466 resultados para Maximization
Resumo:
I Max Bill is an intense giornata of a big fresco. An analysis of the main social, artistic and cultural events throughout the twentieth century is needed in order to trace his career through his masterpieces and architectures. Some of the faces of this hypothetical mural painting are, among others, Le Corbusier, Walter Gropius, Ernesto Nathan Rogers, Kandinskij, Klee, Mondrian, Vatongerloo, Ignazio Silone, while the backcloth is given by artistic avant-gardes, Bauhaus, International Exhibitions, CIAM, war events, reconstruction, Milan Triennali, Venice Biennali, the School of Ulm. Architect, even though more known as painter, sculptor, designer and graphic artist, Max Bill attends the Bauhaus as a student in the years 1927-1929, and from this experience derives the main features of a rational, objective, constructive and non figurative art. His research is devoted to give his art a scientific methodology: each work proceeds from the analysis of a problem to the logical and always verifiable solution of the same problem. By means of composition elements (such as rhythm, seriality, theme and its variation, harmony and dissonance), he faces, with consistent results, themes apparently very distant from each other as the project for the H.f.G. or the design for a font. Mathematics are a constant reference frame as field of certainties, order, objectivity: ‘for Bill mathematics are never confined to a simple function: they represent a climate of spiritual certainties, and also the theme of non attempted in its purest state, objectivity of the sign and of the geometrical place, and at the same time restlessness of the infinity: Limited and Unlimited ’. In almost sixty years of activity, experiencing all artistic fields, Max Bill works, projects, designs, holds conferences and exhibitions in Europe, Asia and Americas, confronting himself with the most influencing personalities of the twentieth century. In such a vast scenery, the need to limit the investigation field combined with the necessity to address and analyse the unpublished and original aspect of Bill’s relations with Italy. The original contribution of the present research regards this particular ‘geographic delimitation’; in particular, beyond the deep cultural exchanges between Bill and a series of Milanese architects, most of all with Rogers, two main projects have been addressed: the realtà nuova at Milan Triennale in 1947, and the Contemporary Art Museum in Florence in 1980. It is important to note that these projects have not been previously investigated, and the former never appears in the sources either. These works, together with the most well-known ones, such as the projects for the VI and IX Triennale, and the Swiss pavilion for the Biennale, add important details to the reference frame of the relations which took place between Zurich and Milan. Most of the occasions for exchanges took part in between the Thirties and the Fifties, years during which Bill underwent a significant period of artistic growth. He meets the Swiss progressive architects and the Paris artists from the Abstraction-Création movement, enters the CIAM, collaborates with Le Corbusier to the third volume of his Complete Works, and in Milan he works and gets confronted with the events related to post-war reconstruction. In these years Bill defines his own working methodology, attaining an artistic maturity in his work. The present research investigates the mentioned time period, despite some necessary exceptions. II The official Max Bill bibliography is naturally wide, including spreading works along with ones more devoted to analytical investigation, mainly written in German and often translated into French and English (Max Bill himself published his works in three languages). Few works have been published in Italian and, excluding the catalogue of the Parma exhibition from 1977, they cannot be considered comprehensive. Many publications are exhibition catalogues, some of which include essays written by Max Bill himself, some others bring Bill’s comments in a educational-pedagogical approach, to accompany the observer towards a full understanding of the composition processes of his art works. Bill also left a great amount of theoretical speculations to encourage a critical reading of his works in the form of books edited or written by him, and essays published in ‘Werk’, magazine of the Swiss Werkbund, and other international reviews, among which Domus and Casabella. These three reviews have been important tools of analysis, since they include tracks of some of Max Bill’s architectural works. The architectural aspect is less investigated than the plastic and pictorial ones in all the main reference manuals on the subject: Benevolo, Tafuri and Dal Co, Frampton, Allenspach consider Max Bill as an artist proceeding in his work from Bauhaus in the Ulm experience . A first filing of his works was published in 2004 in the monographic issue of the Spanish magazine 2G, together with critical essays by Karin Gimmi, Stanislaus von Moos, Arthur Rüegg and Hans Frei, and in ‘Konkrete Architektur?’, again by Hans Frei. Moreover, the monographic essay on the Atelier Haus building by Arthur Rüegg from 1997, and the DPA 17 issue of the Catalonia Polytechnic with contributions of Carlos Martì, Bruno Reichlin and Ton Salvadò, the latter publication concentrating on a few Bill’s themes and architectures. An urge to studying and going in depth in Max Bill’s works was marked in 2008 by the centenary of his birth and by a recent rediscovery of Bill as initiator of the ‘minimalist’ tradition in Swiss architecture. Bill’s heirs are both very active in promoting exhibitions, researching and publishing. Jakob Bill, Max Bill’s son and painter himself, recently published a work on Bill’s experience in Bauhaus, and earlier on he had published an in-depth study on ‘Endless Ribbons’ sculptures. Angela Thomas Schmid, Bill’s wife and art historian, published in end 2008 the first volume of a biography on Max Bill and, together with the film maker Eric Schmid, produced a documentary film which was also presented at the last Locarno Film Festival. Both biography and documentary concentrate on Max Bill’s political involvement, from antifascism and 1968 protest movements to Bill experiences as Zurich Municipality councilman and member of the Swiss Confederation Parliament. In the present research, the bibliography includes also direct sources, such as interviews and original materials in the form of letters correspondence and graphic works together with related essays, kept in the max+binia+jakob bill stiftung archive in Zurich. III The results of the present research are organized into four main chapters, each of them subdivided into four parts. The first chapter concentrates on the research field, reasons, tools and methodologies employed, whereas the second one consists of a short biographical note organized by topics, introducing the subject of the research. The third chapter, which includes unpublished events, traces the historical and cultural frame with particular reference to the relations between Max Bill and the Italian scene, especially Milan and the architects Rogers and Baldessari around the Fifties, searching the themes and the keys for interpretation of Bill’s architectures and investigating the critical debate on the reviews and the plastic survey through sculpture. The fourth and last chapter examines four main architectures chosen on a geographical basis, all devoted to exhibition spaces, investigating Max Bill’s composition process related to the pictorial field. Paintings has surely been easier and faster to investigate and verify than the building field. A doctoral thesis discussed in Lausanne in 1977 investigating Max Bill’s plastic and pictorial works, provided a series of devices which were corrected and adapted for the definition of the interpretation grid for the composition structures of Bill’s main architectures. Four different tools are employed in the investigation of each work: a context analysis related to chapter three results; a specific theoretical essay by Max Bill briefly explaining his main theses, even though not directly linked to the very same work of art considered; the interpretation grid for the composition themes derived from a related pictorial work; the architecture drawing and digital three-dimensional model. The double analysis of the architectural and pictorial fields is functional to underlining the relation among the different elements of the composition process; the two fields, however, cannot be compared and they stay, in Max Bill’s works as in the present research, interdependent though self-sufficient. IV An important aspect of Max Bill production is self-referentiality: talking of Max Bill, also through Max Bill, as a need for coherence instead of a method limitation. Ernesto Nathan Rogers describes Bill as the last humanist, and his horizon is the known world but, as the ‘Concrete Art’ of which he is one of the main representatives, his production justifies itself: Max Bill not only found a method, but he autonomously re-wrote the ‘rules of the game’, derived timeless theoretical principles and verified them through a rich and interdisciplinary artistic production. The most recurrent words in the present research work are synthesis, unity, space and logic. These terms are part of Max Bill’s vocabulary and can be referred to his works. Similarly, graphic settings or analytical schemes in this research text referring to or commenting Bill’s architectural projects were drawn up keeping in mind the concise precision of his architectural design. As for Mies van der Rohe, it has been written that Max Bill took art to ‘zero degree’ reaching in this way a high complexity. His works are a synthesis of art: they conceptually encompass all previous and –considered their developments- most of contemporary pictures. Contents and message are generally explicitly declared in the title or in Bill’s essays on his artistic works and architectural projects: the beneficiary is invited to go through and re-build the process of synthesis generating the shape. In the course of the interview with the Milan artist Getulio Alviani, he tells how he would not write more than a page for an essay on Josef Albers: everything was already evident ‘on the surface’ and any additional sentence would be redundant. Two years after that interview, these pages attempt to decompose and single out the elements and processes connected with some of Max Bill’s works which, for their own origin, already contain all possible explanations and interpretations. The formal reduction in favour of contents maximization is, perhaps, Max Bill’s main lesson.
Resumo:
The objective of this dissertation is to develop and test a predictive model for the passive kinematics of human joints based on the energy minimization principle. To pursue this goal, the tibio-talar joint is chosen as a reference joint, for the reduced number of bones involved and its simplicity, if compared with other sinovial joints such as the knee or the wrist. Starting from the knowledge of the articular surface shapes, the spatial trajectory of passive motion is obtained as the envelop of joint configurations that maximize the surfaces congruence. An increase in joint congruence corresponds to an improved capability of distributing an applied load, allowing the joint to attain a better strength with less material. Thus, joint congruence maximization is a simple geometric way to capture the idea of joint energy minimization. The results obtained are validated against in vitro measured trajectories. Preliminary comparison provide strong support for the predictions of the theoretical model.
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Over the last three decades, international agricultural trade has grown significantly. Technological advances in transportation logistics and storage have created opportunities to ship anything almost anywhere. Bilateral and multilateral trade agreements have also opened new pathways to an increasingly global market place. Yet, international agricultural trade is often constrained by differences in regulatory regimes. The impact of “regulatory asymmetry” is particularly acute for small and medium sized enterprises (SMEs) that lack resources and expertise to successfully operate in markets that have substantially different regulatory structures. As governments seek to encourage the development of SMEs, policy makers often confront the critical question of what ultimately motivates SME export behavior. Specifically, there is considerable interest in understanding how SMEs confront the challenges of regulatory asymmetry. Neoclassical models of the firm generally emphasize expected profit maximization under uncertainty, however these approaches do not adequately explain the entrepreneurial decision under regulatory asymmetry. Behavioral theories of the firm offer a far richer understanding of decision making by taking into account aspirations and adaptive performance in risky environments. This paper develops an analytical framework for decision making of a single agent. Considering risk, uncertainty and opportunity cost, the analysis focuses on the export behavior response of an SME in a situation of regulatory asymmetry. Drawing on the experience of fruit processor in Muzaffarpur, India, who must consider different regulatory environments when shipping fruit treated with sulfur dioxide, the study dissects the firm-level decision using @Risk, a Monte Carlo computational tool.
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This doctoral dissertation presents a new method to asses the influence of clearancein the kinematic pairs on the configuration of planar and spatial mechanisms. The subject has been widely investigated in both past and present scientific literature, and is approached in different ways: a static/kinetostatic way, which looks for the clearance take-up due to the external loads on the mechanism; a probabilistic way, which expresses clearance-due displacements using probability density functions; a dynamic way, which evaluates dynamic effects like the actual forces in the pairs caused by impacts, or the consequent vibrations. This dissertation presents a new method to approach the problem of clearance. The problem is studied from a purely kinematic perspective. With reference to a given mechanism configuration, the pose (position and orientation) error of the mechanism link of interest is expressed as a vector function of the degrees of freedom introduced in each pair by clearance: the presence of clearance in a kinematic pair, in facts, causes the actual pair to have more degrees of freedom than the theoretical clearance-free one. The clearance-due degrees of freedom are bounded by the pair geometry. A proper modelling of clearance-affected pairs allows expressing such bounding through analytical functions. It is then possible to study the problem as a maximization problem, where a continuous function (the pose error of the link of interest) subject to some constraints (the analytical functions bounding clearance- due degrees of freedom) has to be maximize. Revolute, prismatic, cylindrical, and spherical clearance-affected pairs have been analytically modelled; with reference to mechanisms involving such pairs, the solution to the maximization problem has been obtained in a closed form.
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L’obiettivo del lavoro consiste nell’implementare una metodologia operativa volta alla progettazione di reti di monitoraggio e di campagne di misura della qualità dell’aria con l’utilizzo del laboratorio mobile, ottimizzando le posizioni dei dispositivi di campionamento rispetto a differenti obiettivi e criteri di scelta. La revisione e l’analisi degli approcci e delle indicazioni fornite dalla normativa di riferimento e dai diversi autori di lavori scientifici ha permesso di proporre un approccio metodologico costituito da due fasi operative principali, che è stato applicato ad un caso studio rappresentato dal territorio della provincia di Ravenna. La metodologia implementata prevede l’integrazione di numerosi strumenti di supporto alla valutazione dello stato di qualità dell’aria e degli effetti che gli inquinanti atmosferici possono generare su specifici recettori sensibili (popolazione residente, vegetazione, beni materiali). In particolare, la metodologia integra approcci di disaggregazione degli inventari delle emissioni attraverso l’utilizzo di variabili proxy, strumenti modellistici per la simulazione della dispersione degli inquinanti in atmosfera ed algoritmi di allocazione degli strumenti di monitoraggio attraverso la massimizzazione (o minimizzazione) di specifiche funzioni obiettivo. La procedura di allocazione sviluppata è stata automatizzata attraverso lo sviluppo di un software che, mediante un’interfaccia grafica di interrogazione, consente di identificare delle aree ottimali per realizzare le diverse campagne di monitoraggio
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Il presente studio si colloca nell’ambito di una ricerca il cui obiettivo è la formulazione di criteri progettuali finalizzati alla ottimizzazione delle prestazioni energetiche delle cantine di aziende vitivinicole con dimensioni produttive medio-piccole. Nello specifico la ricerca si pone l’obiettivo di individuare degli indicatori che possano valutare l’influenza che le principali variabili progettuali hanno sul fabbisogno energetico dell’edificio e sull’andamento delle temperature all’interno dei locali di conservazione ed invecchiamento del vino. Tali indicatori forniscono informazioni sulla prestazione energetica dell’edificio e sull’idoneità dei locali non climatizzati finalizzata alla conservazione del vino Essendo la progettazione una complessa attività multidisciplinare, la ricerca ha previsto l’ideazione di un programma di calcolo in grado di gestire ed elaborare dati provenienti da diversi ambiti (ingegneristici, architettonici, delle produzioni agroindustriali, ecc.), e di restituire risultati sintetici attraverso indicatori allo scopo individuati. Il programma è stato applicato su un caso-studio aziendale rappresentativo del settore produttivo. Sono stati vagliati gli effetti di due modalità di vendemmia e di quattro soluzioni architettoniche differenti. Le soluzioni edilizie derivano dalla combinazione di diversi isolamenti termici e dalla presenza o meno di locali interrati. Per le analisi sul caso-studio ci si è avvalsi di simulazioni energetiche in regime dinamico, supportate e validate da campagne di monitoraggio termico e meteorologico all’interno dell’azienda oggetto di studio. I risultati ottenuti hanno evidenziato come il programma di calcolo concepito nell’ambito di questo studio individui le criticità dell’edificio in termini energetici e di “benessere termico” del vino e consenta una iterativa revisione delle variabili progettuale indagate. Esso quindi risulta essere uno strumento informatizzato di valutazione a supporto della progettazione, finalizzato ad una ottimizzazione del processo progettuale in grado di coniugare, in maniera integrata, gli obiettivi della qualità del prodotto, della efficienza produttiva e della sostenibilità economica ed ambientale.
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Iterative Closest Point (ICP) is a widely exploited method for point registration that is based on binary point-to-point assignments, whereas the Expectation Conditional Maximization (ECM) algorithm tries to solve the problem of point registration within the framework of maximum likelihood with point-to-cluster matching. In this paper, by fulfilling the implementation of both algorithms as well as conducting experiments in a scenario where dozens of model points must be registered with thousands of observation points on a pelvis model, we investigated and compared the performance (e.g. accuracy and robustness) of both ICP and ECM for point registration in cases without noise and with Gaussian white noise. The experiment results reveal that the ECM method is much less sensitive to initialization and is able to achieve more consistent estimations of the transformation parameters than the ICP algorithm, since the latter easily sinks into local minima and leads to quite different registration results with respect to different initializations. Both algorithms can reach the high registration accuracy at the same level, however, the ICP method usually requires an appropriate initialization to converge globally. In the presence of Gaussian white noise, it is observed in experiments that ECM is less efficient but more robust than ICP.
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Latent class analysis (LCA) and latent class regression (LCR) are widely used for modeling multivariate categorical outcomes in social sciences and biomedical studies. Standard analyses assume data of different respondents to be mutually independent, excluding application of the methods to familial and other designs in which participants are clustered. In this paper, we develop multilevel latent class model, in which subpopulation mixing probabilities are treated as random effects that vary among clusters according to a common Dirichlet distribution. We apply the Expectation-Maximization (EM) algorithm for model fitting by maximum likelihood (ML). This approach works well, but is computationally intensive when either the number of classes or the cluster size is large. We propose a maximum pairwise likelihood (MPL) approach via a modified EM algorithm for this case. We also show that a simple latent class analysis, combined with robust standard errors, provides another consistent, robust, but less efficient inferential procedure. Simulation studies suggest that the three methods work well in finite samples, and that the MPL estimates often enjoy comparable precision as the ML estimates. We apply our methods to the analysis of comorbid symptoms in the Obsessive Compulsive Disorder study. Our models' random effects structure has more straightforward interpretation than those of competing methods, thus should usefully augment tools available for latent class analysis of multilevel data.
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The degree of polarization of a refected field from active laser illumination can be used for object identifcation and classifcation. The goal of this study is to investigate methods for estimating the degree of polarization for refected fields with active laser illumination, which involves the measurement and processing of two orthogonal field components (complex amplitudes), two orthogonal intensity components, and the total field intensity. We propose to replace interferometric optical apparatuses with a computational approach for estimating the degree of polarization from two orthogonal intensity data and total intensity data. Cramer-Rao bounds for each of the three sensing modalities with various noise models are computed. Algebraic estimators and maximum-likelihood (ML) estimators are proposed. Active-set algorithm and expectation-maximization (EM) algorithm are used to compute ML estimates. The performances of the estimators are compared with each other and with their corresponding Cramer-Rao bounds. Estimators for four-channel polarimeter (intensity interferometer) sensing have a better performance than orthogonal intensities estimators and total intensity estimators. Processing the four intensities data from polarimeter, however, requires complicated optical devices, alignment, and four CCD detectors. It only requires one or two detectors and a computer to process orthogonal intensities data and total intensity data, and the bounds and estimator performances demonstrate that reasonable estimates may still be obtained from orthogonal intensities or total intensity data. Computational sensing is a promising way to estimate the degree of polarization.
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Dynamic spectrum access (DSA) aims at utilizing spectral opportunities both in time and frequency domains at any given location, which arise due to variations in spectrum usage. Recently, Cognitive radios (CRs) have been proposed as a means of implementing DSA. In this work we focus on the aspect of resource management in overlaid CRNs. We formulate resource allocation strategies for cognitive radio networks (CRNs) as mathematical optimization problems. Specifically, we focus on two key problems in resource management: Sum Rate Maximization and Maximization of Number of Admitted Users. Since both the above mentioned problems are NP hard due to presence of binary assignment variables, we propose novel graph based algorithms to optimally solve these problems. Further, we analyze the impact of location awareness on network performance of CRNs by considering three cases: Full location Aware, Partial location Aware and Non location Aware. Our results clearly show that location awareness has significant impact on performance of overlaid CRNs and leads to increase in spectrum utilization effciency.
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Fuzzy community detection is to identify fuzzy communities in a network, which are groups of vertices in the network such that the membership of a vertex in one community is in [0,1] and that the sum of memberships of vertices in all communities equals to 1. Fuzzy communities are pervasive in social networks, but only a few works have been done for fuzzy community detection. Recently, a one-step forward extension of Newman’s Modularity, the most popular quality function for disjoint community detection, results into the Generalized Modularity (GM) that demonstrates good performance in finding well-known fuzzy communities. Thus, GMis chosen as the quality function in our research. We first propose a generalized fuzzy t-norm modularity to investigate the effect of different fuzzy intersection operators on fuzzy community detection, since the introduction of a fuzzy intersection operation is made feasible by GM. The experimental results show that the Yager operator with a proper parameter value performs better than the product operator in revealing community structure. Then, we focus on how to find optimal fuzzy communities in a network by directly maximizing GM, which we call it Fuzzy Modularity Maximization (FMM) problem. The effort on FMM problem results into the major contribution of this thesis, an efficient and effective GM-based fuzzy community detection method that could automatically discover a fuzzy partition of a network when it is appropriate, which is much better than fuzzy partitions found by existing fuzzy community detection methods, and a crisp partition of a network when appropriate, which is competitive with partitions resulted from the best disjoint community detections up to now. We address FMM problem by iteratively solving a sub-problem called One-Step Modularity Maximization (OSMM). We present two approaches for solving this iterative procedure: a tree-based global optimizer called Find Best Leaf Node (FBLN) and a heuristic-based local optimizer. The OSMM problem is based on a simplified quadratic knapsack problem that can be solved in linear time; thus, a solution of OSMM can be found in linear time. Since the OSMM algorithm is called within FBLN recursively and the structure of the search tree is non-deterministic, we can see that the FMM/FBLN algorithm runs in a time complexity of at least O (n2). So, we also propose several highly efficient and very effective heuristic algorithms namely FMM/H algorithms. We compared our proposed FMM/H algorithms with two state-of-the-art community detection methods, modified MULTICUT Spectral Fuzzy c-Means (MSFCM) and Genetic Algorithm with a Local Search strategy (GALS), on 10 real-world data sets. The experimental results suggest that the H2 variant of FMM/H is the best performing version. The H2 algorithm is very competitive with GALS in producing maximum modularity partitions and performs much better than MSFCM. On all the 10 data sets, H2 is also 2-3 orders of magnitude faster than GALS. Furthermore, by adopting a simply modified version of the H2 algorithm as a mutation operator, we designed a genetic algorithm for fuzzy community detection, namely GAFCD, where elite selection and early termination are applied. The crossover operator is designed to make GAFCD converge fast and to enhance GAFCD’s ability of jumping out of local minimums. Experimental results on all the data sets show that GAFCD uncovers better community structure than GALS.
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This paper presents a comparison of principal component (PC) regression and regularized expectation maximization (RegEM) to reconstruct European summer and winter surface air temperature over the past millennium. Reconstruction is performed within a surrogate climate using the National Center for Atmospheric Research (NCAR) Climate System Model (CSM) 1.4 and the climate model ECHO-G 4, assuming different white and red noise scenarios to define the distortion of pseudoproxy series. We show how sensitivity tests lead to valuable “a priori” information that provides a basis for improving real world proxy reconstructions. Our results emphasize the need to carefully test and evaluate reconstruction techniques with respect to the temporal resolution and the spatial scale they are applied to. Furthermore, we demonstrate that uncertainties inherent to the predictand and predictor data have to be more rigorously taken into account. The comparison of the two statistical techniques, in the specific experimental setting presented here, indicates that more skilful results are achieved with RegEM as low frequency variability is better preserved. We further detect seasonal differences in reconstruction skill for the continental scale, as e.g. the target temperature average is more adequately reconstructed for summer than for winter. For the specific predictor network given in this paper, both techniques underestimate the target temperature variations to an increasing extent as more noise is added to the signal, albeit RegEM less than with PC regression. We conclude that climate field reconstruction techniques can be improved and need to be further optimized in future applications.
Resumo:
Information theory-based metric such as mutual information (MI) is widely used as similarity measurement for multimodal registration. Nevertheless, this metric may lead to matching ambiguity for non-rigid registration. Moreover, maximization of MI alone does not necessarily produce an optimal solution. In this paper, we propose a segmentation-assisted similarity metric based on point-wise mutual information (PMI). This similarity metric, termed SPMI, enhances the registration accuracy by considering tissue classification probabilities as prior information, which is generated from an expectation maximization (EM) algorithm. Diffeomorphic demons is then adopted as the registration model and is optimized in a hierarchical framework (H-SPMI) based on different levels of anatomical structure as prior knowledge. The proposed method is evaluated using Brainweb synthetic data and clinical fMRI images. Both qualitative and quantitative assessment were performed as well as a sensitivity analysis to the segmentation error. Compared to the pure intensity-based approaches which only maximize mutual information, we show that the proposed algorithm provides significantly better accuracy on both synthetic and clinical data.
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Diseases are believed to arise from dysregulation of biological systems (pathways) perturbed by environmental triggers. Biological systems as a whole are not just the sum of their components, rather ever-changing, complex and dynamic systems over time in response to internal and external perturbation. In the past, biologists have mainly focused on studying either functions of isolated genes or steady-states of small biological pathways. However, it is systems dynamics that play an essential role in giving rise to cellular function/dysfunction which cause diseases, such as growth, differentiation, division and apoptosis. Biological phenomena of the entire organism are not only determined by steady-state characteristics of the biological systems, but also by intrinsic dynamic properties of biological systems, including stability, transient-response, and controllability, which determine how the systems maintain their functions and performance under a broad range of random internal and external perturbations. As a proof of principle, we examine signal transduction pathways and genetic regulatory pathways as biological systems. We employ widely used state-space equations in systems science to model biological systems, and use expectation-maximization (EM) algorithms and Kalman filter to estimate the parameters in the models. We apply the developed state-space models to human fibroblasts obtained from the autoimmune fibrosing disease, scleroderma, and then perform dynamic analysis of partial TGF-beta pathway in both normal and scleroderma fibroblasts stimulated by silica. We find that TGF-beta pathway under perturbation of silica shows significant differences in dynamic properties between normal and scleroderma fibroblasts. Our findings may open a new avenue in exploring the functions of cells and mechanism operative in disease development.
Resumo:
Diseases are believed to arise from dysregulation of biological systems (pathways) perturbed by environmental triggers. Biological systems as a whole are not just the sum of their components, rather ever-changing, complex and dynamic systems over time in response to internal and external perturbation. In the past, biologists have mainly focused on studying either functions of isolated genes or steady-states of small biological pathways. However, it is systems dynamics that play an essential role in giving rise to cellular function/dysfunction which cause diseases, such as growth, differentiation, division and apoptosis. Biological phenomena of the entire organism are not only determined by steady-state characteristics of the biological systems, but also by intrinsic dynamic properties of biological systems, including stability, transient-response, and controllability, which determine how the systems maintain their functions and performance under a broad range of random internal and external perturbations. As a proof of principle, we examine signal transduction pathways and genetic regulatory pathways as biological systems. We employ widely used state-space equations in systems science to model biological systems, and use expectation-maximization (EM) algorithms and Kalman filter to estimate the parameters in the models. We apply the developed state-space models to human fibroblasts obtained from the autoimmune fibrosing disease, scleroderma, and then perform dynamic analysis of partial TGF-beta pathway in both normal and scleroderma fibroblasts stimulated by silica. We find that TGF-beta pathway under perturbation of silica shows significant differences in dynamic properties between normal and scleroderma fibroblasts. Our findings may open a new avenue in exploring the functions of cells and mechanism operative in disease development.