Humanoid Robots

For many years, the human being has been trying, in all ways, to recreate the complex mechanisms that form the human body. Such task is extremely complicated and the results are not totally satisfactory. However, with increasing technological advances based on theoretical and experimental researches, man gets, in a way, to copy or to imitate some systems of the human body. These researches not only intended to create humanoid robots, great part of them constituting autonomous systems, but also, in some way, to offer a higher knowledge of the systems that form the human body, objectifying possible applications in the technology of rehabilitation of human beings, gathering in a whole studies related not only to Robotics, but also to Biomechanics, Biomimmetics, Cybernetics, among other areas. This book presents a series of researches inspired by this ideal, carried through by various researchers worldwide, looking for to analyze and to discuss diverse subjects related to humanoid robots. The presented contributions explore aspects about robotic hands, learning, language, vision and locomotion

New approaches to the study of neurorehabilitation protocols in dogs and cats with acute or chronic spinal cord injury with or without deep pain sensation and possible spinal shock signs

Tese de Doutoramento em Ciências Veterinárias na especialidade Clínica, área científica de ClínicaABSTRACT - Intensive neurorehabilitation protocols (INRP) with rehabilitation modalities and weight supported treadmill training (BWSTT), are suggested as treatment to obtain ambulation in dogs and cats with complete (DPP-), discomplete and incomplete (DPP+) compressive or non-compressive spinal cord injury (SCI), similarly to what is performed in human medicine.The first study is a cohort, prospective, controlled and blinded study that was performed in 22 dogs with T11-L3 Hansen type I, revealing ambulation in 100% of the BWSTT group, within a mean of 4.6 weeks. One other study, a retrospective controlled clinical study, was developed in 367 acute post-surgical dogs, with T10-L3 Hansen type I. A new functional neurorehabilitation scale (FNRS-DPP-) was performed to evaluate the DPP- or discomplete dogs, that were able to achieve spinal reflex locomotion (SRL). A strong significance between groups was verified in the DPP+ (p<0.001), with 99.4% of ambulation. The same difference was seen in the DPP- (p=0.007) with 58,5% of ambulation and a tendency (p=0.058) was observed in regard to DPP recovery, with 37.2% achieving SRL, within a maximum of 3 months. INRP was demonstrated to be safe and ambulation recovery achieved earlier. The same population was included in another study, on 16 dogs with incomplete recovery 3 months after surgery. DPP- were under INRP associated with 4-aminopyridine administration, achieving 78% of SRL at day 45 and automatic micturition within a mean of 62 days. Also, 100% of ambulation in the DPP+ within a mean of 47 days and positive follow-up evolution. Ambulatory status was achieved in 88%, establishing this INRP as a therapeutic option to reduce euthanasia. Non-compressive myelopathies with contusive patterns were also referred in a prospective study of 9 cats that revealed 56% (n=5) of ambulation and 44% (n=4) of SRL, showing that INRP should be considered to improve quality of life and the well-being of our patients. Some dogs may develop spinal shock following SCI, including in acute noncompressive nucleus pulposus extrusion. Thus, a cohort prospective study applied a spinal shock scale as a monitoring tool, suggesting spinal shock as a negative factor for a quick recovery. INRP was shown to be safe, tolerable and feasible, allowing 32% of ambulation within 7 days and 94% within 60 days. Follow-ups until 4 years revealed a positive evolution. These studies should be continued, considering each limitationRESUMO - Nova abordagem aos protocolos de neuroreabilitação em cães e gatos com lesão medular aguda ou crónica, com/sem sensibilidade à dor profunda e choque espinhal. - Os protocolos de neuroreabilitação intensiva (INRP), com as modalidades de reabilitação e o treino locomotor em tapete rolante com suporte de peso (BWSTT), são sugeridos como terapêutica para obter a ambulação em cães e gatos de lesão medular compressiva / não compressiva, completa (DPP-), “discompleta” e incompleta (DPP+), tal como na medicina humana. Assim, apresenta-se o primeiro artigo, estudo de coorte, prospetivo, controlado e cego, em 22 cães com lesão T11-L3 Hansen tipo I, que demonstrou 100% de ambulação no grupo BWSTT, em média de 4.6 semanas. O segundo artigo refere-se ao estudo controlado e retrospetivo de 367 cães pós-cirúrgicos com lesão aguda T10-L3 de Hansen tipo I. A escala de neuroreabilitação funcional (FNRS-DPP-) foi elaborada e aplicada nestes cães, DPP- ou incompletos, capazes de atingir a locomoção espinhal por reflexos (SRL). Verificaram-se diferenças significativas entre grupos, nos DPP+ (p<0,001) com 99,4% de ambulação, e nos DPP- (p=0,007) com 58,5%. Em relação à recuperação da sensibilidade profunda (p=0,058), ocorreu 37.3% de SRL, no máximo em 3 meses. O INRP demonstrou-se seguro e a recuperação foi atingida de forma mais precoce. O mesmo foi estudado em 16 cães com recuperação incompleta 3 meses após cirurgia, sendo associada a administração de 4- aminopiridina nos DPP- com 78% de SRL até 45 dias e micção automática em ~62 dias. Obteve-se 100% de ambulação nos cães DPP+, em ~47 dias, com evolução positiva nas consultas de seguimento. A ambulação total foi de 88%, estabelecendo este INRP como opção terapêutica, reduzindo o número de eutanásias em âmbito clínico. As mielopatias não compressivas foram, também, estudadas. Assim sendo, estudo propectivo em 9 gatos revelou 56% de ambulação e 44% de SRL, demostrando que o INRP poderá ser considerado, no sentido de melhorar a qualidade de vida e bem-estar destes doentes. Após a lesão medular, alguns cães podem desenvolver o choque espinhal, principalmente na extrusão aguda não compressiva do núcleo pulposo. Assim, foi desenvolvido estudo propectivo coorte que elaborou e aplicou escala de choque espinhal para monitorização, sugerindo o choque espinhal como fator negativo para a rápida recuperação. Este INRP revelou-se seguro, tolerável e viável, com 32% de ambulação em 7 dias e 94% em 60 dias. Consultas de seguimento até 4 anos revelaram evolução positiva. Estes estudos devem ser continuados considerando as suas limitações.N/

A Bio-inspired Distributed Control Architecture: Coupled Artificial Signalling Networks

This thesis studies the applicability of computational models inspired by the structure and dynamics of signalling networks to the control of complex control problems. In particular, this thesis presents two different abstractions that aim to capture the signal processing abilities of biological cells: a stand-alone signalling network and a coupled signalling network. While the former mimics the interacting relationships amongst the components in a signalling pathway, the latter replicates the connectionism amongst signalling pathways. After initially investigating the feasibility of these models for controlling two complex numerical dynamical systems, Chirikov's standard map and the Lorenz system, this thesis explores their applicability to a difficult real world control problem, the generation of adaptive rhythmic locomotion patterns within a legged robotic system. The results highlight that the locomotive movements of a six-legged robot could be controlled in order to adapt the robot's trajectory in a range of challenging environments. In this sense, signalling networks are responsible for the robot adaptability and inter limb coordination as they self-adjust their dynamics according to the terrain's irregularities. More generally, the results of this thesis highlight the capacity of coupled signalling networks to decompose non-linear problems into smaller sub-tasks, which can then be independently solved

Engineering Dynamics and Life Sciences

From Preface: This is the fourteenth time when the conference “Dynamical Systems: Theory and Applications” gathers a numerous group of outstanding scientists and engineers, who deal with widely understood problems of theoretical and applied dynamics. Organization of the conference would not have been possible without a great effort of the staff of the Department of Automation, Biomechanics and Mechatronics. The patronage over the conference has been taken by the Committee of Mechanics of the Polish Academy of Sciences and Ministry of Science and Higher Education of Poland. It is a great pleasure that our invitation has been accepted by recording in the history of our conference number of people, including good colleagues and friends as well as a large group of researchers and scientists, who decided to participate in the conference for the first time. With proud and satisfaction we welcomed over 180 persons from 31 countries all over the world. They decided to share the results of their research and many years experiences in a discipline of dynamical systems by submitting many very interesting papers. This year, the DSTA Conference Proceedings were split into three volumes entitled “Dynamical Systems” with respective subtitles: Vibration, Control and Stability of Dynamical Systems; Mathematical and Numerical Aspects of Dynamical System Analysis and Engineering Dynamics and Life Sciences. Additionally, there will be also published two volumes of Springer Proceedings in Mathematics and Statistics entitled “Dynamical Systems in Theoretical Perspective” and “Dynamical Systems in Applications”

Prescription of Ankle-Foot Orthoses for Children with Cerebral Palsy

Purpose: Ankle foot orthoses (AFOs) are frequently prescribed to address gait impairments for children with cerebral palsy (CP). Successful treatment with AFOs depends on optimal prescription, matching the design of the brace to the individual child’s physical impairments; however, research evidence does not exist to help health care professionals decide on the best AFO design to meet each child’s needs. Therefore, this thesis explored current AFO prescription practices, and aimed to improve evidence to assist clinicians in making prescription decisions for children with CP. Methods and Results: To examine the experiences and perspectives of clinicians on AFO prescription for children with CP, we conducted focus groups and semi-structured interviews with 32 clinicians who were involved with AFO prescription for children with CP in five Canadian rehabilitation facilities. Using Interpretive Description as a framework for analysis, we identified three categories from the data: 1) What is made, 2) How it is used, and 3) Factors that support or challenge outcomes. Throughout the interviews, the theme of prescription as a collaborative, iterative, and individualized process emerged. To explore evaluation and clinical decision-making practices of physical therapists for AFO prescription and follow-up, we invited Canadian physical therapists (PTs) working with children who have CP to complete an online survey. Sixty completed responses were received. Three researchers conducted a conventional content analysis to examine the open-ended responses, and descriptive statistics were used to summarize the closed-ended responses. Three themes were identified: 1) Focus on impairment level measures, 2) Inconsistent practices between PTs, and 3) Lack of confidence/knowledge about casting positions and AFO types. To investigate the effects of individualizing the angle of the ankle in the AFO on walking mechanics and function, gait biomechanics were studied in ten children with CP. Fifteen typically-developing children provided normative data. Using three-dimensional gait analysis, kinematics and kinetics were compared between the child’s usual AFO(s) and AFOs that were fabricated with an ankle angle that was individualized for each child. Net responses to the individualized ankle angle were positive for 60% of limbs, negative for 40%. The greatest benefits were observed at the knee, suggesting that this may be a beneficial approach to orthotic intervention for some children with CP. Conclusions: There is limited understanding of how AFOs are prescribed for children with CP in Canada. This thesis highlights the importance of multidisciplinary collaboration, objective evaluation, and individualized clinical problem-solving to facilitate the evolution of the AFO prescription from a medical directive to an orthotic device that optimally benefits the child. This is the first step toward the development of guidelines to help clinicians improve AFO prescription for children with CP

Role of histone methylation in the regulation of COX-2, iNOS, and mPGES-1 gene expression in human chondrocytes: Implication for Osteoarthritis

L'arthrose (OA) est une maladie articulaire dégénérative, classée comme la forme la plus fréquente au monde. Elle est caractérisée par la dégénérescence du cartilage articulaire, l’inflammation de la membrane synoviale, et le remodelage de l’os sous-chondral. Ces changements structurels et fonctionnels sont dues à de nombreux facteurs. Les cytokines, les prostaglandines (PG), et les espèces réactives de l'oxygène sont les principaux médiateurs impliqués dans la pathophysiologie de l'OA. L'interleukine-1β (IL-1β) est une cytokine pro-inflammatoire majeure qui joue un rôle crucial dans l'OA. L'IL-1β induit l'expression de la cyclooxygénase-2 (COX-2), la microsomale prostaglandine E synthase-1 (mPGES-1), la synthase inductible de l'oxyde nitrique (iNOS), ainsi que leurs produits la prostaglandine E2 (PGE2) et l'oxyde nitrique (NO). Ce sont des médiateurs essentiels de la réponse inflammatoire au cours de l'OA qui contribuent aux mécanismes des douleurs, de gonflement, et de destruction des tissus articulaires. Les modifications épigénétiques jouent un rôle très important dans la régulation de l’expression de ces gènes pro-inflammatoires. Parmi ces modifications, la méthylation/ déméthylation des histones joue un rôle critique dans la régulation des gènes. La méthylation/ déméthylation des histones est médiée par deux types d'enzymes: les histones méthyltransférases (HMT) et les histones déméthylases (HDM) qui favorisent l’activation et/ou la répression de la transcription. Il est donc nécessaire de comprendre les mécanismes moléculaires qui contrôlent l’expression des gènes de la COX-2, la mPGES-1, et l’iNOS. L'objectif de cette étude est de déterminer si la méthylation/déméthylation des histones contribute à la régulation de l’expression des gènes COX-2, mPGES-1, et iNOS dans des chondrocytes OA humains induits par l'IL-1β. Nous avons montré que la méthylation de la lysine K4 de l'histone H3 (H3K4) par SET-1A contribue à l’activation des gènes COX-2 et iNOS dans les chondrocytes humains OA induite par l'IL-1β. Nous avons également montré que la lysine K9 de l’histone H3 (H3K9) est déméthylée par LSD1, et que cette déméthylation contribue à l’expression de la mPGES-1 induite par IL-1β dans les chondrocytes humains OA. Nous avons aussi trouvé que les niveaux d'expression des enzymes SET-1A et LSD1 sont élevés au niveau du cartilage OA. Nos résultats montrent, pour la première fois, l'implication de la méthylation/ déméthylation des histones dans la régulation de l’expression des gènes COX-2, mPGES-1, et iNOS. Ces données suggèrent que ces mécanismes pourraient être une cible potentielle pour une intervention pharmacologique dans le traitement de la physiopathologie de l'OA.Osteoarthritis (OA) is a disabling disease classified as the most common form of arthritis worldwide. It is characterized by cartilage degeneration, synovium inflammation, and subchondral bone remodeling resulting in a loss of joint function. These structural and functional changes are due to numerous factors. Cytokines, prostaglandins (PG), and reactive oxygen species are the major mediators implicated in the pathophysiology of OA. Interleukin-1 (IL-1) is a major pro-inflammatory cytokine that plays a crucial role in OA. IL-1 induces the expression of Cyclo-oxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), inducible nitric oxide synthase (iNOS), as well as their products prostaglandin E2 (PGE2) and nitric oxide (NO). These are critical mediators of the inflammatory response during OA causing pain, swelling, and joint tissue destruction. The activation of these pro-inflammatory genes results from different changes at the level of chromatin known as epigenetic modifications. Epigenetic modifications such as DNA methylation and histone modifications play a crucial role in gene expression. Among these modifications, histone methylation/demethylation is the most critical one. Histone methylation/demethylation is mediated by two types of enzymes: histone methyltransferases (HMT) and histone demethylases (HDM) which can either activate or repress transcription. It is therefore necessary to understand the molecular mechanisms which underlie the regulation of COX-2, mPGES-1, and iNOS expression. The objective of this study is to investigate whether histone methylation/demethylation can modulate COX-2, mPGES-1, and iNOS expression in IL-1 induced OA human chondrocytes. We demonstrated that histone H3 lysine K4 (H3K4) methylation by SET-1A contributes to IL-1-induced COX-2 and iNOS expression in human OA Chondrocytes. We showed also that LSD1-mediated demethylation of histone H3 lysine 9 (H3K9) contributes to IL-1β-induced mPGES-1 expression in human OA chondrocytes. We found that levels of SET-1A and LSD1 expression are elevated in OA cartilage as compared with normal cartilage. Our data demonstrates, for the first time, the implication of histone methylation/demethylation in COX-2, mPGES-1, and iNOS regulation suggesting that these mechanisms could be a potential target for pharmacological intervention in the treatment of the pathophysiology of OA

Genetic and epigenetic variation within extracellular matrix genes as risk factors for human tendinopathy

Background and Aims Regular physical activities have shown to have various health benefits however there is always an accompanying risk of developing musculoskeletal soft tissue injuries. Indeed, damaged tendons account for 30-50% of sports-related injuries where the lifetime risk of Achilles tendon pathology (ATP) approaches 50% in runners, and that of patellar tendon pathology (PTP) is 21% in football players. The exact aetiology and mechanisms of tendon pathologies are still under investigation, however extrinsic and intrinsic risk factors (of which genetic) have been identified. Recent genetic association studies found that gene variants within the TNC, COL5A1, MMP3, GDF5 and CASP8 were associated with ATP in a Caucasian Australian and South African population. Furthermore, epigenetic mechanisms such as DNA methylation and microRNA (miRNA) activity have been implicated in a range of diseases but were never investigated for their role in human tendinopathy. Based on the aforementioned information, this thesis aimed at investigating novel candidate genes that may be associated with ATP and to replicate previously conducted studies in a newly recruited case-control population. Additionally, this thesis aimed at investigating potential differences in DNA methylation profiles and miRNA expression levels between healthy and damaged Achilles and patellar tendons. One hundred and thirty six UK Caucasian participants with clinically diagnosed ATP and 131 asymptomatic, unrelated, physically active control participants were recruited for this study. Furthermore, the previously recruited 173 clinically diagnosed ATP participants and 238 asymptomatic, unrelated, physically active control participants from Australia and South Africa (AUS+SA) were also included in the studies of this thesis. Participants within the combined AUS+SA were genotyped for the ELN rs2071307, FBN2 rs331079, ADAM12 rs3740199, ADAMTS2 rs1054480, ADAMTS5 rs226794, ADAMTS14 rs4747096, and TIMP2 rs4789932 variants, and the UK participants were genotyped for the COL5A1 rs71746744, FBN2 rs331079, GDF5 rs143833, MMP3 rs679620, TIMP2 rs4789932 variants using fluorescent based TaqMan® technology. Furthermore, the UK cohort was genotyped for the COL5A1 rs12722 variant using polyacrylamide gel electrophoresis. Moreover, 10 healthy and 10 diseased patellar tendon tissue samples in addition to 4 healthy, and 1 diseased Achilles tendon samples were obtained for the epigenetic studies. The DNA methylation profile within the TIMP2 and GDF5 promoter regions were analysed for all samples using pyrosequencing technology. Furthermore, the expression levels of TIMP2, miR-21, miR-155, and miR-191 were determined by RT-PCR using TaqMan technology. Results and Discussion The genetic association studies conducted showed that the FBN2 rs331079 GG genotype was over-represented among the tendinopathy (TEN) group and that the ELN rs2071307 AA genotype was over-represented in the rupture (RUP) group within the AUS+SA population. Furthermore, the COL5A1 rs12722 and rs71746744 were associated with RUP (TT genotype over-represented in the RUP group, p=0.004; OR=4.2; 95% CI 1.58-11.97) and ATP (DEL allele over-represented in the CON group, p=0.046; OR=1.61; 95% CI 1.01-2.56) respectively in the male UK cohort. The GDF5 rs143833, on the other hand, was not associated with ATP (p=0.538) and showed no sign of gender-specific association (female p=0.737; male p=0.319) in the UK population. Furthermore, the CT genotype for the TIMP2 rs4789932 variant was over-represented (p=0.004; OR=1.77; 95% CI 1.20 - 2.64) in the ATP group of the combined AUS+SA population and the CC genotype was over represented (p=0.016; OR=2.36; 95% CI 1.16 – 5.81) in ATP of the UK male cohort. It was also reported that the MMP3 rs679620 GG genotype was over represented (p=0.027; OR=2.51; 95% CI 1.11 – 5.64) in the UK RUP group. The ADAM12 rs3740199 (p=0.633), ADAMTS2 rs1054480 (p=0.316), ADAMTS5 rs226794 (p=0.342), and ADAMTS14 rs4747096 (p=0.849) gene variants were not associated with ATP in the AUS+SA population. Interestingly, individuals carrying the ADAMTS14 rs4747096 GG genotype within the AUS+SA population and the ELN rs2071307 AA genotype within the AUS population developed their injuries at a significantly (p=0.024; p=0.005, respectively) later stage than other participants. Moreover, UK males diagnosed with tendinosis and carrying the GG genotype at the MMP3 rs679620 locus developed significantly (p=0.003) thicker tendons than other participants with the AA, and AG genotypes. The preliminary epigenetic DNA methylation studies showed no differences in the average methylation profiles of the investigated regions within the TIMP2 (p=0.885) and GDF5 (p=0.333) genes in the patellar tendon samples. Moreover, no DNA methylation differences (p=0.617) were observed in the investigated region of the TIMP2 gene in the Achilles tendon samples. Interestingly, the single ATP sample showed a lower GDF5 average methylation profile than the CON samples. Furthermore, the expression of TIMP2 was up-regulated, and miR-191 was down-regulated in the ATP tissue sample compared to the CON group. The expression levels of miR-21 and miR-151, however, were not different between the two groups. Conclusion This thesis provides evidence that novel genes coding for structural and ECM regulatory enzymes are associated with ATPs in Caucasians. The findings of this thesis should to be replicated in new and larger cohorts from different ethnic backgrounds before being incorporated into multifactorial risk assessment models aiming at reducing the incidence of human tendinopathy

New Insights in the Genetics and Genomics of Adrenocortical Tumors and Pheochromocytomas

This book includes 17 papers published in the Special Issue/Article Collectoin “New Insights in the Genetics and Genomics of adrenocortical tumors and pheochromocytomas” including an editorial, 10 research papers and six review articles. Adrenal tumors represent a hot topic in contemporary endocrine oncology. Significant advancements in the genetics of genomics of these tumors have been made in recent years, and these articles give a useful and comprehensive overview of these issues. Questions regarding molecular pathogenesis, diagnosis (biomarkers) and even treatment are discussed in the papers written by international leaders of the field. Manuscripts are focused on three main topics: i. primary aldosteronism (the most common cause of secondary endocrine hypertension), ii. adrenocortical cancer and iii. pheochromocytoma/paraganglioma, which are the tumors with the highest heritability in humans. The book is edited by Prof. Peter Igaz (Department of Endocrinology, Faculty of Medicine, Semmelweis University)

Design and Experimental Evaluation of a Hybrid Wheeled-Leg Exploration Rover in the Context of Multi-Robot Systems

With this dissertation, the electromechanic design, implementation, locomotion control, and experimental evaluation of a novel type of hybrid wheeled-leg exploration rover are presented. The actively articulated suspension system of the rover is the basis for advanced locomotive capabilities of a mobile exploration robot. The developed locomotion control system abstracts the complex kinematics of the suspension system and provides platform control inputs usable by autonomous behaviors or human remote control. Design and control of the suspension system as well as experimentation with the resulting rover are in the focus of this thesis. The rover is part of a heterogeneous modular multi-robot exploration system with an aspired sample return mission to the lunar south pole or currently hard-to-access regions on Mars. The multi-robot system pursues a modular and reconfigurable design methodology. It combines heterogeneous robots with different locomotion capabilities for enhanced overall performance. Consequently, the design of the multi-robot system is presented as the frame of the rover developments. The requirements for the rover design originating from the deployment in a modular multi-robot system are accentuated and summarized in this thesis