1,633 research outputs found
A computational model of the hypothalamic - pituitary - gonadal axis in female fathead minnows (Pimephales promelas) exposed to 17α-ethynylestradiol and 17β-trenbolone
© 2011 Li et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.Background - Endocrine disrupting chemicals (e.g., estrogens, androgens and their mimics) are known to affect reproduction in fish. 17α-ethynylestradiol is a synthetic estrogen used in birth control pills. 17β-trenbolone is a relatively stable metabolite of trenbolone acetate, a synthetic androgen used as a growth promoter in livestock. Both 17α-ethynylestradiol and 17β-trenbolone have been found in the aquatic environment and affect fish reproduction. In this study, we developed a physiologically-based computational model for female fathead minnows (FHM, Pimephales promelas), a small fish species used in ecotoxicology, to simulate how estrogens (i.e., 17α-ethynylestradiol) or androgens (i.e., 17β-trenbolone) affect reproductive endpoints such as plasma concentrations of steroid hormones (e.g., 17β-estradiol and testosterone) and vitellogenin (a precursor to egg yolk proteins).
Results - Using Markov Chain Monte Carlo simulations, the model was calibrated with data from unexposed, 17α-ethynylestradiol-exposed, and 17β-trenbolone-exposed FHMs. Four Markov chains were simulated, and the chains for each calibrated model parameter (26 in total) converged within 20,000 iterations. With the converged parameter values, we evaluated the model's predictive ability by simulating a variety of independent experimental data. The model predictions agreed with the experimental data well.
Conclusions - The physiologically-based computational model represents the hypothalamic-pituitary-gonadal axis in adult female FHM robustly. The model is useful to estimate how estrogens (e.g., 17α-ethynylestradiol) or androgens (e.g., 17β-trenbolone) affect plasma concentrations of 17β-estradiol, testosterone and vitellogenin, which are important determinants of fecundity in fish.The Medical Research Foundation of Oregon, U.S. Environmental Protection
Agency, and the National Center for Computational Toxicology of the EPA Office of
Research and Development
Hidden Yangian symmetry in sigma model on squashed sphere
We discuss a hidden symmetry of a two-dimensional sigma model on a squashed
S^3. The SU(2) current can be improved so that it can be regarded as a flat
connection. Then we can obtain an infinite number of conserved non-local
charges and show the Yangian algebra by directly checking the Serre relation.
This symmetry is also deduced from the coset structure of the squashed sphere.
The same argument is applicable to the warped AdS_3 spaces via double Wick
rotations.Comment: 11 pages, 1 figure, typos corrected, references adde
Reversing non-local transport through a superconductor by electromagnetic excitations
Superconductors connected to normal metallic electrodes at the nanoscale
provide a potential source of non-locally entangled electron pairs. Such states
would arise from Cooper pairs splitting into two electrons with opposite spins
tunnelling into different leads. In an actual system the detection of these
processes is hindered by the elastic transmission of individual electrons
between the leads, yielding an opposite contribution to the non-local
conductance. Here we show that electromagnetic excitations on the
superconductor can play an important role in altering the balance between these
two processes, leading to a dominance of one upon the other depending on the
spatial symmetry of these excitations. These findings allow to understand some
intriguing recent experimental results and open the possibility to control
non-local transport through a superconductor by an appropriate design of the
experimental geometry.Comment: 6 pages, 3 figure
On the classical equivalence of monodromy matrices in squashed sigma model
We proceed to study the hybrid integrable structure in two-dimensional
non-linear sigma models with target space three-dimensional squashed spheres. A
quantum affine algebra and a pair of Yangian algebras are realized in the sigma
models and, according to them, there are two descriptions to describe the
classical dynamics 1) the trigonometric description and 2) the rational
description, respectively. For every description, a Lax pair is constructed and
the associated monodromy matrix is also constructed. In this paper we show the
gauge-equivalence of the monodromy matrices in the trigonometric and rational
description under a certain relation between spectral parameters and the
rescalings of sl(2) generators.Comment: 32pages, 3figures, references added, introduction and discussion
sections revise
Classical integrability of Schrodinger sigma models and q-deformed Poincare symmetry
We discuss classical integrable structure of two-dimensional sigma models
which have three-dimensional Schrodinger spacetimes as target spaces. The
Schrodinger spacetimes are regarded as null-like deformations of AdS_3. The
original AdS_3 isometry SL(2,R)_L x SL(2,R)_R is broken to SL(2,R)_L x U(1)_R
due to the deformation. According to this symmetry, there are two descriptions
to describe the classical dynamics of the system, 1) the SL(2,R)_L description
and 2) the enhanced U(1)_R description. In the former 1), we show that the
Yangian symmetry is realized by improving the SL(2,R)_L Noether current. Then a
Lax pair is constructed with the improved current and the classical
integrability is shown by deriving the r/s-matrix algebra. In the latter 2), we
find a non-local current by using a scaling limit of warped AdS_3 and that it
enhances U(1)_R to a q-deformed Poincare algebra. Then another Lax pair is
presented and the corresponding r/s-matrices are also computed. The two
descriptions are equivalent via a non-local map.Comment: 20 pages, no figure, further clarification and references adde
UNCLES: Method for the identification of genes differentially consistently co-expressed in a specific subset of datasets
Background: Collective analysis of the increasingly emerging gene expression datasets are required. The recently proposed binarisation of consensus partition matrices (Bi-CoPaM) method can combine clustering results from multiple datasets to identify the subsets of genes which are consistently co-expressed in all of the provided datasets in a tuneable manner. However, results validation and parameter setting are issues that complicate the design of such methods. Moreover, although it is a common practice to test methods by application to synthetic datasets, the mathematical models used to synthesise such datasets are usually based on approximations which may not always be sufficiently representative of real datasets. Results: Here, we propose an unsupervised method for the unification of clustering results from multiple datasets using external specifications (UNCLES). This method has the ability to identify the subsets of genes consistently co-expressed in a subset of datasets while being poorly co-expressed in another subset of datasets, and to identify the subsets of genes consistently co-expressed in all given datasets. We also propose the M-N scatter plots validation technique and adopt it to set the parameters of UNCLES, such as the number of clusters, automatically. Additionally, we propose an approach for the synthesis of gene expression datasets using real data profiles in a way which combines the ground-truth-knowledge of synthetic data and the realistic expression values of real data, and therefore overcomes the problem of faithfulness of synthetic expression data modelling. By application to those datasets, we validate UNCLES while comparing it with other conventional clustering methods, and of particular relevance, biclustering methods. We further validate UNCLES by application to a set of 14 real genome-wide yeast datasets as it produces focused clusters that conform well to known biological facts. Furthermore, in-silico-based hypotheses regarding the function of a few previously unknown genes in those focused clusters are drawn. Conclusions: The UNCLES method, the M-N scatter plots technique, and the expression data synthesis approach will have wide application for the comprehensive analysis of genomic and other sources of multiple complex biological datasets. Moreover, the derived in-silico-based biological hypotheses represent subjects for future functional studies.The National Institute for Health Research (NIHR) under its Programme Grants for Applied Research
Programme (Grant Reference Number RP-PG-0310-1004)
String Theory on Warped AdS_3 and Virasoro Resonances
We investigate aspects of holographic duals to time-like warped AdS_3
space-times--which include G\"odel's universe--in string theory. Using
worldsheet techniques similar to those that have been applied to AdS_3
backgrounds, we are able to identify space-time symmetry algebras that act on
the dual boundary theory. In particular, we always find at least one Virasoro
algebra with computable central charge. Interestingly, there exists a dense set
of points in the moduli space of these models in which there is actually a
second commuting Virasoro algebra, typically with different central charge than
the first. We analyze the supersymmetry of the backgrounds, finding related
enhancements, and comment on possible interpretations of these results. We also
perform an asymptotic symmetry analysis at the level of supergravity, providing
additional support for the worldsheet analysis.Comment: 24 pages + appendice
Warped black holes in 3D general massive gravity
We study regular spacelike warped black holes in the three dimensional
general massive gravity model, which contains both the gravitational
Chern-Simons term and the linear combination of curvature squared terms
characterizing the new massive gravity besides the Einstein-Hilbert term. The
parameters of the metric are found by solving a quartic equation constrained by
an inequality that imposes the absence of closed timelike curves. Explicit
expressions for the central charges are suggested by exploiting the fact that
these black holes are discrete quotients of spacelike warped AdS(3) and a known
formula for the entropy. Previous results obtained separately in topological
massive gravity and in new massive gravity are recovered as special cases.Comment: 38 pages, 7 figures. v2: minor changes, added refs and an appendix on
self-dual and null z-warped black hole
The classical origin of quantum affine algebra in squashed sigma models
We consider a quantum affine algebra realized in two-dimensional non-linear
sigma models with target space three-dimensional squashed sphere. Its affine
generators are explicitly constructed and the Poisson brackets are computed.
The defining relations of quantum affine algebra in the sense of the Drinfeld
first realization are satisfied at classical level. The relation to the
Drinfeld second realization is also discussed including higher conserved
charges. Finally we comment on a semiclassical limit of quantum affine algebra
at quantum level.Comment: 25 pages, 2 figure
Association between Knops blood group polymorphisms and susceptibility to malaria in an endemic area of the Brazilian Amazon
Complement receptor 1 (CR1) gene polymorphisms that are associated with Knops blood group antigens may influence the binding of Plasmodium parasites to erythrocytes, thereby affecting susceptibility to malaria. The aim of this study was to evaluate the genotype and allele and haplotype frequencies of single-nucleotide polymorphisms (SNPs) of Knops blood group antigens and examine their association with susceptibility to malaria in an endemic area of Brazil. One hundred and twenty-six individuals from the Brazilian Amazon were studied. The CR1-genomic fragment was amplified by PCR and six SNPs and haplotypes were identified after DNA sequence analysis. Allele and haplotype frequencies revealed that the Knb allele and H8 haplotype were possibly associated with susceptibility to Plasmodium falciparum. The odds ratios were reasonably high, suggesting a potentially important association between two Knops blood antigens (Knb and KAM+) that confer susceptibility to P. falciparum in individuals from the Brazilian Amazon
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