A Multi-Objective Antenna Placement Genetic Algorithm for Matched Array Synthesis on Complex Platforms

A Multi-Objective Antenna Placement Genetic Algorithm (MO-APGA) has been proposed for the synthesis of matched antenna arrays on complex platforms. The total number of antennas required, their position on the platform, location of loads, loading circuit parameters, decoupling and matching network topology, matching network parameters and feed network parameters are optimized simultaneously. The optimization goal was to provide a given minimum gain, specific gain discrimination between the main and back lobes and broadband performance. This algorithm is developed based on the non-dominated sorting genetic algorithm (NSGA-II) and Minimum Spanning Tree (MST) technique for producing diverse solutions when the number of objectives is increased beyond two. The proposed method is validated through the design of a wideband airborne SAR

New generation genomic platforms in investigation of complex diseases and BEN.

(Full text is available at http://www.manu.edu.mk/prilozi). New generation genomic platforms enable us to decipher the complex genetic basis of complex diseases and Balkan Endemic Nephropathy (BEN) at a high-throughput basis. They give valuable information about predisposing Single Nucleotide Polymorphisms (SNPs), Copy Number Variations (CNVs) or Loss of Heterozygosity (LOH) (using SNP-array) and about disease-causing mutations along the whole sequence of candidate-genes (using Next Generation Sequencing). This information could be used for screening of individuals in risk families and moving the main medicine stream to the prevention. They also might have an impact on more effective treatment. Here we discuss these genomic platforms and report some applications of SNP-array technology in a case with familial nephrotic syndrome. Key words: complex diseases, genome wide association studies, SNP, genomic arrays, next generation sequ-encing.

Towards Certifiable Multicore-based Platforms for Avionics

Work in Progress Session, 21st IEEE Real-Time and Embedded Techonology and Applications Symposium (RTAS 2015). 13 to 16, Apr, 2015, pp 27-28. Seattle, U.S.A..

Ontologies for the interoperability of multiagent electricity markets simulation platforms

Electricity markets worldwide are complex and dynamic environments with very particular characteristics. These are the result of electricity markets’ restructuring and evolution into regional and continental scales, along with the constant changes brought by the increasing necessity for an adequate integration of renewable energy sources. The rising complexity and unpredictability in electricity markets has increased the need for the intervenient entities in foreseeing market behaviour. Market players and regulators are very interested in predicting the market’s behaviour. Market players need to understand the market behaviour and operation in order to maximize their profits, while market regulators need to test new rules and detect market inefficiencies before they are implemented. The growth of usage of simulation tools was driven by the need for understanding those mechanisms and how the involved players' interactions affect the markets' outcomes. Multi-agent based software is particularly well fitted to analyse dynamic and adaptive systems with complex interactions among its constituents, such as electricity markets. Several modelling tools directed to the study of restructured wholesale electricity markets have emerged. Still, they have a common limitation: the lack of interoperability between the various systems to allow the exchange of information and knowledge, to test different market models and to allow market players from different systems to interact in common market environments. This dissertation proposes the development and implementation of ontologies for semantic interoperability between multi-agent simulation platforms in the scope of electricity markets. The added value provided to these platforms is given by enabling them sharing their knowledge and market models with other agent societies, which provides the means for an actual improvement in current electricity markets studies and development. The proposed ontologies are implemented in MASCEM (Multi-Agent Simulator of Competitive Electricity Markets) and tested through the interaction between MASCEM agents and agents from other multi-agent based simulators. The implementation of the proposed ontologies has also required a complete restructuring of MASCEM’s architecture and multi-agent model, which is also presented in this dissertation. The results achieved in the case studies allow identifying the advantages of the novel architecture of MASCEM, and most importantly, the added value of using the proposed ontologies. They facilitate the integration of independent multi-agent simulators, by providing a way for communications to be understood by heterogeneous agents from the various systems.

Synergism/complementarity of recombinant adenoviral vectors and other vaccination platforms during induction of protective immunity against malaria

The lack of immunogenicity of most malaria antigens and the complex immune responses required for achieving protective immunity against this infectious disease have traditionally hampered the development of an efficient human malaria vaccine. The current boom in development of recombinant viral vectors and their use in prime-boost protocols that result in enhanced immune outcomes have increased the number of malaria vaccine candidates that access pre-clinical and clinical trials. In the frontline, adenoviruses and poxviruses seem to be giving the best immunization results in experimental animals and their mutual combination, or their combination with recombinant proteins (formulated in adjuvants and given in sequence or being given as protein/virus admixtures), has been shown to reach unprecedented levels of anti-malaria immunity that predictably will be somehow reproduced in the human setting. However, all this optimism was previously seen in the malaria vaccine development field without many real applicable results to date. We describe here the current state-of-the-art in the field of recombinant adenovirus research for malaria vaccine development, in particular referring to their use in combination with other immunogens in heterologous prime-boost protocols, while trying to simultaneously show our contributions and point of view on this subject.

Identification and characterization of a caspase-2 activating complex

Résumé Les caspases sont des protéases essentielles lors de l'induction de l'apoptose ou pour la maturation de certaines cytokines. Elles peuvent être divisées en deux groupes: les caspases initiatrices, qui sont les premières activées lors d'un signal pro-apoptotique, et les caspases effectrices, qui sont activées par les caspases initiatrices et sont responsables du clivage et de la dégradation des substrats cellulaires. Les caspases initiatrices sont activées dans des complexes de haut poids moléculaire: l'apoptosome pour la caspase-9 et le DISC pour la caspase-8. La caspase-2 est également une caspase initiatrice qui contient un domaine CARD. Cependant son mécanisme d'activation n'est pas encore connu. Lors de cette étude, nous avons découvert et caractérisé le complexe qui permet l'activation de la caspase-2. Ce complexe, appelé le PIDDosome, est composé de PIDD/LRDD, de la protéine adaptatrice RAIDD et de la protéase caspase-2. L'expression forcée de PIDD induit l'activation constitutive de la caspase-2. Cela entraîne la mort ou la sensibilisation à la mort des cellules selon la lignée étudiée. Cet effet est expliqué par une perte du potentiel de membrane de la mitochondrie, certainement dû à un effet direct de la caspase-2. Peu de choses sont connues sur PIDD: c'est une protéine contenant un domaine DD qui peut être induite par p53. Nous avons caractérisé PIDD et montré qu'elle est exprimée de façon ubiquitaire. PIDD est constitutivement auto-clivée environ au milieu de la protéine, ce qui génère deux fragments qui restent liés l'un à l'autre. Le fragment N-terminal a une activité régulatrice et le C-terminal une activité effectrice. De plus, PIDD peut se déplacer entre le cytoplasme et le noyau. Enfin, nous avons découvert que PIDD est également impliquée dans l'induction de NF¬ -κB en réponse à des dommages à l'ADN. PIDD est responsable de la modification par sumo de NEMO, étape nécessaire à l'induction de NF-κB après des dommages à l'ADN. Ainsi PIDD semble être à l'intersection de la décision que prend la cellule entre survivre et réparer les dommages, ou entrer en apoptose. Summary Caspases are a family of proteases that fulfill varied and often critical roles in mammalian apoptosis or proteolytic activation of cytokines. Caspases can be divided into two sub-groups: initiator caspases, which are the first activated after a pro-apoptotic signal, and effector caspases, which are activated by initiator caspases and that are responsible for the cleavage and degradation of cellular components. Initiator caspases are activated in high molecular weight platforms such as the apoptosome for caspase-9 or the DISC for caspase-8. Caspase-2 is a CARD-containing initiator caspase whose mechanism of activation was not yet known. In this study we have identified an activating platform for caspase-2. This high molecular weight complex, called the PIDDosome, is composed of PIDD/LRDD, the adaptor protein RAIDD and caspase-2. Constitutive expression of PIDD led to constitutive activation of caspase-2, which in some cell lines was sufficient to induce cell death while in others it merely sensitizes. Active caspase-2 was found to disturb directly the mitochondria by inducing a partial loss of the transmembrane potential. Very little was known on PIDD. It can be induce by p53 and inhibition of its expression by antisense oligonucleotides diminishes p53-dependent apoptosis. We decided to further characterize PIDD function and expression. PIDD possesses seven LRR, two Zu5 domains and one DD. It is ubiquitously expressed and appears to be constitutively cleaved by auto- processing into two main fragments equal in size. The two fragments remain bound to one another and constitute a regulatory N-terminal fragment and an active C-terminal fragment. In addition, PIDD can shuttle between the cytoplasm and the nucleus. Finally, investigating the possible relevance of new interaction partners, we found that PIDD is implicated in DNA damage-induced NF- κB. PIDD binds to RIP1 and to NEMO. In response to DNA damage, PIDD translocates to the nucleus and mediates sumo- modification of NEMO, a necessary step in DNA damage-induced NF-κB. All together these results raise the possibility that PIDD acts as a molecular switch between proliferation and repair, and apoptosis following DNA damage.

Highly parallel genetic approaches in Mendelian and complex diseases

The recent advance in high-throughput sequencing and genotyping protocols allows rapid investigation of Mendelian and complex diseases on a scale not previously been possible. In my thesis research I took advantage of these modern techniques to study retinitis pigmentosa (RP), a rare inherited disease characterized by progressive loss of photoreceptors and leading to blindness; and hypertension, a common condition affecting 30% of the adult population. Firstly, I compared the performance of different next generation sequencing (NGS) platforms in the sequencing of the RP-linked gene PRPF31. The gene contained a mutation in an intronic repetitive element, which presented difficulties for both classic sequencing methods and NGS. We showed that all NGS platforms are powerful tools to identify rare and common DNA variants, also in case of more complex sequences. Moreover, we evaluated the features of different NGS platforms that are important in re-sequencing projects. The main focus of my thesis was then to investigate the involvement of pre-mRNA splicing factors in autosomal dominant RP (adRP). I screened 5 candidate genes in a large cohort of patients by using long-range PCR as enrichment step, followed by NGS. We tested two different approaches: in one, all target PCRs from all patients were pooled and sequenced as a single DNA library; in the other, PCRs from each patient were separated within the pool by DNA barcodes. The first solution was more cost-effective, while the second one allowed obtaining faster and more accurate results, but overall they both proved to be effective strategies for gene screenings in many samples. We could in fact identify novel missense mutations in the SNRNP200 gene, encoding an essential RNA helicase for splicing catalysis. Interestingly, one of these mutations showed incomplete penetrance in one family with adRP. Thus, we started to study the possible molecular causes underlying phenotypic differences between asymptomatic and affected members of this family. For the study of hypertension, I joined a European consortium to perform genome-wide association studies (GWAS). Thanks to the use of very informative genotyping arrays and of phenotipically well-characterized cohorts, we could identify a novel susceptibility locus for hypertension in the promoter region of the endothelial nitric oxide synthase gene (NOS3). Moreover, we have proven the direct causality of the associated SNP using three different methods: 1) targeted resequencing, 2) luciferase assay, and 3) population study. - Le récent progrès dans le Séquençage à haut Débit et les protocoles de génotypage a permis une plus vaste et rapide étude des maladies mendéliennes et multifactorielles à une échelle encore jamais atteinte. Durant ma thèse de recherche, j'ai utilisé ces nouvelles techniques de séquençage afin d'étudier la retinite pigmentale (RP), une maladie héréditaire rare caractérisée par une perte progressive des photorécepteurs de l'oeil qui entraine la cécité; et l'hypertension, une maladie commune touchant 30% de la population adulte. Tout d'abord, j'ai effectué une comparaison des performances de différentes plateformes de séquençage NGS (Next Generation Sequencing) lors du séquençage de PRPF31, un gène lié à RP. Ce gène contenait une mutation dans un élément répétable intronique, qui présentait des difficultés de séquençage avec la méthode classique et les NGS. Nous avons montré que les plateformes de NGS analysées sont des outils très puissants pour identifier des variations de l'ADN rares ou communes et aussi dans le cas de séquences complexes. De plus, nous avons exploré les caractéristiques des différentes plateformes NGS qui sont importantes dans les projets de re-séquençage. L'objectif principal de ma thèse a été ensuite d'examiner l'effet des facteurs d'épissage de pre-ARNm dans une forme autosomale dominante de RP (adRP). Un screening de 5 gènes candidats issus d'une large cohorte de patients a été effectué en utilisant la long-range PCR comme étape d'enrichissement, suivie par séquençage avec NGS. Nous avons testé deux approches différentes : dans la première, toutes les cibles PCRs de tous les patients ont été regroupées et séquencées comme une bibliothèque d'ADN unique; dans la seconde, les PCRs de chaque patient ont été séparées par code barres d'ADN. La première solution a été la plus économique, tandis que la seconde a permis d'obtenir des résultats plus rapides et précis. Dans l'ensemble, ces deux stratégies se sont démontrées efficaces pour le screening de gènes issus de divers échantillons. Nous avons pu identifier des nouvelles mutations faux-sens dans le gène SNRNP200, une hélicase ayant une fonction essentielle dans l'épissage. Il est intéressant de noter qu'une des ces mutations montre une pénétrance incomplète dans une famille atteinte d'adRP. Ainsi, nous avons commencé une étude sur les causes moléculaires entrainant des différences phénotypiques entre membres affectés et asymptomatiques de cette famille. Lors de l'étude de l'hypertension, j'ai rejoint un consortium européen pour réaliser une étude d'association Pangénomique ou genome-wide association study Grâce à l'utilisation de tableaux de génotypage très informatifs et de cohortes extrêmement bien caractérisées au niveau phénotypique, un nouveau locus lié à l'hypertension a été identifié dans la région promotrice du gène endothélial nitric oxide sinthase (NOS3). Par ailleurs, nous avons prouvé la cause directe du SNP associé au moyen de trois méthodes différentes: i) en reséquençant la cible avec NGS, ii) avec des essais à la luciférase et iii) une étude de population.

A bio-inspired agent-based programming environment for pervasive platforms

Abstract in English : Ubiquitous Computing is the emerging trend in computing systems. Based on this observation this thesis proposes an analysis of the hardware and environmental constraints that rule pervasive platforms. These constraints have a strong impact on the programming of such platforms. Therefore solutions are proposed to facilitate this programming both at the platform and node levels. The first contribution presented in this document proposes a combination of agentoriented programming with the principles of bio-inspiration (Phylogenesys, Ontogenesys and Epigenesys) to program pervasive platforms such as the PERvasive computing framework for modeling comPLEX virtually Unbounded Systems platform. The second contribution proposes a method to program efficiently parallelizable applications on each computing node of this platform. Résumé en Français : Basée sur le constat que les calculs ubiquitaires vont devenir le paradigme de programmation dans les années à venir, cette thèse propose une analyse des contraintes matérielles et environnementale auxquelles sont soumises les plateformes pervasives. Ces contraintes ayant un impact fort sur la programmation des plateformes. Des solutions sont donc proposées pour faciliter cette programmation tant au niveau de l'ensemble des noeuds qu'au niveau de chacun des noeuds de la plateforme. La première contribution présentée dans ce document propose d'utiliser une alliance de programmation orientée agent avec les grands principes de la bio-inspiration (Phylogénèse, Ontogénèse et Épigénèse). Ceci pour répondres aux contraintes de programmation de plateformes pervasives comme la plateforme PERvasive computing framework for modeling comPLEX virtually Unbounded Systems . La seconde contribution propose quant à elle une méthode permettant de programmer efficacement des applications parallélisable sur chaque noeud de calcul de la plateforme

Agent-based management systems for many-core platforms : rigorous design and efficient implementation

Due to various advantages such as flexibility, scalability and updatability, software intensive systems are increasingly embedded in everyday life. The constantly growing number of functions executed by these systems requires a high level of performance from the underlying platform. The main approach to incrementing performance has been the increase of operating frequency of a chip. However, this has led to the problem of power dissipation, which has shifted the focus of research to parallel and distributed computing. Parallel many-core platforms can provide the required level of computational power along with low power consumption. On the one hand, this enables parallel execution of highly intensive applications. With their computational power, these platforms are likely to be used in various application domains: from home use electronics (e.g., video processing) to complex critical control systems. On the other hand, the utilization of the resources has to be efficient in terms of performance and power consumption. However, the high level of on-chip integration results in the increase of the probability of various faults and creation of hotspots leading to thermal problems. Additionally, radiation, which is frequent in space but becomes an issue also at the ground level, can cause transient faults. This can eventually induce a faulty execution of applications. Therefore, it is crucial to develop methods that enable efficient as well as resilient execution of applications. The main objective of the thesis is to propose an approach to design agentbased systems for many-core platforms in a rigorous manner. When designing such a system, we explore and integrate various dynamic reconfiguration mechanisms into agents functionality. The use of these mechanisms enhances resilience of the underlying platform whilst maintaining performance at an acceptable level. The design of the system proceeds according to a formal refinement approach which allows us to ensure correct behaviour of the system with respect to postulated properties. To enable analysis of the proposed system in terms of area overhead as well as performance, we explore an approach, where the developed rigorous models are transformed into a high-level implementation language. Specifically, we investigate methods for deriving fault-free implementations from these models into, e.g., a hardware description language, namely VHDL.

The Guarguaraz Complex and the Neoproterozoic-Cambrian evolution of southwestern Gondwana: Geochemical signatures and geochronological constraints

The Guarguaraz Complex, in western Argentina, comprises a metasedimentary assemblage, associated with mafic sills and ultramafic bodies intruded by basaltic dikes, which are interpreted as Ordovician dismembered ophiolites. Two kinds of dikes are recognized, a group associated with the metasediments and the other ophiolite-related. Both have N-MORB signatures, with epsilon(Nd) between +3.5 and +8.2, indicating a depleted source, and Grenville model ages between 0.99 and 1.62 Ga. A whole-rock Sm-Nd isochron yielded an age of 655 +/- 76 Ma for these mafic rocks, which is compatible with cianobacteria and acritarchae recognized in the clastic metasedimentary platform sequences, that indicate a Neoproterozoic (Vendian)-Cambrian age of deposition. The Guarguaraz metasedimentary-ophiolitic complex represents, therefore, a remnant of an oceanic basin developed to the west of the Grenville-aged Cuyania terrane during the Neoproterozoic. The southernmost extension of these metasedimentary sequences in Cordon del Portillo might represent part of this platform and not fragments of the Chilenia terrane. An extensional event related to the fragmentation of Rodinia is represented by the mafic and ultramafic rocks. The Devonian docking of Chilenia emplaced remnants of ocean floor and slices of the Cuyania terrane (Las Yaretas Gneisses) in tectonic contact with the Neoproterozoic metasediments, marking the Devonian western border of Gondwana. (C) 2009 Elsevier Ltd. All rights reserved.

Three dimensional seismic imaging and earthquake locations in a complex, segmented fault region in Southern Apennines (Italy)

The southern Apennines of Italy have been experienced several destructive earthquakes both in historic and recent times. The present day seismicity, characterized by small-to-moderate magnitude earthquakes, was used like a probe to obatin a deeper knowledge of the fault structures where the largest earthquakes occurred in the past. With the aim to infer a three dimensional seismic image both the problem of data quality and the selection of a reliable and robust tomographic inversion strategy have been faced. The data quality has been obtained to develop optimized procedures for the measurements of P- and S-wave arrival times, through the use of polarization filtering and to the application of a refined re-picking technique based on cross-correlation of waveforms. A technique of iterative tomographic inversion, linearized, damped combined with a strategy of multiscale inversion type has been adopted. The retrieved P-wave velocity model indicates the presence of a strong velocity variation along a direction orthogonal to the Apenninic chain. This variation defines two domains which are characterized by a relatively low and high velocity values. From the comparison between the inferred P-wave velocity model with a portion of a structural section available in literature, the high velocity body was correlated with the Apulia carbonatic platforms whereas the low velocity bodies was associated to the basinal deposits. The deduced Vp/Vs ratio shows that the ratio is lower than 1.8 in the shallower part of the model, while for depths ranging between 5 km and 12 km the ratio increases up to 2.1 in correspondence to the area of higher seismicity. This confirms that areas characterized by higher values are more prone to generate earthquakes as a response to the presence of fluids and higher pore-pressures.

Sequential female assessment drives complex sexual selection on bower shape in a cichlid fish

In many animals, sexual selection on male traits results from female mate choice decisions made during a sequence of courtship behaviors. We use a bower-building cichlid fish, Nyassachromis cf. microcephalus, to show how applying standard selection analysis to data on sequential female assessment provides new insights into sexual selection by mate choice. We first show that the cumulative selection differentials confirm previous results suggesting female choice favors males holding large volcano-shaped sand bowers. The sequential assessment analysis reveals these cumulative differentials are the result of selection acting on different bower dimensions during the courtship sequence; females choose to follow males courting from tall bowers, but choose to engage in premating circling with males holding bowers with large diameter platforms. The approach we present extends standard selection analysis by partitioning the variances of increasingly accurate estimates of male reproductive fitness and is applicable to systems in which sequential female assessment drives sexual selection on male traits.

PM(10) remote sensing from geostationary SEVIRI and polar-orbiting MODIS sensors over the complex terrain of the European Alpine region

The subject of this study is to investigate the capability of spaceborne remote sensing data to predict ground concentrations of PM10 over the European Alpine region using satellite derived Aerosol Optical Depth (AOD) from the geostationary Spinning Enhanced Visible and InfraRed Imager (SEVIRI) and the polar-orbiting MODerate resolution Imaging Spectroradiometer (MODIS). The spatial and temporal resolutions of these aerosol products (10 km and 2 measurements per day for MODIS, ∼ 25 km and observation intervals of 15 min for SEVIRI) permit an evaluation of PM estimation from space at different spatial and temporal scales. Different empirical linear relationships between coincident AOD and PM10 observations are evaluated at 13 ground-based PM measurement sites, with the assumption that aerosols are vertically homogeneously distributed below the planetary Boundary Layer Height (BLH). The BLH and Relative Humidity (RH) variability are assessed, as well as their impact on the parameterization. The BLH has a strong influence on the correlation of daily and hourly time series, whilst RH effects are less clear and smaller in magnitude. Despite its lower spatial resolution and AOD accuracy, SEVIRI shows higher correlations than MODIS (rSEV∼ 0.7, rMOD∼ 0.6) with regard to daily averaged PM10. Advantages from MODIS arise only at hourly time scales in mountainous locations but lower correlations were found for both sensors at this time scale (r∼ 0.45). Moreover, the fraction of days in 2008 with at least one satellite observation was 27% for SEVIRI and 17% for MODIS. These results suggest that the frequency of observations plays an important role in PM monitoring, while higher spatial resolution does not generally improve the PM estimation. Ground-based Sun Photometer (SP) measurements are used to validate the satellite-based AOD in the study region and to discuss the impact of aerosols' micro-physical properties in the empirical models. A lower error limit of 30 to 60% in the PM10 assessment from space is estimated in the study area as a result of AOD uncertainties, variability of aerosols properties and the heterogeneity of ground measurement sites. It is concluded that SEVIRI has a similar capacity to map PM as sensors on board polar-orbiting platforms, with the advantage of a higher number of observations. However, the accuracy represents a serious limitation to the applicability of satellites for ground PM mapping, especially in mountainous areas.

The impact of social presence on team performance in social networking platforms

Next to the extensive use of social networking platforms (SNPs) for communication and relationship building with friends and relatives, SNPs are also increasingly used for enhancing collaboration at work. SNP usage at the workplace is fundamentally different and it is unclear how SNPs can improve collaboration as well as in what way their designs should be modified and adapted to collaboration settings. This research identifies specific SNP functions that enhance social presence as particularly beneficial for collaboration. Consequently, two designs of SNPs, one with high social presence and one with low social presence, are outlined and its impacts on collaboration are discussed. A framework is constructed that illustrates how social presence in SNPs can improve team performance through enhancing transactive memory within teams (intra-group collaboration) and relational capital across teams (inter-group collaboration). In addition, it is outlined how this framework could be evaluated in an experimental setting of teams working on a complex group task.