279 research outputs found
Rapid entry and downregulation of T Cells in the central nervous system During the reinduction of experimental autoimmune encephalomyelitis
We investigated the mechanisms whereby a previous attack of experimental autoimmune encephalomyelitis (EAE) modifies a subsequent attack in the Lewis rat. Active immunization with myelin basic protein (MBP) and complete Freund's adjuvant 28 days after the passive transfer of MBP-sensitized spleen cells induced a second episode of EAE, which occurred earlier than in naive control animals, but was less severe overall. The pattern of neurological signs was also different in rechallenged rats, which had less severe tail and hindlimb weakness but more severe forelimb weakness. In rechallenged rats, inflammation was more severe in the cervical spinal cord, cerebellum, brainstem and cerebrum, but less severe in the lumbar spinal cord, than in controls. The early onset of EAE in rechallenged rats was explained by a memory T cell response to MBP72-89 in the draining lymph node and spleen, and by the enhanced entry of T cells into the central nervous system (CNS). However, the number of alpha beta T cells in the spinal cord of rechallenged rats declined faster than in controls, especially in the lumbosacral cord, where the number of V beta 8.2+ T cells and the frequency of T cells reactive to MBP72-89 rapidly decreased, indicating rapid downregulation of the immune response in the previously inflamed spinal cord. Apoptosis of inflammatory cells in the CNS was increased in the rechallenged rats and is likely to contribute to this downregulation. Furthermore, during the disease course the generation of encephalitogenic T cells in the peripheral lymphoid organs was limited compared with controls. Thus, a previous attack of EAE modifies a subsequent attack through the interaction of the following processes: a memory T cell response to MBP; facilitated T cell entry into the CNS; downregulation of the immune response in the CNS, including increased apoptosis of inflammatory cells; and a limited generation of encephalitogenic T cells in the peripheral lymphoid organs
Debris disk size distributions: steady state collisional evolution with P-R drag and other loss processes
We present a new scheme for determining the shape of the size distribution,
and its evolution, for collisional cascades of planetesimals undergoing
destructive collisions and loss processes like Poynting-Robertson drag. The
scheme treats the steady state portion of the cascade by equating mass loss and
gain in each size bin; the smallest particles are expected to reach steady
state on their collision timescale, while larger particles retain their
primordial distribution. For collision-dominated disks, steady state means that
mass loss rates in logarithmic size bins are independent of size. This
prescription reproduces the expected two phase size distribution, with ripples
above the blow-out size, and above the transition to gravity-dominated
planetesimal strength. The scheme also reproduces the expected evolution of
disk mass, and of dust mass, but is computationally much faster than evolving
distributions forward in time. For low-mass disks, P-R drag causes a turnover
at small sizes to a size distribution that is set by the redistribution
function (the mass distribution of fragments produced in collisions). Thus
information about the redistribution function may be recovered by measuring the
size distribution of particles undergoing loss by P-R drag, such as that traced
by particles accreted onto Earth. Although cross-sectional area drops with
1/age^2 in the PR-dominated regime, dust mass falls as 1/age^2.8, underlining
the importance of understanding which particle sizes contribute to an
observation when considering how disk detectability evolves. Other loss
processes are readily incorporated; we also discuss generalised power law loss
rates, dynamical depletion, realistic radiation forces and stellar wind drag.Comment: Accepted for publication by Celestial Mechanics and Dynamical
Astronomy (special issue on EXOPLANETS
Gamma-ray Observations Under Bright Moonlight with VERITAS
Imaging atmospheric Cherenkov telescopes (IACTs) are equipped with sensitive
photomultiplier tube (PMT) cameras. Exposure to high levels of background
illumination degrades the efficiency of and potentially destroys these
photo-detectors over time, so IACTs cannot be operated in the same
configuration in the presence of bright moonlight as under dark skies. Since
September 2012, observations have been carried out with the VERITAS IACTs under
bright moonlight (defined as about three times the night-sky-background (NSB)
of a dark extragalactic field, typically occurring when Moon illumination >
35%) in two observing modes, firstly by reducing the voltage applied to the
PMTs and, secondly, with the addition of ultra-violet (UV) bandpass filters to
the cameras. This has allowed observations at up to about 30 times previous NSB
levels (around 80% Moon illumination), resulting in 30% more observing time
between the two modes over the course of a year. These additional observations
have already allowed for the detection of a flare from the 1ES 1727+502 and for
an observing program targeting a measurement of the cosmic-ray positron
fraction. We provide details of these new observing modes and their performance
relative to the standard VERITAS observations
Hydrophobic and ionic-interactions in bulk and confined water with implications for collapse and folding of proteins
Water and water-mediated interactions determine thermodynamic and kinetics of
protein folding, protein aggregation and self-assembly in confined spaces. To
obtain insights into the role of water in the context of folding problems, we
describe computer simulations of a few related model systems. The dynamics of
collapse of eicosane shows that upon expulsion of water the linear hydrocarbon
chain adopts an ordered helical hairpin structure with 1.5 turns. The structure
of dimer of eicosane molecules has two well ordered helical hairpins that are
stacked perpendicular to each other. As a prelude to studying folding in
confined spaces we used simulations to understand changes in hydrophobic and
ionic interactions in nano droplets. Solvation of hydrophobic and charged
species change drastically in nano water droplets. Hydrophobic species are
localized at the boundary. The tendency of ions to be at the boundary where
water density is low increases as the charge density decreases. Interaction
between hydrophobic, polar, and charged residue are also profoundly altered in
confined spaces. Using the results of computer simulations and accounting for
loss of chain entropy upon confinement we argue and then demonstrate, using
simulations in explicit water, that ordered states of generic amphiphilic
peptide sequences should be stabilized in cylindrical nanopores
Anthropogenic Space Weather
Anthropogenic effects on the space environment started in the late 19th
century and reached their peak in the 1960s when high-altitude nuclear
explosions were carried out by the USA and the Soviet Union. These explosions
created artificial radiation belts near Earth that resulted in major damages to
several satellites. Another, unexpected impact of the high-altitude nuclear
tests was the electromagnetic pulse (EMP) that can have devastating effects
over a large geographic area (as large as the continental United States). Other
anthropogenic impacts on the space environment include chemical release ex-
periments, high-frequency wave heating of the ionosphere and the interaction of
VLF waves with the radiation belts. This paper reviews the fundamental physical
process behind these phenomena and discusses the observations of their impacts.Comment: 71 pages, 35 figure
Genetic variants in anti-MĂĽllerian hormone-related genes and breast cancer risk: results from the AMBER consortium
Purpose: Circulating anti-Müllerian hormone (AMH) levels are positively associated with time to menopause and breast cancer risk. We examined breast cancer associations with single nucleotide polymorphisms (SNPs) in the AMH gene or its receptor genes, ACVR1 and AMHR2, among African American women. Methods: In the AMBER consortium, we tested 65 candidate SNPs, and 1130 total variants, in or near AMH, ACVR1, and AMHR2 and breast cancer risk. Overall, 3649 cases and 4230 controls contributed to analyses. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were calculated using multivariable logistic regression. Results: After correction for multiple comparisons (false-discovery rate of 5%), there were no statistically significant associations with breast cancer risk. Without correction for multiple testing, four candidate SNPs in ACVR1 and one near AMH were associated with breast cancer risk. In ACVR1, rs13395576[C] was associated with lower breast cancer risk overall (OR 0.84; 95% CI 0.72, 0.97) and for ER+ disease (OR 0.75; CI 0.62, 0.89) (p < 0.05). Rs1220110[A] and rs1220134[T] each had ORs of 0.89–0.90 for postmenopausal and ER+ breast cancer (p ≤ 0.03). Conversely, rs1682130[T] was associated with higher risk of ER+ breast cancer (OR 1.17; 95% CI 1.04, 1.32). Near AMH, rs6510652[T] had ORs of 0.85–0.90 for breast cancer overall and after menopause (p ≤ 0.02). Conclusions: The present results, from a large study of African American women, provide limited support for an association between AMH-related polymorphisms and breast cancer risk and require replication in other studies
Sociocultural considerations in aging men's health: implications and recommendations for the clinician
http://dx.doi.org/10.1016/j.jomh.2009.07.00
Recommended from our members
Energetic particle influence on the Earth's atmosphere
This manuscript gives an up-to-date and comprehensive overview of the effects of energetic particle precipitation (EPP) onto the whole atmosphere, from the lower thermosphere/mesosphere through the stratosphere and troposphere, to the surface. The paper summarizes the different sources and energies of particles, principally
galactic cosmic rays (GCRs), solar energetic particles (SEPs) and energetic electron precipitation (EEP). All the proposed mechanisms by which EPP can affect the atmosphere
are discussed, including chemical changes in the upper atmosphere and lower thermosphere, chemistry-dynamics feedbacks, the global electric circuit and cloud formation. The role of energetic particles in Earth’s atmosphere is a multi-disciplinary problem that requires expertise from a range of scientific backgrounds. To assist with this synergy, summary tables are provided, which are intended to evaluate the level of current knowledge of the effects of energetic particles on processes in the entire atmosphere
- …