1,402 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
Effect of charge distribution on the translocation of an inhomogeneously charged polymer through a nanopore
We investigate the voltage-driven translocation of an inhomogeneously charged
polymer through a nanopore by utilizing discrete and continuous stochastic
models. As a simplified illustration of the effect of charge distribution on
translocation, we consider the translocation of a polymer with a single charged
site in the presence and absence of interactions between the charge and the
pore. We find that the position of the charge that minimizes the translocation
time in the absence of pore--polymer interactions is determined by the entropic
cost of translocation, with the optimum charge position being at the midpoint
of the chain for a rodlike polymer and close to the leading chain end for an
ideal chain. The presence of attractive or repulsive pore--charge interactions
yields a shift in the optimum charge position towards the trailing end and the
leading end of the chain, respectively. Moreover, our results show that strong
attractive or repulsive interactions between the charge and the pore lengthen
the translocation time relative to translocation through an inert pore. We
generalize our results to accommodate the presence of multiple charged sites on
the polymer. Our results provide insight into the effect of charge
inhomogeneity on protein translocation through biological membranes.Comment: Submitted to Journal of Chemical Physic
Disease variants in genomes of 44 centenarians
To identify previously reported disease mutations that are compatible with extraordinary longevity, we screened the coding regions of the genomes of 44 Ashkenazi Jewish centenarians. Individual genome sequences were generated with 30x coverage on the Illumina HiSeq 2000 and single-nucleotide variants were called with the genome analysis toolkit (GATK). We identified 130 coding variants that were annotated as pathogenic or likely pathogenic based on the ClinVar database and that are infrequent in the general population. These variants were previously reported to cause a wide range of degenerative, neoplastic, and cardiac diseases with autosomal dominant, autosomal recessive, and X-linked inheritance. Several of these variants are located in genes that harbor actionable incidental findings, according to the recommendations of the American College of Medical Genetics. In addition, we found risk variants for late-onset neurodegenerative diseases, such as the APOE epsilon4 allele that was even present in a homozygous state in one centenarian who did not develop Alzheimer\u27s disease. Our data demonstrate that the incidental finding of certain reported disease variants in an individual genome may not preclude an extraordinarily long life. When the observed variants are encountered in the context of clinical sequencing, it is thus important to exercise caution in justifying clinical decisions
Efficient detection of RNAāprotein interactions using tethered RNAs
The diverse localization of transcripts in cells suggests that there are many specific RNAāprotein interactions that have yet to be identified. Progress has been limited, however, by the lack of a robust method to detect and isolate the RNA-binding proteins. Here we describe the use of an RNA aptamer, scaffolded to a tRNA, to create an affinity matrix that efficiently pulls down transcript-specific RNA-binding proteins from cell lysates. The addition of the tRNA scaffold to a Streptavidin aptamer (tRSA) increased binding efficiency by ā¼10-fold. The tRSA system with an attached G-quartet sequence also could efficiently and specifically capture endogenous Fragile X Mental Retardation Protein (FMRP), which recognizes this RNA sequence. An alternative method, using biotinylated RNA, captured FMRP less efficiently than did our tRSA method. Finally we demonstrate the identification of novel RNA-binding proteins that interact with intron2 or 3ā²-UTR of the polarity protein Crumbs3 transcript. Proteins captured by these RNA sequences attached to the tRNA scaffold were identified by mass spectrometry. GFP-tagged versions of these proteins also showed specific interaction with either the Crb3 intron2 or 3ā²-UTR. Our tRSA technique should find wide application in mapping the RNAāprotein interactome
A database of microRNA expression patterns in Xenopus laevis
MicroRNAs (miRNAs) are short, non-coding RNAs around 22 nucleotides long. They inhibit gene expression either by translational repression or by causing the degradation of the mRNAs they bind to. Many are highly conserved amongst diverse organisms and have restricted spatio-temporal expression patterns during embryonic development where they are thought to be involved in generating accuracy of developmental timing and in supporting cell fate decisions and tissue identity. We determined the expression patterns of 180 miRNAs in Xenopus laevis embryos using LNA oligonucleotides. In addition we carried out small RNA-seq on different stages of early Xenopus development, identified 44 miRNAs belonging to 29 new families and characterized the expression of 5 of these. Our analyses identified miRNA expression in many organs of the developing embryo. In particular a large number were expressed in neural tissue and in the somites. Surprisingly none of the miRNAs we have looked at show expression in the heart. Our results have been made freely available as a resource in both XenMARK and Xenbase
Religion, Partisanship, and Attitudes Toward Science Policy
We examine issues involving science which have been contested in recent public debate. These ācontested scienceā issues include human evolution, stem-cell research, and climate change. We find that few respondents evince consistently skeptical attitudes toward science issues, and that religious variables are generally strong predictors of attitudes toward individual issues. Furthermore, and contrary to analyses of elite discourse, partisan identification is not generally predictive of attitudes toward contested scientific issues
Understanding the influence of race/Ethnicity, gender, and class on inequalities in academic and non-academic outcomes among eighth-grade students: findings from an intersectionality approach
Socioeconomic, racial/ethnic, and gender inequalities in academic achievement have been widely reported in the US, but how these three axes of inequality intersect to determine academic and non-academic outcomes among school-aged children is not well understood. Using data from the US Early Childhood Longitudinal StudyāKindergarten (ECLS-K; N = 10,115), we apply an intersectionality approach to examine inequalities across eighth-grade outcomes at the intersection of six racial/ethnic and gender groups (Latino girls and boys, Black girls and boys, and White girls and boys) and four classes of socioeconomic advantage/disadvantage. Results of mixture models show large inequalities in socioemotional outcomes (internalizing behavior, locus of control, and self-concept) across classes of advantage/disadvantage. Within classes of advantage/disadvantage, racial/ethnic and gender inequalities are predominantly found in the most advantaged class, where Black boys and girls, and Latina girls, underperform White boys in academic assessments, but not in socioemotional outcomes. In these latter outcomes, Black boys and girls perform better than White boys. Latino boys show small differences as compared to White boys, mainly in science assessments. The contrasting outcomes between racial/ethnic and gender minorities in self-assessment and socioemotional outcomes, as compared to standardized assessments, highlight the detrimental effect that intersecting racial/ethnic and gender discrimination have in patterning academic outcomes that predict success in adult life. Interventions to eliminate achievement gaps cannot fully succeed as long as social stratification caused by gender and racial discrimination is not addressed
Bridging Alone: Religious Conservatism, Marital Homogamy, and Voluntary Association Membership
This study characterizes social insularity of religiously conservative American married couples by examining patterns of voluntary associationmembership. Constructing a dataset of 3938 marital dyads from the second wave of the National Survey of Families and Households, the author investigates whether conservative religious homogamy encourages membership in religious voluntary groups and discourages membership in secular voluntary groups. Results indicate that couplesā shared affiliation with conservative denominations, paired with beliefs in biblical authority and inerrancy, increases the likelihood of religious group membership for husbands and wives and reduces the likelihood of secular group membership for wives, but not for husbands. The social insularity of conservative religious groups appears to be reinforced by homogamyāparticularly by wives who share faith with husbands
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