954 research outputs found
Finite-size and correlation-induced effects in Mean-field Dynamics
The brain's activity is characterized by the interaction of a very large
number of neurons that are strongly affected by noise. However, signals often
arise at macroscopic scales integrating the effect of many neurons into a
reliable pattern of activity. In order to study such large neuronal assemblies,
one is often led to derive mean-field limits summarizing the effect of the
interaction of a large number of neurons into an effective signal. Classical
mean-field approaches consider the evolution of a deterministic variable, the
mean activity, thus neglecting the stochastic nature of neural behavior. In
this article, we build upon two recent approaches that include correlations and
higher order moments in mean-field equations, and study how these stochastic
effects influence the solutions of the mean-field equations, both in the limit
of an infinite number of neurons and for large yet finite networks. We
introduce a new model, the infinite model, which arises from both equations by
a rescaling of the variables and, which is invertible for finite-size networks,
and hence, provides equivalent equations to those previously derived models.
The study of this model allows us to understand qualitative behavior of such
large-scale networks. We show that, though the solutions of the deterministic
mean-field equation constitute uncorrelated solutions of the new mean-field
equations, the stability properties of limit cycles are modified by the
presence of correlations, and additional non-trivial behaviors including
periodic orbits appear when there were none in the mean field. The origin of
all these behaviors is then explored in finite-size networks where interesting
mesoscopic scale effects appear. This study leads us to show that the
infinite-size system appears as a singular limit of the network equations, and
for any finite network, the system will differ from the infinite system
The Weak Gravity Conjecture and the Viscosity Bound with Six-Derivative Corrections
The weak gravity conjecture and the shear viscosity to entropy density bound
place constraints on low energy effective field theories that may help to
distinguish which theories can be UV completed. Recently, there have been
suggestions of a possible correlation between the two constraints. In some
interesting cases, the behavior was precisely such that the conjectures were
mutually exclusive. Motivated by these works, we study the mass to charge and
shear viscosity to entropy density ratios for charged AdS5 black branes, which
are holographically dual to four-dimensional CFTs at finite temperature. We
study a family of four-derivative and six-derivative perturbative corrections
to these backgrounds. We identify the region in parameter space where the two
constraints are satisfied and in particular find that the inclusion of the
next-to-leading perturbative correction introduces wider possibilities for the
satisfaction of both constraints.Comment: 24 pages, 6 figures, v2: published version, refs added, minor
clarificatio
Discovery of Quinazolines That Activate SOS1-Mediated Nucleotide Exchange on RAS.
Proteins in the RAS family are important regulators of cellular signaling and, when mutated, can drive cancer pathogenesis. Despite considerable effort over the last 30 years, RAS proteins have proven to be recalcitrant therapeutic targets. One approach for modulating RAS signaling is to target proteins that interact with RAS, such as the guanine nucleotide exchange factor (GEF) son of sevenless homologue 1 (SOS1). Here, we report hit-to-lead studies on quinazoline-containing compounds that bind to SOS1 and activate nucleotide exchange on RAS. Using structure-based design, we refined the substituents attached to the quinazoline nucleus and built in additional interactions not present in the initial HTS hit. Optimized compounds activate nucleotide exchange at single-digit micromolar concentrations in vitro. In HeLa cells, these quinazolines increase the levels of RAS-GTP and cause signaling changes in the mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) pathway
String Theory on Warped AdS_3 and Virasoro Resonances
We investigate aspects of holographic duals to time-like warped AdS_3
space-times--which include G\"odel's universe--in string theory. Using
worldsheet techniques similar to those that have been applied to AdS_3
backgrounds, we are able to identify space-time symmetry algebras that act on
the dual boundary theory. In particular, we always find at least one Virasoro
algebra with computable central charge. Interestingly, there exists a dense set
of points in the moduli space of these models in which there is actually a
second commuting Virasoro algebra, typically with different central charge than
the first. We analyze the supersymmetry of the backgrounds, finding related
enhancements, and comment on possible interpretations of these results. We also
perform an asymptotic symmetry analysis at the level of supergravity, providing
additional support for the worldsheet analysis.Comment: 24 pages + appendice
Prognosis of acute low back pain: design of a prospective inception cohort study
BACKGROUND: Clinical guidelines generally portray acute low back pain as a benign and self-limiting condition. However, evidence about the clinical course of acute low back pain is contradictory and the risk of subsequently developing chronic low back pain remains uncertain. There are few high quality prognosis studies and none that have measured pain, disability and return to work over a 12 month period. This study aims to provide the first estimates of the one year prognosis of acute low back pain (pain of less than 2 weeks duration) in patients consulting primary care practitioners. A secondary aim is to identify factors that are associated with the prognosis of low back pain. METHODS/DESIGN: The study is a prospective inception cohort study. Consecutive patients consulting general medical practitioners, physiotherapists and chiropractors in the Sydney metropolitan region will complete a baseline questionnaire regarding their back pain. Subsequently these patients will be followed up by telephone 6 weeks, 3 months and 12 months after the initial consultation. Patients will be considered to have recovered from the episode of back pain if they have no pain and no limitation of activity, and have returned to pre-injury work status. Life tables will be generated to determine the one year prognosis of acute low back pain. Prognostic factors will be assessed using Cox regression. DISCUSSION: This study will provide the first estimates of the one year prognosis of acute low back pain in a representative sample of primary care patients
Reaction rates and transport in neutron stars
Understanding signals from neutron stars requires knowledge about the
transport inside the star. We review the transport properties and the
underlying reaction rates of dense hadronic and quark matter in the crust and
the core of neutron stars and point out open problems and future directions.Comment: 74 pages; commissioned for the book "Physics and Astrophysics of
Neutron Stars", NewCompStar COST Action MP1304; version 3: minor changes,
references updated, overview graphic added in the introduction, improvements
in Sec IV.A.
Probing crunching AdS cosmologies
Holographic gravity duals of deformations of CFTs formulated on de Sitter spacetime contain FRW geometries behind a horizon, with cosmological big crunch singularities. Using a specific analytically tractable solution within a particular single scalar truncation of N=8 supergravity on AdS_4, we first probe such crunching cosmologies with spacelike radial geodesics that compute spatially antipodal correlators of large dimension boundary operators. At late times, the geodesics lie on the FRW slice of maximal expansion behind the horizon. The late time two-point functions factorise, and when transformed to the Einstein static universe, they exhibit a temporal non-analyticity determined by the maximal value of the scale factor a_max. Radial geodesics connecting antipodal points necessarily have de Sitter energy E < a_max, while geodesics with E > a_max terminate at the crunch, the two categories of geodesics being separated by the maximal expansion slice.The spacelike crunch singularity is curved ``outward'' in the Penrose diagram for the deformed AdS backgrounds, and thus geodesic limits of the antipodal correlators do not directly probe the crunch. Beyond the geodesic limit, we point out that the scalar wave equation, analytically continued into the FRW patch, has a potential which is singular at the crunch along with complex WKB turning points in the vicinity of the FRW crunch. We then argue that the frequency space Green's function has a branch point determined by a_max which corresponds to the lowest quasinormal frequency
MHC class I A region diversity and polymorphism in macaque species
The HLA-A locus represents a single copy gene that displays abundant allelic polymorphism in the human population, whereas, in contrast, a nonhuman primate species such as the rhesus macaque (Macaca mulatta) possesses multiple HLA-A-like (Mamu-A) genes, which parade varying degrees of polymorphism. The number and combination of transcribed Mamu-A genes present per chromosome display diversity in a population of Indian animals. At present, it is not clearly understood whether these different A region configurations are evolutionarily stable entities. To shed light on this issue, rhesus macaques from a Chinese population and a panel of cynomolgus monkeys (Macaca fascicularis) were screened for various A region-linked variations. Comparisons demonstrated that most A region configurations are old entities predating macaque speciation, whereas most allelic variation (>95%) is of more recent origin. The latter situation contrasts the observations of the major histocompatibility complex class II genes in rhesus and cynomolgus macaques, which share a high number of identical alleles (>30%) as defined by exon 2 sequencing
Observation of associated near-side and away-side long-range correlations in âsNN=5.02ââTeV proton-lead collisions with the ATLAS detector
Two-particle correlations in relative azimuthal angle (ÎÏ) and pseudorapidity (Îη) are measured in âsNN=5.02ââTeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1ââÎŒb-1 of data as a function of transverse momentum (pT) and the transverse energy (ÎŁETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Îη|<5) ânear-sideâ (ÎÏâŒ0) correlation that grows rapidly with increasing ÎŁETPb. A long-range âaway-sideâ (ÎÏâŒÏ) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ÎŁETPb, is found to match the near-side correlation in magnitude, shape (in Îη and ÎÏ) and ÎŁETPb dependence. The resultant ÎÏ correlation is approximately symmetric about Ï/2, and is consistent with a dominant cosâĄ2ÎÏ modulation for all ÎŁETPb ranges and particle pT
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