72 research outputs found
Variance fluctuations in nonstationary time series: a comparative study of music genres
An important problem in physics concerns the analysis of audio time series
generated by transduced acoustic phenomena. Here, we develop a new method to
quantify the scaling properties of the local variance of nonstationary time
series. We apply this technique to analyze audio signals obtained from selected
genres of music. We find quantitative differences in the correlation properties
of high art music, popular music, and dance music. We discuss the relevance of
these objective findings in relation to the subjective experience of music.Comment: 13 pages, 4 fig
Deterministic walks in random networks: an application to thesaurus graphs
In a landscape composed of N randomly distributed sites in Euclidean space, a
walker (``tourist'') goes to the nearest one that has not been visited in the
last \tau steps. This procedure leads to trajectories composed of a transient
part and a final cyclic attractor of period p. The tourist walk presents
universal aspects with respect to \tau and can be done in a wide range of
networks that can be viewed as ordinal neighborhood graphs. As an example, we
show that graphs defined by thesaurus dictionaries share some of the
statistical properties of low dimensional (d=2) Euclidean graphs and are easily
distinguished from random graphs. This approach furnishes complementary
information to the usual clustering coefficient and mean minimum separation
length.Comment: 12 pages, 5 figures, revised version submited to Physica A, corrected
references to figure
Exploratory Behavior, Trap Models and Glass Transitions
A random walk is performed on a disordered landscape composed of sites
randomly and uniformly distributed inside a -dimensional hypercube. The
walker hops from one site to another with probability proportional to , where is the inverse of a formal temperature and
is an arbitrary cost function which depends on the hop distance .
Analytic results indicate that, if and , there
exists a glass transition at . Below
, the average trapping time diverges and the system falls into an
out-of-equilibrium regime with aging phenomena. A L\'evy flight scenario and
applications to exploratory behavior are considered.Comment: 4 pages, 1 figure, new versio
Escaping from cycles through a glass transition
A random walk is performed over a disordered media composed of sites
random and uniformly distributed inside a -dimensional hypercube. The walker
cannot remain in the same site and hops to one of its neighboring sites
with a transition probability that depends on the distance between sites
according to a cost function . The stochasticity level is parametrized by
a formal temperature . In the case , the walk is deterministic and
ergodicity is broken: the phase space is divided in a number of
attractor basins of two-cycles that trap the walker. For , analytic
results indicate the existence of a glass transition at as . Below , the average trapping time in two-cycles diverges and
out-of-equilibrium behavior appears. Similar glass transitions occur in higher
dimensions choosing a proper cost function. We also present some results for
the statistics of distances for Poisson spatial point processes.Comment: 11 pages, 4 figure
Truncated Levy Random Walks and Generalized Cauchy Processes
A continuous Markovian model for truncated Levy random walks is proposed. It
generalizes the approach developed previously by Lubashevsky et al. Phys. Rev.
E 79, 011110 (2009); 80, 031148 (2009), Eur. Phys. J. B 78, 207 (2010) allowing
for nonlinear friction in wondering particle motion and saturation of the noise
intensity depending on the particle velocity. Both the effects have own reason
to be considered and individually give rise to truncated Levy random walks as
shown in the paper. The nonlinear Langevin equation governing the particle
motion was solved numerically using an order 1.5 strong stochastic Runge-Kutta
method and the obtained numerical data were employed to calculate the geometric
mean of the particle displacement during a certain time interval and to
construct its distribution function. It is demonstrated that the time
dependence of the geometric mean comprises three fragments following one
another as the time scale increases that can be categorized as the ballistic
regime, the Levy type regime (superballistic, quasiballistic, or superdiffusive
one), and the standard motion of Brownian particles. For the intermediate Levy
type part the distribution of the particle displacement is found to be of the
generalized Cauchy form with cutoff. Besides, the properties of the random
walks at hand are shown to be determined mainly by a certain ratio of the
friction coefficient and the noise intensity rather then their characteristics
individually.Comment: 7 pages, 3 figure
Self-avoiding walks and connective constants in small-world networks
Long-distance characteristics of small-world networks have been studied by
means of self-avoiding walks (SAW's). We consider networks generated by
rewiring links in one- and two-dimensional regular lattices. The number of
SAW's was obtained from numerical simulations as a function of the number
of steps on the considered networks. The so-called connective constant,
, which characterizes the long-distance
behavior of the walks, increases continuously with disorder strength (or
rewiring probability, ). For small , one has a linear relation , and being constants dependent on the underlying
lattice. Close to one finds the behavior expected for random graphs. An
analytical approach is given to account for the results derived from numerical
simulations. Both methods yield results agreeing with each other for small ,
and differ for close to 1, because of the different connectivity
distributions resulting in both cases.Comment: 7 pages, 5 figure
Classical Infinite-Range-Interaction Heisenberg Ferromagnetic Model: Metastability and Sensitivity to Initial Conditions
A N-sized inertial classical Heisenberg ferromagnet, which consists in a
modification of the well-known standard model, where the spins are replaced by
classical rotators, is studied in the limit of infinite-range interactions. The
usual canonical-ensemble mean-field solution of the inertial classical
-vector ferromagnet (for which recovers the particular Heisenberg
model considered herein) is briefly reviewed, showing the well-known
second-order phase transition. This Heisenberg model is studied numerically
within the microcanonical ensemble, through molecular dynamics.Comment: 18 pages text, and 7 EPS figure
Weak Localization Effect in Superconductors by Radiation Damage
Large reductions of the superconducting transition temperature and
the accompanying loss of the thermal electrical resistivity (electron-phonon
interaction) due to radiation damage have been observed for several A15
compounds, Chevrel phase and Ternary superconductors, and in
the high fluence regime. We examine these behaviors based on the recent theory
of weak localization effect in superconductors. We find a good fitting to the
experimental data. In particular, weak localization correction to the
phonon-mediated interaction is derived from the density correlation function.
It is shown that weak localization has a strong influence on both the
phonon-mediated interaction and the electron-phonon interaction, which leads to
the universal correlation of and resistance ratio.Comment: 16 pages plus 3 figures, revtex, 76 references, For more information,
Plesse see http://www.fen.bilkent.edu.tr/~yjki
Safety and efficacy of vanzacaftor–tezacaftor–deutivacaftor in adults with cystic fibrosis: randomised, double-blind, controlled, phase 2 trials
Background
Elexacaftor–tezacaftor–ivacaftor has been shown to be safe and efficacious in people with cystic fibrosis and at least one F508del allele. Our aim was to identify a novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination capable of further increasing CFTR-mediated chloride transport, with the potential for once-daily dosing.
Methods
We conducted two phase 2 clinical trials to assess the safety and efficacy of a once-daily combination of vanzacaftor–tezacaftor–deutivacaftor in participants with cystic fibrosis who were aged 18 years or older. A phase 2 randomised, double-blind, active-controlled study (VX18-561-101; April 17, 2019, to Aug 20, 2020) was carried out to compare deutivacaftor monotherapy with ivacaftor monotherapy in participants with CFTR gating mutations, following a 4-week ivacaftor monotherapy run-in period. Participants were randomly assigned to receive either ivacaftor 150 mg every 12 h, deutivacaftor 25 mg once daily, deutivacaftor 50 mg once daily, deutivacaftor 150 mg once daily, or deutivacaftor 250 mg once daily in a 1:1:2:2:2 ratio. The primary endpoint was absolute change in ppFEV1 from baseline at week 12. A phase 2 randomised, double-blind, controlled, proof-of-concept study of vanzacaftor–tezacaftor–deutivacaftor (VX18-121-101; April 30, 2019, to Dec 10, 2019) was conducted in participants with cystic fibrosis and heterozygous for F508del and a minimal function mutation (F/MF genotypes) or homozygous for F508del (F/F genotype). Participants with F/MF genotypes were randomly assigned 1:2:2:1 to receive either 5 mg, 10 mg, or 20 mg of vanzacaftor in combination with tezacaftor–deutivacaftor or a triple placebo for 4 weeks, and participants with the F/F genotype were randomly assigned 2:1 to receive either vanzacaftor (20 mg)–tezacaftor–deutivacaftor or tezacaftor–ivacaftor active control for 4 weeks, following a 4-week tezacaftor–ivacaftor run-in period. Primary endpoints for part 1 and part 2 were safety and tolerability and absolute change in ppFEV1 from baseline to day 29. Secondary efficacy endpoints were absolute change from baseline at day 29 in sweat chloride concentrations and Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score. These clinical trials are registered with ClinicalTrials.gov, NCT03911713 and NCT03912233, and are complete.
Findings
In study VX18-561-101, participants treated with deutivacaftor 150 mg once daily (n=23) or deutivacaftor 250 mg once daily (n=24) had mean absolute changes in ppFEV1 of 3·1 percentage points (95% CI –0·8 to 7·0) and 2·7 percentage points (–1·0 to 6·5) from baseline at week 12, respectively, versus –0·8 percentage points (–6·2 to 4·7) with ivacaftor 150 mg every 12 h (n=11); the deutivacaftor safety profile was consistent with the established safety profile of ivacaftor 150 mg every 12 h. In study VX18-121-101, participants with F/MF genotypes treated with vanzacaftor (5 mg)–tezacaftor–deutivacaftor (n=9), vanzacaftor (10 mg)–tezacaftor–deutivacaftor (n=19), vanzacaftor (20 mg)–tezacaftor–deutivacaftor (n=20), and placebo (n=10) had mean changes relative to baseline at day 29 in ppFEV1 of 4·6 percentage points (−1·3 to 10·6), 14·2 percentage points (10·0 to 18·4), 9·8 percentage points (5·7 to 13·8), and 1·9 percentage points (−4·1 to 8·0), respectively, in sweat chloride concentration of −42·8 mmol/L (–51·7 to –34·0), −45·8 mmol/L (95% CI –51·9 to –39·7), −49·5 mmol/L (–55·9 to –43·1), and 2·3 mmol/L (−7·0 to 11·6), respectively, and in CFQ-R respiratory domain score of 17·6 points (3·5 to 31·6), 21·2 points (11·9 to 30·6), 29·8 points (21·0 to 38·7), and 3·3 points (−10·1 to 16·6), respectively. Participants with the F/F genotype treated with vanzacaftor (20 mg)–tezacaftor–deutivacaftor (n=18) and tezacaftor–ivacaftor (n=10) had mean changes relative to baseline (taking tezacaftor–ivacaftor) at day 29 in ppFEV1 of 15·9 percentage points (11·3 to 20·6) and −0·1 percentage points (−6·4 to 6·1), respectively, in sweat chloride concentration of −45·5 mmol/L (−49·7 to −41·3) and −2·6 mmol/L (−8·2 to 3·1), respectively, and in CFQ-R respiratory domain score of 19·4 points (95% CI 10·5 to 28·3) and −5·0 points (−16·9 to 7·0), respectively. The most common adverse events overall were cough, increased sputum, and headache. One participant in the vanzacaftor–tezacaftor–deutivacaftor group had a serious adverse event of infective pulmonary exacerbation and another participant had a serious rash event that led to treatment discontinuation. For most participants, adverse events were mild or moderate in severity.
Interpretation
Once-daily dosing with vanzacaftor–tezacaftor–deutivacaftor was safe and well tolerated and improved lung function, respiratory symptoms, and CFTR function. These results support the continued investigation of vanzacaftor–tezacaftor–deutivacaftor in phase 3 clinical trials compared with elexacaftor–tezacaftor–ivacaftor.
Funding
Vertex Pharmaceuticals
Understanding Network Mobility in Pervasive Markets: Realistic Human Shopping Behavioral Model
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