Neuropeptide Co-Release with Gaba May Explain Functional Non-Monotonic Uncertainty Responses in Dopamine Neurons

Co-release of the inhibitory neurotransmitter GABA and the neuropeptide substance-P (SP) from single axons is a conspicuous feature of the basal ganglia, yet its computational role, if any, has not been resolved. In a new learning model, co-release of GABA and SP from axons of striatal projection neurons emerges as a highly efficient way to compute the uncertainty responses that are exhibited by dopamine (DA) neurons when animals adapt to probabilistic contingencies between rewards and the stimuli that predict their delivery. Such uncertainty-related dopamine release appears to be an adaptive phenotype, because it promotes behavioral switching at opportune times. Understanding the computational linkages between SP and DA in the basal ganglia is important, because Huntington's disease is characterized by massive SP depletion, whereas Parkinson's disease is characterized by massive DA depletion.

Comparison of deterministic, stochastic and fuzzy logic uncertainty modelling for capacity extension projects of DI/WFI pharmaceutical plant utilities with variable/dynamic demand

The last 30 years have seen Fuzzy Logic (FL) emerging as a method either complementing or challenging stochastic methods as the traditional method of modelling uncertainty. But the circumstances under which FL or stochastic methods should be used are shrouded in disagreement, because the areas of application of statistical and FL methods are overlapping with differences in opinion as to when which method should be used. Lacking are practically relevant case studies comparing these two methods. This work compares stochastic and FL methods for the assessment of spare capacity on the example of pharmaceutical high purity water (HPW) utility systems. The goal of this study was to find the most appropriate method modelling uncertainty in industrial scale HPW systems. The results provide evidence which suggests that stochastic methods are superior to the methods of FL in simulating uncertainty in chemical plant utilities including HPW systems in typical cases whereby extreme events, for example peaks in demand, or day-to-day variation rather than average values are of interest. The average production output or other statistical measures may, for instance, be of interest in the assessment of workshops. Furthermore the results indicate that the stochastic model should be used only if found necessary by a deterministic simulation. Consequently, this thesis concludes that either deterministic or stochastic methods should be used to simulate uncertainty in chemical plant utility systems and by extension some process system because extreme events or the modelling of day-to-day variation are important in capacity extension projects. Other reasons supporting the suggestion that stochastic HPW models are preferred to FL HPW models include: 1. The computer code for stochastic models is typically less complex than a FL models, thus reducing code maintenance and validation issues. 2. In many respects FL models are similar to deterministic models. Thus the need for a FL model over a deterministic model is questionable in the case of industrial scale HPW systems as presented here (as well as other similar systems) since the latter requires simpler models. 3. A FL model may be difficult to "sell" to an end-user as its results represent "approximate reasoning" a definition of which is, however, lacking. 4. Stochastic models may be applied with some relatively minor modifications on other systems, whereas FL models may not. For instance, the stochastic HPW system could be used to model municipal drinking water systems, whereas the FL HPW model should or could not be used on such systems. This is because the FL and stochastic model philosophies of a HPW system are fundamentally different. The stochastic model sees schedule and volume uncertainties as random phenomena described by statistical distributions based on either estimated or historical data. The FL model, on the other hand, simulates schedule uncertainties based on estimated operator behaviour e.g. tiredness of the operators and their working schedule. But in a municipal drinking water distribution system the notion of "operator" breaks down. 5. Stochastic methods can account for uncertainties that are difficult to model with FL. The FL HPW system model does not account for dispensed volume uncertainty, as there appears to be no reasonable method to account for it with FL whereas the stochastic model includes volume uncertainty.

Uncertainty visualization in 3D scalar data

One problem in most three-dimensional (3D) scalar data visualization techniques is that they often overlook to depict uncertainty that comes with the 3D scalar data and thus fail to faithfully present the 3D scalar data and have risks which may mislead users’ interpretations, conclusions or even decisions. Therefore this thesis focuses on the study of uncertainty visualization in 3D scalar data and we seek to create better uncertainty visualization techniques, as well as to find out the advantages/disadvantages of those state-of-the-art uncertainty visualization techniques. To do this, we address three specific hypotheses: (1) the proposed Texture uncertainty visualization technique enables users to better identify scalar/error data, and provides reduced visual overload and more appropriate brightness than four state-of-the-art uncertainty visualization techniques, as demonstrated using a perceptual effectiveness user study. (2) The proposed Linked Views and Interactive Specification (LVIS) uncertainty visualization technique enables users to better search max/min scalar and error data than four state-of-the-art uncertainty visualization techniques, as demonstrated using a perceptual effectiveness user study. (3) The proposed Probabilistic Query uncertainty visualization technique, in comparison to traditional Direct Volume Rendering (DVR) methods, enables radiologists/physicians to better identify possible alternative renderings relevant to a diagnosis and the classification probabilities associated to the materials appeared on these renderings; this leads to improved decision support for diagnosis, as demonstrated in the domain of medical imaging. For each hypothesis, we test it by following/implementing a unified framework that consists of three main steps: the first main step is uncertainty data modeling, which clearly defines and generates certainty types of uncertainty associated to given 3D scalar data. The second main step is uncertainty visualization, which transforms the 3D scalar data and their associated uncertainty generated from the first main step into two-dimensional (2D) images for insight, interpretation or communication. The third main step is evaluation, which transforms the 2D images generated from the second main step into quantitative scores according to specific user tasks, and statistically analyzes the scores. As a result, the quality of each uncertainty visualization technique is determined.

Reasoning with imprecise trade-offs in decision making under certainty and uncertainty

In many real world situations, we make decisions in the presence of multiple, often conflicting and non-commensurate objectives. The process of optimizing systematically and simultaneously over a set of objective functions is known as multi-objective optimization. In multi-objective optimization, we have a (possibly exponentially large) set of decisions and each decision has a set of alternatives. Each alternative depends on the state of the world, and is evaluated with respect to a number of criteria. In this thesis, we consider the decision making problems in two scenarios. In the first scenario, the current state of the world, under which the decisions are to be made, is known in advance. In the second scenario, the current state of the world is unknown at the time of making decisions. For decision making under certainty, we consider the framework of multiobjective constraint optimization and focus on extending the algorithms to solve these models to the case where there are additional trade-offs. We focus especially on branch-and-bound algorithms that use a mini-buckets algorithm for generating the upper bound at each node of the search tree (in the context of maximizing values of objectives). Since the size of the guiding upper bound sets can become very large during the search, we introduce efficient methods for reducing these sets, yet still maintaining the upper bound property. We define a formalism for imprecise trade-offs, which allows the decision maker during the elicitation stage, to specify a preference for one multi-objective utility vector over another, and use such preferences to infer other preferences. The induced preference relation then is used to eliminate the dominated utility vectors during the computation. For testing the dominance between multi-objective utility vectors, we present three different approaches. The first is based on a linear programming approach, the second is by use of distance-based algorithm (which uses a measure of the distance between a point and a convex cone); the third approach makes use of a matrix multiplication, which results in much faster dominance checks with respect to the preference relation induced by the trade-offs. Furthermore, we show that our trade-offs approach, which is based on a preference inference technique, can also be given an alternative semantics based on the well known Multi-Attribute Utility Theory. Our comprehensive experimental results on common multi-objective constraint optimization benchmarks demonstrate that the proposed enhancements allow the algorithms to scale up to much larger problems than before. For decision making problems under uncertainty, we describe multi-objective influence diagrams, based on a set of p objectives, where utility values are vectors in Rp, and are typically only partially ordered. These can be solved by a variable elimination algorithm, leading to a set of maximal values of expected utility. If the Pareto ordering is used this set can often be prohibitively large. We consider approximate representations of the Pareto set based on ϵ-coverings, allowing much larger problems to be solved. In addition, we define a method for incorporating user trade-offs, which also greatly improves the efficiency.

Nonlinear parameter retrieval from three- and four-wave mixing in metamaterials

We present a generalized nonlinear susceptibility retrieval method for metamaterials based on transfer matrices and valid in the nondepleted pump approximation. We construct a general formalism to describe the transfer matrix method for nonlinear media and apply it to the processes of three- and four-wave mixing. The accuracy of this approach is verified via finite element simulations. The method is then reversed to give a set of equations for retrieving the nonlinear susceptibility. Finally, we apply the proposed retrieval operation to a three-wave mixing transmission experiment performed on a varactor loaded split ring resonator metamaterial sample and find quantitative agreement with an analytical effective medium theory model. © 2010 The American Physical Society.

Prices versus quantities versus bankable quantities

Quantity-based regulation with banking allows regulated firms to shift obligations across time in response to periods of unexpectedly high or low marginal costs. Despite its wide prevalence in existing and proposed emission trading programs, banking has received limited attention in past welfare analyses of policy choice under uncertainty. We address this gap with a model of banking behavior that captures two key constraints: uncertainty about the future from the firm's perspective and a limit on negative bank values (e.g. borrowing). We show conditions where banking provisions reduce price volatility and lower expected costs compared to quantity policies without banking. For plausible parameter values related to U.S. climate change policy, we find that bankable quantities produce behavior quite similar to price policies for about two decades and, during this period, improve welfare by about a $1 billion per year over fixed quantities. © 2012 Elsevier B.V.

SMERED: A Bayesian Approach to Graphical Record Linkage and De-duplication

We propose a novel unsupervised approach for linking records across arbitrarily many files, while simultaneously detecting duplicate records within files. Our key innovation is to represent the pattern of links between records as a {\em bipartite} graph, in which records are directly linked to latent true individuals, and only indirectly linked to other records. This flexible new representation of the linkage structure naturally allows us to estimate the attributes of the unique observable people in the population, calculate $k$-way posterior probabilities of matches across records, and propagate the uncertainty of record linkage into later analyses. Our linkage structure lends itself to an efficient, linear-time, hybrid Markov chain Monte Carlo algorithm, which overcomes many obstacles encountered by previously proposed methods of record linkage, despite the high dimensional parameter space. We assess our results on real and simulated data.

The FUELCON meta-architecture, II: alternatives for parameter prediction

We continue the discussion of the decision points in the FUELCON metaarchitecture. Having discussed the relation of the original expert system to its sequel projects in terms of an AND/OR tree, we consider one further domain for a neural component: parameter prediction downstream of the core reload candidate pattern generator, thus, a replacement for the NOXER simulator currently in use in the project.

Model sensitivity and uncertainty analysis using roadside air quality measurements

Most of the air quality modelling work has been so far oriented towards deterministic simulations of ambient pollutant concentrations. This traditional approach, which is based on the use of one selected model and one data set of discrete input values, does not reflect the uncertainties due to errors in model formulation and input data. Given the complexities of urban environments and the inherent limitations of mathematical modelling, it is unlikely that a single model based on routinely available meteorological and emission data will give satisfactory short-term predictions. In this study, different methods involving the use of more than one dispersion model, in association with different emission simulation methodologies and meteorological data sets, were explored for predicting best CO and benzene estimates, and related confidence bounds. The different approaches were tested using experimental data obtained during intensive monitoring campaigns in busy street canyons in Paris, France. Three relative simple dispersion models (STREET, OSPM and AEOLIUS) that are likely to be used for regulatory purposes were selected for this application. A sensitivity analysis was conducted in order to identify internal model parameters that might significantly affect results. Finally, a probabilistic methodology for assessing urban air quality was proposed.

A comprehensive copper stockpile leach model: background and parameter sensitivity

The design and development of a comprehensive computational model of a copper stockpile leach process is summarized. The computational fluid dynamic software framework PHYSICA+ and various phenomena were used to model transport phenomena, mineral reaction kinetics, bacterial effects, and heat, energy and acid balances for the overall leach process. In this paper, the performance of the model is investigated, in particular its sensitvity to particle size and ore permeability. A combination of literature and laboratory sources was used to parameterize the model. The simulation results from the leach model are compared with closely controlled column pilot scale tests. The main performance characteristics (e.g. copper recovery rate) predicted by the model compare reasonably well with the experimental data and clearly reflect the qualitiative behavior of the process in many respects. The model is used to provide a measure of the sensitivity of ore permeability on leach behavior, and simulation results are examined for several different particle size distributions.

Reliability analysis for power electronics modules

This paper discusses the reliability of power electronics modules. The approach taken combines numerical modeling techniques with experimentation and accelerated testing to identify failure modes and mechanisms for the power module structure and most importantly the root cause of a potential failure. The paper details results for two types of failure (i) wire bond fatigue and (ii) substrate delamination. Finite element method modeling techniques have been used to predict the stress distribution within the module structures. A response surface optimisation approach has been employed to enable the optimal design and parameter sensitivity to be determined. The response surface is used by a Monte Carlo method to determine the effects of uncertainty in the design.

Uncertainty analysis to minimise risk in designing micro-electronics manufacturing processes

A design methodology based on numerical modelling, integrated with optimisation techniques and statistical methods, to aid the process control of micro and nano-electronics based manufacturing processes is presented in this paper. The design methodology is demonstrated for a micro-machining process called Focused Ion Beam (FIB). This process has been modelled to help understand how a pre-defined geometry of micro- and nano- structures can be achieved using this technology. The process performance is characterised on the basis of developed Reduced Order Models (ROM) and are generated using results from a mathematical model of the Focused Ion Beam and Design of Experiment (DoE) methods. Two ion beam sources, Argon and Gallium ions, have been used to compare and quantify the process variable uncertainties that can be observed during the milling process. The evaluations of the process performance takes into account the uncertainties and variations of the process variables and are used to identify their impact on the reliability and quality of the fabricated structure. An optimisation based design task is to identify the optimal process conditions, by varying the process variables, so that certain quality objectives and requirements are achieved and imposed constraints are satisfied. The software tools used and developed to demonstrate the design methodology are also presented.