High precision astrometry mission for the detection and characterization of nearby habitable planetary systems with the Nearby Earth Astrometric Telescope (NEAT)

A complete census of planetary systems around a volume-limited sample of solar-type stars (FGK dwarfs) in the Solar neighborhood (d a parts per thousand currency signaEuro parts per thousand 15 pc) with uniform sensitivity down to Earth-mass planets within their Habitable Zones out to several AUs would be a major milestone in extrasolar planets astrophysics. This fundamental goal can be achieved with a mission concept such as NEAT-the Nearby Earth Astrometric Telescope. NEAT is designed to carry out space-borne extremely-high-precision astrometric measurements at the 0.05 mu as (1 sigma) accuracy level, sufficient to detect dynamical effects due to orbiting planets of mass even lower than Earth's around the nearest stars. Such a survey mission would provide the actual planetary masses and the full orbital geometry for all the components of the detected planetary systems down to the Earth-mass limit. The NEAT performance limits can be achieved by carrying out differential astrometry between the targets and a set of suitable reference stars in the field. The NEAT instrument design consists of an off-axis parabola single-mirror telescope (D = 1 m), a detector with a large field of view located 40 m away from the telescope and made of 8 small movable CCDs located around a fixed central CCD, and an interferometric calibration system monitoring dynamical Young's fringes originating from metrology fibers located at the primary mirror. The mission profile is driven by the fact that the two main modules of the payload, the telescope and the focal plane, must be located 40 m away leading to the choice of a formation flying option as the reference mission, and of a deployable boom option as an alternative choice. The proposed mission architecture relies on the use of two satellites, of about 700 kg each, operating at L2 for 5 years, flying in formation and offering a capability of more than 20,000 reconfigurations. The two satellites will be launched in a stacked configuration using a Soyuz ST launch vehicle. The NEAT primary science program will encompass an astrometric survey of our 200 closest F-, G- and K-type stellar neighbors, with an average of 50 visits each distributed over the nominal mission duration. The main survey operation will use approximately 70% of the mission lifetime. The remaining 30% of NEAT observing time might be allocated, for example, to improve the characterization of the architecture of selected planetary systems around nearby targets of specific interest (low-mass stars, young stars, etc.) discovered by Gaia, ground-based high-precision radial-velocity surveys, and other programs. With its exquisite, surgical astrometric precision, NEAT holds the promise to provide the first thorough census for Earth-mass planets around stars in the immediate vicinity of our Sun.

An online data access prediction and optimization approach for distributed systems

Current scientific applications have been producing large amounts of data. The processing, handling and analysis of such data require large-scale computing infrastructures such as clusters and grids. In this area, studies aim at improving the performance of data-intensive applications by optimizing data accesses. In order to achieve this goal, distributed storage systems have been considering techniques of data replication, migration, distribution, and access parallelism. However, the main drawback of those studies is that they do not take into account application behavior to perform data access optimization. This limitation motivated this paper which applies strategies to support the online prediction of application behavior in order to optimize data access operations on distributed systems, without requiring any information on past executions. In order to accomplish such a goal, this approach organizes application behaviors as time series and, then, analyzes and classifies those series according to their properties. By knowing properties, the approach selects modeling techniques to represent series and perform predictions, which are, later on, used to optimize data access operations. This new approach was implemented and evaluated using the OptorSim simulator, sponsored by the LHC-CERN project and widely employed by the scientific community. Experiments confirm this new approach reduces application execution time in about 50 percent, specially when handling large amounts of data.

Comparison of different delivery systems of DNA vaccination for the induction of protection against tuberculosis in mice and guinea pigs

The great challenges for researchers working in the field of vaccinology are optimizing DNA vaccines for use in humans or large animals and creating effective single-dose vaccines using appropriated controlled delivery systems. Plasmid DNA encoding the heat-shock protein 65 (hsp65) (DNAhsp65) has been shown to induce protective and therapeutic immune responses in a murine model of tuberculosis (TB). Despite the success of naked DNAhsp65-based vaccine to protect mice against TB, it requires multiple doses of high amounts of DNA for effective immunization. In order to optimize this DNA vaccine and simplify the vaccination schedule, we coencapsulated DNAhsp65 and the adjuvant trehalose dimycolate (TDM) into biodegradable poly (DL-lactide-co-glycolide) (PLGA) microspheres for a single dose administration. Moreover, a single-shot prime-boost vaccine formulation based on a mixture of two different PLGA microspheres, presenting faster and slower release of, respectively, DNAhsp65 and the recombinant hsp65 protein was also developed. These formulations were tested in mice as well as in guinea pigs by comparison with the efficacy and toxicity induced by the naked DNA preparation or BCG. The single-shot prime-boost formulation clearly presented good efficacy and diminished lung pathology in both mice and guinea pigs.

The effects of long-term endurance training on the immune and endocrine systems of elderly men: the role of cytokines and anabolic hormones

Abstract Background a decline in immune and endocrine function occurs with aging. The main purpose of this study was to investigate the impact of long-term endurance training on the immune and endocrine system of elderly men. The possible interaction between these systems was also analysed. Results elderly runners showed a significantly higher T cell proliferative response and IL-2 production than sedentary elderly controls. IL-2 production was similar to that in young adults. Their serum IL-6 levels were significantly lower than their sedentary peers. They also showed significantly lower IL-3 production in comparison to sedentary elderly subjects but similar to the youngs. Anabolic hormone levels did not differ between elderly groups and no clear correlation was found between hormones and cytokine levels. Conclusion highly conditioned elderly men seem to have relatively better preserved immune system than the sedentary elderly men. Long-term endurance training has the potential to decelerate the age-related decline in immune function but not the deterioration in endocrine function.

Geographical distribution of American cutaneous leishmaniasis and its phlebotomine vectors (Diptera: Psychodidae) in the state of São Paulo, Brazil

Abstract Background American cutaneous leishmaniasis (ACL) is a re-emerging disease in the state of São Paulo, Brazil. It is important to understand both the vector and disease distribution to help design control strategies. As an initial step in applying geographic information systems (GIS) and remote sensing (RS) tools to map disease-risk, the objectives of the present work were to: (i) produce a single database of species distributions of the sand fly vectors in the state of São Paulo, (ii) create combined distributional maps of both the incidence of ACL and its sand fly vectors, and (iii) thereby provide individual municipalities with a source of reference material for work carried out in their area. Results A database containing 910 individual records of sand fly occurrence in the state of São Paulo, from 37 different sources, was compiled. These records date from between 1943 to 2009, and describe the presence of at least one of the six incriminated or suspected sand fly vector species in 183/645 (28.4%) municipalities. For the remaining 462 (71.6%) municipalities, we were unable to locate records of any of the six incriminated or suspected sand fly vector species (Nyssomyia intermedia, N. neivai, N. whitmani, Pintomyia fischeri, P. pessoai and Migonemyia migonei). The distribution of each of the six incriminated or suspected vector species of ACL in the state of São Paulo were individually mapped and overlaid on the incidence of ACL for the period 1993 to 1995 and 1998 to 2007. Overall, the maps reveal that the six sand fly vector species analyzed have unique and heterogeneous, although often overlapping, distributions. Several sand fly species - Nyssomyia intermedia and N. neivai - are highly localized, while the other sand fly species - N. whitmani, M. migonei, P. fischeri and P. pessoai - are much more broadly distributed. ACL has been reported in 160/183 (87.4%) of the municipalities with records for at least one of the six incriminated or suspected sand fly vector species, while there are no records of any of these sand fly species in 318/478 (66.5%) municipalities with ACL. Conclusions The maps produced in this work provide basic data on the distribution of the six incriminated or suspected sand fly vectors of ACL in the state of São Paulo, and highlight the complex and geographically heterogeneous pattern of ACL transmission in the region. Further studies are required to clarify the role of each of the six suspected sand fly vector species in different regions of the state of São Paulo, especially in the majority of municipalities where ACL is present but sand fly vectors have not yet been identified.

A rigorous approach to facilitate and guarantee the correctness of the genetic testing management in human genome information systems

Abstract Background Recent medical and biological technology advances have stimulated the development of new testing systems that have been providing huge, varied amounts of molecular and clinical data. Growing data volumes pose significant challenges for information processing systems in research centers. Additionally, the routines of genomics laboratory are typically characterized by high parallelism in testing and constant procedure changes. Results This paper describes a formal approach to address this challenge through the implementation of a genetic testing management system applied to human genome laboratory. We introduced the Human Genome Research Center Information System (CEGH) in Brazil, a system that is able to support constant changes in human genome testing and can provide patients updated results based on the most recent and validated genetic knowledge. Our approach uses a common repository for process planning to ensure reusability, specification, instantiation, monitoring, and execution of processes, which are defined using a relational database and rigorous control flow specifications based on process algebra (ACP). The main difference between our approach and related works is that we were able to join two important aspects: 1) process scalability achieved through relational database implementation, and 2) correctness of processes using process algebra. Furthermore, the software allows end users to define genetic testing without requiring any knowledge about business process notation or process algebra. Conclusions This paper presents the CEGH information system that is a Laboratory Information Management System (LIMS) based on a formal framework to support genetic testing management for Mendelian disorder studies. We have proved the feasibility and showed usability benefits of a rigorous approach that is able to specify, validate, and perform genetic testing using easy end user interfaces.

Molecular gas in the galaxy M83 : Its distribution, kinematics, and relation to star formation

The barred spiral galaxy M83 (NGC5236) has been observed in the 12CO J=1–0 and J=2–1 millimetre lines with the Swedish-ESO Submillimetre Telescope (SEST). The sizes of the CO maps are 100×100, and they cover the entire optical disk. The CO emission is strongly peaked toward the nucleus. The molecular spiral arms are clearly resolved and can be traced for about 360º. The total molecular gas mass is comparable to the total Hi mass, but H2 dominates in the optical disk. Iso-velocity maps show the signature of an inclined, rotating disk, but also the effects of streaming motions along the spiral arms. The dynamical mass is determined and compared to the gas mass. The pattern speed is determined from the residual velocity pattern, and the locations of various resonances are discussed. The molecular gas velocity dispersion is determined, and a trend of decreasing dispersion with increasing galactocentric radius is found. A total gas (H2+Hi+He) mass surface density map is presented, and compared to the critical density for star formation of an isothermal gaseous disk. The star formation rate (SFR) in the disk is estimated using data from various star formation tracers. The different SFR estimates agree well when corrections for extinctions, based on the total gas mass map, are made. The radial SFR distribution shows features that can be associated with kinematic resonances. We also find an increased star formation efficiency in the spiral arms. Different Schmidt laws are fitted to the data. The star formation properties of the nuclear region, based on high angular resolution HST data, are also discussed.

Rich media content adaptation in e-learning systems

The wide use of e-technologies represents a great opportunity for underserved segments of the population, especially with the aim of reintegrating excluded individuals back into society through education. This is particularly true for people with different types of disabilities who may have difficulties while attending traditional on-site learning programs that are typically based on printed learning resources. The creation and provision of accessible e-learning contents may therefore become a key factor in enabling people with different access needs to enjoy quality learning experiences and services. Another e-learning challenge is represented by m-learning (which stands for mobile learning), which is emerging as a consequence of mobile terminals diffusion and provides the opportunity to browse didactical materials everywhere, outside places that are traditionally devoted to education. Both such situations share the need to access materials in limited conditions and collide with the growing use of rich media in didactical contents, which are designed to be enjoyed without any restriction. Nowadays, Web-based teaching makes great use of multimedia technologies, ranging from Flash animations to prerecorded video-lectures. Rich media in e-learning can offer significant potential in enhancing the learning environment, through helping to increase access to education, enhance the learning experience and support multiple learning styles. Moreover, they can often be used to improve the structure of Web-based courses. These highly variegated and structured contents may significantly improve the quality and the effectiveness of educational activities for learners. For example, rich media contents allow us to describe complex concepts and process flows. Audio and video elements may be utilized to add a “human touch” to distance-learning courses. Finally, real lectures may be recorded and distributed to integrate or enrich on line materials. A confirmation of the advantages of these approaches can be seen in the exponential growth of video-lecture availability on the net, due to the ease of recording and delivering activities which take place in a traditional classroom. Furthermore, the wide use of assistive technologies for learners with disabilities injects new life into e-learning systems. E-learning allows distance and flexible educational activities, thus helping disabled learners to access resources which would otherwise present significant barriers for them. For instance, students with visual impairments have difficulties in reading traditional visual materials, deaf learners have trouble in following traditional (spoken) lectures, people with motion disabilities have problems in attending on-site programs. As already mentioned, the use of wireless technologies and pervasive computing may really enhance the educational learner experience by offering mobile e-learning services that can be accessed by handheld devices. This new paradigm of educational content distribution maximizes the benefits for learners since it enables users to overcome constraints imposed by the surrounding environment. While certainly helpful for users without disabilities, we believe that the use of newmobile technologies may also become a fundamental tool for impaired learners, since it frees them from sitting in front of a PC. In this way, educational activities can be enjoyed by all the users, without hindrance, thus increasing the social inclusion of non-typical learners. While the provision of fully accessible and portable video-lectures may be extremely useful for students, it is widely recognized that structuring and managing rich media contents for mobile learning services are complex and expensive tasks. Indeed, major difficulties originate from the basic need to provide a textual equivalent for each media resource composing a rich media Learning Object (LO). Moreover, tests need to be carried out to establish whether a given LO is fully accessible to all kinds of learners. Unfortunately, both these tasks are truly time-consuming processes, depending on the type of contents the teacher is writing and on the authoring tool he/she is using. Due to these difficulties, online LOs are often distributed as partially accessible or totally inaccessible content. Bearing this in mind, this thesis aims to discuss the key issues of a system we have developed to deliver accessible, customized or nomadic learning experiences to learners with different access needs and skills. To reduce the risk of excluding users with particular access capabilities, our system exploits Learning Objects (LOs) which are dynamically adapted and transcoded based on the specific needs of non-typical users and on the barriers that they can encounter in the environment. The basic idea is to dynamically adapt contents, by selecting them from a set of media resources packaged in SCORM-compliant LOs and stored in a self-adapting format. The system schedules and orchestrates a set of transcoding processes based on specific learner needs, so as to produce a customized LO that can be fully enjoyed by any (impaired or mobile) student.

Self-organising coordination systems

Many research fields are pushing the engineering of large-scale, mobile, and open systems towards the adoption of techniques inspired by self-organisation: pervasive computing, but also distributed artificial intelligence, multi-agent systems, social networks, peer-topeer and grid architectures exploit adaptive techniques to make global system properties emerge in spite of the unpredictability of interactions and behaviour. Such a trend is visible also in coordination models and languages, whenever a coordination infrastructure needs to cope with managing interactions in highly dynamic and unpredictable environments. As a consequence, self-organisation can be regarded as a feasible metaphor to define a radically new conceptual coordination framework. The resulting framework defines a novel coordination paradigm, called self-organising coordination, based on the idea of spreading coordination media over the network, and charge them with services to manage interactions based on local criteria, resulting in the emergence of desired and fruitful global coordination properties of the system. Features like topology, locality, time-reactiveness, and stochastic behaviour play a key role in both the definition of such a conceptual framework and the consequent development of self-organising coordination services. According to this framework, the thesis presents several self-organising coordination techniques developed during the PhD course, mainly concerning data distribution in tuplespace-based coordination systems. Some of these techniques have been also implemented in ReSpecT, a coordination language for tuple spaces, based on logic tuples and reactions to events occurring in a tuple space. In addition, the key role played by simulation and formal verification has been investigated, leading to analysing how automatic verification techniques like probabilistic model checking can be exploited in order to formally prove the emergence of desired behaviours when dealing with coordination approaches based on self-organisation. To this end, a concrete case study is presented and discussed.

Simulation studies of correlation functions and relaxation in polymeric systems

We investigate the statics and dynamics of a glassy,non-entangled, short bead-spring polymer melt with moleculardynamics simulations. Temperature ranges from slightlyabove the mode-coupling critical temperature to the liquidregime where features of a glassy liquid are absent. Ouraim is to work out the polymer specific effects on therelaxation and particle correlation. We find the intra-chain static structure unaffected bytemperature, it depends only on the distance of monomersalong the backbone. In contrast, the distinct inter-chainstructure shows pronounced site-dependence effects at thelength-scales of the chain and the nearest neighbordistance. There, we also find the strongest temperaturedependence which drives the glass transition. Both the siteaveraged coupling of the monomer and center of mass (CM) andthe CM-CM coupling are weak and presumably not responsiblefor a peak in the coherent relaxation time at the chain'slength scale. Chains rather emerge as soft, easilyinterpenetrating objects. Three particle correlations arewell reproduced by the convolution approximation with theexception of model dependent deviations. In the spatially heterogeneous dynamics of our system weidentify highly mobile monomers which tend to follow eachother in one-dimensional paths forming ``strings''. Thesestrings have an exponential length distribution and aregenerally short compared to the chain length. Thus, arelaxation mechanism in which neighboring mobile monomersmove along the backbone of the chain seems unlikely.However, the correlation of bonded neighbors is enhanced. When liquids are confined between two surfaces in relativesliding motion kinetic friction is observed. We study ageneric model setup by molecular dynamics simulations for awide range of sliding speeds, temperatures, loads, andlubricant coverings for simple and molecular fluids. Instabilities in the particle trajectories are identified asthe origin of kinetic friction. They lead to high particlevelocities of fluid atoms which are gradually dissipatedresulting in a friction force. In commensurate systemsfluid atoms follow continuous trajectories for sub-monolayercoverings and consequently, friction vanishes at low slidingspeeds. For incommensurate systems the velocity probabilitydistribution exhibits approximately exponential tails. Weconnect this velocity distribution to the kinetic frictionforce which reaches a constant value at low sliding speeds. This approach agrees well with the friction obtaineddirectly from simulations and explains Amontons' law on themicroscopic level. Molecular bonds in commensurate systemslead to incommensurate behavior, but do not change thequalitative behavior of incommensurate systems. However,crossed chains form stable load bearing asperities whichstrongly increase friction.

Scherverhalten kolloidaler Lagenphasen in Rohrströmungen

Kolloidale Suspensionen aus identischen kugelförmigen, geladenen Partikeln in wässrigen Medien stellen ein ideales Modellsystem zur Untersuchung des Gleichgewichtsverhaltens, aber auch des Nicht-Gleichgewichtsverhaltens Weicher Materie dar. So bilden derartige Systeme bei hinreichend starker und langreichweitiger elektrostatischer Repulsion fluid und kristallin geordnete Strukturen aus, die wegen der weitreichenden Analogie zu atomar kondensierter Materie als kolloidale Fluide und Kristalle bezeichnet werden. Von großem Vorteil ist dabei die Möglichkeit zur kontrollierten Einstellung der Wechselwirkung und die gute optische Zugänglichkeit für Mikroskopie und Lichtstreuung sowie die Weichheit der Materialien, aufgrund derer sich auch Zustände fernab des mechanischen Gleichgewichts gezielt präparieren lassen. Themenstellung der vorliegenden Arbeit ist die Untersuchung des Phasenverhaltens und der Fließmechanismen kolloidaler Kristalle in einer Rohrströmung. Im ersten Teil der Arbeit wird gezeigt, dass beim Fluss durch eine zylindrische Röhre Mehrphasenkoexistenz auftritt, wobei ein polykristalliner Kern von einer isotropen Scherschmelze umgeben ist. Zusätzlich treten an der Grenze zwischen diesen Phasen und an der Rohrwand Phasen hexagonal geordneter übereinander hinweggleitender Lagen auf. Der Vergleich zwischen auf der Basis der Navier-Stokes-Gleichung theoretisch berechneten und gemessenen Geschwindigkeitsprofilen zeigt, dass jede dieser Phasen für sich Newtonsches Fließverhalten aufweist. Die Gesamtviskosität ist hingegen durch die mit dem Durchsatz veränderliche Phasenzusammensetzung Nicht-Newtonsch. Damit gelang es, die erstmalig von Würth beschriebene Scherverdünnung auf eine Veränderung der Phasenzusammensetzung zurückzuführen. Im zweiten Teil der Arbeit wurde erstmals das Fließverhalten der Lagenphasen mittels Lichtstreuung und Korrelationsanalyse untersucht. Dafür wurde ein im Prinzip einfacher, aber leistungsstarker Aufbau realisiert, der es erlaubt, die zeitliche Veränderung der Bragg-Reflexe der Lagenphase in radialer und azimutaler Richtung zu verfolgen und mittels Fourieranalyse zu analysieren. In Abhängigkeit vom Durchsatz geht die zunächst rastend gleitende Lagenphase in eine frei gleitende Lagenphase über, wobei charakteristische Veränderungen der Spektren sowie der Korrelationsfunktionen auftreten, die detailliert diskutiert werden. Der Übergang im Gleitmechanismus ist mit einem Verlust der Autokorrelation der Rotationskomponente der periodischen Intra-Lagenverzerrung verbunden, während die Kompressionskomponente erhalten bleibt. Bei hohen Durchflüssen lassen die Reflexbewegungen auf das Auftreten einer Eigenschwingung der frei gleitenden Lagen schließen. Diese Schwingung lässt sich als Rotationsbewegung, gekoppelt mit einer transversalen Auslenkung in Vortexrichtung, beschreiben. Die Ergebnisse erlauben eine detaillierte Diskussion von verschiedenen Modellvorstellungen anderer Autoren.

Genetische Analyse des Somatostatin-Systems

Somatostatin ist ein Molekül mit multifunktinonellem Charakter, dem Neurotransmitter-, Neuromodulator- und (Neuro)-Hormoneigenschaften zugeschrieben werden. Gemäß seiner ubiquitären Verteilung in Geweben beeinflusst es Stoffwechsel- und Entwicklungsprozesse, bis hin zu Lern-und Gedächtnisleistungen. Diese Wirkungen resultieren aus dem lokalen und zeitlichen Zusammenspiel eines Liganden und fünf G-Protein gekoppelter Rezeptoren (SSTR1-5). Zur Charakterisierung der biologischen Bedeutung des Somatostatin-Systems im Gesamtorganismus wurde eine Mutationsanalyse einzelner Systemkomponenten durchgeführt. Sie umfaßte die Inaktivierung der Gene für das Somatostatin-Präpropeptid und die der Rezeptoren SSTR3 und SSTR4 durch Gene Targeting. Die entsprechenden Ausfallmutationen belegen: Weder die Rezeptoren 3 und 4, noch Somatostatin sind für das Überleben des Organismus unter Standardhaltungsbedingungen notwendig. Die entsprechenden Mauslinien zeigen keine unmittelbar auffälligen Einschränkungen ihrer Biologie. Die Somatostatin-Nullmaus wurde zum Hauptgegenstand einer detaillierten Untersuchung aufgrund der übergeordneten Position des Liganden in der Signalkaskade und verfügbaren Hinweisen zu seiner Funktion. Folgende Schlußfolgerungen konnten nach eingehender Analyse gezogen werden: Der Ausfall des Somatostatin-Gens hat erhöhte Plasmakonzentrationen an Wachstumshormon (GH) zur Konsequenz. Dies steht im Einklang mit der Rolle Somatostatins als hemmender Faktor der Wachstumshormon-Freisetzung, die in der Mutante aufgehoben ist. Durch die Somatostatin-Nullmaus wurde zudem deutlich: Somatostatin interagiert als wesentliches Bindeglied zwischen der Wachstums- und Streßachse. Permanent erhöhte Corticosteron-Werte in den Mutanten implizieren einen negativen tonischen Einfluß für die Sekretion von Glukocorticoiden in vivo. Damit zeigt die Knockout-Maus, daß Somatostatin normalerweise als ein entscheidendes inhibierendes Kontrollelement der Steroidfreisetzung fungiert. Verhaltensversuche offenbarten ein Defizit im motorischen Lernen. Somatostatin-Nullmäuse bleiben im Lernparadigma “Rotierender Stabtest” hinter ihren Artgenossen zurück ohne aber generell in Motorik oder Koordination eingeschränkt zu sein. Diese motorischen Lernvorgänge sind von einem funktionierenden Kleinhirn abhängig. Da Somatostatin und seine Rezeptoren kaum im adulten, wohl aber im sich entwickelnden Kleinhirn auftreten, belegt dieses Ergebnis die Funktion transient in der Entwicklung exprimierter Neuropeptide – eine lang bestehende, aber bislang experimentell nicht nachgewiesene Hypothese. Die Überprüfung weiterer physiologischer Parameter und Verhaltenskategorien unter Standard-Laborbedingunggen ergab keine sichtbaren Abweichungen im Vergleich zu Wildtyp-Mäusen. Damit steht nun ein Tiermodell zur weiterführenden Analyse für die Somatostatin-Forschung bereit: In endokrinologischen, elektrophysiologischen und verhaltens-biologischen Experimenten ist nun eine unmittelbare Korrelation selektiv mit dem Somatostatin-Peptid bzw. mit den Rezeptoren 3 und 4 aber auch in Kombination der Ausfallmutationen nach entsprechenden Kreuzungen möglich.

Parallel modeling of the electric field distribution in the brain

The term "Brain Imaging" identi�es a set of techniques to analyze the structure and/or functional behavior of the brain in normal and/or pathological situations. These techniques are largely used in the study of brain activity. In addition to clinical usage, analysis of brain activity is gaining popularity in others recent �fields, i.e. Brain Computer Interfaces (BCI) and the study of cognitive processes. In this context, usage of classical solutions (e.g. f MRI, PET-CT) could be unfeasible, due to their low temporal resolution, high cost and limited portability. For these reasons alternative low cost techniques are object of research, typically based on simple recording hardware and on intensive data elaboration process. Typical examples are ElectroEncephaloGraphy (EEG) and Electrical Impedance Tomography (EIT), where electric potential at the patient's scalp is recorded by high impedance electrodes. In EEG potentials are directly generated from neuronal activity, while in EIT by the injection of small currents at the scalp. To retrieve meaningful insights on brain activity from measurements, EIT and EEG relies on detailed knowledge of the underlying electrical properties of the body. This is obtained from numerical models of the electric �field distribution therein. The inhomogeneous and anisotropic electric properties of human tissues make accurate modeling and simulation very challenging, leading to a tradeo�ff between physical accuracy and technical feasibility, which currently severely limits the capabilities of these techniques. Moreover elaboration of data recorded requires usage of regularization techniques computationally intensive, which influences the application with heavy temporal constraints (such as BCI). This work focuses on the parallel implementation of a work-flow for EEG and EIT data processing. The resulting software is accelerated using multi-core GPUs, in order to provide solution in reasonable times and address requirements of real-time BCI systems, without over-simplifying the complexity and accuracy of the head models.

Effect of drug physicochemical properties on the release from liposomal systems in vitro and in vivo

Liposomes were discovered about 40 years ago by A. Bangham and since then they became very versatile tools in biology, biochemistry and medicine. Liposomes are the smallest artificial vesicles of spherical shape that can be produced from natural untoxic phospholipids and cholesterol. Liposome vesicles can be used as drug carriers and become loaded with a great variety of molecules, such as small drug molecules, proteins, nucleotides and even plasmids. Due to the variability of liposomal compositions they can be used for a large number of applications. In this thesis the β-adrenoceptor antagonists propranolol, metoprolol, atenolol and pindolol, glucose, 18F-Fluorodeoxyglucose (FDG) and Er-DTPA were used for encapsulation in liposomes, characterization and in vitro release studies. Multilamellar vesicles (MLV), large unilamellar vesicles (LUV) and smaller unilamellar vesicles (SUV) were prepared using one of the following lipids: 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DMPC), 1,2-Distearoyl-sn-Glycero-3-Phosphocholine (DSPC), Phospholipone 90H (Ph90H) or a mixture of DSPC and DMPC (1:1). The freeze thawing method was used for preparation of liposomes because it has three advantages (1) avoiding the use of chloroform, which is used in other methods and causes toxicity (2) it is a simple method and (3) it gives high entrapping efficiency. The percentage of entrapping efficiencies (EE) was different depending on the type and phase transition temperature (Tc) of the lipid used. The average particle size and particle size distribution of the prepared liposomes were determined using both dynamic light scattering (DLS) and laser diffraction analyzer (LDA). The average particle size of the prepared liposomes differs according to both liposomal type and lipid type. Dispersion and dialysis techniques were used for the study of the in vitro release of β-adrenoceptor antagonists. The in vitro release rate of β-adrenoceptor antagonists was increased from MLV to LUV to SUV. Regarding the lipid type, β-adrenoceptor antagonists exhibited different in vitro release pattern from one lipid to another. Two different concentrations (50 and 100mg/ml) of Ph90H were used for studying the effect of lipid concentration on the in vitro release of β-adrenoceptor antagonists. It was found that liposomes made from 50 mg/ml Ph90H exhibited higher release rates than liposomes made at 100 mg/ml Ph90H. Also glucose was encapsulated in MLV, LUV and SUV using 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DMPC), 1,2-Distearoyl-sn-Glycero-3-Phosphocholine (DSPC), Phospholipone 90H (Ph90H), soybean lipid (Syb) or a mixture of DSPC and DMPC (1:1). The average particle size and size distribution were determined using laser diffraction analysis. It was found that both EE and average particle size differ depending on both lipid and liposomal types. The in vitro release of glucose from different types of liposomes was performed using a dispersion method. It was found that the in vitro release of glucose from different liposomes is dependent on the lipid type. 18F-FDG was encapsulated in MLV 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DMPC), 1,2-Distearoyl-sn-Glycero-3-Phosphocholine (DSPC), Phospholipone 90H (Ph90H), soybean lipid (Syb) or a mixture of DSPC and DMPC (1:1). FDG-containing LUV and SUV were prepared using Ph90H lipid. The in vitro release of FDG from the different types of lipids was accomplished using a dispersion method. Results similar to that of glucose release were obtained. In vivo imaging of FDG in both uncapsulated FDG and FDG-containing MLV was performed in the brain and the whole body of rats using PET scanner. It was found that the release of FDG from FDG-containing MLV was sustained. In vitro-In vivo correlation was studied using the in vitro release data of FDG from liposomes and in vivo absorption data of FDG from injected liposomes using microPET. Erbium, which is a lanthanide metal, was used as a chelate with DTPA for encapsulation in SUV liposomes for the indirect radiation therapy of cancer. The liposomes were prepared using three different concentrations of soybean lipid (30, 50 and 70 mg/ml). The stability of Er-DTPA SUV liposomes was carried out by storage of the prepared liposomes at three different temperatures (4, 25 and 37 °C). It was found that the release of Er-DTPA complex is temperature dependent, the higher the temperature, the higher the release. There was an inverse relationship between the release of the Er-DTPA complex and the concentration of lipid.

Validation of the CFD code NEPTUNE for a full scale simulator for decay heat removal systems with in-pool heat exchangers

In the present work, a multi physics simulation of an innovative safety system for light water nuclear reactor is performed, with the aim to increase the reliability of its main decay heat removal system. The system studied, denoted by the acronym PERSEO (in Pool Energy Removal System for Emergency Operation) is able to remove the decay power from the primary side of the light water nuclear reactor through a heat suppression pool. The experimental facility, located at SIET laboratories (PIACENZA), is an evolution of the Thermal Valve concept where the triggering valve is installed liquid side, on a line connecting two pools at the bottom. During the normal operation, the valve is closed, while in emergency conditions it opens, the heat exchanger is flooded with consequent heat transfer from the primary side to the pool side. In order to verify the correct system behavior during long term accidental transient, two main experimental PERSEO tests are analyzed. For this purpose, a coupling between the mono dimensional system code CATHARE, which reproduces the system scale behavior, with a three-dimensional CFD code NEPTUNE CFD, allowing a full investigation of the pools and the injector, is implemented. The coupling between the two codes is realized through the boundary conditions. In a first analysis, the facility is simulated by the system code CATHARE V2.5 to validate the results with the experimental data. The comparison of the numerical results obtained shows a different void distribution during the boiling conditions inside the heat suppression pool for the two cases of single nodalization and three volume nodalization scheme of the pool. Finaly, to improve the investigation capability of the void distribution inside the pool and the temperature stratification phenomena below the injector, a two and three dimensional CFD models with a simplified geometry of the system are adopted.