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Functional Electrical Stimulation (FES) is a technique that applies electrical currents to nervous tissue in order to actively induce muscle contraction. Recent research has shown that FES provides a promising treatment to restore functional tasks due to paralysis caused by spinal cord injury, head injury, and stroke, to mention a few. Therefore, the overarching goal of this research work is to develop FES controllers to enable patients with movement-disorder to control their limbs in a desired manner and, in particular, to aid Parkinson's patients to suppress hand tremor. In our effort to develop strategies for muscle stimulation control, we first implement a model-based control technique assuming that all the states are measurable. The Hill-type muscle model coupled with a simplified 2DoF model of the arm is used to study the performance of our proposed adaptive sliding mode controller for simulation purpose. However, in the more practical situations, human limb dynamics are extremely complicate and it is inadequate to use model based controllers, especially considering there are still technical limitations that allow in vivo measurements of muscle activity. To tackle these challenges, we have developed output feedback adaptive control approaches for a class of unknown multi-input multi-output systems. Such control strategies are first developed for linear systems, and then extended to the nonlinear case. The proposed controllers, supported by experimental results, require minimum knowledge of the system dynamics and avoid many restrictive assumptions typically found in the literature. Therefore, we expect that the results introduced in this dissertation can provide a solution for a wide class of nonlinear uncertain systems, with focus on practical issues such as partial state measurement and the presence of mismatched uncertainties. / Ph. D.

This dissertation aims to develop a formal foundation to design an adaptive output feedback predictor for a class of unknown systems where parameters and order are unknown or high-dimensional. We present a reduced-order adaptive output-predictor scheme based on modal reduction and Lyapunov's method. Moreover, the credibility of the proposed reduced-order adaptive output-predictor scheme is validated by mathematical proof, and numerical and experimental studies, such as single pendulum, double pendulum, six-link pendulum, rope as a high-dimensional rope, and EEG data. Then the dissertation goal is to experimentally validate the proposed reduced-order model parameterization technique for tracking uncertain linear time-invariant (LTI) single-input, single-output (SISO) systems. The proposed theory focuses on parameterizing a high-dimensional, uncertain model and introduces a reduced-order adaptive output predictor capable of forecasting the system's output. This predictor utilizes auto-regressive filtered vectors, incorporating the input and output history. The adaptive output predictor is a simplified and known model, making it suitable for controlling high-dimensional, uncertain SISO systems without access to full-state measurements. Specifically, this work establishes the foundation for parameterizing uncertain models, creating a virtual structure that emulates the actual system, and offering a more manageable model for control when the objective is solely to regulate the system's output. The primary focus of this research is to assess the effectiveness and output-tracking capabilities of the proposed approach. These capabilities are extensively examined across diverse platforms and hardware configurations, relying solely on input and output data from the models without incorporating any additional information on the system dynamics. In the first experiment, the predictor's ability to track the angle of a single pendulum, including additional dynamics, is evaluated using only input-output data. The second experiment targets tracking the endpoint of a rope connected to a single pendulum, where the rope emulates a high-dimensional model. A vision system is designed and employed to acquire the rope endpoint position data. Before the rope experiment, a set of experiments is conducted on single pendulum hardware to ensure the accuracy of the vision system's data collection. Comparative analysis between data from object tracking via vision and data acquired through an encoder demonstrates negligible error. Finally, the input and the endpoint output data from the rope experiment are fed into the predictor to assess its capability to track the rope endpoint position without utilizing specific knowledge of the experimental hardware. Achieving negligible error in tracking implies that the predictor provides a simple and accurate representation of the rope dynamics. Consequently, designing a controller for this known model is equivalent to designing a controller for the actual rope system dynamics. The predictor, by closely emulating the behavior of the rope, becomes a reliable surrogate model for control design, simplifying the task of controller design for the complex and uncertain high-dimensional system. Finally, this study introduces a novel approach to enhance controller design for complex brain dynamics by employing a reduced-order adaptive output predictor proposed in [1], fine-tuned with chirp binaural beats. The proposed technique is promising for developing closed-loop controllers in non-invasive brain stimulation therapies, such as binaural beats stimulation, to improve working memory. The study focuses on parameterizing uncertain models and creates a predictor that utilizes auto-regressive filtered vectors to forecast mean phase lock values generated by binaural beats stimulation. The simplified and known model of the predictor proves effective in tracking brain responses, as demonstrated in experiments evaluating its ability to track mean phase locking values. The results indicate negligible tracking error, suggesting the predictor's reliability in representing brain dynamics and simplifying the task of controller design for the complex and uncertain high-dimensional system. / Doctor of Philosophy / This dissertation explores the development of a reduced-order adaptive output predictor for unknown systems with unknown or high-dimensional parameters and order. A reduced-order adaptive output predictor scheme is introduced, validated through mathematical proof, and tested in diverse scenarios, including pendulum systems and EEG data. The focus is on parameterizing uncertain models and creating a simplified adaptive output predictor capable of forecasting system output, specifically for SISO systems. Experimental validation involves tracking the angle of a single pendulum and the endpoint of a high-dimensional rope, demonstrating the predictor's accuracy without detailed knowledge of system dynamics. The study extends its application to complex brain dynamics, using the predictor fine-tuned with chirp binaural beats. Results show promise for developing closed-loop controllers in non-invasive brain stimulation therapies, offering a novel approach to improve working memory via helping to design closed-loop controllers.

No / Design of iterative learning control (ILC) often requires some prior knowledge about a system's control matrix. In some applications, such as uncalibrated visual servoing, this kind of knowledge may be unavailable so that a stable learning control cannot always be achieved. In this paper, a universal ILC is proposed for a class of multi-input multi-output (MIMO) uncertain nonlinear systems with no prior knowledge about the system control gain matrix. It consists of a gain matrix selector from the unmixing set and a learned compensator in a form of the positive definite discrete matrix kernel, corresponding to rough gain matrix probing and refined uncertainty compensating, respectively. Asymptotic convergence for a trajectory tracking within a finite time interval is achieved through repetitive tracking. Simulations and experiments of uncalibrated visual servoing are carried out in order to verify the validity of the proposed control method.

Tidigare forskning har identifierat svårigheter och missuppfattningar kopplade till bokstavssymboler inom algebra. Vi väljer att avgränsa oss till obekanta tal eftersom många elever kan möta svårigheter när bokstäver introduceras i matematikundervisningen. Syftet med denna studie är att bidra med kunskap om hur undervisning om bokstavssymboler i tidigare skolår kan planeras och genomföras utifrån variationsteorin. Syftet besvaras med hjälp av följande frågeställningar: Vilka kritiska aspekter behöver elever i årkurs 1 urskilja för att utveckla förståelse för obekanta tal? Hur förändras elevernas kunskaper om obekanta tal mellan för- och eftertest? Hur kan undervisning planeras och iscensättas utifrån identifierade kritiska aspekter? Studiens teoretiska ramverk är variationsteorin, där centrala begrepp omfattar lärandeobjekt, kritiska aspekter och variationsmönster. Variationsmönster används för att hjälpa eleverna att urskilja kritiska aspekter av ett lärandeobjekt, vilket i denna studie är obekanta tal, genom att synliggöra dessa med olika variationer. Studiens metod inspirerades av Learning Study. Lektionerna genomfördes med två olika undervisningsdesigner som grundades på variationsteoretiska principer. Studiens data består av för- och eftertester och observationsanteckningar från två lektionstillfällen. Resultatet visar att fyra kritiska aspekter har identifierats till det specifika lärandeobjektet, vilka är urskilja att: en ekvation är en likhet som innehåller obekanta tal, det obekanta talet står för ett tal (värde), tidigare kunskaper inom aritmetiken kan användas vid ekvationslösning, till exempel talfakta eller inversa operationer och samma bokstavssymbol kan stå för olika värden beroende på ekvation. Resultatet visar även att elevernas kunskaper utvecklas mellan för- och eftertest, när undervisningarna planeras och iscensätts utifrån variationsteoretiska principer. Slutsatser som kan dras är att variationsteorin kan vara användbar för lärare när de ska identifiera kritiska aspekter och planera lektioner. Efter att ha genomfört två lektioner med årkurs 1 har vi kommit fram till att det är möjligt och fördelaktigt att introducera obekanta tal redan i tidig ålder. / Previous research has identified difficulties and misconceptions associated with letter symbols in algebra. A common difficulty can be interpreting and using unknown numbers. A misconception identified in a few studies is that letter symbols can be perceived to represent positions in the alphabet. We choose to focus on unknown numbers because many students may encounter difficulties when letter symbols are introduced in mathematics. The aim of this study is to investigate the teaching of letter symbols in grade 1. The aim is addressed through the following research questions: What critical aspects do students in grade 1 need to dicern in order to develop an understanding of unknown numbers? How do students' knowledge of unknown numbers change between pre- and post tests? How can teaching be planned and staged based on identified critical aspects?  The theoretical framework of the study is the variation theory of learning, where central concepts include learning object, critical aspects and patterns of variations. Patterns of variation are ursed to help students discern critical aspects of a learning object, which in this study are unknown numbers, by highlighting these through different variations. This method of study was inspired by Learning Study. Lessons was carried out with two different teaching designs, based on principles of variation theory. The study´s data include pre- and posttest and observation protocols from two conducted teaching sessions.  The results indicate that four critical aspects have been identified for the specific learning object, which are discerning that: an equation is an equality containing unknown quantities, the unknown quantity represents a number (value), prior knowledge in arithmetics can be used in equation solving, such as number facts or inverse operations, and the same letter symbol can represent different values depending on the equation. The results also show that students' knowledge evolve between pre- and post tests when teaching is planned and staged based on variation theoretical principles. It is shown that variation theory can be useful for teachers in identifying critical aspects and planning lessons. After conducting two lessons with grade 1, we have concluded that it is possible and beneficial to introduce unknown quantities at an early age.

Current consumption measurements are useful in a wide variety of applications, including power monitoring and fault detection within a lithium battery management system (BMS). This measurement is typically taken using either a shunt resistor or a Hall-effect current transducer. Although both methods have achieved accurate current measurements, shunt resistors have inherent power loss and often require isolation circuitry, and Hall-effect sensors are generally expensive. This work explores a novel alternative to sensing battery current by measuring terminal voltages and cell temperatures and using an unknown input observer (UIO) to estimate the battery current. An accurate model of a LiFePO4 cell is created and is then used to characterize a model of the proposed current estimation technique. Finally, the current estimation technique is implemented in hardware and tested in an online BMS environment. Results show that the current estimation technique is sufficiently accurate for a variety of applications including fault detection and power profiling.

Carcinoma of unknown primary (CUP) is an intriguing clinical finding that is defined as biopsy-proven metastasis from a malignancy in the absence of an identifiable primary site after a complete clinical work-up. CUP is a relatively common clinical entity, accounting for approximately 3–5% of all cancer diagnoses, and consists of a heterogeneous group of tumors that have acquired the capacity to metastasize before the development of a clinically evident primary lesion. Notable advances have been made over the past years in the treatment of well-defined clinical subgroups of CUP, such as women with peritoneal carcinomatosis and young adults with poorly differentiated carcinomas of midline distribution, but for the majority of patients, the prognosis still remains poor. In this review, we highlight recent advances in the diagnosis and treatment of patients with CUP syndrome, and emphasize the importance of identifying several favorable subsets of CUP, amenable to specific treatment options. In addition, we will point out novel diagnostic and therapeutic approaches which will hopefully improve both our understanding and the prognosis of this more or less neglected disease. / Unter dem Cancer of Unknown Primary (CUP)-Syndrom werden diejenigen Tumorerkrankungen zusammengefasst, bei denen auch nach Abschluss der Diagnostik nur Metastasen, jedoch kein Primärtumor gefunden wird. Das CUP-Syndrom macht ca. 3–5% aller neu diagnostizierten Malignomfälle aus und umfasst eine heterogene Gruppe von Tumoren, die die Fähigkeit zur Metastasierung erlangt haben bevor sich ein klinisch manifester Primärtumor entwickelt hat. Obwohl bemerkenswerte Fortschritte in der Behandlung von Patienten mit bestimmten, gut definierten Erkrankungssubgruppen, wie beispielsweise Frauen mit isolierter Peritonealkarzinose oder jungen Erwachsenen mit gering differenzierten Karzinomen mit Mittellinienverteilung, erzielt werden konnten, ist die Prognose bei der Mehrzahl der Patienten nach wie vor schlecht. Wir berichten im weiteren Verlauf dieser Übersichtsarbeit über Fortschritte in der Diagnostik und Therapie von Patienten mit CUPSyndrom und weisen darauf hin, dass es trotz der immer noch sehr schlechten Prognose von großer Bedeutung ist, Patienten mit bestimmten Subtypen des CUP-Syndroms zu identifizieren, die spezifischen Therapien mit der Option auf Heilung zugeführt werden sollten. Darüber hinaus möchten wir auf neuere diagnostische und therapeutische Bestrebungen aufmerksam machen, die das Verständnis und die Prognose dieses auch in der Onkologie bisher stiefmütterlich behandelten Krankheitsbildes hoffentlich verbessern werden. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Em outubro de 2005 a notificação de 17 casos de doença ocular de etiologia desconhecida, envolvendo, em sua maioria, a população infantil da cidade de Araguatins/TO, levou as autoridades locais a pedirem ajuda a Secretaria de Estado da Saúde do Estado do Tocantins no intuito de descobrirem sua etiologia, tratamento e prevenção. Nos pacientes acometidos, os sinais freqüentemente observados foram: intensa hiperemia conjutival, granuloma, episclerite, infiltrado corneano periférico. Na anamnese realizada nos pacientes foi observado que todos tiveram contato com as águas do Rio Araguaia. Os resultados obtidos a partir do processamento das amostras de água, sedimentos e substratos particularmente na vegetação marginal inundada, permitiram confirmar a hipótese de que deveria haver uma fauna rica de esponjas no Araguaia, no trecho fronteiro à cidade de Araguatins A presença intraocular de espícula de esponja de água doce das espécies Drulia uruguayensis e Oncosclera navicela foi confirmada em material avaliado histopatologicamente proveniente de três pacientes que haviam sido submetidos a lensectomia, sugerindo que espículas de água doce poderiam ser um surpreendente novo agente etiológico de patologia ocular. Assim, neste estudo foram realizados ensaios de citotoxicidade com amostras de duas espécies de esponjas coletadas no local. Os resultados indicam que os extratos das esponjas após filtração em filtro Millipore 0,45 μm continuaram apresentando atividade citotóxica, sugerindo haver um componente SOLÚVEL, e não somente espículas, capaz de induzir morte celular na população de células utilizadas. Os indivíduos acometidos foram na maioria do sexo masculino com idade entre 05 e 14 anos. / In October 2005 the notification of 17 cases of eyes disease of unknown etiology, involving, in its majority, the infant population of the city of Araguatins/TO, led the local authorities to ask help to the Secretariate of State of Health of the State of Tocantins in order to discover their etiology, treatment and prevention. In affected patients, the signs frequently observed were: intense hyperemia conjutival, granuloma, episclerite, peripheral cornea infiltrated. In the anamnesis performed in patients was observed that all of them had contact with the waters of the Araguaia river. The results obtained from processing samples of water, sediments and substrates particularly in the vegetation marginal flooded, allowed confirming the hypothesis that there should be a rich fauna sponges in Araguaia, close to the city of Araguatins The presence of spicula of intraocular sponge species of freshwater Drulia uruguayensis and Oncosclera navicela was confirmed in material evaluated histopathologically from three patients who had undergone lensectomy, suggesting that \"spikes freshwater could be a surprising new etiologic agent of pathology ocular\". Thus, in this study was performed cytotoxicity assays with samples from two species of sponges collected in place. The results indicate that the extracts of sponges after filtration Millipore 0.45 μm continued presenting cytotoxic activity, suggesting there is a SOLUBLE component, and not only spikes, capable of inducing cellular death in the population of cells used. The individuals affected were the majority of males aged between 05 and 14 years.