4,439 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
Why are MD simulated protein folding times wrong?
The question of significant deviations of protein folding times simulated using molecular dynamics from experimental values is investigated. It is shown that in the framework of Markov State Model (MSM) describing the conformational dynamics of peptides and proteins, the folding time is very sensitive to the simulation model parameters, such as forcefield and temperature. Using two peptides as examples, we show that the deviations in the folding times can reach an order of magnitude for modest variations of the molecular model. We, therefore, conclude that the folding rate values obtained in molecular dynamics simulations have to be treated with care
Nesiritide: Harmful or Harmless?
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90328/1/phco.26.10.1465.pd
Transformation of spin information into large electrical signals via carbon nanotubes
Spin electronics (spintronics) exploits the magnetic nature of the electron,
and is commercially exploited in the spin valves of disc-drive read heads.
There is currently widespread interest in using industrially relevant
semiconductors in new types of spintronic devices based on the manipulation of
spins injected into a semiconducting channel between a spin-polarized source
and drain. However, the transformation of spin information into large
electrical signals is limited by spin relaxation such that the magnetoresistive
signals are below 1%. We overcome this long standing problem in spintronics by
demonstrating large magnetoresistance effects of 61% at 5 K in devices where
the non-magnetic channel is a multiwall carbon nanotube that spans a 1.5 micron
gap between epitaxial electrodes of the highly spin polarized manganite
La0.7Sr0.3MnO3. This improvement arises because the spin lifetime in nanotubes
is long due the small spin-orbit coupling of carbon, because the high nanotube
Fermi velocity permits the carrier dwell time to not significantly exceed this
spin lifetime, because the manganite remains highly spin polarized up to the
manganite-nanotube interface, and because the interfacial barrier is of an
appropriate height. We support these latter statements regarding the interface
using density functional theory calculations. The success of our experiments
with such chemically and geometrically different materials should inspire
adventure in materials selection for some future spintronicsComment: Content highly modified. New title, text, conclusions, figures and
references. New author include
Gene therapy for carcinoma of the breast: Therapeutic genetic correction strategies
Gene therapy is a therapeutic approach that is designed to correct specific molecular defects that contribute to the cause or progression of cancer. Genes that are mutated or deleted in cancers include the cancer susceptibility genes p53 and BRCA1. Because mutational inactivation of gene function is specific to tumor cells in these settings, cancer gene correction strategies may provide an opportunity for selective targeting without significant toxicity for normal nontumor cells. Both p53 and BRCA1 appear to inhibit cancer cells that lack mutations in these genes, suggesting that the so-called gene correction strategies may have broader potential than initially believed. Increasing knowledge of cancer genetics has identified these and other genes as potential targets for gene replacement therapy. Initial patient trials of p53 and BRCA1 gene therapy have provided some indications of potential efficacy, but have also identified areas of basic and clinical research that are needed before these approaches may be widely used in patient care
A Systematic Review of Online Sex Addiction and Clinical Treatments Using CONSORT Evaluation
Researchers have suggested that the advances of the Internet over the past two decades have gradually eliminated traditional offline methods of obtaining sexual material. Additionally, research on cybersex and/or online sex addictions has increased alongside the development of online technology. The present study extended the findings from Griffiths’ (2012) systematic empirical review of online sex addiction by additionally investigating empirical studies that implemented and/or documented clinical treatments for online sex addiction in adults. A total of nine studies were identified and then each underwent a CONSORT evaluation. The main findings of the present review provide some evidence to suggest that some treatments (both psychological and/or pharmacological) provide positive outcomes among those experiencing difficulties with online sex addiction. Similar to Griffiths’ original review, this study recommends that further research is warranted to establish the efficacy of empirically driven treatments for online sex addiction
Topological crystalline insulator states in Pb(1-x)Sn(x)Se
Topological insulators are a novel class of quantum materials in which
time-reversal symmetry, relativistic (spin-orbit) effects and an inverted band
structure result in electronic metallic states on the surfaces of bulk
crystals. These helical states exhibit a Dirac-like energy dispersion across
the bulk bandgap, and they are topologically protected. Recent theoretical
proposals have suggested the existence of topological crystalline insulators, a
novel class of topological insulators in which crystalline symmetry replaces
the role of time-reversal symmetry in topological protection [1,2]. In this
study, we show that the narrow-gap semiconductor Pb(1-x)Sn(x)Se is a
topological crystalline insulator for x=0.23. Temperature-dependent
magnetotransport measurements and angle-resolved photoelectron spectroscopy
demonstrate that the material undergoes a temperature-driven topological phase
transition from a trivial insulator to a topological crystalline insulator.
These experimental findings add a new class to the family of topological
insulators. We expect these results to be the beginning of both a considerable
body of additional research on topological crystalline insulators as well as
detailed studies of topological phase transitions.Comment: v2: published revised manuscript (6 pages, 3 figures) and
supplementary information (5 pages, 8 figures
Mirroring everyday clinical practice in clinical trial design: a new concept to improve the external validity of randomized double-blind placebo-controlled trials in the pharmacological treatment of major depression
Background: Randomized, double-blind, placebo-controlled trials constitute the gold standard in clinical research when testing the efficacy of new psychopharmacological interventions in the treatment of major depression. However, the blinded use of placebo has been found to influence clinical trial outcomes and may bias patient
selection.
Discussion: To improve clinical trial design in major depression so as to reflect clinical practice more closely we propose to present patients with a balanced view of the benefits of study participation irrespective of their assignment to placebo or active treatment. In addition every participant should be given the option to finally
receive the active medication. A research agenda is outlined to evaluate the impact of the proposed changes on the efficacy of the drug to be evaluated and on the demographic and clinical characteristics of the enrollment fraction with regard to its representativeness of the eligible population.
Summary: We propose a list of measures to be taken to improve the external validity of double-blind, placebocontrolled trials in major depression. The recommended changes to clinical trial design may also be relevant for other psychiatric as well as medical disorders in which expectations regarding treatment outcome may affect the
outcome itself
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