A Slow Axon Antidromic Blockade Hypothesis for Tremor Reduction via Deep Brain Stimulation

Parkinsonian and essential tremor can often be effectively treated by deep brain stimulation. We propose a novel explanation for the mechanism by which this technique ameliorates tremor: a reduction of the delay in the relevant motor control loops via preferential antidromic blockade of slow axons. The antidromic blockade is preferential because the pulses more rapidly clear fast axons, and the distribution of axonal diameters, and therefore velocities, in the involved tracts, is sufficiently long-tailed to make this effect quite significant. The preferential blockade of slow axons, combined with gain adaptation, results in a reduction of the mean delay in the motor control loop, which serves to stabilize the feedback system, thus ameliorating tremor. This theory, without any tuning, accounts for several previously perplexing phenomena, and makes a variety of novel predictions

ALISSA: an automated live-cell imaging system for signal transduction analyses

Probe photobleaching and a specimen’s sensitivity to phototoxicity severely limit the number of possible excitation cycles in time-lapse fluorescent microscopy experiments. Consequently, when a study of cellular processes requires measurements over hours or days, temporal resolution is limited, and spontaneous or rapid events may be missed, thus limiting conclusions about transduction events. We have developed ALISSA, a design framework and reference implementation for an automated live-cell imaging system for signal transduction analysis. It allows an adaptation of image modalities and laser resources tailored to the biological process, and thereby extends temporal resolution from minutes to seconds. The system employs online image analysis to detect cellular events that are then used to exercise microscope control. It consists of a reusable image analysis software for cell segmentation, tracking, and time series extraction, and a measurement-specific process control software that can be easily adapted to various biological settings. We have applied the ALISSA framework to the analysis of apoptosis as a demonstration case for slow onset and rapid execution signaling. The demonstration provides a clear proof-of-concept for ALISSA, and offers guidelines for its application in a broad spectrum of signal transduction studies

A Rewriting-Logic-Based Technique for Modeling Thermal Systems

This paper presents a rewriting-logic-based modeling and analysis technique for physical systems, with focus on thermal systems. The contributions of this paper can be summarized as follows: (i) providing a framework for modeling and executing physical systems, where both the physical components and their physical interactions are treated as first-class citizens; (ii) showing how heat transfer problems in thermal systems can be modeled in Real-Time Maude; (iii) giving the implementation in Real-Time Maude of a basic numerical technique for executing continuous behaviors in object-oriented hybrid systems; and (iv) illustrating these techniques with a set of incremental case studies using realistic physical parameters, with examples of simulation and model checking analyses.Comment: In Proceedings RTRTS 2010, arXiv:1009.398

Systems medicine and integrated care to combat chronic noncommunicable diseases

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems

Re-visiting Meltsner: Policy Advice Systems and the Multi-Dimensional Nature of Professional Policy Analysis

10.2139/ssrn.15462511-2

Transmission probability of a random orthodromic spike as a function of axonal delay, at different antidromic blocking frequencies.

<p>Computations here were based on <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073456#pone.0073456.e011" target="_blank">equation (2</a>). If we negglet the refractory period, the blockade is complete when the axonal delay exceeds one-half of the interval between antidromic spikes.</p