Use of uniform designs in combination with neural networks for viral infection process development

This work aimed to compare the predictive capacity of empirical models, based on the uniform design utilization combined to artificial neural networks with respect to classical factorial designs in bioprocess, using as example the rabies virus replication in BHK-21 cells. The viral infection process parameters under study were temperature (34°C, 37°C), multiplicity of infection (0.04, 0.07, 0.1), times of infection, and harvest (24, 48, 72 hours) and the monitored output parameter was viral production. A multilevel factorial experimental design was performed for the study of this system. Fractions of this experimental approach (18, 24, 30, 36 and 42 runs), defined according uniform designs, were used as alternative for modelling through artificial neural network and thereafter an output variable optimization was carried out by means of genetic algorithm methodology. Model prediction capacities for all uniform design approaches under study were better than that found for classical factorial design approach. It was demonstrated that uniform design in combination with artificial neural network could be an efficient experimental approach for modelling complex bioprocess like viral production. For the present study case, 67% of experimental resources were saved when compared to a classical factorial design approach. In the near future, this strategy could replace the established factorial designs used in the bioprocess development activities performed within biopharmaceutical organizations because of the improvements gained in the economics of experimentation that do not sacrifice the quality of decisions.

Tool condition monitoring of aluminum oxide grinding wheel in dressing operation using acoustic emission and neural networks

The grinding operation gives workpieces their final finish, minimizing surface roughness through the interaction between the abrasive grains of a tool (grinding wheel) and the workpiece. However, excessive grinding wheel wear due to friction renders the tool unsuitable for further use, thus requiring the dressing operation to remove and/or sharpen the cutting edges of the worn grains to render them reusable. The purpose of this study was to monitor the dressing operation using the acoustic emission (AE) signal and statistics derived from this signal, classifying the grinding wheel as sharp or dull by means of artificial neural networks. An aluminum oxide wheel installed on a surface grinding machine, a signal acquisition system, and a single-point dresser were used in the experiments. Tests were performed varying overlap ratios and dressing depths. The root mean square values and two additional statistics were calculated based on the raw AE data. A multilayer perceptron neural network was used with the Levenberg-Marquardt learning algorithm, whose inputs were the aforementioned statistics. The results indicate that this method was successful in classifying the conditions of the grinding wheel in the dressing process, identifying the tool as "sharp''(with cutting capacity) or "dull''(with loss of cutting capacity), thus reducing the time and cost of the operation and minimizing excessive removal of abrasive material from the grinding wheel.

The use of artificial neural networks in analysing the nutritional ecology of Chrysomya megacephala (F.) (Diptera: Calliphoridae), compared with a statistical model

Artificial neural networks (ANNs) have been widely applied to the resolution of complex biological problems. An important feature of neural models is that their implementation is not precluded by the theoretical distribution shape of the data used. Frequently, the performance of ANNs over linear or non-linear regression-based statistical methods is deemed to be significantly superior if suitable sample sizes are provided, especially in multidimensional and non-linear processes. The current work was aimed at utilising three well-known neural network methods in order to evaluate whether these models would be able to provide more accurate outcomes in relation to a conventional regression method in pupal weight predictions of Chrysomya megacephala, a species of blowfly (Diptera: Calliphoridae), using larval density (i.e. the initial number of larvae), amount of available food and pupal size as input data. It was possible to notice that the neural networks yielded more accurate performances in comparison with the statistical model (multiple regression). Assessing the three types of networks utilised (Multi-layer Perceptron, Radial Basis Function and Generalised Regression Neural Network), no considerable differences between these models were detected. The superiority of these neural models over a classical statistical method represents an important fact, because more accurate models may clarify several intricate aspects concerning the nutritional ecology of blowflies.

Damage detection in beams by using artificial neural networks and dynamical parameters

In this paper is presented a multilayer perceptron neural network combined with the Nelder-Mead Simplex method to detect damage in multiple support beams. The input parameters are based on natural frequencies and modal flexibility. It was considered that only a number of modes were available and that only vertical degrees of freedom were measured. The reliability of the proposed methodology is assessed from the generation of random damages scenarios and the definition of three types of errors, which can be found during the damage identification process. Results show that the methodology can reliably determine the damage scenarios. However, its application to large beams may be limited by the high computational cost of training the neural network.

Hierarchical multi-label classification using local neural networks

Hierarchical multi-label classification is a complex classification task where the classes involved in the problem are hierarchically structured and each example may simultaneously belong to more than one class in each hierarchical level. In this paper, we extend our previous works, where we investigated a new local-based classification method that incrementally trains a multi-layer perceptron for each level of the classification hierarchy. Predictions made by a neural network in a given level are used as inputs to the neural network responsible for the prediction in the next level. We compare the proposed method with one state-of-the-art decision-tree induction method and two decision-tree induction methods, using several hierarchical multi-label classification datasets. We perform a thorough experimental analysis, showing that our method obtains competitive results to a robust global method regarding both precision and recall evaluation measures.

Deep learning for computer vision: a comparison between convolutional neural networks and hierarchical temporal memories on object recognition tasks

In recent years, Deep Learning techniques have shown to perform well on a large variety of problems both in Computer Vision and Natural Language Processing, reaching and often surpassing the state of the art on many tasks. The rise of deep learning is also revolutionizing the entire field of Machine Learning and Pattern Recognition pushing forward the concepts of automatic feature extraction and unsupervised learning in general. However, despite the strong success both in science and business, deep learning has its own limitations. It is often questioned if such techniques are only some kind of brute-force statistical approaches and if they can only work in the context of High Performance Computing with tons of data. Another important question is whether they are really biologically inspired, as claimed in certain cases, and if they can scale well in terms of "intelligence". The dissertation is focused on trying to answer these key questions in the context of Computer Vision and, in particular, Object Recognition, a task that has been heavily revolutionized by recent advances in the field. Practically speaking, these answers are based on an exhaustive comparison between two, very different, deep learning techniques on the aforementioned task: Convolutional Neural Network (CNN) and Hierarchical Temporal memory (HTM). They stand for two different approaches and points of view within the big hat of deep learning and are the best choices to understand and point out strengths and weaknesses of each of them. CNN is considered one of the most classic and powerful supervised methods used today in machine learning and pattern recognition, especially in object recognition. CNNs are well received and accepted by the scientific community and are already deployed in large corporation like Google and Facebook for solving face recognition and image auto-tagging problems. HTM, on the other hand, is known as a new emerging paradigm and a new meanly-unsupervised method, that is more biologically inspired. It tries to gain more insights from the computational neuroscience community in order to incorporate concepts like time, context and attention during the learning process which are typical of the human brain. In the end, the thesis is supposed to prove that in certain cases, with a lower quantity of data, HTM can outperform CNN.

An insulin infusion advisory system based on autotuning nonlinear model-predictive control

This paper aims at the development and evaluation of a personalized insulin infusion advisory system (IIAS), able to provide real-time estimations of the appropriate insulin infusion rate for type 1 diabetes mellitus (T1DM) patients using continuous glucose monitors and insulin pumps. The system is based on a nonlinear model-predictive controller (NMPC) that uses a personalized glucose-insulin metabolism model, consisting of two compartmental models and a recurrent neural network. The model takes as input patient's information regarding meal intake, glucose measurements, and insulin infusion rates, and provides glucose predictions. The predictions are fed to the NMPC, in order for the latter to estimate the optimum insulin infusion rates. An algorithm based on fuzzy logic has been developed for the on-line adaptation of the NMPC control parameters. The IIAS has been in silico evaluated using an appropriate simulation environment (UVa T1DM simulator). The IIAS was able to handle various meal profiles, fasting conditions, interpatient variability, intraday variation in physiological parameters, and errors in meal amount estimations.

Activation of the parieto-premotor network is associated with vivid motor imagery - a parametric FMRI study

The present study examined the neural basis of vivid motor imagery with parametrical functional magnetic resonance imaging. 22 participants performed motor imagery (MI) of six different right-hand movements that differed in terms of pointing accuracy needs and object involvement, i.e., either none, two big or two small squares had to be pointed at in alternation either with or without an object grasped with the fingers. After each imagery trial, they rated the perceived vividness of motor imagery on a 7-point scale. Results showed that increased perceived imagery vividness was parametrically associated with increasing neural activation within the left putamen, the left premotor cortex (PMC), the posterior parietal cortex of the left hemisphere, the left primary motor cortex, the left somatosensory cortex, and the left cerebellum. Within the right hemisphere, activation was found within the right cerebellum, the right putamen, and the right PMC. It is concluded that the perceived vividness of MI is parametrically associated with neural activity within sensorimotor areas. The results corroborate the hypothesis that MI is an outcome of neural computations based on movement representations located within motor areas.

Computational fluids domain reduction to a simplified fluid network

The primary goal of this project is to demonstrate the practical use of data mining algorithms to cluster a solved steady-state computational fluids simulation (CFD) flow domain into a simplified lumped-parameter network. A commercial-quality code, “cfdMine” was created using a volume-weighted k-means clustering that that can accomplish the clustering of a 20 million cell CFD domain on a single CPU in several hours or less. Additionally agglomeration and k-means Mahalanobis were added as optional post-processing steps to further enhance the separation of the clusters. The resultant nodal network is considered a reduced-order model and can be solved transiently at a very minimal computational cost. The reduced order network is then instantiated in the commercial thermal solver MuSES to perform transient conjugate heat transfer using convection predicted using a lumped network (based on steady-state CFD). When inserting the lumped nodal network into a MuSES model, the potential for developing a “localized heat transfer coefficient” is shown to be an improvement over existing techniques. Also, it was found that the use of the clustering created a new flow visualization technique. Finally, fixing clusters near equipment newly demonstrates a capability to track temperatures near specific objects (such as equipment in vehicles).

An insulin infusion advisory system for type 1 diabetes patients based on non-linear model predictive control methods

In this paper, an Insulin Infusion Advisory System (IIAS) for Type 1 diabetes patients, which use insulin pumps for the Continuous Subcutaneous Insulin Infusion (CSII) is presented. The purpose of the system is to estimate the appropriate insulin infusion rates. The system is based on a Non-Linear Model Predictive Controller (NMPC) which uses a hybrid model. The model comprises a Compartmental Model (CM), which simulates the absorption of the glucose to the blood due to meal intakes, and a Neural Network (NN), which simulates the glucose-insulin kinetics. The NN is a Recurrent NN (RNN) trained with the Real Time Recurrent Learning (RTRL) algorithm. The output of the model consists of short term glucose predictions and provides input to the NMPC, in order for the latter to estimate the optimum insulin infusion rates. For the development and the evaluation of the IIAS, data generated from a Mathematical Model (MM) of a Type 1 diabetes patient have been used. The proposed control strategy is evaluated at multiple meal disturbances, various noise levels and additional time delays. The results indicate that the implemented IIAS is capable of handling multiple meals, which correspond to realistic meal profiles, large noise levels and time delays.

Investigation on the evolution of an indoor robotic localization system based on wireless networks

This work addresses the evolution of an artificial neural network (ANN) to assist in the problem of indoor robotic localization. We investigate the design and building of an autonomous localization system based on information gathered from wireless networks (WN). The article focuses on the evolved ANN, which provides the position of a robot in a space, as in a Cartesian coordinate system, corroborating with the evolutionary robotic research area and showing its practical viability. The proposed system was tested in several experiments, evaluating not only the impact of different evolutionary computation parameters but also the role of the transfer functions on the evolution of the ANN. Results show that slight variations in the parameters lead to significant differences on the evolution process and, therefore, in the accuracy of the robot position.

NETWORK TOPOLOGY IN HUMAN PROTEIN INTERACTION DATA PREDICTS FUNCTIONAL ASSOCIATION

High-throughput assays, such as yeast two-hybrid system, have generated a huge amount of protein-protein interaction (PPI) data in the past decade. This tremendously increases the need for developing reliable methods to systematically and automatically suggest protein functions and relationships between them. With the available PPI data, it is now possible to study the functions and relationships in the context of a large-scale network. To data, several network-based schemes have been provided to effectively annotate protein functions on a large scale. However, due to those inherent noises in high-throughput data generation, new methods and algorithms should be developed to increase the reliability of functional annotations. Previous work in a yeast PPI network (Samanta and Liang, 2003) has shown that the local connection topology, particularly for two proteins sharing an unusually large number of neighbors, can predict functional associations between proteins, and hence suggest their functions. One advantage of the work is that their algorithm is not sensitive to noises (false positives) in high-throughput PPI data. In this study, we improved their prediction scheme by developing a new algorithm and new methods which we applied on a human PPI network to make a genome-wide functional inference. We used the new algorithm to measure and reduce the influence of hub proteins on detecting functionally associated proteins. We used the annotations of the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) as independent and unbiased benchmarks to evaluate our algorithms and methods within the human PPI network. We showed that, compared with the previous work from Samanta and Liang, our algorithm and methods developed in this study improved the overall quality of functional inferences for human proteins. By applying the algorithms to the human PPI network, we obtained 4,233 significant functional associations among 1,754 proteins. Further comparisons of their KEGG and GO annotations allowed us to assign 466 KEGG pathway annotations to 274 proteins and 123 GO annotations to 114 proteins with estimated false discovery rates of <21% for KEGG and <30% for GO. We clustered 1,729 proteins by their functional associations and made pathway analysis to identify several subclusters that are highly enriched in certain signaling pathways. Particularly, we performed a detailed analysis on a subcluster enriched in the transforming growth factor β signaling pathway (P<10-50) which is important in cell proliferation and tumorigenesis. Analysis of another four subclusters also suggested potential new players in six signaling pathways worthy of further experimental investigations. Our study gives clear insight into the common neighbor-based prediction scheme and provides a reliable method for large-scale functional annotations in this post-genomic era.

An Early-Warning System for Hypo-/Hyperglycemic Events Based on Fusion of Adaptive Prediction Models

Introduction: Early warning of future hypoglycemic and hyperglycemic events can improve the safety of type 1 diabetes mellitus (T1DM) patients. The aim of this study is to design and evaluate a hypoglycemia / hyperglycemia early warning system (EWS) for T1DM patients under sensor-augmented pump (SAP) therapy. Methods: The EWS is based on the combination of data-driven online adaptive prediction models and a warning algorithm. Three modeling approaches have been investigated: (i) autoregressive (ARX) models, (ii) auto-regressive with an output correction module (cARX) models, and (iii) recurrent neural network (RNN) models. The warning algorithm performs postprocessing of the models′ outputs and issues alerts if upcoming hypoglycemic/hyperglycemic events are detected. Fusion of the cARX and RNN models, due to their complementary prediction performances, resulted in the hybrid autoregressive with an output correction module/recurrent neural network (cARN)-based EWS. Results: The EWS was evaluated on 23 T1DM patients under SAP therapy. The ARX-based system achieved hypoglycemic (hyperglycemic) event prediction with median values of accuracy of 100.0% (100.0%), detection time of 10.0 (8.0) min, and daily false alarms of 0.7 (0.5). The respective values for the cARX-based system were 100.0% (100.0%), 17.5 (14.8) min, and 1.5 (1.3) and, for the RNN-based system, were 100.0% (92.0%), 8.4 (7.0) min, and 0.1 (0.2). The hybrid cARN-based EWS presented outperforming results with 100.0% (100.0%) prediction accuracy, detection 16.7 (14.7) min in advance, and 0.8 (0.8) daily false alarms. Conclusion: Combined use of cARX and RNN models for the development of an EWS outperformed the single use of each model, achieving accurate and prompt event prediction with few false alarms, thus providing increased safety and comfort.

The structural substrate of brain function: analysis of brain structural networks based on diffusion-weighted imaging

The brain is a complex neural network with a hierarchical organization and the mapping of its elements and connections is an important step towards the understanding of its function. Recent developments in diffusion-weighted imaging have provided the opportunity to reconstruct the whole-brain structural network in-vivo at a large scale level and to study the brain structural substrate in a framework that is close to the current understanding of brain function. However, methods to construct the connectome are still under development and they should be carefully evaluated. To this end, the first two studies included in my thesis aimed at improving the analytical tools specific to the methodology of brain structural networks. The first of these papers assessed the repeatability of the most common global and local network metrics used in literature to characterize the connectome, while in the second paper the validity of further metrics based on the concept of communicability was evaluated. Communicability is a broader measure of connectivity which accounts also for parallel and indirect connections. These additional paths may be important for reorganizational mechanisms in the presence of lesions as well as to enhance integration in the network. These studies showed good to excellent repeatability of global network metrics when the same methodological pipeline was applied, but more variability was detected when considering local network metrics or when using different thresholding strategies. In addition, communicability metrics have been found to add some insight into the integration properties of the network by detecting subsets of nodes that were highly interconnected or vulnerable to lesions. The other two studies used methods based on diffusion-weighted imaging to obtain knowledge concerning the relationship between functional and structural connectivity and about the etiology of schizophrenia. The third study integrated functional oscillations measured using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) as well as diffusion-weighted imaging data. The multimodal approach that was applied revealed a positive relationship between individual fluctuations of the EEG alpha-frequency and diffusion properties of specific connections of two resting-state networks. Finally, in the fourth study diffusion-weighted imaging was used to probe for a relationship between the underlying white matter tissue structure and season of birth in schizophrenia patients. The results are in line with the neurodevelopmental hypothesis of early pathological mechanisms as the origin of schizophrenia. The different analytical approaches selected in these studies also provide arguments for discussion of the current limitations in the analysis of brain structural networks. To sum up, the first studies presented in this thesis illustrated the potential of brain structural network analysis to provide useful information on features of brain functional segregation and integration using reliable network metrics. In the other two studies alternative approaches were presented. The common discussion of the four studies enabled us to highlight the benefits and possibilities for the analysis of the connectome as well as some current limitations.

Multi-Model Data Fusion to Improve an Early Warning System for Hypo-/Hyperglycemic Events

Correct predictions of future blood glucose levels in individuals with Type 1 Diabetes (T1D) can be used to provide early warning of upcoming hypo-/hyperglycemic events and thus to improve the patient's safety. To increase prediction accuracy and efficiency, various approaches have been proposed which combine multiple predictors to produce superior results compared to single predictors. Three methods for model fusion are presented and comparatively assessed. Data from 23 T1D subjects under sensor-augmented pump (SAP) therapy were used in two adaptive data-driven models (an autoregressive model with output correction - cARX, and a recurrent neural network - RNN). Data fusion techniques based on i) Dempster-Shafer Evidential Theory (DST), ii) Genetic Algorithms (GA), and iii) Genetic Programming (GP) were used to merge the complimentary performances of the prediction models. The fused output is used in a warning algorithm to issue alarms of upcoming hypo-/hyperglycemic events. The fusion schemes showed improved performance with lower root mean square errors, lower time lags, and higher correlation. In the warning algorithm, median daily false alarms (DFA) of 0.25%, and 100% correct alarms (CA) were obtained for both event types. The detection times (DT) before occurrence of events were 13.0 and 12.1 min respectively for hypo-/hyperglycemic events. Compared to the cARX and RNN models, and a linear fusion of the two, the proposed fusion schemes represents a significant improvement.