3,807 research outputs found
Conformational selection in protein binding and function
Protein binding and function often involves conformational changes. Advanced
NMR experiments indicate that these conformational changes can occur in the
absence of ligand molecules (or with bound ligands), and that the ligands may
'select' protein conformations for binding (or unbinding). In this review, we
argue that this conformational selection requires transition times for ligand
binding and unbinding that are small compared to the dwell times of proteins in
different conformations, which is plausible for small ligand molecules. Such a
separation of timescales leads to a decoupling and temporal ordering of
binding/unbinding events and conformational changes. We propose that
conformational-selection and induced-change processes (such as induced fit) are
two sides of the same coin, because the temporal ordering is reversed in
binding and unbinding direction. Conformational-selection processes can be
characterized by a conformational excitation that occurs prior to a binding or
unbinding event, while induced-change processes exhibit a characteristic
conformational relaxation that occurs after a binding or unbinding event. We
discuss how the ordering of events can be determined from relaxation rates and
effective on- and off-rates determined in mixing experiments, and from the
conformational exchange rates measured in advanced NMR or single-molecule FRET
experiments. For larger ligand molecules such as peptides, conformational
changes and binding events can be intricately coupled and exhibit aspects of
conformational-selection and induced-change processes in both binding and
unbinding direction.Comment: review article; 10 pages, 4 figures, Protein Sci. 201
Improving reconfigurable systems reliability by combining periodical test and redundancy techniques: a case study
This paper revises and introduces to the field of reconfigurable computer systems, some traditional techniques used in the fields of fault-tolerance and testing of digital circuits. The target area is that of on-board spacecraft electronics, as this class of application is a good candidate for the use of reconfigurable computing technology. Fault tolerant strategies are used in order for the system to adapt itself to the severe conditions found in space. In addition, the paper describes some problems and possible solutions for the use of reconfigurable components, based on programmable logic, in space applications
The Toric SO(10) F-Theory Landscape
Supergravity theories in more than four dimensions with grand unified gauge
symmetries are an important intermediate step towards the ultraviolet
completion of the Standard Model in string theory. Using toric geometry, we
classify and analyze six-dimensional F-theory vacua with gauge group SO(10)
taking into account Mordell-Weil U(1) and discrete gauge factors. We determine
the full matter spectrum of these models, including charged and neutral SO(10)
singlets. Based solely on the geometry, we compute all matter multiplicities
and confirm the cancellation of gauge and gravitational anomalies independent
of the base space. Particular emphasis is put on symmetry enhancements at the
loci of matter fields and to the frequent appearance of superconformal points.
They are linked to non-toric K\"ahler deformations which contribute to the
counting of degrees of freedom. We compute the anomaly coefficients for these
theories as well by using a base-independent blow-up procedure and
superconformal matter transitions. Finally, we identify six-dimensional
supergravity models which can yield the Standard Model with high-scale
supersymmetry by further compactification to four dimensions in an Abelian flux
background.Comment: 64 pages, 40 pages appendices, 18 figures, 6 Tables, references
added, published versio
Estimation and uncertainty of reversible Markov models
Reversibility is a key concept in Markov models and Master-equation models of
molecular kinetics. The analysis and interpretation of the transition matrix
encoding the kinetic properties of the model relies heavily on the
reversibility property. The estimation of a reversible transition matrix from
simulation data is therefore crucial to the successful application of the
previously developed theory. In this work we discuss methods for the maximum
likelihood estimation of transition matrices from finite simulation data and
present a new algorithm for the estimation if reversibility with respect to a
given stationary vector is desired. We also develop new methods for the
Bayesian posterior inference of reversible transition matrices with and without
given stationary vector taking into account the need for a suitable prior
distribution preserving the meta- stable features of the observed process
during posterior inference. All algorithms here are implemented in the PyEMMA
software - http://pyemma.org - as of version 2.0
‘MSM-ing’ as a networking concept: becoming a global health category
This article explores the creation of ‘MSM’ as global health category over the course of the HIV and AIDS epidemic, and across country contexts from India to southern and eastern Africa. We conceive of ‘MSM’ as a mode of ‘doing’ and ‘becoming’: ‘MSM-ing’, so to speak. Actor-network perspectives and ethnographic reflections are engaged to elucidate ‘MSM’ as a term that both enables and inhibits communications about sexualities and risks. We consider the term as a plural form of evidencing that offers wider perspectives on flows and boundaries in global health–knowledge making and HIV prevention
The ISCIP Analyst, Volume IX, Issue 2
This repository item contains a single issue of The ISCIP Analyst, an analytical review journal published from 1996 to 2010 by the Boston University Institute for the Study of Conflict, Ideology, and Policy
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