1,068 research outputs found
High-throughput discovery of post-transcriptional cis-regulatory elements
Validation of 8mers found in the main screen. (PDF 280ĂÂ kb
Co-dimension 2 Geodesic Active Contours for MRA Segmentation
Automatic and semi-automatic magnetic resonance angiography (MRA)s segmentation techniques can potentially save radiologists larges amounts of time required for manual segmentation and cans facilitate further data analysis. The proposed MRAs segmentation method uses a mathematical modeling technique whichs is well-suited to the complicated curve-like structure of bloods vessels. We define the segmentation task as ans energy minimization over all 3D curves and use a level set methods to search for a solution. Ours approach is an extension of previous level set segmentations techniques to higher co-dimension
Probabilistic Search for Object Segmentation and Recognition
The problem of searching for a model-based scene interpretation is analyzed
within a probabilistic framework. Object models are formulated as generative
models for range data of the scene. A new statistical criterion, the truncated
object probability, is introduced to infer an optimal sequence of object
hypotheses to be evaluated for their match to the data. The truncated
probability is partly determined by prior knowledge of the objects and partly
learned from data. Some experiments on sequence quality and object segmentation
and recognition from stereo data are presented. The article recovers classic
concepts from object recognition (grouping, geometric hashing, alignment) from
the probabilistic perspective and adds insight into the optimal ordering of
object hypotheses for evaluation. Moreover, it introduces point-relation
densities, a key component of the truncated probability, as statistical models
of local surface shape.Comment: 18 pages, 5 figure
Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs
Most metazoan microRNAs (miRNAs) target many genes for repression, but the nematode lsy-6 miRNA is much less proficient. Here we show that the low proficiency of lsy-6 can be recapitulated in HeLa cells and that miR-23, a mammalian miRNA, also has low proficiency in these cells. Reporter results and array data indicate two properties of these miRNAs that impart low proficiency: their weak predicted seed-pairing stability (SPS) and their high target-site abundance (TA). These two properties also explain differential propensities of small interfering RNAs (siRNAs) to repress unintended targets. Using these insights, we expand the TargetScan tool for quantitatively predicting miRNA regulation (and siRNA off-targeting) to model differential miRNA (and siRNA) proficiencies, thereby improving prediction performance. We propose that siRNAs designed to have both weaker SPS and higher TA will have fewer off-targets without compromised on-target activity.National Institutes of Health (U.S.) (grant GM067031)Seoul National University (Research Settlement Fund)Howard Hughes Medical Institute (Investigator
Identity-by-descent estimation with population- and pedigree-based imputation in admixed family data
Background: In the past few years, imputation approaches have been mainly used in population-based designs of genome-wide association studies, although both family- and population-based imputation methods have been proposed. With the recent surge of family-based designs, family-based imputation has become more important. Imputation methods for both designs are based on identity-by-descent (IBD) information. Apart from imputation, the use of IBD information is also common for several types of genetic analysis, including pedigree-based linkage analysis.
Methods: We compared the performance of several family- and population-based imputation methods in large pedigrees provided by Genetic Analysis Workshop 19 (GAW19). We also evaluated the performance of a new IBD mapping approach that we propose, which combines IBD information from known pedigrees with information from unrelated individuals.
Results: Different combinations of the imputation methods have varied imputation accuracies. Moreover, we showed gains from the use of both known pedigrees and unrelated individuals with our IBD mapping approach over the use of known pedigrees only.
Conclusions: Our results represent accuracies of different combinations of imputation methods that may be useful for data sets similar to the GAW19 pedigree data. Our IBD mapping approach, which uses both known pedigree and unrelated individuals, performed better than classical linkage analysis
Hysteresis and the dynamic phase transition in thin ferromagnetic films
Hysteresis and the non-equilibrium dynamic phase transition in thin magnetic
films subject to an oscillatory external field have been studied by Monte Carlo
simulation. The model under investigation is a classical Heisenberg spin system
with a bilinear exchange anisotropy in a planar thin film geometry with
competing surface fields. The film exhibits a non-equilibrium phase transition
between dynamically ordered and dynamically disordered phases characterized by
a critical temperature Tcd, whose location of is determined by the amplitude H0
and frequency w of the applied oscillatory field. In the presence of competing
surface fields the critical temperature of the ferromagnetic-paramagnetic
transition for the film is suppressed from the bulk system value, Tc, to the
interface localization-delocalization temperature Tci. The simulations show
that in general Tcd < Tci for the model film. The profile of the time-dependent
layer magnetization across the film shows that the dynamically ordered and
dynamically disordered phases coexist within the film for T < Tcd. In the
presence of competing surface fields, the dynamically ordered phase is
localized at one surface of the film.Comment: PDF file, 21 pages including 8 figure pages; added references,typos
added; to be published in PR
Effective Interactions and Volume Energies in Charge-Stabilized Colloidal Suspensions
Charge-stabilized colloidal suspensions can be conveniently described by
formally reducing the macroion-microion mixture to an equivalent one-component
system of pseudo-particles. Within this scheme, the utility of a linear
response approximation for deriving effective interparticle interactions has
been demonstrated [M. J. Grimson and M. Silbert, Mol. Phys. 74, 397 (1991)].
Here the response approach is extended to suspensions of finite-sized macroions
and used to derive explicit expressions for (1) an effective electrostatic pair
interaction between pseudo-macroions and (2) an associated volume energy that
contributes to the total free energy. The derivation recovers precisely the
form of the DLVO screened-Coulomb effective pair interaction for spherical
macroions and makes manifest the important influence of the volume energy on
thermodynamic properties of deionized suspensions. Excluded volume corrections
are implicitly incorporated through a natural modification of the inverse
screening length. By including nonlinear response of counterions to macroions,
the theory may be generalized to systematically investigate effective many-body
interactions.Comment: 13 pages (J. Phys.: Condensed Matter, in press
A Framework for Methodological Choice and Evidence Assessment for Studies Using External Comparators from Real-World Data.
Several approaches have been proposed recently to accelerate the pathway from drug discovery to patient access. These include novel designs such as using controls external to the clinical trial where standard randomised controls are not feasible. In parallel, there has been rapid growth in the application of routinely collected healthcare 'real-world' data for post-market safety and effectiveness studies. Thus, using real-world data to establish an external comparator arm in clinical trials is a natural next step. Regulatory authorities have begun to endorse the use of external comparators in certain circumstances, with some positive outcomes for new drug approvals. Given the potential to introduce bias associated with observational studies, there is a need for recommendations on how external comparators should be best used. In this article, we propose an evaluation framework for real-world data external comparator studies that enables full assessment of available evidence and related bias. We define the principle of exchangeability and discuss the applicability of criteria described by Pocock for consideration of the exchangeability of the external and trial populations. We explore how trial designs using real-world data external comparators fit within the evidence hierarchy and propose a four-step process for good conduct of external comparator studies. This process is intended to maximise the quality of evidence based on careful study design and the combination of covariate balancing, bias analysis and combining outcomes
Stability of Colloidal Quasicrystals
Freezing of charge-stabilized colloidal suspensions and relative stabilities
of crystals and quasicrystals are studied using thermodynamic perturbation
theory. Macroion interactions are modelled by effective pair potentials
combining electrostatic repulsion with polymer-depletion or van der Waals
attraction. Comparing free energies -- counterion terms included -- for
elementary crystals and rational approximants to icosahedral quasicrystals,
parameters are identified for which one-component quasicrystals are stabilized
by a compromise between packing entropy and cohesive energy.Comment: 6 pages, 4 figure
The microRNA.org resource: targets and expression
MicroRNA.org (http://www.microrna.org) is a comprehensive resource of microRNA target predictions and expression profiles. Target predictions are based on a development of the miRanda algorithm which incorporates current biological knowledge on target rules and on the use of an up-to-date compendium of mammalian microRNAs. MicroRNA expression profiles are derived from a comprehensive sequencing project of a large set of mammalian tissues and cell lines of normal and disease origin. Using an improved graphical interface, a user can explore (i) the set of genes that are potentially regulated by a particular microRNA, (ii) the implied cooperativity of multiple microRNAs on a particular mRNA and (iii) microRNA expression profiles in various tissues. To facilitate future updates and development, the microRNA.org database structure and software architecture is flexibly designed to incorporate new expression and target discoveries. The web resource provides users with functional information about the growing number of microRNAs and their interaction with target genes in many species and facilitates novel discoveries in microRNA gene regulation
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