At chemical synapses, an arriving electric signal induces the fusion of vesicles with the presynaptic membrane, thereby releasing neurotransmitters into the synaptic cleft. After a fusion event, both the release site and the vesicle undergo a recovery process before becoming available for reuse again. Of central interest is the question which of the two restoration steps acts as the limiting factor during neurotransmission under high-frequency sustained stimulation. In order to investigate this question, we introduce a novel non-linear reaction network which involves explicit recovery steps for both the vesicles and the release sites, and includes the induced time-dependent output current. The associated reaction dynamics are formulated by means of ordinary differential equations (ODEs), as well as via the associated stochastic jump process. While the stochastic jump model describes a single release site, the average over many release sites is close to the ODE solution and shares its periodic structure. The reason for this can be traced back to the insight that recovery dynamics of vesicles and release sites are statistically almost independent. A sensitivity analysis on the recovery rates based on the ODE formulation reveals that neither the vesicle nor the release site recovery step can be identified as the essential rate-limiting step but that the rate-limiting feature changes over the course of stimulation. Under sustained stimulation the dynamics given by the ODEs exhibits transient changes leading from an initial depression of the postsynaptic response to an asymptotic periodic orbit, while the individual trajectories of the stochastic jump model lack the oscillatory behavior and asymptotic periodicity of the ODE-solution.
The rostrocaudal patterning of the neural tube is a key event in early brain development. This process is mainly driven by a gradient of WNT, which defines the fate of the present neural progenitor cells in a dose dependent matter and leads to a subdivision of the tube into forebrain, midbrain and hindbrain. Although this process is extensively studied experimentally both in vivo and in vitro, an integrated view of the responsible genetic circuitry is currently lacking. In this work, we present a minimal gene regulatory model for rostrocaudal neural tube patterning. The model's nodes and architecture are determined in a data driven way, leading to a tristable configuration of mutually repressing brain regions. Analysis of the parameter sensitivity and simulations of knockdown and overexpression cases show that repression of hindbrain fate is a promising strategy for the improvement of current protocols for the generation of dopaminergic neurons in vitro. Furthermore, we combine the model with an existing model for dorsoventral neural tube patterning, to test its capabilities in an in vivo setting, by predicting the steady state pattern of a realistic three-dimensional neural tube. This reveals that the rostrocaudal pattern stacks dorsoventrally in the caudal half of the neural tube. Finally, we simulate morphogen secretion overexpression, which highlights the sensitivity of neural tube patterning to the morphogen levels.
Purpose of Study:
Little research exists on the correlation between time spent with participants in Critical Time Intervention–modeled programs, such as Coordinated Behavioral Care's (CBC) Pathway Home, and successful completion of the programs. This study explored associations between the total amount of time spent with participants in the initial 3 months of the program and positive program outcomes.
Methodology and Sample:
Data on total time spent with participants in their initial phase of the program were gathered from Pathway Home participants who were enrolled in the program from 2016 to 2019 and then were compared with program outcomes.
Results:
The study found positive correlations between amount of time spent with participants and the attendance of a behavioral health appointment within 1 month of community entry, and positive disenrollment outcomes. This study did not find predictive significance of time spent.
Implications for Case Management Practice:
Time spent with participants is a significant variable to study, yet more research is needed on its relationship to positive outcomes.
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