43 research outputs found
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
Die Folgen der dem Kinde angebornen oder in seinen ersten Lebensjahren eingetretenen Taubstummheit, wenn nicht durch Unterricht und Erziehung denselben entgegengearbeitet wird
Allgemeine Andeutung der GrundsĂ€tze und GrundzĂŒge zur Ertheilung eines elementarischen materiellen Sprachunterrichts
Analyse und Konzeption eines Hitzeschildexperimentes mit einer C/SiC-Faserkeramikkachel fĂŒr die Expresskapsel
Effectiveness of aripiprazole once-monthly in schizophrenia patients pretreated with oral aripiprazole: a 6-month, real-life non-interventional study
Abstract Background In this study, the treatment of schizophrenia patients with aripiprazole once-monthly (AOM) was evaluated under real-life conditions in a naturalistic setting. Methods This multicenter, prospective, non-interventional study included 242 patients (ageâ=â43.1â±â15.1 years, 55.0% male) who were monitored during 6 months of AOM treatment. Endpoints included measurements of psychopathology (Brief Psychiatric Rating Scale, BPRS) and severity of illness scales (Clinical Global Impressions-Severity, CGI-S, and -Improvement, CGI-I). Furthermore, treatment-related adverse events (TRAEs) were recorded. Results At baseline, the mean BPRS total score was 54.1â±â15.6, the mean CGI-S was 4.8â±â0.8 and the most frequent illness category was âmarkedly illâ (41.7%). Patients had been pretreated with oral aripiprazole for a mean duration of 9.7 months (SD: 22.3) and 87.9% were deemed by their clinician as âclinically stableâ and for a mean of 5.9 months. The difference in global BPRS after 6 months was ââ13.8 (SD: 16.0; 95% CI: [ââ15.9; ââ11.7]; pâ<â0.001). The proportion of patients with high CGI-S scores decreased and the proportion of patients with low scores increased significantly (pâ<â0.001, respectively). BPRS scores improved numerically especially well in younger patients â€35 years, CGI-S scores decreased significantly more in this population. TRAEs were rare, with low incidences of extrapyramidal symptoms (2.9%) or weight increase (0.4%). Conclusions Treatment with AOM showed satisfying effectiveness in outpatients with further improvement of psychopathology after oral aripiprazole treatment for a considerable duration and even after having achieved clinically judged âstabilityâ. Our findings indicate a robust therapeutic effect of AOM and substantiate previous results from randomized controlled trials under real-world routine conditions
Correction to: Effectiveness of aripiprazole once-monthly in schizophrenia patients pretreated with oral aripiprazole: a 6-month, real-life non-interventional study
Following publication of the original articl