423 research outputs found
Informing aerial total counts with demographic models: population growth of Serengeti elephants not explained purely by demography
Conservation management is strongly shaped by the interpretation of population trends. In the Serengeti ecosystem, Tanzania, aerial total counts indicate a striking increase in elephant abundance compared to all previous censuses. We developed a simple age-structured population model to guide interpretation of this reported increase, focusing on three possible causes: (1) in situ population growth, (2) immigration from Kenya, and (3) differences in counting methodologies over time. No single cause, nor the combination of two causes, adequately explained the observed population growth. Under the assumptions of maximum in situ growth and detection bias of 12.7% in previous censuses, conservative estimates of immigration from Kenya were between 250 and 1,450 individuals. Our results highlight the value of considering demography when drawing conclusions about the causes of population trends. The issues we illustrate apply to other species that have undergone dramatic changes in abundance, as well as many elephant populations
Practical guide to glucocorticoid induced hyperglycaemia and diabetes
Glucocorticoids, also known as steroids, are a class of anti-inflammatory drugs utilised widely in clinical practice for a variety of conditions. They are associated with a range of side effects including abnormalities of glucose metabolism. Multiple guidelines have been published to illustrate best management of glucocorticoid-induced hyperglycaemia and diabetes in a variety of settings. This article discusses current best clinical practice including diagnosis, investigations and ongoing management of glucocorticoid-induced dysglycaemia in both in- and outpatient settings
Indirect Impact of PD-1/PD-L1 Blockade on a Murine Model of NK Cell Exhaustion
The induction of exhaustion on effector immune cells is an important limiting factor
for cancer immunotherapy efficacy as these cells undergo a hierarchical loss of
proliferation and cytolytic activity due to chronic stimulation. Targeting PD-1 has shown
unprecedented clinical benefits for many cancers, which have been attributed to the
prevention of immune suppression and exhaustion with enhanced anti-tumor responses.
In this study, we sought to evaluate the role of the PD-1/PD-L1 pathway in murine
natural killer (NK) cell activation, function, and exhaustion. In an in vivo IL-2-dependent
exhaustion mouse model, neutralization of the PD-1/PD-L1 pathway improved NK
cell activation after chronic stimulation when compared to control-treated mice. These
cells displayed higher proliferative capabilities and enhanced granzyme B production.
However, the blockade of these molecules during long-term in vitro IL-2 stimulation did
not alter the progression of NK cell exhaustion (NCE), suggesting an indirect involvement
of PD-1/PD-L1 on NCE. Given the expansion of CD8 T cells and regulatory T cells (Tregs)
observed upon acute and chronic stimulation with IL-2, either of these two populations
could influence NK cell homeostasis after PD-L1/PD-1 therapy. Importantly, CD8 T cell
activation and functional phenotype were indeed enhanced by PD-1/PD-L1 therapy,
particularly with anti-PD-1 treatment that resulted in the highest upregulation of CD25
during chronic stimulation and granted an advantage for IL-2 over NK cells. These
results indicate a competition for resources between NK and CD8 T cells that arguably
delays the onset of NCE rather than improving its activation during chronic stimulation.
Supporting this notion, the depletion of CD8 T cells reversed the benefits of PD-1 therapy
on chronically stimulated NK cells. These data suggest a bystander effect of anti-PD1
on NK cells, resulting from the global competition that exists between NK and CD8 T
cells for IL-2 as a key regulator of these cellsâ activation. Thus, achieving an equilibrium
between these immune cells might be important to accomplish long-term efficacy during
anti-PD-1/IL-2 therapy
Thermodynamic Description of the Relaxation of Two-Dimensional Euler Turbulence Using Tsallis Statistics
Euler turbulence has been experimentally observed to relax to a
metaequilibrium state that does not maximize the Boltzmann entropy, but rather
seems to minimize enstrophy. We show that a recent generalization of
thermodynamics and statistics due to Tsallis is capable of explaining this
phenomenon in a natural way. The maximization of the generalized entropy
for this system leads to precisely the same profiles predicted by the
Restricted Minimum Enstrophy theory of Huang and Driscoll. This makes possible
the construction of a comprehensive thermodynamic description of Euler
turbulence.Comment: 15 pages, RevTe
Are social phobia and paranoia related, and which comes first?
.001), also with a dose response, i.e. more PS symptoms yield more SPh symptoms. PS emerging after SPh was not significant. This study confirmed the association of SPh and PS in a general population. Possibly this is caused by shared underlying psychological and behavioural processes. There was some indication that paranoid ideation precedes the development of SPh, but this must be considered with caution. Clinical implications are discussed. Keywords: paranoid symptoms; social phobia; comorbidity; general population surve
The Volume of some Non-spherical Horizons and the AdS/CFT Correspondence
We calculate the volumes of a large class of Einstein manifolds, namely
Sasaki-Einstein manifolds which are the bases of Ricci-flat affine cones
described by polynomial embedding relations in C^n. These volumes are important
because they allow us to extend and test the AdS/CFT correspondence. We use
these volumes to extend the central charge calculation of Gubser (1998) to the
generalized conifolds of Gubser, Shatashvili, and Nekrasov (1999). These
volumes also allow one to quantize precisely the D-brane flux of the AdS
supergravity solution. We end by demonstrating a relationship between the
volumes of these Einstein spaces and the number of holomorphic polynomials
(which correspond to chiral primary operators in the field theory dual) on the
corresponding affine cone.Comment: 25 pp, LaTeX, 1 figure, v2: refs adde
Reporters for the analysis of N-glycosylation in Candida albicans
Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.Peer reviewedPublisher PD
Dibaryon Spectroscopy
The AdS/CFT correspondence relates dibaryons in superconformal gauge theories
to holomorphic curves in Kaehler-Einstein surfaces. The degree of the
holomorphic curves is proportional to the gauge theory conformal dimension of
the dibaryons. Moreover, the number of holomorphic curves should match, in an
appropriately defined sense, the number of dibaryons. Using AdS/CFT backgrounds
built from the generalized conifolds of Gubser, Shatashvili, and Nekrasov
(1999), we show that the gauge theory prediction for the dimension of
dibaryonic operators does indeed match the degree of the corresponding
holomorphic curves. For AdS/CFT backgrounds built from cones over del Pezzo
surfaces, we are able to match the degree of the curves to the conformal
dimension of dibaryons for the n'th del Pezzo surface, n=1,2,...,6. Also, for
the del Pezzos and the A_k type generalized conifolds, for the dibaryons of
smallest conformal dimension, we are able to match the number of holomorphic
curves with the number of possible dibaryon operators from gauge theory.Comment: 30 pages, 6 figures, corrected refs; v3 typos correcte
Rare genetic variation in UNC13A may modify survival in amyotrophic lateral sclerosis
Our objective was to identify whether rare genetic variation in amyotrophic lateral sclerosis (ALS) candidate survival genes modifies ALS survival. Candidate genes were selected based on evidence for modifying ALS survival. Each tail of the extreme 1.5% of survival was selected from the UK MND DNA Bank and all samples available underwent whole genome sequencing. A replication set from the Netherlands was used for validation. Sequences of candidate survival genes were extracted and variants passing quality control with a minor allele frequency â€0.05 were selected for association testing. Analysis was by burden testing using SKAT. Candidate survival genes UNC13A, KIFAP3, and EPHA4 were tested for association in a UK sample comprising 25 short survivors and 25 long survivors. Results showed that only SNVs in UNC13A were associated with survival (p = 6.57âĂâ10â3). SNV rs10419420:Gâ>âA was found exclusively in long survivors (3/25) and rs4808092:Gâ>âA exclusively in short survivors (4/25). These findings were not replicated in a Dutch sample. In conclusion, population specific rare variants of UNC13A may modulate survival in ALS
An optimization principle for deriving nonequilibrium statistical models of Hamiltonian dynamics
A general method for deriving closed reduced models of Hamiltonian dynamical
systems is developed using techniques from optimization and statistical
estimation. As in standard projection operator methods, a set of resolved
variables is selected to capture the slow, macroscopic behavior of the system,
and the family of quasi-equilibrium probability densities on phase space
corresponding to these resolved variables is employed as a statistical model.
The macroscopic dynamics of the mean resolved variables is determined by
optimizing over paths of these probability densities. Specifically, a cost
function is introduced that quantifies the lack-of-fit of such paths to the
underlying microscopic dynamics; it is an ensemble-averaged, squared-norm of
the residual that results from submitting a path of trial densities to the
Liouville equation. The evolution of the macrostate is estimated by minimizing
the time integral of the cost function. The value function for this
optimization satisfies the associated Hamilton-Jacobi equation, and it
determines the optimal relation between the statistical parameters and the
irreversible fluxes of the resolved variables, thereby closing the reduced
dynamics. The resulting equations for the macroscopic variables have the
generic form of governing equations for nonequilibrium thermodynamics, and they
furnish a rational extension of the classical equations of linear irreversible
thermodynamics beyond the near-equilibrium regime. In particular, the value
function is a thermodynamic potential that extends the classical dissipation
function and supplies the nonlinear relation between thermodynamics forces and
fluxes
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