Computational and Biochemical Approaches to Molecular Epidemiology

Mining activity in Butte, Montana has taken place, or continues to take place, within the urban residence of Butte itself. This has led to urban areas with high concentrations of toxic metals such as arsenic, lead, copper, zinc, mercury and cadmium. Advances in protein study and gene sequencing has opened the possibility of finding molecular biomarkers whose presence, absence or morphological changes could indicate disease processes in populations exposed to environmental toxins. While in principle, biomarkers can be any chemicals or metabolites, as well as proteins and genes that are indicative of exposure to xenobiotics, this study seeks to identify changes in cellular pathways that suggest chronic (or acute) exposure to low-levels of metals associated with historical mining activities on the Butte Hill that could cause oxidative stress or other stress to the cell.

Assessments and Computational Simulations in Support of a Time-Varying Mass Flow Rate Measurement Technique for Pulsatile Gas Flow

This thesis covers the correction, and verification, development, and implementation of a computational fluid dynamics (CFD) model for an orifice plate meter. Past results were corrected and further expanded on with compressibility effects of acoustic waves being taken into account. One dynamic pressure difference transducer measures the time-varying differential pressure across the orifice meter. A dynamic absolute pressure measurement is also taken at the inlet of the orifice meter, along with a suitable temperature measurement of the mean flow gas. Together these three measurements allow for an incompressible CFD simulation (using a well-tested and robust model) for the cross-section independent time-varying mass flow rate through the orifice meter. The mean value of this incompressible mass flow rate is then corrected to match the mean of the measured flow rate( obtained from a Coriolis meter located up stream of the orifice meter). Even with the mean and compressibility corrections, significant differences in the measured mass flow rates at two orifice meters in a common flow stream were observed. This means that the compressibility effects associated with pulsatile gas flows is significant in the measurement of the time-varying mass flow rate. Future work (with the approach and initial runs covered here) will provide an indirect verification of the reported mass flow rate measurements.

XML for Model Specification in Neuroscience

One of the main roles of the Neural Open Markup Language, NeuroML, is to facilitate cooperation in building, simulating, testing and publishing models of channels, neurons and networks of neurons. MorphML, which was developed as a common format for exchange of neural morphology data, is distributed as part of NeuroML but can be used as a stand-alone application. In this collection of tutorials and workshop summary, we provide an overview of these XML schemas and provide examples of their use in down-stream applications. We also summarize plans for the further development of XML specifications for modeling channels, channel distributions, and network connectivity.

SNNAP: A Tool for Teaching Neuroscience

Simulation tools aid in learning neuroscience by providing the student with an interactive environment to carry out simulated experiments and test hypotheses. The field of neuroscience is well suited for the use of simulation tools since nerve cell signaling can be described by mathematical equations and solved by computer. Neural signaling entails the propagation of electrical current along nerve membrane and transmission to neighboring neurons through synaptic connections. Action potentials and synaptic transmission can be simulated and results displayed for visualization and analysis. The neurosimulator SNNAP (Simulator for Neural Networks and Action Potentials) is a simulation environment that provides users with editors for model building, simulator engine and visual display editor. This paper presents several modeling examples that illustrate some of the capabilities and features of SNNAP. First, the Hodgkin-Huxley (HH) model is presented and the threshold phenomenon is illustrated. Second, small neural networks are described with HH models using various synaptic connections available with SNNAP. Synaptic connections may be modulated through facilitation or depression with SNNAP. A study of vesicle pool dynamics is presented using an AMPA receptor model. Finally, a central pattern generator model of the Aplysia feeding circuit is illustrated as an example of a complex network that may be studied with SNNAP. Simulation code is provided for each case study described and tasks are suggested for further investigation.

Curricular Integration of Simulations in Neuroscience - Instructional and Technical Perspectives

In recent years interactive media and tools, like scientific simulations and simulation environments or dynamic data visualizations, became established methods in the neural and cognitive sciences. Hence, university teachers of neural and cognitive sciences are faced with the challenge to integrate these media into the neuroscientific curriculum. Especially simulations and dynamic visualizations offer great opportunities for teachers and learners, since they are both illustrative and explorable. However, simulations bear instructional problems: they are abstract, demand some computer skills and conceptual knowledge about what simulations intend to explain. By following two central questions this article provides an overview on possible approaches to be applied in neuroscience education and opens perspectives for their curricular integration: (i) How can complex scientific media be transformed for educational use in an efficient and (for students on all levels) comprehensible manner and (ii) by what technical infrastructure can this transformation be supported? Exemplified by educational simulations for the neurosciences and their application in courses, answers to these questions are proposed a) by introducing a specific educational simulation approach for the neurosciences b) by introducing an e-learning environment for simulations, and c) by providing examples of curricular integration on different levels which might help academic teachers to integrate newly created or existing interactive educational resources in their courses.

Ragu: a free tool for the analysis of EEG and MEG event-related scalp field data using global randomization statistics

We present a program (Ragu; Randomization Graphical User interface) for statistical analyses of multichannel event-related EEG and MEG experiments. Based on measures of scalp field differences including all sensors, and using powerful, assumption-free randomization statistics, the program yields robust, physiologically meaningful conclusions based on the entire, untransformed, and unbiased set of measurements. Ragu accommodates up to two within-subject factors and one between-subject factor with multiple levels each. Significance is computed as function of time and can be controlled for type II errors with overall analyses. Results are displayed in an intuitive visual interface that allows further exploration of the findings. A sample analysis of an ERP experiment illustrates the different possibilities offered by Ragu. The aim of Ragu is to maximize statistical power while minimizing the need for a-priori choices of models and parameters (like inverse models or sensors of interest) that interact with and bias statistics.

Flow disturbances in stent-related coronary evaginations: a computational fluid-dynamic simulation study

Aims: Angiographic ectasias and aneurysms in stented segments have been associated with late stent thrombosis. Using optical coherence tomography (OCT), some stented segments show coronary evaginations reminiscent of ectasias. The purpose of this study was to explore, using computational fluid-dynamic (CFD) simulations, whether OCT-detected coronary evaginations can induce local changes in blood flow. Methods and results: OCT-detected evaginations are defined as outward bulges in the luminal vessel contour between struts, with the depth of the bulge exceeding the actual strut thickness. Evaginations can be characterised cross ectionally by depth and along the stented segment by total length. Assuming an ellipsoid shape, we modelled 3-D evaginations with different sizes by varying the depth from 0.2-1.0 mm, and the length from 1-9 mm. For the flow simulation we used average flow velocity data from non-diseased coronary arteries. The change in flow with varying evagination sizes was assessed using a particle tracing test where the particle transit time within the segment with evagination was compared with that of a control vessel. The presence of the evagination caused a delayed particle transit time which increased with the evagination size. The change in flow consisted locally of recirculation within the evagination, as well as flow deceleration due to a larger lumen - seen as a deflection of flow towards the evagination. Conclusions: CFD simulation of 3-D evaginations and blood flow suggests that evaginations affect flow locally, with a flow disturbance that increases with increasing evagination size.

Computational tools to investigate genetic cardiac channelopathies

The aim of this perspective article is to share with the community of ion channel scientists our thoughts and expectations regarding the increasing role that computational tools will play in the future of our field. The opinions and comments detailed here are the result of a 3-day long international exploratory workshop that took place in October 2013 and that was supported by the Swiss National Science Foundation.