478 research outputs found
Laplace's rule of succession in information geometry
Laplace's "add-one" rule of succession modifies the observed frequencies in a
sequence of heads and tails by adding one to the observed counts. This improves
prediction by avoiding zero probabilities and corresponds to a uniform Bayesian
prior on the parameter. The canonical Jeffreys prior corresponds to the
"add-one-half" rule. We prove that, for exponential families of distributions,
such Bayesian predictors can be approximated by taking the average of the
maximum likelihood predictor and the \emph{sequential normalized maximum
likelihood} predictor from information theory. Thus in this case it is possible
to approximate Bayesian predictors without the cost of integrating or sampling
in parameter space
Blinking statistics of a molecular beacon triggered by end-denaturation of DNA
We use a master equation approach based on the Poland-Scheraga free energy
for DNA denaturation to investigate the (un)zipping dynamics of a denaturation
wedge in a stretch of DNA, that is clamped at one end. In particular, we
quantify the blinking dynamics of a fluorophore-quencher pair mounted within
the denaturation wedge. We also study the behavioural changes in the presence
of proteins, that selectively bind to single-stranded DNA. We show that such a
setup could be well-suited as an easy-to-implement nanodevice for sensing
environmental conditions in small volumes.Comment: 14 pages, 5 figures, LaTeX, IOP style. Accepted to J Phys Cond Mat
special issue on diffusio
Characterization of some groups of gram-negative nonfermentative bacteria by the carbon source alkalinization technique.
A total of 541 gram-negative nonfermentative bacterial strains comprising 26 species and unclassified groups were characterized by routine diagnostic and carbon substrate alkalinization techniques. These microorganisms were tested for the ability to cause alkalinization of a basal medium on a total of 217 substrates. We found that 58 carbon substrates had some discriminatory potential. We also performed 30 routine diagnostic tests. The results of these studies were evaluated by numerical taxonomy techniques. A cluster analysis of the results by the Jaccard coefficient method identified 30 clusters at the 45% level. We identified 39 tests that separated most of the groups. Groups of similar organisms or organisms that were difficult to identify were analyzed, and tests that were differential were identified. Because of variability within the clusters, further studies utilizing deoxyribonucleic acid-deoxyribonucleic acid homologies should be undertaken
Laboratory Exercises Caenorhabditis elegans as an Undergraduate Educational Tool for Teaching RNAi*
Discovery of RNA-mediated interference (RNAi) is widely recognized as one of the most significant molecular biology breakthroughs in the past 10 years. There is a need for science educators to develop teaching tools and laboratory activities that demonstrate the power of this new technology and help students to better understand the RNAi process. C. elegans is an ideal model organism for the undergraduate laboratory because of the simplicity of worm maintenance, its well-studied genetic background, and the fact that it can be employed as a model organism in laboratory environments where vertebrate research is restricted. Certain unique features of C. elegans make it a very suitable organism for RNAi studies. Specifically, nematode strains highly sensitive to RNAi are readily available from public sources, and RNAi induction by a feeding method is an uncomplicated procedure that lends itself readily as an educational tool. In this article, we provide a detailed depiction of the use of C. elegans as an RNAi educational tool, describing two separate RNAi-based experiments. One is a qualitative experiment where students can examine the effects of knocking down the unc-22 gene involved in the regulation of muscle contraction, which results in a ''twitching'' phenotype. The other experiment is a quantitative RNAi experiment, where students measure the effect of knocking down the lsy-2 gene involved in neuronal development. Although these experiments are designed for a college-level study, nematode research projects can also be accomplished in secondary school facilities
Bubble dynamics in DNA
The formation of local denaturation zones (bubbles) in double-stranded DNA is
an important example for conformational changes of biological macromolecules.
We study the dynamics of bubble formation in terms of a Fokker-Planck equation
for the probability density to find a bubble of size n base pairs at time t, on
the basis of the free energy in the Poland-Scheraga model. Characteristic
bubble closing and opening times can be determined from the corresponding first
passage time problem, and are sensitive to the specific parameters entering the
model. A multistate unzipping model with constant rates recently applied to DNA
breathing dynamics [G. Altan-Bonnet et al, Phys. Rev. Lett. 90, 138101 (2003)]
emerges as a limiting case.Comment: 9 pages, 2 figure
End-Monomer Dynamics in Semiflexible Polymers
Spurred by an experimental controversy in the literature, we investigate the end-monomer dynamics of semiflexible polymers through Brownian hydrodynamic simulations and dynamic mean-field theory. Precise experimental observations over the last few years of end-monomer dynamics in the diffusion of double-stranded DNA have given conflicting results: one study indicated an unexpected Rouse-like scaling of the mean squared displacement (MSD) 〈r2(t)〉 ~ t1/2 at intermediate times, corresponding to fluctuations at length scales larger than the persistence length but smaller than the coil size; another study claimed the more conventional Zimm scaling 〈r2(t)〉 ~ t2/3 in the same time range. Using hydrodynamic simulations, analytical and scaling theories, we find a novel intermediate dynamical regime where the effective local exponent of the end-monomer MSD, α(t) = d log〈r2(t)〉/d log t, drops below the Zimm value of 2/3 for sufficiently long chains. The deviation from the Zimm prediction increases with chain length, though it does not reach the Rouse limit of 1/2. The qualitative features of this intermediate regime, found in simulations and in an improved mean-field theory for semiflexible polymers, in particular the variation of α(t) with chain and persistence lengths, can be reproduced through a heuristic scaling argument. Anomalously low values of the effective exponent α are explained by hydrodynamic effects related to the slow crossover from dynamics on length scales smaller than the persistence length to dynamics on larger length scales
Weak selection and stability of localized distributions in Ostwald ripening
We support and generalize a weak selection rule predicted recently for the
self-similar asymptotics of the distribution function (DF) in the
zero-volume-fraction limit of Ostwald ripening (OR). An asymptotic perturbation
theory is developed that, when combined with an exact invariance property of
the system, yields the selection rule, predicts a power-law convergence towards
the selected self-similar DF and agrees well with our numerical simulations for
the interface- and diffusion-controlled OR.Comment: 4 pages, 2 figures, submitted to PR
Decay of isolated surface features driven by the Gibbs-Thomson effect in analytic model and simulation
A theory based on the thermodynamic Gibbs-Thomson relation is presented which
provides the framework for understanding the time evolution of isolated
nanoscale features (i.e., islands and pits) on surfaces. Two limiting cases are
predicted, in which either diffusion or interface transfer is the limiting
process. These cases correspond to similar regimes considered in previous works
addressing the Ostwald ripening of ensembles of features. A third possible
limiting case is noted for the special geometry of "stacked" islands. In these
limiting cases, isolated features are predicted to decay in size with a power
law scaling in time: A is proportional to (t0-t)^n, where A is the area of the
feature, t0 is the time at which the feature disappears, and n=2/3 or 1. The
constant of proportionality is related to parameters describing both the
kinetic and equilibrium properties of the surface. A continuous time Monte
Carlo simulation is used to test the application of this theory to generic
surfaces with atomic scale features. A new method is described to obtain
macroscopic kinetic parameters describing interfaces in such simulations.
Simulation and analytic theory are compared directly, using measurements of the
simulation to determine the constants of the analytic theory. Agreement between
the two is very good over a range of surface parameters, suggesting that the
analytic theory properly captures the necessary physics. It is anticipated that
the simulation will be useful in modeling complex surface geometries often seen
in experiments on physical surfaces, for which application of the analytic
model is not straightforward.Comment: RevTeX (with .bbl file), 25 pages, 7 figures from 9 Postscript files
embedded using epsf. Submitted to Phys. Rev. B A few minor changes made on
9/24/9
MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors
BACKGROUND
MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated.
METHODS
Tissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets.
RESULTS
Widespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a "seedless" binding site within its 3'UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change.
CONCLUSIONS
Expression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re-expression has the potential as a therapeutic strategy against PDAC and other KRAS-driven cancers
- …