2,134 research outputs found
An antibody raised against a pathogenic serpin variant induces mutant-like behaviour in the wild-type protein
A monoclonal antibody (mAb) that binds to a transient intermediate may act as a catalyst for the corresponding reaction; here we show this principle can extend on a macro molecular scale to the induction of mutant-like oligomerization in a wild-type protein. Using the common pathogenic E342K (Z) variant of α1-antitrypsin as antigen-whose native state is susceptible to the formation of a proto-oligomeric intermediate-we have produced a mAb (5E3) that increases the rate of oligomerization of the wild-type (M) variant. Employing ELISA, gel shift, thermal stability and FRET time-course experiments, we show that mAb5E3 does not bind to the native state of α1-antitrypsin, but recognizes a cryptic epitope in the vicinity of the post-helix A loop and strand 4C that is revealed upon transition to the polymerization intermediate, and which persists in the ensuing oligomer. This epitope is not shared by loop-inserted monomeric conformations. We show the increased amenity to polymerization by either the pathogenic E342K mutation or the binding of mAb5E3 occurs without affecting the energetic barrier to polymerization. As mAb5E3 also does not alter the relative stability of the monomer to intermediate, it acts in a manner similar to the E342K mutant, by facilitating the conformational interchange between these two states
Nature of the spin-glass phase at experimental length scales
We present a massive equilibrium simulation of the three-dimensional Ising
spin glass at low temperatures. The Janus special-purpose computer has allowed
us to equilibrate, using parallel tempering, L=32 lattices down to T=0.64 Tc.
We demonstrate the relevance of equilibrium finite-size simulations to
understand experimental non-equilibrium spin glasses in the thermodynamical
limit by establishing a time-length dictionary. We conclude that
non-equilibrium experiments performed on a time scale of one hour can be
matched with equilibrium results on L=110 lattices. A detailed investigation of
the probability distribution functions of the spin and link overlap, as well as
of their correlation functions, shows that Replica Symmetry Breaking is the
appropriate theoretical framework for the physically relevant length scales.
Besides, we improve over existing methodologies to ensure equilibration in
parallel tempering simulations.Comment: 48 pages, 19 postscript figures, 9 tables. Version accepted for
publication in the Journal of Statistical Mechanic
Thermodynamic glass transition in a spin glass without time-reversal symmetry
Spin glasses are a longstanding model for the sluggish dynamics that appears
at the glass transition. However, spin glasses differ from structural glasses
for a crucial feature: they enjoy a time reversal symmetry. This symmetry can
be broken by applying an external magnetic field, but embarrassingly little is
known about the critical behaviour of a spin glass in a field. In this context,
the space dimension is crucial. Simulations are easier to interpret in a large
number of dimensions, but one must work below the upper critical dimension
(i.e., in d<6) in order for results to have relevance for experiments. Here we
show conclusive evidence for the presence of a phase transition in a
four-dimensional spin glass in a field. Two ingredients were crucial for this
achievement: massive numerical simulations were carried out on the Janus
special-purpose computer, and a new and powerful finite-size scaling method.Comment: 10 pages, 6 figure
In-situ, time resolved monitoring of uranium in BFS:OPC grout. Part 1: Corrosion in water vapour
Uranium encapsulated in grout was exposed to water vapour for extended periods of time. Through synchrotron x-ray powder difraction and tomography measurements, uranium dioxide was determined the dominant corrosion product over a 50-week time period. The oxide growth rate initiated rapidly, with rates comparable to the U+H2O reaction. Over time, the reaction rate decreased and eventually plateaued to a rate similar to the U+H2O+O2 reaction. This behaviour was not attributed to oxygen ingress, but instead the decreasing permeability of the grout, limiting oxidising species access to the metal surface
Corrosion of uranium in liquid water under vacuum contained conditions. Part 1:The initial binary U + H <sub>2</sub> O <sub>(l)</sub> system
Corrosion of uranium in liquid water under contained conditions with a headspace deuterium overpressure. Part 2:The ternary U + H <sub>2</sub> O <sub>(l)</sub> + D <sub>2</sub> system
Janus II: a new generation application-driven computer for spin-system simulations
This paper describes the architecture, the development and the implementation
of Janus II, a new generation application-driven number cruncher optimized for
Monte Carlo simulations of spin systems (mainly spin glasses). This domain of
computational physics is a recognized grand challenge of high-performance
computing: the resources necessary to study in detail theoretical models that
can make contact with experimental data are by far beyond those available using
commodity computer systems. On the other hand, several specific features of the
associated algorithms suggest that unconventional computer architectures, which
can be implemented with available electronics technologies, may lead to order
of magnitude increases in performance, reducing to acceptable values on human
scales the time needed to carry out simulation campaigns that would take
centuries on commercially available machines. Janus II is one such machine,
recently developed and commissioned, that builds upon and improves on the
successful JANUS machine, which has been used for physics since 2008 and is
still in operation today. This paper describes in detail the motivations behind
the project, the computational requirements, the architecture and the
implementation of this new machine and compares its expected performances with
those of currently available commercial systems.Comment: 28 pages, 6 figure
The three dimensional Ising spin glass in an external magnetic field: the role of the silent majority
We perform equilibrium parallel-tempering simulations of the 3D Ising
Edwards-Anderson spin glass in a field. A traditional analysis shows no signs
of a phase transition. Yet, we encounter dramatic fluctuations in the behaviour
of the model: Averages over all the data only describe the behaviour of a small
fraction of it. Therefore we develop a new approach to study the equilibrium
behaviour of the system, by classifying the measurements as a function of a
conditioning variate. We propose a finite-size scaling analysis based on the
probability distribution function of the conditioning variate, which may
accelerate the convergence to the thermodynamic limit. In this way, we find a
non-trivial spectrum of behaviours, where a part of the measurements behaves as
the average, while the majority of them shows signs of scale invariance. As a
result, we can estimate the temperature interval where the phase transition in
a field ought to lie, if it exists. Although this would-be critical regime is
unreachable with present resources, the numerical challenge is finally well
posed.Comment: 42 pages, 19 figures. Minor changes and added figure (results
unchanged
Large random correlations in individual mean field spin glass samples
We argue that complex systems must possess long range correlations and
illustrate this idea on the example of the mean field spin glass model. Defined
on the complete graph, this model has no genuine concept of distance, but the
long range character of correlations is translated into a broad distribution of
the spin-spin correlation coefficients for almost all realizations of the
random couplings. When we sample the whole phase space we find that this
distribution is so broad indeed that at low temperatures it essentially becomes
uniform, with all possible correlation values appearing with the same
probability. The distribution of correlations inside a single phase space
valley is also studied and found to be much narrower.Comment: Added a few references and a comment phras
Monte Carlo Methods for Rough Free Energy Landscapes: Population Annealing and Parallel Tempering
Parallel tempering and population annealing are both effective methods for
simulating equilibrium systems with rough free energy landscapes. Parallel
tempering, also known as replica exchange Monte Carlo, is a Markov chain Monte
Carlo method while population annealing is a sequential Monte Carlo method.
Both methods overcome the exponential slowing associated with high free energy
barriers. The convergence properties and efficiency of the two methods are
compared. For large systems, population annealing initially converges to
equilibrium more rapidly than parallel tempering for the same amount of
computational work. However, parallel tempering converges exponentially and
population annealing inversely in the computational work so that ultimately
parallel tempering approaches equilibrium more rapidly than population
annealing.Comment: 10 pages, 3 figure
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