48 research outputs found
Models and simulations for the photometric lsst astronomical time series classification challenge (Plasticc)
We describe the simulated data sample for the "Photometric LSST Astronomical Time Series Classification Challenge" (PLAsTiCC), a publicly available challenge to classify transient and variable events that will be observed by the Large Synoptic Survey Telescope (LSST), a new facility expected to start in the early 2020s. The challenge was hosted by Kaggle, ran from 2018 September 28 to 2018 December 17, and included 1,094 teams competing for prizes. Here we provide details of the 18 transient and variable source models, which were not revealed until after the challenge, and release the model libraries at this https URL. We describe the LSST Operations Simulator used to predict realistic observing conditions, and we describe the publicly available SNANA simulation code used to transform the models into observed fluxes and uncertainties in the LSST passbands (ugrizy). Although PLAsTiCC has finished, the publicly available models and simulation tools are being used within the astronomy community to further improve classification, and to study contamination in photometrically identified samples of type Ia supernova used to measure properties of dark energy. Our simulation framework will continue serving as a platform to improve the PLAsTiCC models, and to develop new models
Transfection of IL-10 expression vectors into endothelial cultures attenuates α4β7-dependent lymphocyte adhesion mediated by MAdCAM-1
BACKGROUND: Enhanced expression of MAdCAM-1 (mucosal addressin cell adhesion molecule-1) is associated with the onset and progression of inflammatory bowel disease. The clinical significance of elevated MAdCAM-1 expression is supported by studies showing that immunoneutralization of MAdCAM-1, or its ligands reduce inflammation and mucosal damage in models of colitis. Interleukin-10 (IL-10) is an endogenous anti-inflammatory and immunomodulatory cytokine that has been shown to prevent inflammation and injury in several animal studies, however clinical IL-10 treatment remains insufficient because of difficulties in the route of IL-10 administration and its biological half-life. Here, we examined the ability of introducing an IL-10 expression vector into endothelial cultures to reduce responses to a proinflammatory cytokine, TNF-α METHODS: A human IL-10 expression vector was transfected into high endothelial venular ('HEV') cells (SVEC4-10); we then examined TNF-α induced lymphocyte adhesion to lymphatic endothelial cells and TNF-α induced expression of MAdCAM-1 and compared these responses to control monolayers. RESULTS: Transfection of the IL-10 vector into endothelial cultures significantly reduced TNF-α induced, MAdCAM-1 dependent lymphocyte adhesion (compared to non-transfected cells). IL-10 transfected endothelial cells expressed less than half (46 ± 6.6%) of the MAdCAM-1 induced by TNF-α (set as 100%) in non-transfected (control) cells. CONCLUSION: Our results suggest that gene therapy of the gut microvasculature with IL-10 vectors may be useful in the clinical treatment of IBD
Disease-Associated Mutant Ubiquitin Causes Proteasomal Impairment and Enhances the Toxicity of Protein Aggregates
Protein homeostasis is critical for cellular survival and its dysregulation has been implicated in Alzheimer's disease (AD) and other neurodegenerative disorders. Despite the growing appreciation of the pathogenic mechanisms involved in familial forms of AD, much less is known about the sporadic cases. Aggregates found in both familial and sporadic AD often include proteins other than those typically associated with the disease. One such protein is a mutant form of ubiquitin, UBB+1, a frameshift product generated by molecular misreading of a wild-type ubiquitin gene. UBB+1 has been associated with multiple disorders. UBB+1 cannot function as a ubiquitin molecule, and it is itself a substrate for degradation by the ubiquitin/proteasome system (UPS). Accumulation of UBB+1 impairs the proteasome system and enhances toxic protein aggregation, ultimately resulting in cell death. Here, we describe a novel model system to investigate how UBB+1 impairs UPS function and whether it plays a causal role in protein aggregation. We expressed a protein analogous to UBB+1 in yeast (Ubext) and demonstrated that it caused UPS impairment. Blocking ubiquitination of Ubext or weakening its interactions with other ubiquitin-processing proteins reduced the UPS impairment. Expression of Ubext altered the conjugation of wild-type ubiquitin to a UPS substrate. The expression of Ubext markedly enhanced cellular susceptibility to toxic protein aggregates but, surprisingly, did not induce or alter nontoxic protein aggregates in yeast. Taken together, these results suggest that Ubext interacts with more than one protein to elicit impairment of the UPS and affect protein aggregate toxicity. Furthermore, we suggest a model whereby chronic UPS impairment could inflict deleterious consequences on proper protein aggregate sequestration
Spacelike Singularities and Hidden Symmetries of Gravity
We review the intimate connection between (super-)gravity close to a
spacelike singularity (the "BKL-limit") and the theory of Lorentzian Kac-Moody
algebras. We show that in this limit the gravitational theory can be
reformulated in terms of billiard motion in a region of hyperbolic space,
revealing that the dynamics is completely determined by a (possibly infinite)
sequence of reflections, which are elements of a Lorentzian Coxeter group. Such
Coxeter groups are the Weyl groups of infinite-dimensional Kac-Moody algebras,
suggesting that these algebras yield symmetries of gravitational theories. Our
presentation is aimed to be a self-contained and comprehensive treatment of the
subject, with all the relevant mathematical background material introduced and
explained in detail. We also review attempts at making the infinite-dimensional
symmetries manifest, through the construction of a geodesic sigma model based
on a Lorentzian Kac-Moody algebra. An explicit example is provided for the case
of the hyperbolic algebra E10, which is conjectured to be an underlying
symmetry of M-theory. Illustrations of this conjecture are also discussed in
the context of cosmological solutions to eleven-dimensional supergravity.Comment: 228 pages. Typos corrected. References added. Subject index added.
Published versio
The Hubble Constant
I review the current state of determinations of the Hubble constant, which
gives the length scale of the Universe by relating the expansion velocity of
objects to their distance. There are two broad categories of measurements. The
first uses individual astrophysical objects which have some property that
allows their intrinsic luminosity or size to be determined, or allows the
determination of their distance by geometric means. The second category
comprises the use of all-sky cosmic microwave background, or correlations
between large samples of galaxies, to determine information about the geometry
of the Universe and hence the Hubble constant, typically in a combination with
other cosmological parameters. Many, but not all, object-based measurements
give values of around 72-74km/s/Mpc , with typical errors of 2-3km/s/Mpc.
This is in mild discrepancy with CMB-based measurements, in particular those
from the Planck satellite, which give values of 67-68km/s/Mpc and typical
errors of 1-2km/s/Mpc. The size of the remaining systematics indicate that
accuracy rather than precision is the remaining problem in a good determination
of the Hubble constant. Whether a discrepancy exists, and whether new physics
is needed to resolve it, depends on details of the systematics of the
object-based methods, and also on the assumptions about other cosmological
parameters and which datasets are combined in the case of the all-sky methods.Comment: Extensively revised and updated since the 2007 version: accepted by
Living Reviews in Relativity as a major (2014) update of LRR 10, 4, 200
Physics, Astrophysics and Cosmology with Gravitational Waves
Gravitational wave detectors are already operating at interesting sensitivity
levels, and they have an upgrade path that should result in secure detections
by 2014. We review the physics of gravitational waves, how they interact with
detectors (bars and interferometers), and how these detectors operate. We study
the most likely sources of gravitational waves and review the data analysis
methods that are used to extract their signals from detector noise. Then we
consider the consequences of gravitational wave detections and observations for
physics, astrophysics, and cosmology.Comment: 137 pages, 16 figures, Published version
<http://www.livingreviews.org/lrr-2009-2
Relativistic Dynamics and Extreme Mass Ratio Inspirals
It is now well-established that a dark, compact object (DCO), very likely a
massive black hole (MBH) of around four million solar masses is lurking at the
centre of the Milky Way. While a consensus is emerging about the origin and
growth of supermassive black holes (with masses larger than a billion solar
masses), MBHs with smaller masses, such as the one in our galactic centre,
remain understudied and enigmatic. The key to understanding these holes - how
some of them grow by orders of magnitude in mass - lies in understanding the
dynamics of the stars in the galactic neighbourhood. Stars interact with the
central MBH primarily through their gradual inspiral due to the emission of
gravitational radiation. Also stars produce gases which will subsequently be
accreted by the MBH through collisions and disruptions brought about by the
strong central tidal field. Such processes can contribute significantly to the
mass of the MBH and progress in understanding them requires theoretical work in
preparation for future gravitational radiation millihertz missions and X-ray
observatories. In particular, a unique probe of these regions is the
gravitational radiation that is emitted by some compact stars very close to the
black holes and which could be surveyed by a millihertz gravitational wave
interferometer scrutinizing the range of masses fundamental to understanding
the origin and growth of supermassive black holes. By extracting the
information carried by the gravitational radiation, we can determine the mass
and spin of the central MBH with unprecedented precision and we can determine
how the holes "eat" stars that happen to be near them.Comment: Update from the first version, 151 pages, accepted for publication @
Living Reviews in Relativit
The disruption of proteostasis in neurodegenerative diseases
Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio