Anomalous relaxation kinetics of biological lattice-ligand binding models

We discuss theoretical models for the cooperative binding dynamics of ligands to substrates, such as dimeric motor proteins to microtubules or more extended macromolecules like tropomyosin to actin filaments. We study the effects of steric constraints, size of ligands, binding rates and interaction between neighboring proteins on the binding dynamics and binding stoichiometry. Starting from an empty lattice the binding dynamics goes, quite generally, through several stages. The first stage represents fast initial binding closely resembling the physics of random sequential adsorption processes. Typically this initial process leaves the system in a metastable locked state with many small gaps between blocks of bound molecules. In a second stage the gaps annihilate slowly as the ligands detach and reattach. This results in an algebraic decay of the gap concentration and interesting scaling behavior. Upon identifying the gaps with particles we show that the dynamics in this regime can be explained by mapping it onto various reaction-diffusion models. The final approach to equilibrium shows some interesting dynamic scaling properties. We also discuss the effect of cooperativity on the equilibrium stoichiometry, and their consequences for the interpretation of biochemical and image reconstruction results.Comment: REVTeX, 20 pages, 17 figures; review, to appear in Chemical Physics; v2: minor correction

Stronger Neural Modulation by Visual Motion Intensity in Autism Spectrum Disorders

Theories of autism spectrum disorders (ASD) have focused on altered perceptual integration of sensory features as a possible core deficit. Yet, there is little understanding of the neuronal processing of elementary sensory features in ASD. For typically developed individuals, we previously established a direct link between frequency-specific neural activity and the intensity of a specific sensory feature: Gamma-band activity in the visual cortex increased approximately linearly with the strength of visual motion. Using magnetoencephalography (MEG), we investigated whether in individuals with ASD neural activity reflect the coherence, and thus intensity, of visual motion in a similar fashion. Thirteen adult participants with ASD and 14 control participants performed a motion direction discrimination task with increasing levels of motion coherence. A polynomial regression analysis revealed that gamma-band power increased significantly stronger with motion coherence in ASD compared to controls, suggesting excessive visual activation with increasing stimulus intensity originating from motion-responsive visual areas V3, V6 and hMT/V5. Enhanced neural responses with increasing stimulus intensity suggest an enhanced response gain in ASD. Response gain is controlled by excitatory-inhibitory interactions, which also drive high-frequency oscillations in the gamma-band. Thus, our data suggest that a disturbed excitatoryinhibitory balance underlies enhanced neural responses to coherent motion in ASD

Assessing composition in modeling approaches

Modeling approaches are based on various paradigms, e.g., aspect-oriented, feature-oriented, object-oriented, and logic-based. Modeling approaches may cover requirements models to low-level design models, are developed for various purposes, use various means of composition, and thus are difficult to compare. However, such comparisons are critical to help practitioners know under which conditions approaches are most applicable, and how they might be successfully generalized and combined to achieve end-to-end methods. This paper reports on work done at the 2nd International Comparing Modeling Approaches (CMA) workshop towards the goal of identifying potential comprehensive modeling methodologies with a particular emphasis on composition: (i) an improved set of comparison criteria; (ii) 19 assessments of modeling approaches based on the comparison criteria and a common, focused case study

Comparison of glideback and flyback boosters

© American Institute of Aeronautics and AstronauticsM. R. Tetlow; U. M. Schottle; G. M. Schneide

Fibrosis and adventitious bursae in plantar fat pad of forefoot: MR imaging findings in asymptomatic volunteers and MR imaging-histologic comparison

PURPOSE: To retrospectively evaluate plantar fat pad (PFP) signal intensity alterations in magnetic resonance (MR) imaging studies of asymptomatic volunteers and to compare PFP alterations with histopathologic findings in cadavers and patients. MATERIALS AND METHODS: After appropriate institutional review board approval and any required informed consent were obtained, MR imaging studies of 70 asymptomatic volunteers (35 women, 35 men; mean age, 45 years; range, 21-69 years) obtained for another investigation were retrospectively analyzed by two musculoskeletal radiologists in consensus. The location, signal intensity, margin, extent, and size of PFP alterations were determined. MR imaging-histopathologic comparison was performed in six cadaveric feet and six feet of symptomatic patients (one woman, five men; mean age, 43 years; range, 31-60 years). For volunteers, the relationship between PFP alterations and Morton neuroma, age, and sex was analyzed by using the Fisher exact test, Spearman rank correlation, and the Wilcoxon rank sum test, respectively. Bonferroni correction was applied, and P < .01 was considered to indicate a significant difference. RESULTS: Fifty-nine (84%) volunteers had PFP signal intensity alterations. Forty-nine (70%), six (9%), one (1%), four (6%), and 43 (61%) volunteers had alterations beneath the first, second, third, fourth, and fifth metatarsal heads, respectively. Ninety-four (91%) of 103 signal intensity alterations were in the form of hypointensity on T2-weighted images. Blurred margins were present in 90 (87%) alterations. Ninety percent of all PFP alterations in asymptomatic volunteers were 14 mm or smaller. The relationship between PFP alterations and Morton neuroma, age, and sex was not statistically significant. In cadaveric forefeet, PFP alterations corresponded histopathologically to a variable amount of fibrosis. In nine PFP alterations, development of fluid-containing spaces resembling bursae was present. Among the six patients with PFP alterations, histopathologic examination revealed fibrosis and adventitious bursae in two, fibrosis with inflammation in three, and a soft-tissue chondroma in one. CONCLUSION: PFP signal intensity alterations are commonly seen in asymptomatic volunteers under the first and fifth metatarsal heads. At histologic examination, PFP signal intensity alterations correspond most commonly to fibrosis and adventitious bursae