Diffusion of a Deformable Body in a random Flow

We consider a deformable body immersed in an incompressible liquid that is randomly stirred. Sticking to physical situations in which the body departs only slightly from its spherical shape, we calculate the diffusion constant of the body. We give explicitly the dependence of the diffusion constant on the velocity correlations in the liquid and on the size of the body. We emphasize the particular case in which the random velocity field follows from thermal agitation.Comment: 9 pages, 2 figures, late

Protein-DNA computation by stochastic assembly cascade

The assembly of RecA on single-stranded DNA is measured and interpreted as a stochastic finite-state machine that is able to discriminate fine differences between sequences, a basic computational operation. RecA filaments efficiently scan DNA sequence through a cascade of random nucleation and disassembly events that is mechanistically similar to the dynamic instability of microtubules. This iterative cascade is a multistage kinetic proofreading process that amplifies minute differences, even a single base change. Our measurements suggest that this stochastic Turing-like machine can compute certain integral transforms.Comment: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC129313/ http://www.pnas.org/content/99/18/11589.abstrac

Power-Law Behavior of Power Spectra in Low Prandtl Number Rayleigh-Benard Convection

The origin of the power-law decay measured in the power spectra of low Prandtl number Rayleigh-Benard convection near the onset of chaos is addressed using long time numerical simulations of the three-dimensional Boussinesq equations in cylindrical domains. The power-law is found to arise from quasi-discontinuous changes in the slope of the time series of the heat transport associated with the nucleation of dislocation pairs and roll pinch-off events. For larger frequencies, the power spectra decay exponentially as expected for time continuous deterministic dynamics.Comment: (10 pages, 6 figures

Discerning Aggregation in Homogeneous Ensembles: A General Description of Photon Counting Spectroscopy in Diffusing Systems

In order to discern aggregation in solutions, we present a quantum mechanical analog of the photon statistics from fluorescent molecules diffusing through a focused beam. A generating functional is developed to fully describe the experimental physical system as well as the statistics. Histograms of the measured time delay between photon counts are fit by an analytical solution describing the static as well as diffusing regimes. To determine empirical fitting parameters, fluorescence correlation spectroscopy is used in parallel to the photon counting. For expedient analysis, we find that the distribution's deviation from a single Poisson shows a difference between two single fluor moments or a double fluor aggregate of the same total intensities. Initial studies were performed on fixed-state aggregates limited to dimerization. However preliminary results on reactive species suggest that the method can be used to characterize any aggregating system.Comment: 30 pages, 5 figure

Multiple-length-scale elastic instability mimics parametric resonance of nonlinear oscillators

Spatially confined rigid membranes reorganize their morphology in response to the imposed constraints. A crumpled elastic sheet presents a complex pattern of random folds focusing the deformation energy while compressing a membrane resting on a soft foundation creates a regular pattern of sinusoidal wrinkles with a broad distribution of energy. Here, we study the energy distribution for highly confined membranes and show the emergence of a new morphological instability triggered by a period-doubling bifurcation. A periodic self-organized focalization of the deformation energy is observed provided an up-down symmetry breaking, induced by the intrinsic nonlinearity of the elasticity equations, occurs. The physical model, exhibiting an analogy with parametric resonance in nonlinear oscillator, is a new theoretical toolkit to understand the morphology of various confined systems, such as coated materials or living tissues, e.g., wrinkled skin, internal structure of lungs, internal elastica of an artery, brain convolutions or formation of fingerprints. Moreover, it opens the way to new kind of microfabrication design of multiperiodic or chaotic (aperiodic) surface topography via self-organization.Comment: Submitted for publicatio

Spiral Defects in Motility Assays: A Measure of Motor Protein Force

In a commonly used motility assay, cytoskeletal filaments are observed as they glide over a surface coated with motor proteins. Defects in the motion frequently interrupt the flow of filaments. Examination of one such defect, in which a filament adopts a spiral form and rotates about a fixed point, provides a simple measure of the force exerted by the motor proteins. We demonstrate the universality of this approach by estimating the elementary forces of both myosin and kinesin

Treatment Preferences of Adult Patients with Attention-Deficit/Hyperactivity Disorder – A Discrete Choice Experiment

Jeff Schein,1 Martin Cloutier,2 Marjolaine Gauthier-Loiselle,2 Maryaline Catillon,3 Yan Meng,4 Beatrice Libchaber,2 Fanny Jiang,2 Ann Childress5 1Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, NJ, USA; 2Analysis Group, Inc, Montréal, QC, Canada; 3Analysis Group, Inc, New York, NY, USA; 4Analysis Group, Inc, London, UK; 5Center for Psychiatry and Behavioral Medicine, Las Vegas, NV, USACorrespondence: Maryaline Catillon, Analysis Group, Inc, 151 West 42nd Street, 23rd Floor, New York, NY, 10036, USA, Tel +1 857 222 6863, Email [email protected]: Understanding patient preferences for treatments may facilitate shared decision-making. This study assessed adult patient preferences for attention-deficit/hyperactivity disorder (ADHD) treatments in a sample of 600 patients in the United States (US).Methods: A web-based discrete choice experiment (DCE) survey was conducted among treated adults with ADHD. Participants were recruited from Dynata’s US panel (06/22/2023-07/06/2023). Attributes and levels, identified based on clinical inputs and published data, included efficacy and safety. Participants’ preferences were estimated using conditional logistic regression. Willingness to trade-off and attributes’ relative importance were calculated. Overall preferences for treatment profiles approximating centanafadine, lisdexamfetamine, atomoxetine, and viloxazine were estimated using adjusted total utilities. Results were stratified by current treatment status. Sensitivity analyses including participants who passed validity tests were conducted.Results: Among the 600 participants (mean age 37.9 years; 66.2% female; 50.8% treated), all attributes had a statistically significant impact on preferences for ADHD treatments (p 60% of relative importance in decision-making. Participants were willing to forgo 0.59, 0.57, 0.49, 0.32, and 0.17 percentage points of symptom improvement to achieve one-percentage-point reduced risk of insomnia, nausea, anxiety, feeling jittery, and dry mouth, respectively. Centanafadine profile had consistently higher adjusted total utilities than its comparators. Similar results were obtained in the subgroup and sensitivity analyses.Conclusion: Efficacy was the most important attribute for patients when making treatment decision, but taken together, AEs had greater relative importance than efficacy alone. Accordingly, a profile resembling that of centanafadine would be preferred by an average patient compared to key competitors due to its favorable safety profile. These findings may help improve treatment decision-making, enhance treatment satisfaction, and foster adherence.Keywords: ADHD, decision-making, discrete choice experiment, patient-centered care, patient satisfaction, patient preference, utilit