106 research outputs found
Experimentally Constrained Molecular Relaxation: The Case of Glassy GeSe2
An ideal atomistic model of a disordered material should contradict no
experiments,and should also be consistent with accurate force fields (either
{\it ab initio}or empirical). We make significant progress toward jointly
satisfying {\it both} of these criteria using a hybrid reverse Monte Carlo
approach in conjunction with approximate first principles molecular dynamics.
We illustrate the method by studying the complex binary glassy material
g-GeSe. By constraining the model to agree with partial structure factors
and {\it ab initio} simulation, we obtain a 647-atom model in close agreement
with experiment, including the first sharp diffraction peak in the static
structure factor. We compute the electronic state densities and compare to
photoelectron spectroscopies. The approach is general and flexible.Comment: 6 pages, 4 figure
Scope and limitations of iodothyronine deiodinases in hypothyroidism.
The coordinated expression and activity of the iodothyronine deiodinases regulate thyroid hormone levels in hypothyroidism. Once heralded as the pathway underpinning adequate thyroid-hormone replacement therapy with levothyroxine, the role of these enzymes has come into question as they have been implicated in both an inability to normalize serum levels of tri-iodothyronine (T3) and the incomplete resolution of hypothyroid symptoms. These observations, some of which were validated in animal models of levothyroxine monotherapy, challenge the paradigm that tissue levels of T3 and thyroid-hormone signalling can be fully restored by administration of levothyroxine alone. The low serum levels of T3 observed among patients receiving levothyroxine monotherapy occur as a consequence of type 2 iodothyronine deiodinase (DIO2) in the hypothalamus being fairly insensitive to ubiquitination. In addition, residual symptoms of hypothyroidism have been linked to a prevalent polymorphism in the DIO2 gene that might be a risk factor for neurodegenerative disease. Here, we discuss how these novel findings underscore the clinical importance of iodothyronine deiodinases in hypothyroidism and how an improved understanding of these enzymes might translate to therapeutic advances in the care of millions of patients with this condition
Reverse Monte Carlo modeling of liquid water with the explicit use of the SPC/E interatomic potential
Reverse Monte Carlo modeling of liquid water, based on one neutron and one
X-ray diffraction data set, applying also the most popular interatomic
potential for water, SPC/E, has been performed. The strictly rigid geometry of
SPC/E water molecules had to be loosened somewhat, in order to be able to
produce a good fit to both sets of experimental data. In the final particle
configurations, regularly shaped water molecules and straight hydrogen bonding
angles were found to be consistent with diffraction results. It has been
demonstrated that explicit use of interatomic potentials in RMC has a role to
play in future structural modeling of water and aqueous solutions.Comment: 8 pages, 5 figures, submitted to The Journal of Chemical Physic
Fitting in a complex chi^2 landscape using an optimized hypersurface sampling
Fitting a data set with a parametrized model can be seen geometrically as
finding the global minimum of the chi^2 hypersurface, depending on a set of
parameters {P_i}. This is usually done using the Levenberg-Marquardt algorithm.
The main drawback of this algorithm is that despite of its fast convergence, it
can get stuck if the parameters are not initialized close to the final
solution. We propose a modification of the Metropolis algorithm introducing a
parameter step tuning that optimizes the sampling of parameter space. The
ability of the parameter tuning algorithm together with simulated annealing to
find the global chi^2 hypersurface minimum, jumping across chi^2{P_i} barriers
when necessary, is demonstrated with synthetic functions and with real data
Inclusion of Experimental Information in First Principles Modeling of Materials
We propose a novel approach to model amorphous materials using a first
principles density functional method while simultaneously enforcing agreement
with selected experimental data. We illustrate our method with applications to
amorphous silicon and glassy GeSe. The structural, vibrational and
electronic properties of the models are found to be in agreement with
experimental results. The method is general and can be extended to other
complex materials.Comment: 11 pages, 8 PostScript figures, submitted to J. Phys.: Condens.
Matter in honor of Mike Thorpe's 60th birthda
Reverse Monte Carlo modeling of amorphous silicon
An implementation of the Reverse Monte Carlo algorithm is presented for the
study of amorphous tetrahedral semiconductors. By taking into account a number
of constraints that describe the tetrahedral bonding geometry along with the
radial distribution function, we construct a model of amorphous silicon using
the reverse monte carlo technique. Starting from a completely random
configuration, we generate a model of amorphous silicon containing 500 atoms
closely reproducing the experimental static structure factor and bond angle
distribution and in improved agreement with electronic properties. Comparison
is made to existing Reverse Monte Carlo models, and the importance of suitable
constraints beside experimental data is stressed.Comment: 6 pages, 4 PostScript figure
Vibrational and structural properties of glass: Advances from a combined modeling approach
We present experimental measurements and ab initio simulations of the crystalline and amorphous phases of . The calculated Raman, infrared, and vibrational density of states (VDOS) spectra are in excellent agreement with experimental measurements and contain the signatures of all the peculiar local structures of the amorphous phase, namely, bridging and nonbridging (double-bonded or terminal) oxygens and tetrahedral units associated with , , and species ( denotes the various types of tetrahedra, with being the number of bridging oxygen atoms that connect the tetrahedra to the rest of the network). In order to reveal the internal structure of the vibrational spectrum, the characteristics of vibrational modes in different frequency ranges are investigated using a mode-projection approach at different symmetries based on the symmetry group. In particular, the VDOS spectrum in the range from to is dominated by bending () motions related to bridging oxygen and phosphorus ( band) atoms, while the high-frequency doublet zone ( is associated mostly with the asymmetric (() and symmetric () stretching modes, and most prominent peak around (exp. ) is mainly due to asymmetric stretching vibrations supported by double-bonded oxygen atoms. The lower-frequency range below is shown to arise from a mixture of bending ( and () and rotation () modes. The scissors bending () and rotation () modes are well localized below , whereas the ( bending modes spread further into the range . The projections of the eigenmodes onto , , and species yield well-defined contributions at frequencies in striking correspondence with the positions of the Raman and infrared bands
Disturbed Expression of Splicing Factors in Renal Cancer Affects Alternative Splicing of Apoptosis Regulators, Oncogenes, and Tumor Suppressors
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer. One of the processes disturbed in this cancer type is alternative splicing, although phenomena underlying these disturbances remain unknown. Alternative splicing consists of selective removal of introns and joining of residual exons of the primary transcript, to produce mRNA molecules of different sequence. Splicing aberrations may lead to tumoral transformation due to synthesis of impaired splice variants with oncogenic potential. In this paper we hypothesized that disturbed alternative splicing in ccRCC may result from improper expression of splicing factors, mediators of splicing reactions. METHODOLOGY/PRINCIPAL FINDINGS: Using real-time PCR and Western-blot analysis we analyzed expression of seven splicing factors belonging to SR proteins family (SF2/ASF, SC35, SRp20, SRp75, SRp40, SRp55 and 9G8), and one non-SR factor, hnRNP A1 (heterogeneous nuclear ribonucleoprotein A1) in 38 pairs of tumor-control ccRCC samples. Moreover, we analyzed splicing patterns of five genes involved in carcinogenesis and partially regulated by analyzed splicing factors: RON, CEACAM1, Rac1, Caspase-9, and GLI1. CONCLUSIONS/SIGNIFICANCE: We found that the mRNA expression of splicing factors was disturbed in tumors when compared to paired controls, similarly as levels of SF2/ASF and hnRNP A1 proteins. The correlation coefficients between expression levels of specific splicing factors were increased in tumor samples. Moreover, alternative splicing of five analyzed genes was also disturbed in ccRCC samples and splicing pattern of two of them, Caspase-9 and CEACAM1 correlated with expression of SF2/ASF in tumors. We conclude that disturbed expression of splicing factors in ccRCC may possibly lead to impaired alternative splicing of genes regulating tumor growth and this way contribute to the process of carcinogenesis
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