1,807 research outputs found
The Sound of Topology in the AdS/CFT Correspondence
Using the gauge/gravity correspondence, we study the properties of 2-point
correlation functions of finite-temperature strongly coupled gauge field
theories, defined on a curved space of general spatial topology with a dual
black hole description. We derive approximate asymptotic expressions for the
correlation functions and their poles, supported by exact numerical
calculations, and study their dependence on the dimension of spacetime and the
spatial topology. The asymptotic structure of the correlation functions depends
on the relation between the spatial curvature and the temperature, and is
noticeable when they are of the same order. In the case of a hyperbolic
topology, a specific temperature is identified for which exact analytical
solutions exist for all types of perturbations. The asymptotic structure of the
correlation functions poles is found to behave in a non-smooth manner when
approaching this temperature.Comment: 65 pages, LaTeX, 21 figures, 1 table; fixed a small error in
subsection 3.
MemBrain: Improving the Accuracy of Predicting Transmembrane Helices
Prediction of transmembrane helices (TMH) in α helical membrane proteins provides valuable information about the protein topology when the high resolution structures are not available. Many predictors have been developed based on either amino acid hydrophobicity scale or pure statistical approaches. While these predictors perform reasonably well in identifying the number of TMHs in a protein, they are generally inaccurate in predicting the ends of TMHs, or TMHs of unusual length. To improve the accuracy of TMH detection, we developed a machine-learning based predictor, MemBrain, which integrates a number of modern bioinformatics approaches including sequence representation by multiple sequence alignment matrix, the optimized evidence-theoretic K-nearest neighbor prediction algorithm, fusion of multiple prediction window sizes, and classification by dynamic threshold. MemBrain demonstrates an overall improvement of about 20% in prediction accuracy, particularly, in predicting the ends of TMHs and TMHs that are shorter than 15 residues. It also has the capability to detect N-terminal signal peptides. The MemBrain predictor is a useful sequence-based analysis tool for functional and structural characterization of helical membrane proteins; it is freely available at http://chou.med.harvard.edu/bioinf/MemBrain/
Generating Temperature Flow for eta/s with Higher Derivatives: From Lifshitz to AdS
We consider charged dilatonic black branes in AdS_5 and examine the effects
of perturbative higher derivative corrections on the ratio of shear viscosity
to entropy density eta/s of the dual plasma. The structure of eta/s is
controlled by the relative hierarchy between the two scales in the plasma, the
temperature and the chemical potential. In this model the background
near-horizon geometry interpolates between a Lifshitz-like brane at low
temperature, and an AdS brane at high temperatures -- with AdS asymptotics in
both cases. As a result, in this construction the viscosity to entropy ratio
flows as a function of temperature, from a value in the IR which is sensitive
to the dynamical exponent z, to the simple result expected for an AdS brane in
the UV. Coupling the scalar directly to the higher derivative terms generates
additional temperature dependence, and leads to a particularly interesting
structure for eta/s in the IR.Comment: Plots and references added. Journal version of the pape
Potentials of Mean Force for Protein Structure Prediction Vindicated, Formalized and Generalized
Understanding protein structure is of crucial importance in science, medicine
and biotechnology. For about two decades, knowledge based potentials based on
pairwise distances -- so-called "potentials of mean force" (PMFs) -- have been
center stage in the prediction and design of protein structure and the
simulation of protein folding. However, the validity, scope and limitations of
these potentials are still vigorously debated and disputed, and the optimal
choice of the reference state -- a necessary component of these potentials --
is an unsolved problem. PMFs are loosely justified by analogy to the reversible
work theorem in statistical physics, or by a statistical argument based on a
likelihood function. Both justifications are insightful but leave many
questions unanswered. Here, we show for the first time that PMFs can be seen as
approximations to quantities that do have a rigorous probabilistic
justification: they naturally arise when probability distributions over
different features of proteins need to be combined. We call these quantities
reference ratio distributions deriving from the application of the reference
ratio method. This new view is not only of theoretical relevance, but leads to
many insights that are of direct practical use: the reference state is uniquely
defined and does not require external physical insights; the approach can be
generalized beyond pairwise distances to arbitrary features of protein
structure; and it becomes clear for which purposes the use of these quantities
is justified. We illustrate these insights with two applications, involving the
radius of gyration and hydrogen bonding. In the latter case, we also show how
the reference ratio method can be iteratively applied to sculpt an energy
funnel. Our results considerably increase the understanding and scope of energy
functions derived from known biomolecular structures
Wall roughness induces asymptotic ultimate turbulence
Turbulence is omnipresent in Nature and technology, governing the transport
of heat, mass, and momentum on multiple scales. For real-world applications of
wall-bounded turbulence, the underlying surfaces are virtually always rough;
yet characterizing and understanding the effects of wall roughness for
turbulence remains a challenge, especially for rotating and thermally driven
turbulence. By combining extensive experiments and numerical simulations, here,
taking as example the paradigmatic Taylor-Couette system (the closed flow
between two independently rotating coaxial cylinders), we show how wall
roughness greatly enhances the overall transport properties and the
corresponding scaling exponents. If only one of the walls is rough, we reveal
that the bulk velocity is slaved to the rough side, due to the much stronger
coupling to that wall by the detaching flow structures. If both walls are
rough, the viscosity dependence is thoroughly eliminated in the boundary layers
and we thus achieve asymptotic ultimate turbulence, i.e. the upper limit of
transport, whose existence had been predicted by Robert Kraichnan in 1962
(Phys. Fluids {\bf 5}, 1374 (1962)) and in which the scalings laws can be
extrapolated to arbitrarily large Reynolds numbers
Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities
Laboratory evaluation of patients with developmental delay/intellectual disability, congenital anomalies, and dysmorphic features has changed significantly in the last several years with the introduction of microarray technologies. Using these techniques, a patient’s genome can be examined for gains or losses of genetic material too small to be detected by standard G-banded chromosome studies. This increased resolution of microarray technology over conventional cytogenetic analysis allows for identification of chromosomal imbalances with greater precision, accuracy, and technical sensitivity. A variety of array-based platforms are now available for use in clinical practice, and utilization strategies are evolving. Thus, a review of the utility and limitations of these techniques and recommendations regarding present and future application in the clinical setting are presented in this study
Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.
We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease
Physiological IRE-1-XBP-1 and PEK-1 Signaling in Caenorhabditis elegans Larval Development and Immunity
Endoplasmic reticulum (ER) stress activates the Unfolded Protein Response, a compensatory signaling response that is mediated by the IRE-1, PERK/PEK-1, and ATF-6 pathways in metazoans. Genetic studies have implicated roles for UPR signaling in animal development and disease, but the function of the UPR under physiological conditions, in the absence of chemical agents administered to induce ER stress, is not well understood. Here, we show that in Caenorhabditis elegans XBP-1 deficiency results in constitutive ER stress, reflected by increased basal levels of IRE-1 and PEK-1 activity under physiological conditions. We define a dynamic, temperature-dependent requirement for XBP-1 and PEK-1 activities that increases with immune activation and at elevated physiological temperatures in C. elegans. Our data suggest that the negative feedback loops involving the activation of IRE-1-XBP-1 and PEK-1 pathways serve essential roles, not only at the extremes of ER stress, but also in the maintenance of ER homeostasis under physiological conditions.National Institutes of Health (U.S.) (grant R01-GM084477
Venous Graft-Derived Cells Participate in Peripheral Nerve Regeneration
Background: Based on growing evidence that some adult multipotent cells necessary for tissue regeneration reside in the walls of blood vessels and the clinical success of vein wrapping for functional repair of nerve damage, we hypothesized that the repair of nerves via vein wrapping is mediated by cells migrating from the implanted venous grafts into the nerve bundle. Methodology/Principal Findings: To test the hypothesis, severed femoral nerves of rats were grafted with venous grafts from animals of the opposite sex. Nerve regeneration was impaired when decellularized or irradiated venous grafts were used in comparison to untreated grafts, supporting the involvement of venous graft-derived cells in peripheral nerve repair. Donor cells bearing Y chromosomes integrated into the area of the host injured nerve and participated in remyelination and nerve regeneration. The regenerated nerve exhibited proper axonal myelination, and expressed neuronal and glial cell markers. Conclusions/Significance: These novel findings identify the mechanism by which vein wrapping promotes nerve regeneration. © 2011 Lavasani et al
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