Computational framework to support integration of biomolecular and clinical data within a translational approach

Background The use of the knowledge produced by sciences to promote human health is the main goal of translational medicine. To make it feasible we need computational methods to handle the large amount of information that arises from bench to bedside and to deal with its heterogeneity. A computational challenge that must be faced is to promote the integration of clinical, socio-demographic and biological data. In this effort, ontologies play an essential role as a powerful artifact for knowledge representation. Chado is a modular ontology-oriented database model that gained popularity due to its robustness and flexibility as a generic platform to store biological data; however it lacks supporting representation of clinical and socio-demographic information. Results We have implemented an extension of Chado – the Clinical Module - to allow the representation of this kind of information. Our approach consists of a framework for data integration through the use of a common reference ontology. The design of this framework has four levels: data level, to store the data; semantic level, to integrate and standardize the data by the use of ontologies; application level, to manage clinical databases, ontologies and data integration process; and web interface level, to allow interaction between the user and the system. The clinical module was built based on the Entity-Attribute-Value (EAV) model. We also proposed a methodology to migrate data from legacy clinical databases to the integrative framework. A Chado instance was initialized using a relational database management system. The Clinical Module was implemented and the framework was loaded using data from a factual clinical research database. Clinical and demographic data as well as biomaterial data were obtained from patients with tumors of head and neck. We implemented the IPTrans tool that is a complete environment for data migration, which comprises: the construction of a model to describe the legacy clinical data, based on an ontology; the Extraction, Transformation and Load (ETL) process to extract the data from the source clinical database and load it in the Clinical Module of Chado; the development of a web tool and a Bridge Layer to adapt the web tool to Chado, as well as other applications. Conclusions Open-source computational solutions currently available for translational science does not have a model to represent biomolecular information and also are not integrated with the existing bioinformatics tools. On the other hand, existing genomic data models do not represent clinical patient data. A framework was developed to support translational research by integrating biomolecular information coming from different “omics” technologies with patient’s clinical and socio-demographic data. This framework should present some features: flexibility, compression and robustness. The experiments accomplished from a use case demonstrated that the proposed system meets requirements of flexibility and robustness, leading to the desired integration. The Clinical Module can be accessed in http://dcm.ffclrp.usp.br/caib/pg=iptrans webcite.

“Features of two proteins of Leptospira interrogans with potential role in host-pathogen interactions”

Abstract Background Leptospirosis is considered a re-emerging infectious disease caused by pathogenic spirochaetes of the genus Leptospira. Pathogenic leptospires have the ability to survive and disseminate to multiple organs after penetrating the host. Leptospires were shown to express surface proteins that interact with the extracellular matrix (ECM) and to plasminogen (PLG). This study examined the interaction of two putative leptospiral proteins with laminin, collagen Type I, collagen Type IV, cellular fibronectin, plasma fibronectin, PLG, factor H and C4bp. Results We show that two leptospiral proteins encoded by LIC11834 and LIC12253 genes interact with laminin in a dose - dependent and saturable mode, with dissociation equilibrium constants (KD) of 367.5 and 415.4 nM, respectively. These proteins were named Lsa33 and Lsa25 (Leptospiral surface adhesin) for LIC11834 and LIC12253, respectively. Metaperiodate - treated laminin reduced Lsa25 - laminin interaction, suggesting that sugar moieties of this ligand participate in this interaction. The Lsa33 is also PLG - binding receptor, with a KD of 23.53 nM, capable of generating plasmin in the presence of an activator. Although in a weak manner, both proteins interact with C4bp, a regulator of complement classical route. In silico analysis together with proteinase K and immunoflorescence data suggest that these proteins might be surface exposed. Moreover, the recombinant proteins partially inhibited leptospiral adherence to immobilized laminin and PLG. Conclusions We believe that these multifunctional proteins have the potential to participate in the interaction of leptospires to hosts by mediating adhesion and by helping the bacteria to escape the immune system and to overcome tissue barriers. To our knowledge, Lsa33 is the first leptospiral protein described to date with the capability of binding laminin, PLG and C4bp in vitro.

A arquitetura patrimonial através dos jogos digitais

O presente artigo pretende ressaltar o potencial dos jogos digitais como instrumento de assimilação do conhecimento em arquitetura patrimonial, através da pesquisa Patrimônio arquitetônico, design e educação: desenvolvimento de Sistemas Interativos Lúdicos (jogos educativos em meio digital). Nesta pesquisa foram desenvolvidos jogos digitais a partir do levantamento das características arquitetônicas dos edifícios de relevância histórica e cultural da cidade de São Carlos. Através da interação e exploração da interface digital pelo usuário, a apropriação do conhecimento ocorre de uma forma lúdica e criativa. Por meio da manipulação desses jogos, os alunos, cidadãos e visitantes podem aproximar-se da educação patrimonial adquirindo consciência histórica e aprendendo a valorizar as origens da cidade e a arquitetura do município. Ressalta-se a importância das metodologias que permitem viabilizar o desenvolvimento dos jogos eletrônicos (desenho e linguagem de programação) e que se apresentam como importantes ferramentas de representação da arquitetura. Por fim, destaca-se a importância da educação patrimonial para a formação do cidadão e preservação do patrimônio cultural.

Mechanical Alterations in airway smooth muscle after interaction with indoor pollutant – A mathematical model.

The viscoelasticity of mammalian lung is determined by the mechanical properties and structural regulation of the airway smooth muscle (ASM). The exposure to polluted air may deteriorate these properties with harmful consequences to individual health. Formaldehyde (FA) is an important indoor pollutant found among volatile organic compounds. This pollutant permeates through the smooth muscle tissue forming covalent bonds between proteins in the extracellular matrix and intracellular protein structure changing mechanical properties of ASM and inducing asthma symptoms, such as airway hyperresponsiveness, even at low concentrations. In the experimental scenario, the mechanical effect of FA is the stiffening of the tissue, but the mechanism behind this effect is not fully understood. Thus, the aim of this study is to reproduce the mechanical behavior of the ASM, such as contraction and stretching, under FA action or not. For this, it was created a two-dimensional viscoelastic network model based on Voronoi tessellation solved using Runge-Kutta method of fourth order. The equilibrium configuration was reached when the forces in different parts of the network were equal. This model simulates the mechanical behavior of ASM through of a network of dashpots and springs. This dashpot-spring mechanical coupling mimics the composition of the actomyosin machinery of ASM through the contraction of springs to a minimum length. We hypothesized that formation of covalent bonds, due to the FA action, can be represented in the model by a simple change in the elastic constant of the springs, while the action of methacholine (MCh) reduce the equilibrium length of the spring. A sigmoid curve of tension as a function of MCh doses was obtained, showing increased tension when the muscle strip was exposed to FA. Our simulations suggest that FA, at a concentration of 0.1 ppm, can affect the elastic properties of the smooth muscle ¯bers by a factor of 120%. We also analyze the dynamic mechanical properties, observing the viscous and elastic behavior of the network. Finally, the proposed model, although simple, incorporates the phenomenology of both MCh and FA and reproduces experimental results observed with in vitro exposure of smooth muscle to FA. Thus, this new mechanical approach incorporates several well know features of the contractile system of the cells in a tissue level model. The model can also be used in different biological scales.

Mechanical alterations in airway smooth muscle after interaction with indoor pollutant - A mathematical model

The viscoelasticity of mammalian lung is determined by the mechanical properties and structural regulation of the airway smooth muscle (ASM). The exposure to polluted air may deteriorate these properties with harmful consequences to individual health. Formaldehyde (FA) is an important indoor pollutant found among volatile organic compounds. This pollutant permeates through the smooth muscle tissue forming covalent bonds between proteins in the extracellular matrix and intracellular protein structure changing mechanical properties of ASM and inducing asthma symptoms, such as airway hyperresponsiveness, even at low concentrations. In the experimental scenario, the mechanical effect of FA is the stiffening of the tissue, but the mechanism behind this effect is not fully w1derstood. Thus, the aim of this study is to reproduce the mechanical behavior of the ASM, such as contraction and stretching, under FA action or not. For this, it was created a two-dimensional viscoelastic network model based on Voronoi tessellation solved using Runge-Kutta method of fourth order. The equilibrium configuration was reached when the forces in different parts of the network were equal. This model simulates the mechanical behavior of ASM through of a network of dashpots and springs. This dashpot-spring mechanical coupling mimics the composition of the actomyosin machinery of ASM through the contraction of springs to a minimum length. We hypothesized that formation of covalent bonds, due to the FA action, can be represented in the model by a simple change in the elastic constant of the springs, while the action of methacholinc (MCh) reduce the equilibrium length of the spring. A sigmoid curve of tension as a function of MCh doses was obtained, showing increased tension when the muscle strip was exposed to FA. Our simulations suggest that FA, at a concentration of 0.1 ppm, can affect the elastic properties of the smooth muscle fibers by a factor of 120%. We also analyze the dynamic mechanical properties, observing the viscous and elastic behavior of the network. Finally, the proposed model, although simple, ir1corporates the phenomenology of both MCh and FA and reproduces experirnental results observed with ir1 vitro exposure of smooth muscle to .FA. Thus, this new mechanical approach incorporates several well know features of the contractile system of the cells ir1 a tissue level model. The model can also be used in different biological scales.

Specification, execution and verification of interaction protocols: an approach based on computational logic

Interaction protocols establish how different computational entities can interact with each other. The interaction can be finalized to the exchange of data, as in 'communication protocols', or can be oriented to achieve some result, as in 'application protocols'. Moreover, with the increasing complexity of modern distributed systems, protocols are used also to control such a complexity, and to ensure that the system as a whole evolves with certain features. However, the extensive use of protocols has raised some issues, from the language for specifying them to the several verification aspects. Computational Logic provides models, languages and tools that can be effectively adopted to address such issues: its declarative nature can be exploited for a protocol specification language, while its operational counterpart can be used to reason upon such specifications. In this thesis we propose a proof-theoretic framework, called SCIFF, together with its extensions. SCIFF is based on Abductive Logic Programming, and provides a formal specification language with a clear declarative semantics (based on abduction). The operational counterpart is given by a proof procedure, that allows to reason upon the specifications and to test the conformance of given interactions w.r.t. a defined protocol. Moreover, by suitably adapting the SCIFF Framework, we propose solutions for addressing (1) the protocol properties verification (g-SCIFF Framework), and (2) the a-priori conformance verification of peers w.r.t. the given protocol (AlLoWS Framework). We introduce also an agent based architecture, the SCIFF Agent Platform, where the same protocol specification can be used to program and to ease the implementation task of the interacting peers.

Interactive theorem provers: issues faced as a user and tackled as a developer

Interactive theorem provers (ITP for short) are tools whose final aim is to certify proofs written by human beings. To reach that objective they have to fill the gap between the high level language used by humans for communicating and reasoning about mathematics and the lower level language that a machine is able to “understand” and process. The user perceives this gap in terms of missing features or inefficiencies. The developer tries to accommodate the user requests without increasing the already high complexity of these applications. We believe that satisfactory solutions can only come from a strong synergy between users and developers. We devoted most part of our PHD designing and developing the Matita interactive theorem prover. The software was born in the computer science department of the University of Bologna as the result of composing together all the technologies developed by the HELM team (to which we belong) for the MoWGLI project. The MoWGLI project aimed at giving accessibility through the web to the libraries of formalised mathematics of various interactive theorem provers, taking Coq as the main test case. The motivations for giving life to a new ITP are: • study the architecture of these tools, with the aim of understanding the source of their complexity • exploit such a knowledge to experiment new solutions that, for backward compatibility reasons, would be hard (if not impossible) to test on a widely used system like Coq. Matita is based on the Curry-Howard isomorphism, adopting the Calculus of Inductive Constructions (CIC) as its logical foundation. Proof objects are thus, at some extent, compatible with the ones produced with the Coq ITP, that is itself able to import and process the ones generated using Matita. Although the systems have a lot in common, they share no code at all, and even most of the algorithmic solutions are different. The thesis is composed of two parts where we respectively describe our experience as a user and a developer of interactive provers. In particular, the first part is based on two different formalisation experiences: • our internship in the Mathematical Components team (INRIA), that is formalising the finite group theory required to attack the Feit Thompson Theorem. To tackle this result, giving an effective classification of finite groups of odd order, the team adopts the SSReflect Coq extension, developed by Georges Gonthier for the proof of the four colours theorem. • our collaboration at the D.A.M.A. Project, whose goal is the formalisation of abstract measure theory in Matita leading to a constructive proof of Lebesgue’s Dominated Convergence Theorem. The most notable issues we faced, analysed in this part of the thesis, are the following: the difficulties arising when using “black box” automation in large formalisations; the impossibility for a user (especially a newcomer) to master the context of a library of already formalised results; the uncomfortable big step execution of proof commands historically adopted in ITPs; the difficult encoding of mathematical structures with a notion of inheritance in a type theory without subtyping like CIC. In the second part of the manuscript many of these issues will be analysed with the looking glasses of an ITP developer, describing the solutions we adopted in the implementation of Matita to solve these problems: integrated searching facilities to assist the user in handling large libraries of formalised results; a small step execution semantic for proof commands; a flexible implementation of coercive subtyping allowing multiple inheritance with shared substructures; automatic tactics, integrated with the searching facilities, that generates proof commands (and not only proof objects, usually kept hidden to the user) one of which specifically designed to be user driven.

Smile detection for user interfaces

[EN]Perceptual User Interfaces (PUIs) aim at facilitating human-computer interaction with the aid of human-like capacities (computer vision, speech recognition, etc.). In PUIs, the human face is a central element, since it conveys not only identity but also other important information, particularly with respect to the user’s mood or emotional state. This paper describes both a face detector and a smile detector for PUIs. Both are suitable for real-time interaction.

Per un museo virtuale dell'informatica. Un supporto automatico per creare "visite museali"

The subject of the present research is related to the field of computer technology applied to support intellectual activities such as text translation, screenwriting and content organization of popular and education courses, especially concerning museum visits. The research has started with the deep analysis of the cognitive process which characterizes a screenwriter while working. This choice has been made because a screenplay is not only an aid to the realization of a show but, more in general, it can be considered as the planning of an education, popular and formative intellectual activity. After this analysis, the research has focused on the specific area of the planning, description and introduction of topics related to the history of science, and in particular, of computer science. To focus on this area it has been fundamental to analyse subjects concerning the didactics of museum visits organization. The aim was to find out the guide lines that a teacher should follow when planning the visit of a museum (virtual museum of the history of computer science). The consequent designing and realisation of an automatic support system for the description and the production of a formative, education and popular multimedia product (for the history of computer science), has been possible thanks to the results achieved through this research. The system obtained is provided by the following features: ·management of multimedia slides (such as texts, video, audio or images) which can be classified on the bases of the topic and of the profile of the user; ·automatic creation of a sequence of multimedia slides which introduce the topic; ·management of the interaction with the user to check and give validity to the product. The most innovative aspect of the present research is represented by the fact that the product is realised on the bases of the profile of the user.

Creazione e sviluppo di corpora multimediali. Nuove metodologie di ricerca nella traduzione audiovisiva

The construction and use of multimedia corpora has been advocated for a while in the literature as one of the expected future application fields of Corpus Linguistics. This research project represents a pioneering experience aimed at applying a data-driven methodology to the study of the field of AVT, similarly to what has been done in the last few decades in the macro-field of Translation Studies. This research was based on the experience of Forlixt 1, the Forlì Corpus of Screen Translation, developed at the University of Bologna’s Department of Interdisciplinary Studies in Translation, Languages and Culture. As a matter of fact, in order to quantify strategies of linguistic transfer of an AV product, we need to take into consideration not only the linguistic aspect of such a product but all the meaning-making resources deployed in the filmic text. Provided that one major benefit of Forlixt 1 is the combination of audiovisual and textual data, this corpus allows the user to access primary data for scientific investigation, and thus no longer rely on pre-processed material such as traditional annotated transcriptions. Based on this rationale, the first chapter of the thesis sets out to illustrate the state of the art of research in the disciplinary fields involved. The primary objective was to underline the main repercussions on multimedia texts resulting from the interaction of a double support, audio and video, and, accordingly, on procedures, means, and methods adopted in their translation. By drawing on previous research in semiotics and film studies, the relevant codes at work in visual and acoustic channels were outlined. Subsequently, we concentrated on the analysis of the verbal component and on the peculiar characteristics of filmic orality as opposed to spontaneous dialogic production. In the second part, an overview of the main AVT modalities was presented (dubbing, voice-over, interlinguistic and intra-linguistic subtitling, audio-description, etc.) in order to define the different technologies, processes and professional qualifications that this umbrella term presently includes. The second chapter focuses diachronically on various theories’ contribution to the application of Corpus Linguistics’ methods and tools to the field of Translation Studies (i.e. Descriptive Translation Studies, Polysystem Theory). In particular, we discussed how the use of corpora can favourably help reduce the gap existing between qualitative and quantitative approaches. Subsequently, we reviewed the tools traditionally employed by Corpus Linguistics in regard to the construction of traditional “written language” corpora, to assess whether and how they can be adapted to meet the needs of multimedia corpora. In particular, we reviewed existing speech and spoken corpora, as well as multimedia corpora specifically designed to investigate Translation. The third chapter reviews Forlixt 1's main developing steps, from a technical (IT design principles, data query functions) and methodological point of view, by laying down extensive scientific foundations for the annotation methods adopted, which presently encompass categories of pragmatic, sociolinguistic, linguacultural and semiotic nature. Finally, we described the main query tools (free search, guided search, advanced search and combined search) and the main intended uses of the database in a pedagogical perspective. The fourth chapter lists specific compilation criteria retained, as well as statistics of the two sub-corpora, by presenting data broken down by language pair (French-Italian and German-Italian) and genre (cinema’s comedies, television’s soapoperas and crime series). Next, we concentrated on the discussion of the results obtained from the analysis of summary tables reporting the frequency of categories applied to the French-Italian sub-corpus. The detailed observation of the distribution of categories identified in the original and dubbed corpus allowed us to empirically confirm some of the theories put forward in the literature and notably concerning the nature of the filmic text, the dubbing process and Italian dubbed language’s features. This was possible by looking into some of the most problematic aspects, like the rendering of socio-linguistic variation. The corpus equally allowed us to consider so far neglected aspects, such as pragmatic, prosodic, kinetic, facial, and semiotic elements, and their combination. At the end of this first exploration, some specific observations concerning possible macrotranslation trends were made for each type of sub-genre considered (cinematic and TV genre). On the grounds of this first quantitative investigation, the fifth chapter intended to further examine data, by applying ad hoc models of analysis. Given the virtually infinite number of combinations of categories adopted, and of the latter with searchable textual units, three possible qualitative and quantitative methods were designed, each of which was to concentrate on a particular translation dimension of the filmic text. The first one was the cultural dimension, which specifically focused on the rendering of selected cultural references and on the investigation of recurrent translation choices and strategies justified on the basis of the occurrence of specific clusters of categories. The second analysis was conducted on the linguistic dimension by exploring the occurrence of phrasal verbs in the Italian dubbed corpus and by ascertaining the influence on the adoption of related translation strategies of possible semiotic traits, such as gestures and facial expressions. Finally, the main aim of the third study was to verify whether, under which circumstances, and through which modality, graphic and iconic elements were translated into Italian from an original corpus of both German and French films. After having reviewed the main translation techniques at work, an exhaustive account of possible causes for their non-translation was equally provided. By way of conclusion, the discussion of results obtained from the distribution of annotation categories on the French-Italian corpus, as well as the application of specific models of analysis allowed us to underline possible advantages and drawbacks related to the adoption of a corpus-based approach to AVT studies. Even though possible updating and improvement were proposed in order to help solve some of the problems identified, it is argued that the added value of Forlixt 1 lies ultimately in having created a valuable instrument, allowing to carry out empirically-sound contrastive studies that may be usefully replicated on different language pairs and several types of multimedia texts. Furthermore, multimedia corpora can also play a crucial role in L2 and translation teaching, two disciplines in which their use still lacks systematic investigation.

Body ares networks for human motor assessment

Healthcare, Human Computer Interfaces (HCI), Security and Biometry are the most promising application scenario directly involved in the Body Area Networks (BANs) evolution. Both wearable devices and sensors directly integrated in garments envision a word in which each of us is supervised by an invisible assistant monitoring our health and daily-life activities. New opportunities are enabled because improvements in sensors miniaturization and transmission efficiency of the wireless protocols, that achieved the integration of high computational power aboard independent, energy-autonomous, small form factor devices. Application’s purposes are various: (I) data collection to achieve off-line knowledge discovery; (II) user notification of his/her activities or in case a danger occurs; (III) biofeedback rehabilitation; (IV) remote alarm activation in case the subject need assistance; (V) introduction of a more natural interaction with the surrounding computerized environment; (VI) users identification by physiological or behavioral characteristics. Telemedicine and mHealth [1] are two of the leading concepts directly related to healthcare. The capability to borne unobtrusiveness objects supports users’ autonomy. A new sense of freedom is shown to the user, not only supported by a psychological help but a real safety improvement. Furthermore, medical community aims the introduction of new devices to innovate patient treatments. In particular, the extension of the ambulatory analysis in the real life scenario by proving continuous acquisition. The wide diffusion of emerging wellness portable equipment extended the usability of wearable devices also for fitness and training by monitoring user performance on the working task. The learning of the right execution techniques related to work, sport, music can be supported by an electronic trainer furnishing the adequate aid. HCIs made real the concept of Ubiquitous, Pervasive Computing and Calm Technology introduced in the 1988 by Marc Weiser and John Seeley Brown. They promotes the creation of pervasive environments, enhancing the human experience. Context aware, adaptive and proactive environments serve and help people by becoming sensitive and reactive to their presence, since electronics is ubiquitous and deployed everywhere. In this thesis we pay attention to the integration of all the aspects involved in a BAN development. Starting from the choice of sensors we design the node, configure the radio network, implement real-time data analysis and provide a feedback to the user. We present algorithms to be implemented in wearable assistant for posture and gait analysis and to provide assistance on different walking conditions, preventing falls. Our aim, expressed by the idea to contribute at the development of a non proprietary solutions, driven us to integrate commercial and standard solutions in our devices. We use sensors available on the market and avoided to design specialized sensors in ASIC technologies. We employ standard radio protocol and open source projects when it was achieved. The specific contributions of the PhD research activities are presented and discussed in the following. • We have designed and build several wireless sensor node providing both sensing and actuator capability making the focus on the flexibility, small form factor and low power consumption. The key idea was to develop a simple and general purpose architecture for rapid analysis, prototyping and deployment of BAN solutions. Two different sensing units are integrated: kinematic (3D accelerometer and 3D gyroscopes) and kinetic (foot-floor contact pressure forces). Two kind of feedbacks were implemented: audio and vibrotactile. • Since the system built is a suitable platform for testing and measuring the features and the constraints of a sensor network (radio communication, network protocols, power consumption and autonomy), we made a comparison between Bluetooth and ZigBee performance in terms of throughput and energy efficiency. Test in the field evaluate the usability in the fall detection scenario. • To prove the flexibility of the architecture designed, we have implemented a wearable system for human posture rehabilitation. The application was developed in conjunction with biomedical engineers who provided the audio-algorithms to furnish a biofeedback to the user about his/her stability. • We explored off-line gait analysis of collected data, developing an algorithm to detect foot inclination in the sagittal plane, during walk. • In collaboration with the Wearable Lab – ETH, Zurich, we developed an algorithm to monitor the user during several walking condition where the user carry a load. The remainder of the thesis is organized as follows. Chapter I gives an overview about Body Area Networks (BANs), illustrating the relevant features of this technology and the key challenges still open. It concludes with a short list of the real solutions and prototypes proposed by academic research and manufacturers. The domain of the posture and gait analysis, the methodologies, and the technologies used to provide real-time feedback on detected events, are illustrated in Chapter II. The Chapter III and IV, respectively, shown BANs developed with the purpose to detect fall and monitor the gait taking advantage by two inertial measurement unit and baropodometric insoles. Chapter V reports an audio-biofeedback system to improve balance on the information provided by the use centre of mass. A walking assistant based on the KNN classifier to detect walking alteration on load carriage, is described in Chapter VI.

Thermal relaxation for particle systems in interaction with several bosonic heat reservoirs

The present thesis is concerned with the study of a quantum physical system composed of a small particle system (such as a spin chain) and several quantized massless boson fields (as photon gasses or phonon fields) at positive temperature. The setup serves as a simplified model for matter in interaction with thermal "radiation" from different sources. Hereby, questions concerning the dynamical and thermodynamic properties of particle-boson configurations far from thermal equilibrium are in the center of interest. We study a specific situation where the particle system is brought in contact with the boson systems (occasionally referred to as heat reservoirs) where the reservoirs are prepared close to thermal equilibrium states, each at a different temperature. We analyze the interacting time evolution of such an initial configuration and we show thermal relaxation of the system into a stationary state, i.e., we prove the existence of a time invariant state which is the unique limit state of the considered initial configurations evolving in time. As long as the reservoirs have been prepared at different temperatures, this stationary state features thermodynamic characteristics as stationary energy fluxes and a positive entropy production rate which distinguishes it from being a thermal equilibrium at any temperature. Therefore, we refer to it as non-equilibrium stationary state or simply NESS. The physical setup is phrased mathematically in the language of C*-algebras. The thesis gives an extended review of the application of operator algebraic theories to quantum statistical mechanics and introduces in detail the mathematical objects to describe matter in interaction with radiation. The C*-theory is adapted to the concrete setup. The algebraic description of the system is lifted into a Hilbert space framework. The appropriate Hilbert space representation is given by a bosonic Fock space over a suitable L2-space. The first part of the present work is concluded by the derivation of a spectral theory which connects the dynamical and thermodynamic features with spectral properties of a suitable generator, say K, of the time evolution in this Hilbert space setting. That way, the question about thermal relaxation becomes a spectral problem. The operator K is of Pauli-Fierz type. The spectral analysis of the generator K follows. This task is the core part of the work and it employs various kinds of functional analytic techniques. The operator K results from a perturbation of an operator L0 which describes the non-interacting particle-boson system. All spectral considerations are done in a perturbative regime, i.e., we assume that the strength of the coupling is sufficiently small. The extraction of dynamical features of the system from properties of K requires, in particular, the knowledge about the spectrum of K in the nearest vicinity of eigenvalues of the unperturbed operator L0. Since convergent Neumann series expansions only qualify to study the perturbed spectrum in the neighborhood of the unperturbed one on a scale of order of the coupling strength we need to apply a more refined tool, the Feshbach map. This technique allows the analysis of the spectrum on a smaller scale by transferring the analysis to a spectral subspace. The need of spectral information on arbitrary scales requires an iteration of the Feshbach map. This procedure leads to an operator-theoretic renormalization group. The reader is introduced to the Feshbach technique and the renormalization procedure based on it is discussed in full detail. Further, it is explained how the spectral information is extracted from the renormalization group flow. The present dissertation is an extension of two kinds of a recent research contribution by Jakšić and Pillet to a similar physical setup. Firstly, we consider the more delicate situation of bosonic heat reservoirs instead of fermionic ones, and secondly, the system can be studied uniformly for small reservoir temperatures. The adaption of the Feshbach map-based renormalization procedure by Bach, Chen, Fröhlich, and Sigal to concrete spectral problems in quantum statistical mechanics is a further novelty of this work.

Query rewriting in information retrieval: automatic context extraction from local user documents to improve query results

The central objective of research in Information Retrieval (IR) is to discover new techniques to retrieve relevant information in order to satisfy an Information Need. The Information Need is satisfied when relevant information can be provided to the user. In IR, relevance is a fundamental concept which has changed over time, from popular to personal, i.e., what was considered relevant before was information for the whole population, but what is considered relevant now is specific information for each user. Hence, there is a need to connect the behavior of the system to the condition of a particular person and his social context; thereby an interdisciplinary sector called Human-Centered Computing was born. For the modern search engine, the information extracted for the individual user is crucial. According to the Personalized Search (PS), two different techniques are necessary to personalize a search: contextualization (interconnected conditions that occur in an activity), and individualization (characteristics that distinguish an individual). This movement of focus to the individual's need undermines the rigid linearity of the classical model overtaken the ``berry picking'' model which explains that the terms change thanks to the informational feedback received from the search activity introducing the concept of evolution of search terms. The development of Information Foraging theory, which observed the correlations between animal foraging and human information foraging, also contributed to this transformation through attempts to optimize the cost-benefit ratio. This thesis arose from the need to satisfy human individuality when searching for information, and it develops a synergistic collaboration between the frontiers of technological innovation and the recent advances in IR. The search method developed exploits what is relevant for the user by changing radically the way in which an Information Need is expressed, because now it is expressed through the generation of the query and its own context. As a matter of fact the method was born under the pretense to improve the quality of search by rewriting the query based on the contexts automatically generated from a local knowledge base. Furthermore, the idea of optimizing each IR system has led to develop it as a middleware of interaction between the user and the IR system. Thereby the system has just two possible actions: rewriting the query, and reordering the result. Equivalent actions to the approach was described from the PS that generally exploits information derived from analysis of user behavior, while the proposed approach exploits knowledge provided by the user. The thesis went further to generate a novel method for an assessment procedure, according to the "Cranfield paradigm", in order to evaluate this type of IR systems. The results achieved are interesting considering both the effectiveness achieved and the innovative approach undertaken together with the several applications inspired using a local knowledge base.

Bifidobacterium - Human Host Interaction: Role of Human Plasminogen

Bifidobacterium is an important genus of the human gastrointestinal microbiota, affecting several host physiological features. Despite the numerous Bifidobacterium related health-promoting activities, there is still a dearth of information about the molecular mechanisms at the basis of the interaction between this microorganism and the host. Bacterial surface associated proteins may play an important role in this interaction because of their ability to intervene with host molecules, as recently reported for the host protein plasminogen. Plasminogen is the zymogen of the trypsin-like serine protease plasmin, an enzyme with a broad substrate specificity. Aim of this thesis is to deepen the knowledge about the interaction between Bifidobacterium and the human plasminogen system and its role in the Bifidobacterium-host interaction process. As a bifidobacterial model, B. animalis subsp. lactis BI07 has been used because of its large usage in dairy and pharmaceutical preparations. We started from the molecular characterization of the interaction between plasminogen and one bifidobacterial plasminogen receptor, DnaK, a cell wall protein showing high affinity for plasminogen, and went on with the study of the impact of intestinal environmental factors, such as bile salts and inflammation, on the plasminogen-mediated Bifidobacterium-host interaction. According to our in vitro findings, by enhancing the activation of the bifidobacterial bound plasminogen to plasmin, the host inflammatory response results in the decrease of the bifidobacterial adhesion to the host enterocytes, favouring bacterial migration to the luminal compartment. Conversely, in the absence of inflammation, plasminogen acts as a molecular bridge between host enterocytes and bifidobacteria, enhancing Bifidobacterium adhesion. Furthermore, adaptation to physiological concentrations of bile salts enhances the capability of this microorganism to interact with the host plasminogen system. The host plasminogen system thus represents an important and flexible tool used by bifidobacteria in the cross-talk with the host.

Design, development and first evaluation of a client/server system for managing and querying linguistic corpora

This thesis is concerned with the role played by software tools in the analysis and dissemination of linguistic corpora and their contribution to a more widespread adoption of corpora in different fields. Chapter 1 contains an overview of some of the most relevant corpus analysis tools available today, presenting their most interesting features and some of their drawbacks. Chapter 2 begins with an explanation of the reasons why none of the available tools appear to satisfy the requirements of the user community and then continues with technical overview of the current status of the new system developed as part of this work. This presentation is followed by highlights of features that make the system appealing to users and corpus builders (i.e. scholars willing to make their corpora available to the public). The chapter concludes with an indication of future directions for the projects and information on the current availability of the software. Chapter 3 describes the design of an experiment devised to evaluate the usability of the new system in comparison to another corpus tool. Usage of the tool was tested in the context of a documentation task performed on a real assignment during a translation class in a master's degree course. In chapter 4 the findings of the experiment are presented on two levels of analysis: firstly a discussion on how participants interacted with and evaluated the two corpus tools in terms of interface and interaction design, usability and perceived ease of use. Then an analysis follows of how users interacted with corpora to complete the task and what kind of queries they submitted. Finally, some general conclusions are drawn and areas for future work are outlined.