41 research outputs found
Long-Term Safety of a Coordinated Delivery Tablet of Enteric-Coated Aspirin 325 mg and Immediate-Release Omeprazole 40 mg for Secondary Cardiovascular Disease Prevention in Patients at GI Risk
Introduction: In two, 6-month, randomized, double-blind Phase 3 trials, PA32540 (enteric-coated aspirin 325 mg and immediate-release omeprazole 40 mg) compared to aspirin alone was associated with fewer endoscopic gastric and duodenal ulcers in patients requiring aspirin therapy for secondary cardiovascular disease (CVD) prevention who were at risk for upper gastrointestinal (UGI) events. Aims: In this 12-month, open-label, multicenter Phase 3 study, we evaluated the long-term cardiovascular and gastrointestinal safety of PA32540 in subjects who were taking aspirin 325 mg daily for =3 months for secondary CVD prevention and were at risk for aspirin-associated UGI events. Enrolled subjects received PA32540 once daily for up to 12 months and were assessed at baseline, month 1, month 6, and month 12. Results: The overall safety population consisted of 379 subjects, and 290 subjects (76%) were on PA32540 for =348 days (12-month completers). Adverse events (AEs) caused study withdrawal in 13.5% of subjects, most commonly gastroesophageal reflux disease (1.1%). Treatment-emergent AEs occurred in 76% of the safety population (11% treatment-related) and 73% of 12-month completers (8% treatment-related). The most common treatment-related AE was dyspepsia (2%). One subject had a gastric ulcer observed on for-cause endoscopy. There were five cases of adjudicated nonfatal myocardial infarction, one nonfatal stroke, and one cardiovascular death, but none considered treatment-related. Conclusions: Long-term treatment with PA32540 once daily for up to 12 months in subjects at risk for aspirin-associated UGI events is not associated with any new or unexpected safety events
Effect of initial conditions on the speed of reaction-diffusion fronts
The effect of initial conditions on the speed of propagating fronts in reaction-diffusion equations is examined in the framework of the Hamilton-Jacobi theory. We study the transition between quenched and nonquenched fronts both analytically and numerically for parabolic and hyperbolic reaction diffusion. Nonhomogeneous media are also analyzed and the effect of algebraic initial conditions is also discussed
Bose-Einstein Condensate in Weak 3d Isotropic Speckle Disorder
The effect of a weak three-dimensional (3d) isotropic laser speckle disorder
on various thermodynamic properties of a dilute Bose gas is considered at zero
temperature. First, we summarize the derivation of the autocorrelation function
of laser speckles in 1d and 2d following the seminal work of Goodman. The goal
of this discussion is to show that a Gaussian approximation of this function,
proposed in some recent papers, is inconsistent with the general background of
laser speckle theory. Then we propose a possible experimental realization for
an isotropic 3d laser speckle potential and derive its corresponding
autocorrelation function. Using a Fourier transform of that function, we
calculate both condensate depletion and sound velocity of a Bose-Einstein
condensate as disorder ensemble averages of such a weak laser speckle potential
within a perturbative solution of the Gross-Pitaevskii equation. By doing so,
we reproduce the expression of the normalfluid density obtained earlier within
the treatment of Landau. This physically transparent derivation shows that
condensate particles, which are scattered by disorder, form a gas of
quasiparticles which is responsible for the normalfluid component
Spin-parity dependent tunneling of magnetization in single-molecule magnets
Single-molecule magnets facilitate the study of quantum tunneling of
magnetization at the mesoscopic level. The spin-parity effect is among the
fundamental predictions that have yet to be clearly observed. It is predicted
that quantum tunneling is suppressed at zero transverse field if the total spin
of the magnetic system is half-integer (Kramers degeneracy) but is allowed in
integer spin systems. The Landau-Zener method is used to measure the tunnel
splitting as a function of transverse field. Spin-parity dependent tunneling is
established by comparing the transverse field dependence of the tunnel
splitting of integer and half-integer spin systems.Comment: 4 pages, 6 figure
On the Problem of Dynamical Localization in the Nonlinear Schrödinger Equation with a Random Potential
Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network
Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism