82 research outputs found
The molecular organization of differentially curved caveolae indicates bendable structural units at the plasma membrane
Caveolae are small coated plasma membrane invaginations with diverse functions. Caveolae undergo curvature changes. Yet, it is unclear which proteins regulate this process. To address this gap, we develop a correlative stimulated emission depletion (STED) fluorescence and platinum replica electron microscopy imaging (CLEM) method to image proteins at single caveolae. Caveolins and cavins are found at all caveolae, independent of curvature. EHD2 is detected at both low and highly curved caveolae. Pacsin2 associates with low curved caveolae and EHBP1 with mostly highly curved caveolae. Dynamin is absent from caveolae. Cells lacking dynamin show no substantial changes to caveolae, suggesting that dynamin is not directly involved in caveolae curvature. We propose a model where caveolins, cavins, and EHD2 assemble as a cohesive structural unit regulated by intermittent associations with pacsin2 and EHBP1. These coats can flatten and curve to enable lipid traffic, signaling, and changes to the surface area of the cell
Deep Underground Science and Engineering Laboratory - Preliminary Design Report
The DUSEL Project has produced the Preliminary Design of the Deep Underground
Science and Engineering Laboratory (DUSEL) at the rehabilitated former
Homestake mine in South Dakota. The Facility design calls for, on the surface,
two new buildings - one a visitor and education center, the other an experiment
assembly hall - and multiple repurposed existing buildings. To support
underground research activities, the design includes two laboratory modules and
additional spaces at a level 4,850 feet underground for physics, biology,
engineering, and Earth science experiments. On the same level, the design
includes a Department of Energy-shepherded Large Cavity supporting the Long
Baseline Neutrino Experiment. At the 7,400-feet level, the design incorporates
one laboratory module and additional spaces for physics and Earth science
efforts. With input from some 25 science and engineering collaborations, the
Project has designed critical experimental space and infrastructure needs,
including space for a suite of multidisciplinary experiments in a laboratory
whose projected life span is at least 30 years. From these experiments, a
critical suite of experiments is outlined, whose construction will be funded
along with the facility. The Facility design permits expansion and evolution,
as may be driven by future science requirements, and enables participation by
other agencies. The design leverages South Dakota's substantial investment in
facility infrastructure, risk retirement, and operation of its Sanford
Laboratory at Homestake. The Project is planning education and outreach
programs, and has initiated efforts to establish regional partnerships with
underserved populations - regional American Indian and rural populations
LSST Science Book, Version 2.0
A survey that can cover the sky in optical bands over wide fields to faint
magnitudes with a fast cadence will enable many of the exciting science
opportunities of the next decade. The Large Synoptic Survey Telescope (LSST)
will have an effective aperture of 6.7 meters and an imaging camera with field
of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over
20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with
fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a
total point-source depth of r~27.5. The LSST Science Book describes the basic
parameters of the LSST hardware, software, and observing plans. The book
discusses educational and outreach opportunities, then goes on to describe a
broad range of science that LSST will revolutionize: mapping the inner and
outer Solar System, stellar populations in the Milky Way and nearby galaxies,
the structure of the Milky Way disk and halo and other objects in the Local
Volume, transient and variable objects both at low and high redshift, and the
properties of normal and active galaxies at low and high redshift. It then
turns to far-field cosmological topics, exploring properties of supernovae to
z~1, strong and weak lensing, the large-scale distribution of galaxies and
baryon oscillations, and how these different probes may be combined to
constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at
http://www.lsst.org/lsst/sciboo
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 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
point-source depth in a single visit in will be (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 with
, and will be imaged multiple times in six bands, ,
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 region about 800 times (summed over all six bands) during the
anticipated 10 years of operations, and yield a coadded map to . 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
Innovation in health economic modelling of service improvements for longer-term depression: demonstration in a local health community
Background
The purpose of the analysis was to develop a health economic model to estimate the costs and health benefits of alternative National Health Service (NHS) service configurations for people with longer-term depression.
Method
Modelling methods were used to develop a conceptual and health economic model of the current configuration of services in Sheffield, England for people with longer-term depression. Data and assumptions were synthesised to estimate cost per Quality Adjusted Life Years (QALYs).
Results
Three service changes were developed and resulted in increased QALYs at increased cost. Versus current care, the incremental cost-effectiveness ratio (ICER) for a self-referral service was Β£11,378 per QALY. The ICER was Β£2,227 per QALY for the dropout reduction service and Β£223 per QALY for an increase in non-therapy services. These results were robust when compared to current cost-effectiveness thresholds and accounting for uncertainty.
Conclusions
Cost-effective service improvements for longer-term depression have been identified. Also identified were limitations of the current evidence for the long term impact of services
Raymond Gibson (1938β2023): in memoriam
On 29 January 2023, Raymond (Ray) Gibson (Fig. 1), Professor Emeritus of Liverpool John Moores University, died in a hospital on the Wirral. He lived a very busy life, rich in travels and scientific discoveries, and he was one of the most authoritative world experts in the taxonomy of nemerteans. Ray was born on 23 November 1938 in Catterick Village in Yorkshire. He gained his Private Pilotβs License aged 17 and had several adventures in the small plane. In 1965 after leaving the Royal Airforce as a qualified pilot he got his B.Sc. in Zoology First class degree from Leeds University and in 1968 gained his Ph.D. from Leeds University. Ray began his interest in nemerteans when he was a student at Leeds University. His Ph.D. supervisor was Dr. Joe Jennings, who at the time was researching the nutrition and digestion of nemerteans and βturbellariansβ (a grade of free-living platyhelminths). Rayβs first articles on the nutrition and biology of Malacobdella grossa were published when he was at Leeds University (Gibson 1967, 1968; Gibson & Jennings 1969). In 1971 Ray joined the Liverpool Regional College of Technology (this became Liverpool Polytechnic and then Liverpool John Moores University), where he worked for 30 years. His first book (Gibson 1972) is an excellent summary of knowledge on nemertean biology at the time and has βentangledβ (rather than βhookedβ) young students worldwide in the following generations into this field. Rayβs exploratory enthusiasm was unmatched. He would come early in the morning and spend the day in concentrated writing, microscopy, or figure preparation. An ashtray was ever present next to his microscope and cigarettes and black coffee were all he needed to sustain him through the long days. For a long time, the histology unit was complete with the all-pervasive smell of xylene. He supervised post-graduates from many countries and backgrounds, teaching them the intricacies of paraffin sectioning and histochemistry.Peer reviewe
From Toxins Targeting Ligand Gated Ion Channels to Therapeutic Molecules
Ligand-gated ion channels (LGIC) play a central role in inter-cellular communication. This key function has two consequences: (i) these receptor channels are major targets for drug discovery because of their potential involvement in numerous human brain diseases; (ii) they are often found to be the target of plant and animal toxins. Together this makes toxin/receptor interactions important to drug discovery projects. Therefore, toxins acting on LGIC are presented and their current/potential therapeutic uses highlighted
Nicotinic acetylcholine receptors in attention circuitry: the role of layer VI neurons of prefrontal cortex
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