522 research outputs found
Stellar Population Diagnostics of Elliptical Galaxy Formation
Major progress has been achieved in recent years in mapping the properties of
passively-evolving, early-type galaxies (ETG) from the local universe all the
way to redshift ~2. Here, age and metallicity estimates for local cluster and
field ETGs are reviewed as based on color-magnitude, color-sigma, and
fundamental plane relations, as well as on spectral-line indices diagnostics.
The results of applying the same tools at high redshifts are then discussed,
and their consistency with the low-redshift results is assessed. Most low- as
well as high-redshift (z~1) observations consistently indicate 1) a formation
redshift z>~3 for the bulk of stars in cluster ETGs, with their counterparts in
low-density environments being on average ~1-2 Gyr younger, i.e., formed at
z>~1.5-2, 2) the duration of the major star formation phase anticorrelates with
galaxy mass, and the oldest stellar populations are found in the most massive
galaxies. With increasing redshift there is evidence for a decrease in the
number density of ETGs, especially of the less massive ones, whereas existing
data appear to suggest that most of the most-massive ETGs were already fully
assembled at z~1. Beyond this redshift, the space density of ETGs starts
dropping significantly, and as ETGs disappear, a population of massive,
strongly clustered, starburst galaxies progressively becomes more and more
prominent, which makes them the likely progenitors to ETGs.Comment: To appear on Annual Review of Astronomy & Astrophysics, Vol. 44
(2006). 46 pages with 16 figures. Replaced version includes updated
references, few typos less, and replaces Fig. 11 and Fig. 16 which had been
skrewed u
Intra- and interfamily phenotypic diversity in pain syndromes associated with a gain-of-function variant of NaV1.7
<p>Abstract</p> <p>Background</p> <p>Sodium channel Na<sub>V</sub>1.7 is preferentially expressed within dorsal root ganglia (DRG), trigeminal ganglia and sympathetic ganglion neurons and their fine-diamter axons, where it acts as a threshold channel, amplifying stimuli such as generator potentials in nociceptors. Gain-of-function mutations and variants (single amino acid substitutions) of Na<sub>V</sub>1.7 have been linked to three pain syndromes: Inherited Erythromelalgia (IEM), Paroxysmal Extreme Pain Disorder (PEPD), and Small Fiber Neuropathy (SFN). IEM is characterized clinically by burning pain and redness that is usually focused on the distal extremities, precipitated by mild warmth and relieved by cooling, and is caused by mutations that hyperpolarize activation, slow deactivation, and enhance the channel ramp response. PEPD is characterized by perirectal, periocular or perimandibular pain, often triggered by defecation or lower body stimulation, and is caused by mutations that severely impair fast-inactivation. SFN presents a clinical picture dominated by neuropathic pain and autonomic symptoms; gain-of-function variants have been reported to be present in approximately 30% of patients with biopsy-confirmed idiopathic SFN, and functional testing has shown altered fast-inactivation, slow-inactivation or resurgent current. In this paper we describe three patients who house the Na<sub>V</sub>1.7/I228M variant.</p> <p>Methods</p> <p>We have used clinical assessment of patients, quantitative sensory testing and skin biopsy to study these patients, including two siblings in one family, in whom genomic screening demonstrated the I228M Na<sub>V</sub>1.7 variant. Electrophysiology (voltage-clamp and current-clamp) was used to test functional effects of the variant channel.</p> <p>Results</p> <p>We report three different clinical presentations of the I228M Na<sub>V</sub>1.7 variant: presentation with severe facial pain, presentation with distal (feet, hands) pain, and presentation with scalp discomfort in three patients housing this Na<sub>V</sub>1.7 variant, two of which are from a single family. We also demonstrate that the Na<sub>V</sub>1.7/I228M variant impairs slow-inactivation, and produces hyperexcitability in both trigeminal ganglion and DRG neurons.</p> <p>Conclusion</p> <p>Our results demonstrate intra- and interfamily phenotypic diversity in pain syndromes produced by a gain-of-function variant of Na<sub>V</sub>1.7.</p
Accreting Protoplanets in the LkCa 15 Transition Disk
Exoplanet detections have revolutionized astronomy, offering new insights
into solar system architecture and planet demographics. While nearly 1900
exoplanets have now been discovered and confirmed, none are still in the
process of formation. Transition discs, protoplanetary disks with inner
clearings best explained by the influence of accreting planets, are natural
laboratories for the study of planet formation. Some transition discs show
evidence for the presence of young planets in the form of disc asymmetries or
infrared sources detected within their clearings, as in the case of LkCa 15.
Attempts to observe directly signatures of accretion onto protoplanets have
hitherto proven unsuccessful. Here we report adaptive optics observations of
LkCa 15 that probe within the disc clearing. With accurate source positions
over multiple epochs spanning 2009 - 2015, we infer the presence of multiple
companions on Keplerian orbits. We directly detect H{\alpha} emission from the
innermost companion, LkCa 15 b, evincing hot (~10,000 K) gas falling deep into
the potential well of an accreting protoplanet.Comment: 35 pages, 3 figures, 1 table, 9 extended data item
Debris Disks: Probing Planet Formation
Debris disks are the dust disks found around ~20% of nearby main sequence
stars in far-IR surveys. They can be considered as descendants of
protoplanetary disks or components of planetary systems, providing valuable
information on circumstellar disk evolution and the outcome of planet
formation. The debris disk population can be explained by the steady
collisional erosion of planetesimal belts; population models constrain where
(10-100au) and in what quantity (>1Mearth) planetesimals (>10km in size)
typically form in protoplanetary disks. Gas is now seen long into the debris
disk phase. Some of this is secondary implying planetesimals have a Solar
System comet-like composition, but some systems may retain primordial gas.
Ongoing planet formation processes are invoked for some debris disks, such as
the continued growth of dwarf planets in an unstirred disk, or the growth of
terrestrial planets through giant impacts. Planets imprint structure on debris
disks in many ways; images of gaps, clumps, warps, eccentricities and other
disk asymmetries, are readily explained by planets at >>5au. Hot dust in the
region planets are commonly found (<5au) is seen for a growing number of stars.
This dust usually originates in an outer belt (e.g., from exocomets), although
an asteroid belt or recent collision is sometimes inferred.Comment: Invited review, accepted for publication in the 'Handbook of
Exoplanets', eds. H.J. Deeg and J.A. Belmonte, Springer (2018
A painful neuropathy-associated Nav1.7 mutant leads to time-dependent degeneration of small-diameter axons associated with intracellular Ca2+ dysregulation and decrease in ATP levels
Small fiber neuropathy is a painful sensory nervous system disorder characterized by damage to unmyelinated C- and thinly
myelinated Ad- nerve fibers, clinically manifested by burning pain in the distal extremities and dysautonomia. The clinical
onset in adulthood suggests a time-dependent process. The mechanisms that underlie nerve fiber injury in small fiber
neuropathy are incompletely understood, although roles for energetic stress have been suggested. In the present study,
we report time-dependent degeneration of neurites from dorsal root ganglia neurons in culture expressing small fiber
neuropathy-associated G856D mutant Nav1.7 channels and demonstrate a time-dependent increase in intracellular calcium
levels [Ca2\ufe]i and reactive oxygen species, together with a decrease in ATP levels. Together with a previous clinical report of
burning pain in the feet and hands associated with reduced levels of Na\ufe/K\ufe-ATPase in humans with high altitude sickness,
the present results link energetic stress and reactive oxygen species production with the development of a painful neuropathy
that preferentially affects small-diameter axons
Heartbeat of the Sun from Principal Component Analysis and prediction of solar activity on a millenium timescale
yesWe derive two principal components (PCs) of temporal magnetic field variations over the solar
cycles 21–24 from full disk magnetograms covering about 39% of data variance, with σ = 0.67.
These PCs are attributed to two main magnetic waves travelling from the opposite hemispheres
with close frequencies and increasing phase shift. Using symbolic regeression analysis we also derive
mathematical formulae for these waves and calculate their summary curve which we show is linked
to solar activity index. Extrapolation of the PCs backward for 800 years reveals the two 350-year
grand cycles superimposed on 22 year-cycles with the features showing a remarkable resemblance
to sunspot activity reported in the past including the Maunder and Dalton minimum. The summary
curve calculated for the next millennium predicts further three grand cycles with the closest grand
minimum occurring in the forthcoming cycles 26–27 with the two magnetic field waves separating
into the opposite hemispheres leading to strongly reduced solar activity. These grand cycle variations
are probed by α − Ω dynamo model with meridional circulation. Dynamo waves are found generated
with close frequencies whose interaction leads to beating effects responsible for the grand cycles
(350–400 years) superimposed on a standard 22 year cycle. This approach opens a new era in
investigation and confident prediction of solar activity on a millenium timescale
Vaccination with Plasmodium knowlesi AMA1 Formulated in the Novel Adjuvant Co-Vaccine HT™ Protects against Blood-Stage Challenge in Rhesus Macaques
Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a leading blood stage vaccine candidate. Plasmodium knowlesi AMA1 (PkAMA1) was produced and purified using similar methodology as for clinical grade PfAMA1 yielding a pure, conformational intact protein. Combined with the adjuvant CoVaccine HT™, PkAMA1 was found to be highly immunogenic in rabbits and the efficacy of the PkAMA1 was subsequently tested in a rhesus macaque blood-stage challenge model. Six rhesus monkeys were vaccinated with PkAMA1 and a control group of 6 were vaccinated with PfAMA1. A total of 50 µg AMA1 was administered intramuscularly three times at 4 week intervals. One of six rhesus monkeys vaccinated with PkAMA1 was able to control parasitaemia, upon blood stage challenge with P. knowlesi H-strain. Four out of the remaining five showed a delay in parasite onset that correlated with functional antibody titres. In the PfAMA1 vaccinated control group, five out of six animals had to be treated with antimalarials 8 days after challenge; one animal did not become patent during the challenge period. Following a rest period, animals were boosted and challenged again. Four of the six rhesus monkeys vaccinated with PkAMA1 were able to control the parasitaemia, one had a delayed onset of parasitaemia and one animal was not protected, while all control animals required treatment. To confirm that the control of parasitaemia was AMA1-related, animals were allowed to recover, boosted and re-challenged with P. knowlesi Nuri strain. All control animals had to be treated with antimalarials by day 8, while five out of six PkAMA1 vaccinated animals were able to control parasitaemia. This study shows that: i) Yeast-expressed PkAMA1 can protect against blood stage challenge; ii) Functional antibody levels as measured by GIA correlated inversely with the day of onset and iii) GIA IC50 values correlated with estimated in vivo growth rates
Is annual surveillance of all treated hypothyroid patients necessary?
Peer reviewedPublisher PD
A Longitudinal Study of Medicaid Coverage for Tobacco Dependence Treatments in Massachusetts and Associated Decreases in Hospitalizations for Cardiovascular Disease
Thomas Land and colleagues show that among Massachusetts Medicaid subscribers, use of a comprehensive tobacco cessation pharmacotherapy benefit was followed by a substantial decrease in claims for hospitalizations for acute myocardial infarction and acute coronary heart disease
A review of elliptical and disc galaxy structure, and modern scaling laws
A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their
models to describe the radial distribution of stars in `nebulae'. This article
reviews the progress since then, providing both an historical perspective and a
contemporary review of the stellar structure of bulges, discs and elliptical
galaxies. The quantification of galaxy nuclei, such as central mass deficits
and excess nuclear light, plus the structure of dark matter halos and cD galaxy
envelopes, are discussed. Issues pertaining to spiral galaxies including dust,
bulge-to-disc ratios, bulgeless galaxies, bars and the identification of
pseudobulges are also reviewed. An array of modern scaling relations involving
sizes, luminosities, surface brightnesses and stellar concentrations are
presented, many of which are shown to be curved. These 'redshift zero'
relations not only quantify the behavior and nature of galaxies in the Universe
today, but are the modern benchmark for evolutionary studies of galaxies,
whether based on observations, N-body-simulations or semi-analytical modelling.
For example, it is shown that some of the recently discovered compact
elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to
appear in "Planets, Stars and Stellar
Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references
incl. many somewhat forgotten, pioneer papers. Original submission to
Springer: 07-June-201
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