626 research outputs found
On the Design of Fault-Tolerant Logical Topologies in Wavelength-RoutedNetworks supporting Packet Datagrams
Thyroxine Binding to Type III Iodothyronine Deiodinase
Iodothyronine deiodinases (Dios) are important selenoproteins that control the concentration of the active thyroid hormone (TH) triiodothyronine through regioselective deiodination. The X-ray structure of a truncated monomer of Type III Dio (Dio3), which deiodinates TH inner rings through a selenocysteine (Sec) residue, revealed a thioredoxin-fold catalytic domain supplemented with an unstructured Ω-loop. Loop dynamics are driven by interactions of the conserved Trp207 with solvent in multi-microsecond molecular dynamics simulations of the Dio3 thioredoxin(Trx)-fold domain. Hydrogen bonding interactions of Glu200 with residues conserved across the Dio family anchor the loop\u27s N-terminus to the active site Ser-Cys-Thr-Sec sequence. A key long-lived loop conformation coincides with the opening of a cryptic pocket that accommodates thyroxine (T4) through an I…Se halogen bond to Sec170 and the amino acid group with a polar cleft. The Dio3-T4 complex is stabilized by an I…O halogen bond between an outer ring iodine and Asp211, consistent with Dio3 selectivity for inner ring deiodination. Non-conservation of residues, such as Asp211, in other Dio types in the flexible portion of the loop sequence suggests a mechanism for regioselectivity through Dio type-specific loop conformations. Cys168 is proposed to attack the selenenyl iodide intermediate to regenerate Dio3 based upon structural comparison with related Trx-fold proteins
Optimizing Performance of Continuous-Time Stochastic Systems using Timeout Synthesis
We consider parametric version of fixed-delay continuous-time Markov chains
(or equivalently deterministic and stochastic Petri nets, DSPN) where
fixed-delay transitions are specified by parameters, rather than concrete
values. Our goal is to synthesize values of these parameters that, for a given
cost function, minimise expected total cost incurred before reaching a given
set of target states. We show that under mild assumptions, optimal values of
parameters can be effectively approximated using translation to a Markov
decision process (MDP) whose actions correspond to discretized values of these
parameters
Use of partial least squares regression to impute SNP genotypes in Italian Cattle breeds
Background
The objective of the present study was to test the ability of the partial least squares regression technique to impute genotypes from low density single nucleotide polymorphisms (SNP) panels i.e. 3K or 7K to a high density panel with 50K SNP. No pedigree information was used.
Methods
Data consisted of 2093 Holstein, 749 Brown Swiss and 479 Simmental bulls genotyped with the Illumina 50K Beadchip. First, a single-breed approach was applied by using only data from Holstein animals. Then, to enlarge the training population, data from the three breeds were combined and a multi-breed analysis was performed. Accuracies of genotypes imputed using the partial least squares regression method were compared with those obtained by using the Beagle software. The impact of genotype imputation on breeding value prediction was evaluated for milk yield, fat content and protein content.
Results
In the single-breed approach, the accuracy of imputation using partial least squares regression was around 90 and 94% for the 3K and 7K platforms, respectively; corresponding accuracies obtained with Beagle were around 85% and 90%. Moreover, computing time required by the partial least squares regression method was on average around 10 times lower than computing time required by Beagle. Using the partial least squares regression method in the multi-breed resulted in lower imputation accuracies than using single-breed data. The impact of the SNP-genotype imputation on the accuracy of direct genomic breeding values was small. The correlation between estimates of genetic merit obtained by using imputed versus actual genotypes was around 0.96 for the 7K chip.
Conclusions
Results of the present work suggested that the partial least squares regression imputation method could be useful to impute SNP genotypes when pedigree information is not available
Prediction of extreme events in the OFC model on a small world network
We investigate the predictability of extreme events in a dissipative
Olami-Feder-Christensen model on a small world topology. Due to the mechanism
of self-organized criticality, it is impossible to predict the magnitude of the
next event knowing previous ones, if the system has an infinite size. However,
by exploiting the finite size effects, we show that probabilistic predictions
of the occurrence of extreme events in the next time step are possible in a
finite system. In particular, the finiteness of the system unavoidably leads to
repulsive temporal correlations of extreme events. The predictability of those
is higher for larger magnitudes and for larger complex network sizes. Finally,
we show that our prediction analysis is also robust by remarkably reducing the
accessible number of events used to construct the optimal predictor.Comment: 5 pages, 4 figure
Symbolic Analysis of Timed Petri Nets
In timed Petri nets temporal properties are associated with transitions as transition firing times (or occurrence times). Specific properties of timed nets, such as boundedness or absence of deadlocks, can depend upon temporal properties and sometimes even a small change of these properties has a significant effect on the net’s behavior (e.g., a bounded net becomes unbounded or vice versa). The objective of symbolic analysis of timed nets is to provide information about the net’s behavior which is independent of specific temporal properties, i.e., which describes preperties of the whole class of timed nets with the same structure
Programmable models of growth and mutation of cancer-cell populations
In this paper we propose a systematic approach to construct mathematical
models describing populations of cancer-cells at different stages of disease
development. The methodology we propose is based on stochastic Concurrent
Constraint Programming, a flexible stochastic modelling language. The
methodology is tested on (and partially motivated by) the study of prostate
cancer. In particular, we prove how our method is suitable to systematically
reconstruct different mathematical models of prostate cancer growth - together
with interactions with different kinds of hormone therapy - at different levels
of refinement.Comment: In Proceedings CompMod 2011, arXiv:1109.104
Properties of Foreshocks and Aftershocks of the Non-Conservative SOC Olami-Feder-Christensen Model: Triggered or Critical Earthquakes?
Following Hergarten and Neugebauer [2002] who discovered aftershock and
foreshock sequences in the Olami-Feder-Christensen (OFC) discrete block-spring
earthquake model, we investigate to what degree the simple toppling mechanism
of this model is sufficient to account for the properties of earthquake
clustering in time and space. Our main finding is that synthetic catalogs
generated by the OFC model share practically all properties of real seismicity
at a qualitative level, with however significant quantitative differences. We
find that OFC catalogs can be in large part described by the concept of
triggered seismicity but the properties of foreshocks depend on the mainshock
magnitude, in qualitative agreement with the critical earthquake model and in
disagreement with simple models of triggered seismicity such as the Epidemic
Type Aftershock Sequence (ETAS) model [Ogata, 1988]. Many other features of OFC
catalogs can be reproduced with the ETAS model with a weaker clustering than
real seismicity, i.e. for a very small average number of triggered earthquakes
of first generation per mother-earthquake.Comment: revtex, 19 pages, 8 eps figure
Characterization of degenerative mitral valve disease: differences between fibroelastic deficiency and Barlow's disease
Degenerative mitral valve disease causing mitral valve prolapse is the most common cause of primary mitral regurgitation, with two distinct phenotypes generally recognized with some major differences, i.e., fibroelastic deficiency (FED) and Barlow's disease. The aim of this review was to describe the main histological, clinical and echocardiographic features of patients with FED and Barlow's disease, highlighting the differences in diagnosis, risk stratification and patient management, but also the still significant gaps in understanding the exact pathophysiology of these two phenotypes.Genetics of disease, diagnosis and treatmen
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