144 research outputs found
Computational Method for Phase Space Transport with Applications to Lobe Dynamics and Rate of Escape
Lobe dynamics and escape from a potential well are general frameworks
introduced to study phase space transport in chaotic dynamical systems. While
the former approach studies how regions of phase space are transported by
reducing the flow to a two-dimensional map, the latter approach studies the
phase space structures that lead to critical events by crossing periodic orbit
around saddles. Both of these frameworks require computation with curves
represented by millions of points-computing intersection points between these
curves and area bounded by the segments of these curves-for quantifying the
transport and escape rate. We present a theory for computing these intersection
points and the area bounded between the segments of these curves based on a
classification of the intersection points using equivalence class. We also
present an alternate theory for curves with nontransverse intersections and a
method to increase the density of points on the curves for locating the
intersection points accurately.The numerical implementation of the theory
presented herein is available as an open source software called Lober. We used
this package to demonstrate the application of the theory to lobe dynamics that
arises in fluid mechanics, and rate of escape from a potential well that arises
in ship dynamics.Comment: 33 pages, 17 figure
Differential recognition of canonical NF-κB dimers by Importin α3
Nuclear translocation of the p50/p65 heterodimer is essential for NF-κB signaling. In unstimulated cells, p50/p65 is retained by the inhibitor IκBα in the cytoplasm that masks the p65-nuclear localization sequence (NLS). Upon activation, p50/p65 is translocated into the nucleus by the adapter importin α3 and the receptor importin β. Here, we describe a bipartite NLS in p50/p65, analogous to nucleoplasmin NLS but exposed in trans. Importin α3 accommodates the p50- and p65-NLSs at the major and minor NLS-binding pockets, respectively. The p50-NLS is the predominant binding determinant, while the p65-NLS induces a conformational change in the Armadillo 7 of importin α3 that stabilizes a helical conformation of the p65-NLS. Neither conformational change was observed for importin α1, which makes fewer bonds with the p50/p65 NLSs, explaining the preference for α3. We propose that importin α3 discriminates between the transcriptionally active p50/p65 heterodimer and p50/p50 and p65/65 homodimers, ensuring fidelity in NF-κB signaling
Efficient Dynamic Importance Sampling of Rare Events in One Dimension
Exploiting stochastic path integral theory, we obtain \emph{by simulation}
substantial gains in efficiency for the computation of reaction rates in
one-dimensional, bistable, overdamped stochastic systems. Using a well-defined
measure of efficiency, we compare implementations of ``Dynamic Importance
Sampling'' (DIMS) methods to unbiased simulation. The best DIMS algorithms are
shown to increase efficiency by factors of approximately 20 for a
barrier height and 300 for , compared to unbiased simulation. The
gains result from close emulation of natural (unbiased), instanton-like
crossing events with artificially decreased waiting times between events that
are corrected for in rate calculations. The artificial crossing events are
generated using the closed-form solution to the most probable crossing event
described by the Onsager-Machlup action. While the best biasing methods require
the second derivative of the potential (resulting from the ``Jacobian'' term in
the action, which is discussed at length), algorithms employing solely the
first derivative do nearly as well. We discuss the importance of
one-dimensional models to larger systems, and suggest extensions to
higher-dimensional systems.Comment: version to be published in Phys. Rev.
Mechanical Systems with Symmetry, Variational Principles, and Integration Algorithms
This paper studies variational principles for mechanical systems with symmetry and their applications to integration algorithms. We recall some general features of how to reduce variational principles in the presence of a symmetry group along with general features of integration algorithms for mechanical systems. Then we describe some integration algorithms based directly on variational principles using a
discretization technique of Veselov. The general idea for these variational integrators is to directly discretize Hamilton’s principle rather than the equations of motion in a way that preserves the original systems invariants, notably the symplectic form and, via a discrete version of Noether’s theorem, the momentum map. The resulting mechanical integrators are second-order accurate, implicit, symplectic-momentum algorithms. We apply these integrators to the rigid body and the double spherical pendulum to show that the techniques are competitive with existing integrators
Deep Sequencing the Transcriptome Reveals Seasonal Adaptive Mechanisms in a Hibernating Mammal
Mammalian hibernation is a complex phenotype involving metabolic rate reduction, bradycardia, profound hypothermia, and a reliance on stored fat that allows the animal to survive for months without food in a state of suspended animation. To determine the genes responsible for this phenotype in the thirteen-lined ground squirrel (Ictidomys tridecemlineatus) we used the Roche 454 platform to sequence mRNA isolated at six points throughout the year from three key tissues: heart, skeletal muscle, and white adipose tissue (WAT). Deep sequencing generated approximately 3.7 million cDNA reads from 18 samples (6 time points ×3 tissues) with a mean read length of 335 bases. Of these, 3,125,337 reads were assembled into 140,703 contigs. Approximately 90% of all sequences were matched to proteins in the human UniProt database. The total number of distinct human proteins matched by ground squirrel transcripts was 13,637 for heart, 12,496 for skeletal muscle, and 14,351 for WAT. Extensive mitochondrial RNA sequences enabled a novel approach of using the transcriptome to construct the complete mitochondrial genome for I. tridecemlineatus. Seasonal and activity-specific changes in mRNA levels that met our stringent false discovery rate cutoff (1.0×10−11) were used to identify patterns of gene expression involving various aspects of the hibernation phenotype. Among these patterns are differentially expressed genes encoding heart proteins AT1A1, NAC1 and RYR2 controlling ion transport required for contraction and relaxation at low body temperatures. Abundant RNAs in skeletal muscle coding ubiquitin pathway proteins ASB2, UBC and DDB1 peak in October, suggesting an increase in muscle proteolysis. Finally, genes in WAT that encode proteins involved in lipogenesis (ACOD, FABP4) are highly expressed in August, but gradually decline in expression during the seasonal transition to lipolysis
Complications and pitfalls of lumbar interlaminar and transforaminal epidural injections
Lumbar interlaminar and transforaminal epidural injections are used in the treatment of lumbar radicular pain and other lumbar spinal pain syndromes. Complications from these procedures arise from needle placement and the administration of medication. Potential risks include infection, hematoma, intravascular injection of medication, direct nerve trauma, subdural injection of medication, air embolism, disc entry, urinary retention, radiation exposure, and hypersensitivity reactions. The objective of this article is to review the complications of lumbar interlaminar and transforaminal epidural injections and discuss the potential pitfalls related to these procedures. We performed a comprehensive literature review through a Medline search for relevant case reports, clinical trials, and review articles. Complications from lumbar epidural injections are extremely rare. Most if not all complications can be avoided by careful technique with accurate needle placement, sterile precautions, and a thorough understanding of the relevant anatomy and contrast patterns on fluoroscopic imaging
Synchrotron Radiation Small-angle solution scattering using the mixed-mode pixel array detector
Solution small-angle X-ray scattering (SAXS) measurements were obtained using a 128  128 pixel X-ray mixed-mode pixel array detector (MMPAD) with an 860 ms readout time. The MMPAD offers advantages for SAXS experiments: a pixel full-well of >2  10 7 10 keV X-rays, a maximum flux rate of 10 8 X-rays pixel À1 s À1 , and a sub-pixel point-spread function. Data from the MMPAD were quantitatively compared with data from a charge-coupled device (CCD) fiberoptically coupled to a phosphor screen. MMPAD solution SAXS data from lysozyme solutions were of equal or better quality than data captured by the CCD. The read-noise (normalized by pixel area) of the MMPAD was less than that of the CCD by an average factor of 3.0. Short sample-to-detector distances were required owing to the small MMPAD area (19.2 mm  19.2 mm), and were revealed to be advantageous with respect to detector read-noise. As predicted by the Shannon sampling theory and confirmed by the acquisition of lysozyme solution SAXS curves, the MMPAD at short distances is capable of sufficiently sampling a solution SAXS curve for protein shape analysis. The readout speed of the MMPAD was demonstrated by continuously monitoring lysozyme sample evolution as radiation damage accumulated. These experiments prove that a small suitably configured MMPAD is appropriate for time-resolved solution scattering measurements
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