical transient discovered during the Hubble Space Telescope Cluster Supernova Survey. The transient brightened over a period of ~;;100 days, reached a peak magnitude of ~;;21.0 in both i_775 and z_850, and then declined over a similar timescale. There is no host galaxy or progenitor star detected at the location of the transient to a 3 sigma upper limit of i_775 = 26.4 and z_850 = 26.1, giving a corresponding lower limit on the flux increase of a factor of ~;;120. Multiple spectra show five broad absorption bands between 4100 AA and 6500 AA and a mostly featureless continuum longward of 6500 AA. The shape of the lightcurve is inconsistent with microlensing. The transient's spectrum, in addition to being inconsistent with all known supernova types, is not matched to any spectrum in the Sloan Digital Sky Survey (SDSS) database. We suggest that the transient may be one of a new class

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks

Mechanical design of the optical modules intended for IceCube-Gen2

IceCube-Gen2 is an expansion of the IceCube neutrino observatory at the South Pole that aims to increase the sensitivity to high-energy neutrinos by an order of magnitude. To this end, about 10,000 new optical modules will be installed, instrumenting a fiducial volume of about 8 km3. Two newly developed optical module types increase IceCube’s current sensitivity per module by a factor of three by integrating 16 and 18 newly developed four-inch PMTs in specially designed 12.5-inch diameter pressure vessels. Both designs use conical silicone gel pads to optically couple the PMTs to the pressure vessel to increase photon collection efficiency. The outside portion of gel pads are pre-cast onto each PMT prior to integration, while the interiors are filled and cast after the PMT assemblies are installed in the pressure vessel via a pushing mechanism. This paper presents both the mechanical design, as well as the performance of prototype modules at high pressure (70 MPa) and low temperature (−40∘C), characteristic of the environment inside the South Pole ice