Predictive Dynamic Simulation of Healthy Sit-to-Stand Movement

This thesis situates itself at the intersection of biomedical modelling and predictive simulation to synthesize healthy human sit-to-stand movement. While the importance of sit-to-stand to physical and social well-being is known, the reasons for why and how people come to perform sit-to-stand the way we do is largely unknown. This thesis establishes the determinants of sit-to-stand in healthy people so that future researchers may investigate the effects of compromised health on sit-to-stand and then explore means of intervening to preserve and restore this motion. Previous researchers have predicted how a person rises from seated. However aspects of their models, most commonly contact and muscle models, are biomechanically inconsistent and restrict their application. These researchers also have not validated their prediction results. To address these limitations and further the study of sit-to-stand prediction, the underlying themes of this thesis are in biomechanical modelling, predictive simulation, and validation. The goal of predicting sit-to-stand inspired the creation of three new models: a model of biomechanics, a model of motion, and performance criteria as a model of preference. First, the human is represented as three rigid links in the sagittal plane. As buttocks are kinetically important to sit-to-stand, a new constitutive model of buttocks is made from experimental force-deformation data. Ten muscles responsible for flexion and extension of the hips, knees, and ankles are defined in the model. Second, candidate sit-to-stand trajectories are described geometrically by a set of Bézier curves, for the first time. Third, with the assumption that healthy people naturally prioritize mechanical efficiency, disinclination to a motion is described as a cost function of joint torques, muscle stresses, and physical infeasibility including slipping and falling. This new dynamic optimization routine allows for motions of gradually increasing complexity, by adding control points to the Bézier curves, while the model's performance is improving. By comparing the predictive simulation results to normative sit-to-stand as described in the literature, for the first time, it is possible to say that the use of these models and optimal control strategy together has produced motions characteristic of healthy sit-to-stand. This work bridges the gap between predictive simulation results and experimental human results and in doing so establishes a benchmark in sit-to-stand prediction. In predicting healthy sit-to-stand, it makes a necessary step toward predicting pathological sit-to-stand, and then to predicting the results of intervention to inform medical design and planning

How deep is deep enough? -- Quantifying class separability in the hidden layers of deep neural networks

Deep neural networks typically outperform more traditional machine learning models in their ability to classify complex data, and yet is not clear how the individual hidden layers of a deep network contribute to the overall classification performance. We thus introduce a Generalized Discrimination Value (GDV) that measures, in a non-invasive manner, how well different data classes separate in each given network layer. The GDV can be used for the automatic tuning of hyper-parameters, such as the width profile and the total depth of a network. Moreover, the layer-dependent GDV(L) provides new insights into the data transformations that self-organize during training: In the case of multi-layer perceptrons trained with error backpropagation, we find that classification of highly complex data sets requires a temporal {\em reduction} of class separability, marked by a characteristic 'energy barrier' in the initial part of the GDV(L) curve. Even more surprisingly, for a given data set, the GDV(L) is running through a fixed 'master curve', independently from the total number of network layers. Furthermore, applying the GDV to Deep Belief Networks reveals that also unsupervised training with the Contrastive Divergence method can systematically increase class separability over tens of layers, even though the system does not 'know' the desired class labels. These results indicate that the GDV may become a useful tool to open the black box of deep learning

Integration of Leaky-Integrate-and-Fire-Neurons in Deep Learning Architectures

Up to now, modern Machine Learning is mainly based on fitting high dimensional functions to enormous data sets, taking advantage of huge hardware resources. We show that biologically inspired neuron models such as the Leaky-Integrate-and-Fire (LIF) neurons provide novel and efficient ways of information encoding. They can be integrated in Machine Learning models, and are a potential target to improve Machine Learning performance. Thus, we derived simple update-rules for the LIF units from the differential equations, which are easy to numerically integrate. We apply a novel approach to train the LIF units supervisedly via backpropagation, by assigning a constant value to the derivative of the neuron activation function exclusively for the backpropagation step. This simple mathematical trick helps to distribute the error between the neurons of the pre-connected layer. We apply our method to the IRIS blossoms image data set and show that the training technique can be used to train LIF neurons on image classification tasks. Furthermore, we show how to integrate our method in the KERAS (tensorflow) framework and efficiently run it on GPUs. To generate a deeper understanding of the mechanisms during training we developed interactive illustrations, which we provide online. With this study we want to contribute to the current efforts to enhance Machine Intelligence by integrating principles from biology

How incidents impact congestion on roadways: A queuing network approach

Motivated by the need for transportation infrastructure and incident management planning, we study traffic density under non-recurrent congestion. This paper provides an analytical solution approximating the stationary distribution of traffic density in roadways where deterioration of service occurs unpredictably. The proposed solution generalizes a queuing model discussed in the literature to long segments that are not space-homogeneous. We compare single and tandem queuing approaches to segments of different lengths and verify whether each model is appropriate. A single-queue approach works sufficiently well in segments with similar traffic behavior across space. In contrast, a tandem-queue approach more appropriately describes the density behavior for long segments with sections having distinct traffic characteristics. These models have a comparable fit to the ones generated using a lognormal distribution. However, they also have interpretable parameters, directly connecting the distribution of congestion to the dynamics of roadway behavior. The proposed models are general, adaptable, and tractable, thus being instrumental in infrastructure and incident management

NMR-spektroskopische Untersuchungen des nicht-nativen Zustands der C-terminalen Domäne des Prionenproteins aus Mensch und Maus

Die genetische Information innerhalb einer Zelle kodiert nicht nur die spezifische Struktur und Funktion von Proteinen, sondern auch die Entstehung dieser Struktur durch den Prozess der Proteinfaltung. Aus zahlreichen experimentellen und theoretischen Studien wurde offensichtlich, dass Faltung und Entfaltung von Proteinen in vielen zellulären Prozessen eine entscheidende Rolle spielt. Diese Beobachtungen führten zu der zwangsläufigen Erkenntnis, dass das Unvermögen von Proteinen sich korrekt zu falten oder korrekt gefaltet zu bleiben der Auslöser für viele verschiedene Arten biologischen Fehlverhaltens ist und infolgedessen unterschiedliche Krankheitsformen mit sich bringt. Die strukturelle und dynamische Charakterisierung von nicht-nativen Proteinzuständen ist daher eine wichtige Grundlage einerseits zur Erforschung der krankheitsauslösenden Prozesse, andererseits aber auch zum generellen Verständnis der Proteinfaltung an sich. Allein hochauflösende NMR-Experimente können detaillierte Informationen über Struktur und Dynamiken solcher Zustände auf atomarer Ebene liefern. In der vorliegenden Arbeit wurde die C-terminale Domäne des humanen Prionenproteins [hPrP(121-230)] unter Bedingungen untersucht, bei denen dieses Protein permanent in einem nicht-nativen Zustand vorliegt. Dies wurde durch die Verwendung einer hochmolaren Harnstofflösung (8 M, pH 2,0) erreicht. Zur Untersuchung dieses nicht-nativen Zustands mittels NMR wurde das PrP(121-230) in E.coli-Zellen isotopenmarkiert exprimiert und in Mengen von einigen Milligramm aufgereinigt. Nach der sequentiellen Zuordnung der 13Ca-, 13Cb-, 13CO-, 1Ha- und 1HN-Resonanzen konnte aus den sekundären chemischen Verschiebungen auf Regionen innerhalb der Polypeptidkette geschlossen werden, die erhöhte b-faltblattartige Konformationsanteile enthalten. Heteronukleare Relaxa-tionsraten wurden zur Untersuchung der konformationellen Dynamik herangezogen. Auch hier konnten Regionen verminderter Mobilität (hydrophobe Cluster) nachgewiesen werden, die mit den zuvor entdeckten Bereichen aus der Analyse der chemischen Verschiebungen übereinstimmten. Die Messung von R1r-Relaxationsraten erbrachte zudem keine Hinweise auf konformationellen Austausch auf der μs-ms-Zeitskala. Weiterhin wurde der Einfluss der Disulfidbrücke auf Konformation und Dynamik des hPrP(121-230) untersucht. Dies wurde durch die Reduktion der Disulfidbrücke und die anschließende Methylierung der beiden Cysteine erreicht. Im Gegensatz zu der Analyse der chemischen Verschiebungen zeigte die Auswertung der konformationellen Dynamiken dramatische Unterschiede zwischen den oxidierten und reduzierten Zuständen des hPrP(121-230). Insbesondere im Bereich um die beiden Cysteine konnten große Unterschiede festgestellt werden; im reduzierten Zustand führte die zusätzliche Bewegungsfreiheit zu erhöhten Dynamiken und gab den Blick auf zusätzliche hydrophobe Bereiche frei, die im oxidierten Zustand durch hohe Relaxationsraten verdeckt geblieben waren. Ein weiterer wesentlicher Unterschied zwischen dem oxidierten und dem reduzierten Zustand des hPrP(121-230), der mit Hilfe des Fluoreszenzfarbstoffes Thioflavin T beschrieben werden konnte, bestand in der Fähigkeit Fibrillen auszubilden; während das oxidierte hPrP diese Eigenschaft besaß, führte der Verlust der intakten Disulfidbrücke zu einer Proteinkonformation, die nicht mehr zur Bildung von fibrillären Strukturen im Stande war. Im weiteren Verlauf der Arbeit wurden die strukturellen, dynamischen und kinetischen Charakteristika des hPrP(121-230) mit denen des murinen Prionenproteins mPrP(121-232) sowohl im oxidierten als auch im reduzierten Zustand verglichen. Auf der Basis der chemischen Verschiebungen und der heteronuklearen Relaxationsdaten konnte gezeigt werden, dass beide Proteine in den jeweiligen komplementären Zuständen (oxidiert bzw. reduziert) sehr ähnliche strukturelle und dynamische Eigenschaften besitzen. Aufgrund einiger Aminosäureaustausche in den beiden Proteinsequenzen kommt es jedoch zu kleineren Unterschieden, die jedoch nur in lokalen Bereichen der Polypeptidkette zum Tragen kommen. Somit konnte gezeigt werden, dass das mPrP(121-232) als ein geeignetes Modellsystem für das humane Prionenprotein dienen kann. Abschließend wurde der Einfluss von insgesamt zwölf verschiedenen Punktmutationen, die beim Menschen mit Prionenerkrankungen assoziiert sind, auf das Aggregationsverhalten des mPrP(121-232) untersucht. Dabei fiel zum einen auf, dass die Aggregation mit zunehmender Proteinkonzentration schneller verlief, zum anderen aber auch, dass es insbesondere bei geringen Proteinkonzentrationen zu signifikanten Unterschieden in der Aggregationsgeschwindigkeit der verschiedenen mutierten Proteinkonstrukte kommt. Zusammenfassend ist festzustellen, dass in dieser Arbeit strukturelle und dynamische Eigenschaften der nicht-nativen Zustände von hPrP(121-230) und mPrP(121-232) sowohl im oxidierten als auch im reduzierten Zustand durch die Verwendung von NMRspektroskopischen Experimenten charakterisiert werden konnten. Zudem konnte mit Hilfe von Fluoreszenzspektroskopie das Aggregationsverhalten der einzelnen Proteinzustände beschrieben und in einem ersten Schritt der Einfluss von verschiedenen Punktmutationen auf die Aggregationsgeschwindigkeit ermittelt werden

Anthropocene U: Academic responses and responsibilities at Lakehead University

This thesis explores the stories of six faculty members and administrators at Lakehead University who are responding to the Anthropocene through their academic work. Their stories suggest that there are barriers facing academic engagement with the Anthropocene and the associated possibilities for action are uniquely empowered by the particular position and privileges of higher education; rich tensions arise in exploring the response-ability of the academy to the Anthropocene. I consider the planetary and pedagogical contexts from which this research develops. Then, turning to participant stories, I look to appreciative inquiry, narrative inquiry, and place inquiry to guide my interactions with their experiences in ways that intend to grow the community of scholars responding to the Anthropocene at one Canadian university, Lakehead University in Thunder Bay, Ontario. I next introduce the participants and the site of research through a series of vignettes, and explore the experiences of participants as they work to respond to the current moment on the planet. Their stories begin to illustrate the parallels between how neoliberalism has helped usher in the Anthropocene and has shaped the university in ways that minimize its ability to respond. The final chapter speaks to possibility and presents participants’ visions for a University more responsive to the Anthropocene, illustrated by photographs of places that reflect participants’ understandings of what is possible and that integrate place-voice into the research. This thesis concludes by summarizing key themes, and by daring readers to consider their own response-abilities in the Anthropocene

O dilema do consenso na solução dos conflitos metaindividuais

Orientador: Professor Doutor Elton VenturiDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Jurídicas, Programa de Pós-Graduação em Direito. Defesa : Curitiba, 02/08/2022Inclui referências: p. 104-110Resumo: O desenvolvimento social e civilizatório da sociedade humana esteve sempre dependente do aprimoramento das noções de Justiça. Com as duas guerras mundiais que marcaram a primeira metade do século XX, a democracia passou a exigir da justiça uma evolução constante no índice de proteção aos direitos fundamentais, porque eles mesmos representam a ampliação dos ideais democráticos. O pioneirismo do sistema judiciário americano ao determinar a dessegregação racial a partir do caso Brown v. Board of Education e ao utilizar as structural injunctions para tornar efetivas as decisões que garantiram a equalização dos direitos sociais mostraram um caminho independente para que outras instituições se habilitassem na permanente construção da democracia. Além do papel sempre relevante dos tribunais, a experiência brasileira apresenta o singular desenho constitucional que dotou o Ministério Público de ferramentas especialmente preparadas à defesa dos direitos metaindividuais. A construção da Usina de Belo Monte é um bom exemplo da desenvoltura dessas ferramentas que serviram à estruturação de conflitos envolvendo o direito ao meio ambiente equilibrado e à preservação das comunidades humanas que habitavam e sobreviviam a partir do ecossistema do Rio Xingu. A partir da análise de casos práticos e de abalizada doutrina, a presente dissertação pretendeu superar o suposto dilema que permeia a solução consensual dos conflitos metaindividuais, firmando a compreensão de que tanto o Judiciário quanto o Ministério Público são instituições que, embora muito próximas, cumprem papéis distintos no desenho do Estado Democrático. À intervenção judicial deve ser atribuído um papel proeminente na solução de um litígio apenas quando os instrumentos disponibilizados ao Ministério Público pela Constituição Federal não se mostrem suficientes a garantir uma proteção consensual dos bens comuns.Abstract: The development of human society as well as his civilizational progress has always relied upon the comprehension of the aims of Justice. The experience of World Wars, that grievously delineate the first half of the 20th century, demanded a continued development in the protection of fundamental rights, also recognizing that they themselves represent one of the most important faces of democratic ideals. The pioneering experiences of the American judicial system in determining racial desegregation in the case Brown v. Board of Education and the use of structural injunctions to make decisions effective enlighten an independent path that should be trailed by other institutions in the permanent duty of improving the democratic system. In addition to the relevant role of the courts, the Brazilian experience presents the unique constitutional design that has endowed the Ministério Público with special tools just wellcrafted for the defense of meta-individual rights. The construction of the Belo Monte Power Plant is a good example of the resourcefulness of these tools that served to structure disputes involving the right to the balanced environment and the preservation of human communities that inhabited and survived from the Xingu River ecosystem. From the analysis of practical cases and assigned doctrine, this dissertation aimed to overcome the supposed dilemma that permeates the consensual solution of meta-individual disputes, establishing the understanding that both the Judiciary and the Ministério Público are institutions that, although very close, fulfill distinct roles in the design of the Democratic State. Judicial intervention should be given a prominent role in the settlement of a dispute only when the tools used by the Ministério Público are not enough to ensure consensual protection of the common property.Résumé : Le développement social et civilisateur de la société humaine a toujours été lié à l'amélioration de la compréhension de la justice. L'impact des deux guerres mondiales qui a marqué la première moitié du 20ème siècle a déterminé la suprématie de la démocratie et une évolution constante de la protection des droits fondamentaux, eux-mêmes signes de l'expansion des idéaux démocratiques. L'innovation du système judiciaire américain portée par la déségrégation raciale à partir de l'arrêt Brown v. Board of Education et l'utilisation des structural injonctions pour rendre efficaces les décisions qui ont assuré l'égalité social ont montré une voie indépendante viables à d'autres institutions dans le travail constant de construction de la démocratie. En plus du rôle toujours pertinent des tribunaux, l'expérience brésilienne présente la conception constitutionnelle unique qui a doté le ministère public d'outils spécialement préparés pour la défense des droits méta-individuels. La construction de la centrale électrique de Belo Monte est un bon exemple de l'ingéniosité de ces outils et de sa utilisation pour structurer les disputes autour du droit à un environnement équilibré et de la préservation des communautés humaines qui habitaient et survivaient à l'écosystème du bassin du Xingu. À partir de l'analyse de cas pratiques et de la doctrine assignée, cette thèse visait à surmonter le dilemme supposé qui imprègne la solution consensuelle des disputes métaindividuels, en établissant la compréhension que le pouvoir judiciaire et le ministère public sont des institutions qui, bien que très proches, remplissent des rôles distincts dans la conception de l'État démocratique. L'intervention judiciaire ne devrait jouer un rôle de premier plan dans le règlement d'un litige que lorsque les instruments mis à la disposition du ministère public par la Constitution fédérale ne sont pas suffisants pour assurer une protection consensuelle des biens communs