246 research outputs found
ER/K linked GPCR-G protein fusions systematically modulate second messenger response in cells.
FRET and BRET approaches are well established for detecting ligand induced GPCR-G protein interactions in cells. Currently, FRET/BRET assays rely on co-expression of GPCR and G protein, and hence depend on the stoichiometry and expression levels of the donor and acceptor probes. On the other hand, GPCR-G protein fusions have been used extensively to understand the selectivity of GPCR signaling pathways. However, the signaling properties of fusion proteins are not consistent across GPCRs. In this study, we describe and characterize novel sensors based on the Systematic Protein Affinity Strength Modulation (SPASM) technique. Sensors consist of a GPCR and G protein tethered by an ER/K linker flanked by FRET probes. SPASM sensors are tested for the β2-, α1-, and α2- adrenergic receptors, and adenosine type 1 receptor (A1R), tethered to Gαs-XL, Gαi2, or Gαq subunits. Agonist stimulation of β2-AR and α2-AR increases FRET signal comparable to co-expressed FRET/BRET sensors. SPASM sensors also retain signaling through the endogenous G protein milieu. Importantly, ER/K linker length systematically tunes the GPCR-G protein interaction, with consequent modulation of second messenger signaling for cognate interactions. SPASM GPCR sensors serve the dual purpose of detecting agonist-induced changes in GPCR-G protein interactions, and linking these changes to downstream signaling
Extreme events in discrete nonlinear lattices
We perform statistical analysis on discrete nonlinear waves generated though
modulational instability in the context of the Salerno model that interpolates
between the intergable Ablowitz-Ladik (AL) equation and the nonintegrable
discrete nonlinear Schrodinger (DNLS) equation. We focus on extreme events in
the form of discrete rogue or freak waves that may arise as a result of rapid
coalescence of discrete breathers or other nonlinear interaction processes. We
find power law dependence in the wave amplitude distribution accompanied by an
enhanced probability for freak events close to the integrable limit of the
equation. A characteristic peak in the extreme event probability appears that
is attributed to the onset of interaction of the discrete solitons of the AL
equation and the accompanied transition from the local to the global
stochasticity monitored through the positive Lyapunov exponent of a nonlinear
map.Comment: 5 pages, 4 figures; reference added, figure 2 correcte
Freak Waves in Random Oceanic Sea States
Freak waves are very large, rare events in a random ocean wave train. Here we
study the numerical generation of freak waves in a random sea state
characterized by the JONSWAP power spectrum. We assume, to cubic order in
nonlinearity, that the wave dynamics are governed by the nonlinear Schroedinger
(NLS) equation. We identify two parameters in the power spectrum that control
the nonlinear dynamics: the Phillips parameter and the enhancement
coefficient . We discuss how freak waves in a random sea state are more
likely to occur for large values of and . Our results are
supported by extensive numerical simulations of the NLS equation with random
initial conditions. Comparison with linear simulations are also reported.Comment: 7 pages, 6 figures, to be published in Phys. Rev. Let
Volume changes in solids induced by chemical alteration
It is a fundamental issue in material
science to understand the mechanical effects of chemical alterations. Often the
replacement of one chemical component by another in a solid induces local volume
changes. Experiments on chemical alteration in “model” materials reveal an intricate
dynamics of elastic stress build-up, fracturing and creation of porosity. In that way
permeability is increased and provides a positive feedback on the process rate.
Important examples from geology are presented
Experimental pressure solution compaction of synthetic halite/calcite aggregates.
Experimental observations are reported of weakening of sediment-like aggregates by addition of hard particles. Sieved mixtures of calcite and halite grains are experimentally compacted in drained pressure cells in the presence of a saturated aqueous solution. The individual halite grains deform easily by pressure solution creep whereas calcite grains act as hard objects and resist compaction. The fastest rate of compaction of the mixed aggregate is not obtained for a 100% halite aggregate but for a content of halite grains between 45% and 75%. We propose that this unusual compaction behavior reflects the competition between two mechanisms at the grain scale: intergranular pressure solution at grain contacts and grain boundary healing between halite grains that prevent further compaction
Structure of plastically compacting granular packings
The developing structure in systems of compacting ductile grains were studied
experimentally in two and three dimensions. In both dimensions, the peaks of
the radial distribution function were reduced, broadened, and shifted compared
with those observed in hard disk- and sphere systems. The geometrical
three--grain configurations contributing to the second peak in the radial
distribution function showed few but interesting differences between the
initial and final stages of the two dimensional compaction. The evolution of
the average coordination number as function of packing fraction is compared
with other experimental and numerical results from the literature. We conclude
that compaction history is important for the evolution of the structure of
compacting granular systems.Comment: 12 pages, 12 figure
Role of friction-induced torque in stick-slip motion
We present a minimal quasistatic 1D model describing the kinematics of the
transition from static friction to stick-slip motion of a linear elastic block
on a rigid plane. We show how the kinematics of both the precursors to
frictional sliding and the periodic stick-slip motion are controlled by the
amount of friction-induced torque at the interface. Our model provides a
general framework to understand and relate a series of recent experimental
observations, in particular the nucleation location of micro-slip instabilities
and the build up of an asymmetric field of real contact area.Comment: 6 pages, 5 figure
Linear and Nonlinear Rogue Wave Statistics in the Presence of Random Currents
We review recent progress in modeling the probability distribution of wave
heights in the deep ocean as a function of a small number of parameters
describing the local sea state. Both linear and nonlinear mechanisms of rogue
wave formation are considered. First, we show that when the average wave
steepness is small and nonlinear wave effects are subleading, the wave height
distribution is well explained by a single "freak index" parameter, which
describes the strength of (linear) wave scattering by random currents relative
to the angular spread of the incoming random sea. When the average steepness is
large, the wave height distribution takes a very similar functional form, but
the key variables determining the probability distribution are the steepness,
and the angular and frequency spread of the incoming waves. Finally, even
greater probability of extreme wave formation is predicted when linear and
nonlinear effects are acting together.Comment: 25 pages, 12 figure
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