Vision-based methods for state estimation and control of robotic systems with application to mobile and surgical robots

For autonomous systems that need to perceive the surrounding environment for the accomplishment of a given task, vision is a highly informative exteroceptive sensory source. When gathering information from the available sensors, in fact, the richness of visual data allows to provide a complete description of the environment, collecting geometrical and semantic information (e.g., object pose, distances, shapes, colors, lights). The huge amount of collected data allows to consider both methods exploiting the totality of the data (dense approaches), or a reduced set obtained from feature extraction procedures (sparse approaches). This manuscript presents dense and sparse vision-based methods for control and sensing of robotic systems. First, a safe navigation scheme for mobile robots, moving in unknown environments populated by obstacles, is presented. For this task, dense visual information is used to perceive the environment (i.e., detect ground plane and obstacles) and, in combination with other sensory sources, provide an estimation of the robot motion with a linear observer. On the other hand, sparse visual data are extrapolated in terms of geometric primitives, in order to implement a visual servoing control scheme satisfying proper navigation behaviours. This controller relies on visual estimated information and is designed in order to guarantee safety during navigation. In addition, redundant structures are taken into account to re-arrange the internal configuration of the robot and reduce its encumbrance when the workspace is highly cluttered. Vision-based estimation methods are relevant also in other contexts. In the field of surgical robotics, having reliable data about unmeasurable quantities is of great importance and critical at the same time. In this manuscript, we present a Kalman-based observer to estimate the 3D pose of a suturing needle held by a surgical manipulator for robot-assisted suturing. The method exploits images acquired by the endoscope of the robot platform to extrapolate relevant geometrical information and get projected measurements of the tool pose. This method has also been validated with a novel simulator designed for the da Vinci robotic platform, with the purpose to ease interfacing and employment in ideal conditions for testing and validation. The Kalman-based observers mentioned above are classical passive estimators, whose system inputs used to produce the proper estimation are theoretically arbitrary. This does not provide any possibility to actively adapt input trajectories in order to optimize specific requirements on the performance of the estimation. For this purpose, active estimation paradigm is introduced and some related strategies are presented. More specifically, a novel active sensing algorithm employing visual dense information is described for a typical Structure-from-Motion (SfM) problem. The algorithm generates an optimal estimation of a scene observed by a moving camera, while minimizing the maximum uncertainty of the estimation. This approach can be applied to any robotic platforms and has been validated with a manipulator arm equipped with a monocular camera

Effect of aberrant ribosome biogenesis on wild-type and mutant p53 in cancer cells

2012/2013The tumor suppressor p53 plays a central role in the protection against DNA damage and other forms of stress, primarily by inducing cell cycle arrest or apoptosis. Missense mutation of p53, which is one of the most frequent genetic alterations detected in human cancers, inactivates these growth regulatory functions; in addition, mutant p53 often acquires tumor-promoting activities (gain-of-function). A complete and thorough understanding of the signaling circuitry that regulates wild-type and mutant p53 functions is therefore a primary objective for basic cancer research, since it may lead to development of important tools for diagnosis and therapy of tumors. One crucial component of such knowledge is the molecular mechanism leading to protein activation. Deregulated ribosome biogenesis is commonly observed in cancers as a result of increased biosynthetic demand due to uncontrolled cell proliferation. Cells actively monitor the fidelity of ribosome biogenesis, activating cellular checkpoints when this process is altered. Indeed, perturbations to many aspects of ribosome biogenesis generate a “nucleolar stress” that triggers a p53 response. Evidence in animal models indicates that the ribosomal-p53 checkpoint is indeed important for tumor suppression in vivo. In the recent past, we identified the nucleolar protein GTPBP4 as a novel p53 interactor, and established a functional link between the two proteins by demonstrating that GTPBP4 depletion promotes p53 accumulation and activation. In this Thesis, I demonstrate that GTPBP4 depletion affects 28S rRNA processing, generating a “nucleolar stress” responsible for p53 stabilization. The molecular mechanism responsible for such accumulation relies on the binding of ribosomal proteins to Mdm2. In parallel, I report that the same molecular mechanism leading to wild-type p53 stabilization upon ribosomal stress, can also promote mutant p53 accumulation in cancer cells. Thus, deregulated ribosome biogenesis may contribute to the stability of mutant p53 in tumors. These results collectively suggest that upon alterations in ribosome biogenesis, the TP53 status may be critical to drive the nucleolar surveillance pathway towards a tumor suppressive or oncogenic outcome.L’oncosoppressore p53 svolge un ruolo cruciale nella protezione della cellula da danni al DNA e da altre forme di stress, principalmente inducendo arresto del ciclo cellulare e apoptosi. Mutazioni missenso nel gene TP53 sono le alterazioni genetiche più frequenti trovate nei tumori umani ed inattivano queste funzioni regolative; oltre a questo, p53 mutata acquisisce nuove proprietà oncogeniche (gain-of-function). Capire i meccanismi regolativi che sono alla base delle funzioni di p53 wild-type e mutata è quindi un fondamentale obiettivo per la ricerca di base nel cancro, dal momento che può portare allo sviluppo di importanti strumenti sia diagnostici che terapeutici. Un aspetto fondamentale di tale ricerca è la comprensione dei meccanismi molecolari responsabili dell’attivazione della proteina. La sintesi dei ribosomi è frequentemente deregolata nei tumori, in quanto le cellule hanno un aumentato fabbisogno biosintetico a causa dell’incontrollata proliferazione. La cellula monitora attivamente la fedeltà della sintesi dei ribosomi, attivando meccanismi molecolari quando questo processo è compromesso. Infatti, alterazioni ad ogni livello nella sintesi dei ribosomi genera uno “stress nucleolare” che attiva la risposta di p53. Alcune evidenze in modelli animali infatti suggeriscono l’importanza delle funzioni oncosoppressive dell’asse molecolare costituito dalle proteine ribosomali e p53. In un lavoro pubblicato recentemente, abbiamo identificato la proteina nucleolare GTPBP4 come nuovo interattore di p53, inoltre abbiamo dimostrato un collegamento funzionale tra le due proteine, in quanto la deplezione di GTPBP4 promuove l’accumulo e l’attivazione di p53. In questa Tesi ho dimostrato che la deplezione di GTPBP4 altera il processamento del RNA ribosomale 28S, causando uno “stress nucleolare” responsabile per la stabilizzazione di p53. Il meccanismo molecolare necessario per la stabilizzazione di p53 dipende dal legame di proteine ribosomali a Mdm2. In parallelo, ho dimostrato che lo stesso meccanismo molecolare responsabile dell’accumulo di p53 wild-type in seguito allo stress ribosomiale, può indurre la stabilizzazione anche di p53 mutata. Quindi, un’alterata sintesi ribosomale può contribuire alla stabilità di mutant p53. Questi risultati suggeriscono che in seguito ad alterazioni nella sintesi dei ribosomi, lo stato di p53 può essere critico nel determinare se la risposta cellulare sia di natura oncosoppressiva oppure oncogenica.XXV Ciclo198

On the use of the Peak Stress Method for the calculation of Residual Notch Stress Intensity Factors: a preliminary investigation

Residual stresses induced by welding processes significantly affect the engineering properties of structural components. If the toe region of a butt-welded joint is modeled as a sharp V-notch, the distribution of the residual stresses in that zone is asymptotic with a singularity degree which follows either the linear-elastic or the elastic-plastic solution, depending on aspects such as clamping conditions, welding parameters, material and dimension of plates. The intensity of the local residual stress fields is quantified by the Residual Notch Stress Intensity Factors (R-NSIFs), which can be used in principle to include the residual stress effect in the fatigue assessment of welded joints. Due to the need of extremely refined meshes and to the high computational resources required by non-linear transient analyses, the R-NSIFs have been calculated in literature only by means of 2D models. It is of interest to propose new coarse-mesh-based approaches which allow residual stresses to be calculated with less computational effort. This work is aimed to investigate the level of accuracy of the Peak Stress Method in the R-NSIFs evaluation

What-if analysis: A visual analytics approach to Information Retrieval evaluation

This paper focuses on the innovative visual analytics approach realized by the Visual Analytics Tool for Experimental Evaluation (VATE2) system, which eases and makes more effective the experimental evaluation process by introducing the what-if analysis. The what-if analysis is aimed at estimating the possible effects of a modification to an Information Retrieval (IR) system, in order to select the most promising fixes before implementing them, thus saving a considerable amount of effort. VATE2 builds on an analytical framework which models the behavior of the systems in order to make estimations, and integrates this analytical framework into a visual part which, via proper interaction and animations, receives input and provides feedback to the user. We conducted an experimental evaluation to assess the numerical performances of the analytical model and a validation of the visual analytics prototype with domain experts. Both the numerical evaluation and the user validation have shown that VATE2 is effective, innovative, and useful

The CLAIRE visual analytics system for analysing IR evaluation data

In this paper, we describe Combinatorial visuaL Analytics system for Information Retrieval Evaluation (CLAIRE), a Visual Analytics (VA) system for exploring and making sense of the performances of a large amount of Information Retrieval (IR) systems, in order to quickly and intuitively grasp which system configurations are preferred, what are the contributions of the different components and how these components interact together

Applicazioni di meccanica della frattura all’analisi di stabilitá delle fessure nelle dighe in calcestruzzo

RIASSUNTO. Nel presente lavoro si propone una disamina delle applicazioni di meccanica della frattura all’analisi del processo fessurativo nelle dighe in calcestruzzo. In tale contesto, ripercorrendo gli studi pionieristici e i casi di studio affrontati negli anni 1980 e 1990, si illustra nel dettaglio come applicare le metodologie proprie della meccanica della frattura elastica lineare alla valutazione della stabilità delle fessure e della loro lunghezza critica. Tale disamina riguarderà sia sollecitazioni quasi-statiche, quali il peso proprio e la pressione idrostatica esercitata dall’acqua, che sollecitazioni sismiche, tema di particolare complessità ed attualità. Infine, si illustreranno le problematiche relative alla corretta valutazione dei parametri meccanici per strutture ciclopiche quali le dighe, tenendo propriamente in conto i forti effetti di scala osservati sperimentalmente. ABSTRACT. In the present study, a detailed analysis of the applications of fracture mechanics to the phenomenon of fracture taking place in concrete dams is proposed. In this context, recalling the pioneering approaches and the case studies proposed in the 1980s and in the 1990s, it will be shown how to apply the methodologies of linear elastic fracture mechanics to the assessment of crack stability and to the determination of the corresponding critical crack length. Such an analysis will concern both quasi-static loads, such as the weight load and the hydraulic pressure, as well as seismic actions, a topic of high complexity and actuality. Finally, the problems related to the proper evaluation of the mechanical parameters of huge structures such as dams will be analyzed, taking into account the strong size-scale effects observed in experimental tests

Emerging role of the KRAS-PDK1 axis in pancreatic cancer

Pancreatic cancer is a highly aggressive tumour that is very resistant to treatments and it is rarely diagnosed early because of absence of specific symptoms. Therefore, the prognosis for this disease is very poor and it has the grim supremacy in terms of unfavourable survival rates. There have been great advances in survival rates for many types of cancers over the past few decades but hardly any change for pancreatic cancer. Mutations of the Ras oncogene are the most frequent oncogenic alterations in human cancers. The frequency of KRAS mutations in pancreatic cancer is around 90%. Given the well-established role of KRAS in cancer it is not surprising that it is one of the most attractive targets for cancer therapy. Nevertheless, during the last thirty years all attempts to target directly KRAS protein have failed. Therefore, it is crucial to identify downstream KRAS effectors in order to develop specific drugs able to counteract activation of this pathway. Among the different signalling pathways activated by oncogenic KRAS, the phosphoinositide 3-Kinase (PI3K) pathway is emerging as one of the most critical KRAS effector. In turn, PI3K activates several parallel pathways making the identification of the precise effectors activated by KRAS/PI3K more difficult. Recent data identify 3-phosphoinositide-dependent protein kinase 1 as a key tumour-initiating event downstream KRAS interaction with PI3K in pancreatic cancer

Clinical study of effectiveness of an anorganic bone matrix and cell-binding peptide (ABM/P-15), PepGen-P15®: application in advanced periodontal lesions of dogs

Os mecanismos biológicos desenvolvidos para aumentar a qualidade da regeneração óssea e da reparação tecidual de sítios periodontais específicos continuam a ser um desafio e têm sido complementado pela capacidade de adesão celular do colágeno do tipo I, promovida por um peptídeo sintético de adesão celular (P-15), associado a uma matriz inorgânica de osso (MIO) para formar MIO/P-15. O objetivo deste estudo foi avaliar a perda do nível clínico de inserção e a resposta da bolsa periodontal em dentes após 3 e 6 meses da aplicação de enxerto com MIO/P-15. Vinte e um cães do Hospital Veterinário da Universidade de São Paulo foram anestesiados para realização de tratamento periodontal e 132 faces dentais com perda de nível clínico de inserção foram tratadas, sendo que 36,4% (48 faces) receberam o peptídeo de adesão celular e 63,6% (84 faces) compuseram o grupo controle que recebeu tratamento convencional (retalho muco-gengival e aplainamento radicular). O procedimento foi documentado através de radiografia intra-oral e todas as sondagens de bolsas periodontais foram fotografadas. Depois de 3 e de 6 meses, os animais foram re-anestesiados a fim de se obter novas avaliações, radiografias, fotografias e sondagens periodontais. As 48 faces com perda de nível clínico de inserção que receberam material de enxertia apresentaram taxa de 40% de recuperação do nível clínico de inserção após 6 meses. O grupo controle de faces dentais não apresentou alteração do nível clínico de inserção. A face palatina foi a que apresentou melhor taxa de regeneração (40%) e os dentes caninos e molares mostraram as melhores respostas (57,14% e 65%, respectivamente). Não houve sinais de infecção pós-cirúrgica relacionadas à falta de higienização oral dos animais. Pode-se concluir que o MIO/P-15 auxilia na regeneração e re-aderência das estruturas periodontais, incluindo osso alveolar. Sua aplicação mostrou-se fácil e prática e a incidência de complicações pós-cirúrgicas foi baixa. Ainda assim, mais estudos e pesquisas são necessários para que se avalie a quantidade e a qualidade do osso e do ligamento periodontal formados.The development of biologic modalities designed to enhance bone regeneration and wound healing of specific periodontal sites continues to be a challenge and has been accomplished through the cell binding activity of Type-I collagen. These have been provided by a synthetic cell biding peptide (P-15), associated to a anorganic bone matrix (ABM) to form ABM/P-15. The aim of this study was to evaluate the attachment loss and periodontal pocket response in teeth after 3 and 6 months with ABM/P-15 graft application. Twenty one dogs from the Veterinary Hospital, University of São Paulo, were anesthetized in order to accomplish periodontal treatment and 132 teeth faces with attachment loss were treated. From these, 36.4% (48 faces) received cell binding peptide and 63.6% (84 faces) compounded the control group that received conventional treatment (muco-gingival flap and root planning). The procedure was documented by intra-oral radiography and all periodontal probings were photographed. After 3 and 6 months, the animals were re-anesthetized in order to accomplish new photography, radiography and periodontal probing exams. The 48 attachment loss faces that received graft material exhibited 40% of regeneration rate after 6 months. The control faces did not change their attachment level. The palatal face presented the better regeneration rates (40%) and the canines and molars teeth showed the better responses (57.14% and 65%, respectively). There was no post-surgical infection related to absence of oral home care. It can be concluded that ABM/P-15 helps a more rapidly periodontal structure re-attachment and regeneration, including alveolar bone. Its application was easy and practical, and the post-surgical complications incidence was low. Nevertheless, more work is necessary to evaluate the amount and the quality of formed bone and periodontal ligament

Towards Meaningful Statements in IR Evaluation. Mapping Evaluation Measures to Interval Scales

Recently, it was shown that most popular IR measures are not interval-scaled, implying that decades of experimental IR research used potentially improper methods, which may have produced questionable results. However, it was unclear if and to what extent these findings apply to actual evaluations and this opened a debate in the community with researchers standing on opposite positions about whether this should be considered an issue (or not) and to what extent. In this paper, we first give an introduction to the representational measurement theory explaining why certain operations and significance tests are permissible only with scales of a certain level. For that, we introduce the notion of meaningfulness specifying the conditions under which the truth (or falsity) of a statement is invariant under permissible transformations of a scale. Furthermore, we show how the recall base and the length of the run may make comparison and aggregation across topics problematic. Then we propose a straightforward and powerful approach for turning an evaluation measure into an interval scale, and describe an experimental evaluation of the differences between using the original measures and the interval-scaled ones. For all the regarded measures - namely Precision, Recall, Average Precision, (Normalized) Discounted Cumulative Gain, Rank-Biased Precision and Reciprocal Rank - we observe substantial effects, both on the order of average values and on the outcome of significance tests. For the latter, previously significant differences turn out to be insignificant, while insignificant ones become significant. The effect varies remarkably between the tests considered but overall, on average, we observed a 25% change in the decision about which systems are significantly different and which are not