Closed-loop investigation of the dynamical properties of cardiomyocyte electrophysiology by means of Dynamic clamp and Mathematical modelling

The research field of my PhD concerns mathematical modeling and numerical simulation, applied to the cardiac electrophysiology analysis at a single cell level. This is possible thanks to the development of mathematical descriptions of single cellular components, ionic channels, pumps, exchangers and subcellular compartments. Due to the difficulties of vivo experiments on human cells, most of the measurements are acquired in vitro using animal models (e.g. guinea pig, dog, rabbit). Moreover, to study the cardiac action potential and all its features, it is necessary to acquire more specific knowledge about single ionic currents that contribute to the cardiac activity. Electrophysiological models of the heart have become very accurate in recent years giving rise to extremely complicated systems of differential equations. Although describing the behavior of cardiac cells quite well, the models are computationally demanding for numerical simulations and are very difficult to analyze from a mathematical (dynamical-systems) viewpoint. Simplified mathematical models that capture the underlying dynamics to a certain extent are therefore frequently used. The results presented in this thesis have confirmed that a close integration of computational modeling and experimental recordings in real myocytes, as performed by dynamic clamp, is a useful tool in enhancing our understanding of various components of normal cardiac electrophysiology, but also arrhythmogenic mechanisms in a pathological condition, especially when fully integrated with experimental data.

Seawater carbonate chemistry, nutrients and growth rate during experiments with coral Astrangia poculata and field observations, 2010

Zooxanthellate colonies of the scleractinian coral Astrangia poculata were grown under combinations of ambient and elevated nutrients (5 µM NO, 0.3 µM PO4, and 2nM Fe) and CO2 (780 ppmv) treatments for a period of 6 months. Coral calcification rates, estimated from buoyant weights, were not significantly affected by moderately elevated nutrients at ambient CO2 and were negatively affected by elevated CO2 at ambient nutrient levels. However, calcification by corals reared under elevated nutrients combined with elevated CO2 was not significantly different from that of corals reared under ambient conditions, suggesting that CO2 enrichment can lead to nutrient limitation in zooxanthellate corals. A conceptual model is proposed to explain how nutrients and CO2 interact to control zooxanthellate coral calcification. Nutrient limited corals are unable to utilize an increase in dissolved inorganic carbon (DIC) as nutrients are already limiting growth, thus the effect of elevated CO2 on saturation state drives the calcification response. Under nutrient replete conditions, corals may have the ability to utilize more DIC, thus the calcification response to CO2 becomes the product of a negative effect on saturation state and a positive effect on gross carbon fixation, depending upon which dominates, the calcification response can be either positive or negative. This may help explain how the range of coral responses found in different studies of ocean acidification can be obtained.

Description, geochemistry, mineralogy and isotopes of sulfides from ODP Site 193-1189, PACMANUS field

Chemical and isotopic data for rare massive and semimassive sulfide samples cored at Site 1189 (Roman Ruins, PACMANUS) suggest their genetic relationship with sulfide chimneys at the seafloor. Sand collected from the hammer drill after commencement of Hole 1189B indicates that at least the lower section of the cased interval was occupied by material similar to the stockwork zone cored from 31 to ~100 meters below seafloor (mbsf) in this hole, but with increased content of barite, sphalerite, and lead-bearing minerals. Fractional crystallization of ascending hydrothermal fluid involving early precipitation of pyrite may explain vertical mineralogical and chemical zoning within the stockwork conduit and the high base and precious metal contents of Roman Ruins chimneys. A mineralized volcaniclastic unit cored deep in Hole 1189A possibly represents the lateral fringe of the conduit system. Lead isotope ratios in the sulfides differ slightly but significantly from those of fresh lavas from Pual Ridge, implying that at least some of the Pb within the Roman Ruins hydrothermal system derived from a deeper, more radiogenic source than the enclosing altered volcanic rocks.

Electrostatic plasma instabilities excited by a high‐frequency electric field

The electrostatic plasma waves excited by a uniform, alternating electric field of arbitrary intensity are studied on the basis of the Vlasov equation; their dispersion relation, which involves the determinant of either of two infinite matrices, is derived. For ω0 ≫ ωpi (ω0 being the applied frequency and ωpi the ion plasma frequency) the waves may be classified in two groups, each satisfying a simple condition; this allows writing the dispersion relation in closed form. Both groups coalesce (resonance) if (a) ω0  ≈  ωpe/r (r any integer) and (b) the wavenumber k is small. A nonoscillatory instability is found; its distinction from the DuBois‐Goldman instability and its physical origin are discussed. Conditions for its excitation (in particular, upper limits to ω0,k, and k⋅vE,vE being the field‐induced electron velocity), and simple equations for the growth rate are given off‐resonance and at ω0  ≈  ωpi. The dependence of both threshold and maximum growth rate on various parameters is discussed, and the results are compared with those of Silin and Nishikawa. The threshold at ω0  ≈  ωpi/r,r  ≠  1, is studied.

Magnetic self-field effects on bare-tether current collection

It has been recently suggested that the magnetic field created by the current in a bare tether could sensibly reduce its electron collection capability in the magnetised ionosphere, a region of closed magnetic surfaces disconnecting the cylinder from infinity. In this paper, the ohmic voltage drop along the tether is taken into account in considering self-field effects. Separate analyses are carried out for the thrust and power generation and drag modes of operation, which are affected in different ways. In the power generation and drag modes, bias decreases as current increases along the tether, starting at the anodic, positively-biased end (upper end in the usual, eastward-flying spacecraft); in the thrust mode of operation, bias increases as current increases along the tether, starting at the lower end. When the ohmic voltage drop is considered, self-field effects are shown to be weak, in all cases, for tape tethers, and for circular cross-section tethers just conductive in a thin outer layer. Self-field effects might become important, in the drag case only, for tethers with fully conductive cross sections that are unrealistically heavy.

Gravitational actions upon a tether in a non-uniform gravity field with arbitrary number of zonal harmonics

We develop general closed-form expressions for the mutual gravitational potential, resultant and torque acting upon a rigid tethered system moving in a non-uniform gravity field produced by an attracting body with revolution symmetry, such that an arbitrary number of zonal harmonics is considered. The final expressions are series expansion in two small parameters related to the reference radius of the primary and the length of the tether, respectively, each of which are scaled by the mutual distance between their centers of mass. A few numerical experiments are performed to study the convergence behavior of the final expressions, and conclude that for high precision applications it might be necessary to take into account additional perturbation terms, which come from the mutual Two-Body interaction.

A management model for closed-loop supply chains of reusable articles

This PhD dissertation is framed in the emergent fields of Reverse Logistics and ClosedLoop Supply Chain (CLSC) management. This subarea of supply chain management has gained researchers and practitioners' attention over the last 15 years to become a fully recognized subdiscipline of the Operations Management field. More specifically, among all the activities that are included within the CLSC area, the focus of this dissertation is centered in direct reuse aspects. The main contribution of this dissertation to current knowledge is twofold. First, a framework for the so-called reuse CLSC is developed. This conceptual model is grounded in a set of six case studies conducted by the author in real industrial settings. The model has also been contrasted with existing literature and with academic and professional experts on the topic as well. The framework encompasses four building blocks. In the first block, a typology for reusable articles is put forward, distinguishing between Returnable Transport Items (RTI), Reusable Packaging Materials (RPM), and Reusable Products (RP). In the second block, the common characteristics that render reuse CLSC difficult to manage from a logistical standpoint are identified, namely: fleet shrinkage, significant investment and limited visibility. In the third block, the main problems arising in the management of reuse CLSC are analyzed, such as: (1) define fleet size dimension, (2) control cycle time and promote articles rotation, (3) control return rate and prevent shrinkage, (4) define purchase policies for new articles, (5) plan and control reconditioning activities, and (6) balance inventory between depots. Finally, in the fourth block some solutions to those issues are developed. Firstly, problems (2) and (3) are addressed through the comparative analysis of alternative strategies for controlling cycle time and return rate. Secondly, a methodology for calculating the required fleet size is elaborated (problem (1)). This methodology is valid for different configurations of the physical flows in the reuse CLSC. Likewise, some directions are pointed out for further development of a similar method for defining purchase policies for new articles (problem (4)). The second main contribution of this dissertation is embedded in the solutions part (block 4) of the conceptual framework and comprises a two-level decision problem integrating two mixed integer linear programming (MILP) models that have been formulated and solved to optimality using AIMMS as modeling language, CPLEX as solver and Excel spreadsheet for data introduction and output presentation. The results obtained are analyzed in order to measure in a client-supplier system the economic impact of two alternative control strategies (recovery policies) in the context of reuse. In addition, the models support decision-making regarding the selection of the appropriate recovery policy against the characteristics of demand pattern and the structure of the relevant costs in the system. The triangulation of methods used in this thesis has enabled to address the same research topic with different approaches and thus, the robustness of the results obtained is strengthened.

Towards Closed-loop Deep Brain Stimulation: Behavior Recognition from Human STN

Deep brain stimulation (DBS) provides significant therapeutic benefit for movement disorders such as Parkinson’s disease (PD). Current DBS devices lack real-time feedback (thus are open loop) and stimulation parameters are adjusted during scheduled visits with a clinician. A closed-loop DBS system may reduce power consumption and side effects by adjusting stimulation parameters based on patient’s behavior. Thus behavior detection is a major step in designing such systems. Various physiological signals can be used to recognize the behaviors. Subthalamic Nucleus (STN) Local field Potential (LFP) is a great candidate signal for the neural feedback, because it can be recorded from the stimulation lead and does not require additional sensors. This thesis proposes novel detection and classification techniques for behavior recognition based on deep brain LFP. Behavior detection from such signals is the vital step in developing the next generation of closed-loop DBS devices. LFP recordings from 13 subjects are utilized in this study to design and evaluate our method. Recordings were performed during the surgery and the subjects were asked to perform various behavioral tasks. Various techniques are used understand how the behaviors modulate the STN. One method studies the time-frequency patterns in the STN LFP during the tasks. Another method measures the temporal inter-hemispheric connectivity of the STN as well as the connectivity between STN and Pre-frontal Cortex (PFC). Experimental results demonstrate that different behaviors create different m odulation patterns in STN and it’s connectivity. We use these patterns as features to classify behaviors. A method for single trial recognition of the patient’s current task is proposed. This method uses wavelet coefficients as features and support vector machine (SVM) as the classifier for recognition of a selection of behaviors: speech, motor, and random. The proposed method is 82.4% accurate for the binary classification and 73.2% for classifying three tasks. As the next step, a practical behavior detection method which asynchronously detects behaviors is proposed. This method does not use any priori knowledge of behavior onsets and is capable of asynchronously detect the finger movements of PD patients. Our study indicates that there is a motor-modulated inter-hemispheric connectivity between LFP signals recorded bilaterally from STN. We utilize a non-linear regression method to measure this inter-hemispheric connectivity and to detect the finger movements. Our experimental results using STN LFP recorded from eight patients with PD demonstrate this is a promising approach for behavior detection and developing novel closed-loop DBS systems.

Closed-Loop Deep Brain Stimulation: Bidirectional Neuroprosthetics for Tremor and BCI

Thesis (Ph.D.)--University of Washington, 2016-06

Photodegradation of polyaromatic hydrocarbons in passive air samplers: Field testing different deployment chambers

Semi-permeable membrane devices (SPMDs) were loaded with deuterated anthracene and pyrene as performance reference compounds (PRCs) and deployed at a test site in four different chambers (open and closed box chamber, bowl chamber and cage chamber) for 29 days. The losses of PRCs and the uptake of polyaromatic hydrocarbons (PAHs) from the ambient air were quantified. UV-B levels measured in each deployment chamber indicated that SPMDs would be exposed to the most UV-B in the cage chamber and open box chamber. Significantly less PAHs were quantified in SPMDs deployed in the cage chamber and open box chamber compared to samplers from the other two chambers, suggesting that photodegradation of PAHs had occurred. The loss of PRCs confirmed these results but also showed that photodegradation was occurring in the closed box chamber. The bowl chamber appears to provide the best protection from the influence of direct photodegradation. (c) 2006 Elsevier Ltd. All rights reserved.

Electronic Education in the Field of Electrical Engineering Disciplines. Combined Didactic Interactive Program System

At present in the educational process of electrical engineering disciplines electronic learning program, providing control over reproductive educational-cognitive activity (the decision of standard problems) and universal modeling program systems, for instance Electronics Workbench, giving a chance of organizing productive, in particular research activity are basically used. However universal modeling program systems can not provide auto control over educational-cognitive activity because of the absence of the feedback with students. The combined didactic interactive program system, providing the closed directed auto control over both the reproductive and productive heuristic educational-cognitive activity of the student is offered.

Methodology for Language Analysis and Generation in Closed Domains: Pharmaceutical Leaflet

The best results in the application of computer science systems to automatic translation are obtained in word processing when texts pertain to specific thematic areas, with structures well defined and a concise and limited lexicon. In this article we present a plan of systematic work for the analysis and generation of language applied to the field of pharmaceutical leaflet, a type of document characterized by format rigidity and precision in the use of lexicon. We propose a solution based in the use of one interlingua as language pivot between source and target languages; we are considering Spanish and Arab languages in this case of application.

Optical Control of Magnetic Feshbach Resonances by Closed-Channel Electromagnetically Induced Transparency

Optical control of interactions in ultracold gases opens new fields of research by creating ``designer" interactions with high spatial and temporal resolution. However, previous optical methods using single optical fields generally suffer from atom loss due to spontaneous scattering. This thesis reports new optical methods, employing two optical fields to control interactions in ultracold gases, while suppressing spontaneous scattering by quantum interference. In this dissertation, I will discuss the experimental demonstration of two optical field methods to control narrow and broad magnetic Feshbach resonances in an ultracold gas of $^6$Li atoms. The narrow Feshbach resonance is shifted by $30$ times its width and atom loss suppressed by destructive quantum interference. Near the broad Feshbach resonance, the spontaneous lifetime of the atoms is increased from $0.5$ ms for single field methods to $400$ ms using our two optical field method. Furthermore, I report on a new theoretical model, the continuum-dressed state model, that calculates the optically induced scattering phase shift for both the broad and narrow Feshbach resonances by treating them in a unified manner. The continuum-dressed state model fits the experimental data both in shape and magnitude using only one free parameter. Using the continuum-dressed state model, I illustrate the advantages of our two optical field method over single-field optical methods.

Field data on methane fluxes, temperature, soil gas profiles and microbial activities in ponds of the northeast Siberian polygonal tundra

The data files give the basic field and laboratory data on five ponds in the northeast Siberian Arctic tundra on Samoylov. The files contain water and soil temperature data of the ponds, methane fluxes, measured with closed chambers in the centres without vascular plants and the margins with vascular plants, the contribution of plant mediated fluxes on total methane fluxes, the gas concentrations (methane and dissolved inorganic carbon, oxygen) in the soil and the water column of the ponds, microbial activities (methane production, methane oxidation, aerobic and anaerobic carbon dioxide production), total carbon pools in the different horizons of the bottom soils, soil bulk density, soil substance density, and soil porosity.

Fluctuations in and out of equilibrium: Thermalization, quantum measurements and Coulomb disorder

This purely theoretical thesis covers aspects of two contemporary research fields: the non-equilibrium dynamics in quantum systems and the electronic properties of three-dimensional topological insulators. In the first part we investigate the non-equilibrium dynamics in closed quantum systems. Thanks to recent technologies, especially from the field of ultracold quantum gases, it is possible to realize such systems in the laboratory. The focus is on the influence of hydrodynamic slow modes on the thermalization process. Generic systems in equilibrium, either classical or quantum, in equilibrium are described by thermodynamics. This is characterized by an ensemble of maximal entropy, but constrained by macroscopically conserved quantities. We will show that these conservation laws slow down thermalization and the final equilibrium state can be approached only algebraically in time. When the conservation laws are violated thermalization takes place exponential in time. In a different study we calculate probability distributions of projective quantum measurements. Newly developed quantum microscopes provide the opportunity to realize new measurement protocols which go far beyond the conventional measurements of correlation functions. The second part of this thesis is dedicated to a new class of materials known as three-dimensional topological insulators. Also here new experimental techniques have made it possible to fabricate these materials to a high enough quality that their topological nature is revealed. However, their transport properties are not fully understood yet. Motivated by unusual experimental results in the optical conductivity we have investigated the formation and thermal destruction of spatially localized electron- and hole-doped regions. These are caused by charged impurities which are introduced into the material in order to make the bulk insulating. Our theoretical results are in agreement with the experiment and can explain the results semi-quantitatively. Furthermore, we study emergent lengthscales in the bulk as well as close to the conducting surface.