42 research outputs found
Polymer translocation through a nanopore under an applied external field
We investigate the dynamics of polymer translocation through a nanopore under
an externally applied field using the 2D fluctuating bond model with
single-segment Monte Carlo moves. We concentrate on the influence of the field
strength , length of the chain , and length of the pore on forced
translocation. As our main result, we find a crossover scaling for the
translocation time with the chain length from for
relatively short polymers to for longer chains, where
is the Flory exponent. We demonstrate that this crossover is due to the
change in the dependence of the translocation velocity v on the chain length.
For relatively short chains , which crosses over to for long polymers. The reason for this is that with increasing
there is a high density of segments near the exit of the pore, which slows down
the translocation process due to slow relaxation of the chain. For the case of
a long nanopore for which , the radius of gyration along
the pore, is smaller than the pore length, we find no clear scaling of the
translocation time with the chain length. For large , however, the
asymptotic scaling is recovered. In this regime, is almost independent of . We have previously found that for a polymer,
which is initially placed in the middle of the pore, there is a minimum in the
escape time for . We show here that this minimum
persists for a weak fields such that is less than some critical value,
but vanishes for large values of .Comment: 25 Pages, 10 figures. Submitted to J. Chem. Phys. J. Chem. Phys. 124,
in press (2006
Multivariate multi-way analysis of multi-source data
Motivation: Analysis of variance (ANOVA)-type methods are the default tool for the analysis of data with multiple covariates. These tools have been generalized to the multivariate analysis of high-throughput biological datasets, where the main challenge is the problem of small sample size and high dimensionality. However, the existing multi-way analysis methods are not designed for the currently increasingly important experiments where data is obtained from multiple sources. Common examples of such settings include integrated analysis of metabolic and gene expression profiles, or metabolic profiles from several tissues in our case, in a controlled multi-way experimental setup where disease status, medical treatment, gender and time-series are usual covariates
Driven polymer translocation through a nanopore: a manifestation of anomalous diffusion
We study the translocation dynamics of a polymer chain threaded through a
nanopore by an external force. By means of diverse methods (scaling arguments,
fractional calculus and Monte Carlo simulation) we show that the relevant
dynamic variable, the translocated number of segments , displays an {\em
anomalous} diffusive behavior even in the {\em presence} of an external force.
The anomalous dynamics of the translocation process is governed by the same
universal exponent , where is the Flory
exponent and - the surface exponent, which was established recently
for the case of non-driven polymer chain threading through a nanopore. A closed
analytic expression for the probability distribution function , which
follows from the relevant {\em fractional} Fokker - Planck equation, is derived
in terms of the polymer chain length and the applied drag force . It is
found that the average translocation time scales as . Also the corresponding time dependent
statistical moments, and reveal unambiguously the anomalous nature of the translocation
dynamics and permit direct measurement of in experiments. These
findings are tested and found to be in perfect agreement with extensive Monte
Carlo (MC) simulations.Comment: 6 pages, 4 figures, accepted to Europhys. Lett; some references were
supplemented; typos were correcte
Chaperone-assisted translocation of a polymer through a nanopore
Using Langevin dynamics simulations, we investigate the dynamics of
chaperone-assisted translocation of a flexible polymer through a nanopore. We
find that increasing the binding energy between the chaperone and
the chain and the chaperone concentration can greatly improve the
translocation probability. Particularly, with increasing the chaperone
concentration a maximum translocation probability is observed for weak binding.
For a fixed chaperone concentration, the histogram of translocation time
has a transition from long-tailed distribution to Gaussian distribution with
increasing . rapidly decreases and then almost saturates with
increasing binding energy for short chain, however, it has a minimum for longer
chains at lower chaperone concentration. We also show that has a minimum
as a function of the chaperone concentration. For different , a
nonuniversal dependence of on the chain length is also observed.
These results can be interpreted by characteristic entropic effects for
flexible polymers induced by either crowding effect from high chaperone
concentration or the intersegmental binding for the high binding energy.Comment: 10 pages, to appear in J. Am. Chem. So
The Potential and Challenges of Nanopore Sequencing
A nanopore-based device provides single-molecule detection and analytical capabilities that are achieved by electrophoretically driving molecules in solution through a nano-scale pore. The nanopore provides a highly confined space within which single nucleic acid polymers can be analyzed at high throughput by one of a variety of means, and the perfect processivity that can be enforced
in a narrow pore ensures that the native order of the nucleobases in a polynucleotide is reflected in the sequence of signals that is detected. Kilobase length polymers (single-stranded genomic DNA or RNA) or small molecules (e.g., nucleosides) can be identified and characterized without amplification or labeling, a unique analytical capability that makes inexpensive, rapid DNA sequencing
a possibility. Further research and development to overcome current challenges to nanopore identification of each successive nucleotide in a DNA strand offers the prospect of ‘third generation’ instruments that will sequence a diploid mammalian genome for ~$1,000 in ~24 h.Molecular and Cellular BiologyPhysic
CDK19 is disrupted in a female patient with bilateral congenital retinal folds, microcephaly and mild mental retardation
Microcephaly, mental retardation and congenital retinal folds along with other systemic features have previously been reported as a separate clinical entity. The sporadic nature of the syndrome and lack of clear inheritance patterns pointed to a genetic heterogeneity. Here, we report a genetic analysis of a female patient with microcephaly, congenital bilateral falciform retinal folds, nystagmus, and mental retardation. Karyotyping revealed a de novo pericentric inversion in chromosome 6 with breakpoints in 6p12.1 and 6q21. Fluorescence in situ hybridization analysis narrowed down the region around the breakpoints, and the breakpoint at 6q21 was found to disrupt the CDK19 gene. CDK19 was found to be expressed in a diverse range of tissues including fetal eye and fetal brain. Quantitative PCR of the CDK19 transcript from Epstein–Barr virus-transformed lymphoblastoid cell lines of the patient revealed ~50% reduction in the transcript (p = 0.02), suggesting haploinsufficiency of the gene. cdk8, the closest orthologue of human CDK19 in Drosophila has been shown to play a major role in eye development. Conditional knock-down of Drosophila cdk8 in multiple dendrite (md) neurons resulted in 35% reduced dendritic branching and altered morphology of the dendritic arbour, which appeared to be due in part to a loss of small higher order branches. In addition, Cdk8 mutant md neurons showed diminished dendritic fields revealing an important role of the CDK19 orthologue in the developing nervous system of Drosophila. This is the first time the CDK19 gene, a component of the mediator co-activator complex, has been linked to a human disease
Auralization applying the parametric room acoustic modeling technique - the div auralization system
Presented at the 8th International Conference on Auditory Display (ICAD), Kyoto, Japan, July 2-5, 2002.The primary goal of this paper is to give a general view on room acoustic modeling and auralization, and especially to describe the current status of the DIVA auralization system. We have been building the system for several years, and it has evolved a lot during that time. It is a room acoustic modeling and auralization system suitable for both real-time and non-realtime acoustic rendering, and it is designed for research purposes. It applies the parametric room impulse response rendering technique described in the article. In this paper we review the architecture and design principles of the system. A description of recent advances is given and results of perceptual evaluations are presented