EMMA 2--a MAGE-compliant system for the collaborative analysis and integration of microarray data

Background: Understanding transcriptional regulation by genome-wide microarray studies can contribute to unravel complex relationships between genes. Attempts to standardize the annotation of microarray data include the Minimum Information About a Microarray Experiment (MIAME) recommendations, the MAGE-ML format for data interchange, and the use of controlled vocabularies or ontologies. The existing software systems for microarray data analysis implement the mentioned standards only partially and are often hard to use and extend. Integration of genomic annotation data and other sources of external knowledge using open standards is therefore a key requirement for future integrated analysis systems. Results: The EMMA 2 software has been designed to resolve shortcomings with respect to full MAGE-ML and ontology support and makes use of modern data integration techniques. We present a software system that features comprehensive data analysis functions for spotted arrays, and for the most common synthesized oligo arrays such as Agilent, Affymetrix and NimbleGen. The system is based on the full MAGE object model. Analysis functionality is based on R and Bioconductor packages and can make use of a compute cluster for distributed services. Conclusion: Our model-driven approach for automatically implementing a full MAGE object model provides high flexibility and compatibility. Data integration via SOAP-based web-services is advantageous in a distributed client-server environment as the collaborative analysis of microarray data is gaining more and more relevance in international research consortia. The adequacy of the EMMA 2 software design and implementation has been proven by its application in many distributed functional genomics projects. Its scalability makes the current architecture suited for extensions towards future transcriptomics methods based on high-throughput sequencing approaches which have much higher computational requirements than microarrays.

Synthetic Circuits for Feedback and Detection in Bacteria

Synthetic biology, by co-opting molecular machinery from existing organisms, can be used as a tool for building new genetic systems from scratch, for understanding natural networks through perturbation, or for hybrid circuits that piggy-back on existing cellular infrastructure. Although the toolbox for genetic circuits has greatly expanded in recent years, it is still difficult to separate the circuit function from its specific molecular implementation. In this thesis, we discuss the function-driven design of two synthetic circuit modules, and use mathematical models to understand the fundamental limits of circuit topology versus operating regimes as determined by the specific molecular implementation. First, we describe a protein concentration tracker circuit that sets the concentration of an output protein relative to the concentration of a reference protein. The functionality of this circuit relies on a single negative feedback loop that is implemented via small programmable protein scaffold domains. We build a mass-action model to understand the relevant timescales of the tracking behavior and how the input/output ratios and circuit gain might be tuned with circuit components. Second, we design an event detector circuit with permanent genetic memory that can record order and timing between two chemical events. This circuit was implemented using bacteriophage integrases that recombine specific segments of DNA in response to chemical inputs. We simulate expected population-level outcomes using a stochastic Markov-chain model, and investigate how inferences on past events can be made from differences between single-cell and population-level responses. Additionally, we present some preliminary investigations on spatial patterning using the event detector circuit as well as the design of stationary phase promoters for growth-phase dependent activation. These results advance our understanding of synthetic gene circuits, and contribute towards the use of circuit modules as building blocks for larger and more complex synthetic networks.

Towards Distributed Model Transformations with LinTra

Performance and scalability of model transformations are becoming prominent topics in Model-Driven Engineering. In previous works we introduced LinTra, a platform for executing model transformations in parallel. LinTra is based on the Linda model of a coordination language and is intended to be used as a middleware where high-level model transformation languages are compiled. In this paper we present the initial results of our analyses on the scalability of out-place model-to-model transformation executions in LinTra when the models and the processing elements are distributed over a set of machines.

Towards flexible parsing of structured textual model representations

Existing parsers for textual model representation formats such as XMI and HUTN are unforgiving and fail upon even the smallest inconsistency between the structure and naming of metamodel elements and the contents of serialised models. In this paper, we demonstrate how a fuzzy parsing approach can transparently and automatically resolve a number of these inconsistencies, and how it can eventually turn XML into a human-readable and editable textual model representation format for particular classes of models.

Development and validation of a computationally efficient pseudo 3D model for planar SOFC integrated with a heating furnace

Efficient numerical models facilitate the study and design of solid oxide fuel cells (SOFCs), stacks, and systems. Whilst the accuracy and reliability of the computed results are usually sought by researchers, the corresponding modelling complexities could result in practical difficulties regarding the implementation flexibility and computational costs. The main objective of this article is to adapt a simple but viable numerical tool for evaluation of our experimental rig. Accordingly, a model for a multi-layer SOFC surrounded by a constant temperature furnace is presented, trained and validated against experimental data. The model consists of a four-layer structure including stand, two interconnects, and PEN (Positive electrode-Electrolyte-Negative electrode); each being approximated by a lumped parameter model. The heating process through the surrounding chamber is also considered. We used a set of V-I characteristics data for parameter adjustment followed by model verification against two independent sets of data. The model results show a good agreement with practical data, offering a significant improvement compared to reduced models in which the impact of external heat loss is neglected. Furthermore, thermal analysis for adiabatic and non-adiabatic process is carried out to capture the thermal behaviour of a single cell followed by a polarisation loss assessment. Finally, model-based design of experiment is demonstrated for a case study.

Integration of a graph-based model indexer in commercial modelling tools

Softeam has over 20 years of experience providing UML-based modelling solutions, such as its Modelio modelling tool, and its Constellation enterprise model management and collaboration environment. Due to the increasing number and size of the models used by Softeam’s clients, Softeam joined the MONDO FP7 EU research project, which worked on solutions for these scalability challenges and produced the Hawk model indexer among other results. This paper presents the technical details and several case studies on the integration of Hawk into Softeam’s toolset. The first case study measured the performance of Hawk’s Modelio support using varying amounts of memory for the Neo4j backend. In another case study, Hawk was integrated into Constellation to provide scalable global querying of model repositories. Finally, the combination of Hawk and the Epsilon Generation Language was compared against Modelio for document generation: for the largest model, Hawk was two orders of magnitude faster.

Story Driven Web Applications

Kern der vorliegenden Arbeit ist die Modellierung komplexer Webapplikationen mit dem Story-Driven-Modeling Ansatz.Ziel ist es hierbei,die komplette Applikation allein durch die Spezifikation von Modellen zu entwickeln. Das händische Erstellen von Quelltext ist nicht notwendig. Die vorliegende Arbeit zeigt sowohl den Forschungsweg, der die angestrebte Modellierung von Webapplikationen ermöglicht, als auch die resultierenden Ergebnisse auf. Zur Unterstützung des Entwicklungsprozesses wird weiterhin ein modellgetriebener Softwareentwicklungsprozess vorgestellt, der die Modellierung einer Webapplikation von der Aufnahme der Anforderungen, bis zur abschließenden Erzeugung des Quelltextes durch Codegenerierung aus den spezifizierten Modellen, abdeckt. Für den definierten Prozess wird ferner Werkzeugunterstützung innerhalb der Fujaba Toolsuite bereitgestellt. Im Rahmen der vorliegenden Arbeit wurde die bestehede Toolsuite hierzu um alle zur Prozessunterstützung notwendigen Werkzeuge erweitert. Darüber hinaus wurden im Rahmen der vorliegenden Arbeit die in Fujaba bestehenden Werkzeuge erweitert, um neben den klassischen Möglichkeiten zur Modellierung komplexer Java-Applikationen auch die Erzeugung von Webapplikationen zu ermöglichen. Neben der genauen Beschreibung des Entwicklungsprozesses werden im Rahmen dieser Arbeit die entstehenden Webapplikationen mit ihren spezifischen Eigenschaften genau beschrieben. Zur Erzeugung dieser Applikationen wird neben dem Entwicklungsprozess die Diagrammart der Workflowdiagramme eingeführt und beschrieben. Diese Diagramme dienen der Abbildung des intendierten Userworkflows der Applikation im Rahmen der Anforderungsanalyse und stellen im weiteren Entwicklungsverlauf ein dediziertes Entwicklungsartefakt dar. Basierend auf den Workflowdiagrammen werden sowohl die grafische Benutzerschnittstelle der Webapplikation beschrieben, als auch ein Laufzeitsystem initialisiert, welches basierend auf den im Workflowdiagramm abgebildeten Abläufen die Anwendung steuert. Dieses Laufzeitsystem wurde im Rahmen der vorliegenden Arbeit entwickelt und in der Prozessunterstützung verankert. Alle notwendigen Änderungen und Anpassungen und Erweiterungen an bereits bestehenden Teilen der Fujaba Toolsuite werden unter dem Aspekt der Erstellung clientseitiger Datenmodelle einer Webapplikation genau beschrieben und in Verbindung mit den zu erfüllenden Voraussetzungen erläutert. In diesem Zusammenhang wird ebenfalls beschrieben, wie Graphtransformationen zur Umsetzung von Businesslogik auf der Clientseite einer Webapplikation eingesetzt werden können und auf welche Weise Datenmodelländerungen zwischen unterschiedlichen Clients synchronisiert werden können. Insgesamt zeigt die vorliegende Arbeit einen Weg auf, den bestehenden Ansatz des StoryDriven-Modeling für die Erzeugung von Webapplikationen einzusetzen. Durch die im Rahmen dieser Arbeit beschriebene Herangehensweise werden hierbei gleichzeitig Webbrowser zu einer neuen Klasse von Graphersetzungs-Engines erweitert, indem Graphtransformationen innerhalb der Ajax-Engine des Browsers ausgeliefert und ausgeführt werden.

Design and implementation of motorbike lean angle observers

This thesis focuses on the investigation and the implementation of different observers for the estimation of the roll angle of a motorbike. The central core of the activity is applying a Model-Based design in order to outline, simulate and implement the filters with the aim of a final comparison of the performances. This approach is crucially underlined among the chapters that articulate this document: first the design and tuning of an Extended Kalman Filter and a Complementary Filter in a pure simulation environment emphasize the most accurate choice for the particular problem. After this, several steps were performed in order to move from the aforementioned simulation environment to a real hardware application. In conclusion, several sensor configurations were tested and compared in order to highlight which sensor suite gives the best performances.

Model-Based validation of Driver Drowsiness Detection System for ADAS

The work described in this Master’s Degree thesis was born after the collaboration with the company Maserati S.p.a, an Italian luxury car maker with its headquarters located in Modena, in the heart of the Italian Motor Valley, where I worked as a stagiaire in the Virtual Engineering team between September 2021 and February 2022. This work proposes the validation using real-world ECUs of a Driver Drowsiness Detection (DDD) system prototype based on different detection methods with the goal to overcome input signal losses and system failures. Detection methods of different categories have been chosen from literature and merged with the goal of utilizing the benefits of each of them, overcoming their limitations and limiting as much as possible their degree of intrusiveness to prevent any kind of driving distraction: an image processing-based technique for human physical signals detection as well as methods based on driver-vehicle interaction are used. A Driver-In-the-Loop simulator is used to gather real data on which a Machine Learning-based algorithm will be trained and validated. These data come from the tests that the company conducts in its daily activities so confidential information about the simulator and the drivers will be omitted. Although the impact of the proposed system is not remarkable and there is still work to do in all its elements, the results indicate the main advantages of the system in terms of robustness against subsystem failures and signal losses.

Celiachia e Design: strumenti a supporto dei pazienti celiaci neo-diagnosticati

La tesi affronta il tema del design applicato all’ambito healthcare, in particolare la ricerca è indirizzata all’approfondimento della malattia celiaca. Attraverso un approccio integrato al design, è stato progettato un servizio volto a sostenere il paziente celiaco neo-diagnosticato nei 30 giorni immediatamente successivi alla diagnosi. Il progetto si compone di una serie di strumenti riprogettati a partire dai servizi promossi dall’Associazione Italiana Celiachia, disegnati a misura di utente, con l’obiettivo di semplificare il contatto con l’Associazione e coinvolgere, informare e sensibilizzare, sia gli attori interni che gli attori esterni al contesto. È stato studiato l’aspetto psicologico e psico-sociale della malattia per una progettazione che tenesse conto dei reali bisogni e delle necessità dei pazienti celiaci, così che l’esperienza di diagnosi risulti meno impattante e sia facilitato il passaggio verso un cambiamento dello stile di vita.

Integrare gli approcci all'innovazione Data Science e Design Thinking: analisi teorica e applicazione al caso della sanità parmense

Nel panorama aziendale odierno, risulta essere di fondamentale importanza la capacità, da parte di un’azienda o di una società di servizi, di orientare in modo programmatico la propria innovazione in modo tale da poter essere competitivi sul mercato. In molti casi, questo e significa investire una cospicua somma di denaro in progetti che andranno a migliorare aspetti essenziali del prodotto o del servizio e che avranno un importante impatto sulla trasformazione digitale dell’azienda. Lo studio che viene proposto riguarda in particolar modo due approcci che sono tipicamente in antitesi tra loro proprio per il fatto che si basano su due tipologie di dati differenti, i Big Data e i Thick Data. I due approcci sono rispettivamente il Data Science e il Design Thinking. Nel corso dei seguenti capitoli, dopo aver definito gli approcci di Design Thinking e Data Science, verrà definito il concetto di blending e la problematica che ruota attorno all’intersezione dei due metodi di innovazione. Per mettere in evidenza i diversi aspetti che riguardano la tematica, verranno riportati anche casi di aziende che hanno integrato i due approcci nei loro processi di innovazione, ottenendo importanti risultati. In particolar modo verrà riportato il lavoro di ricerca svolto dall’autore riguardo l'esame, la classificazione e l'analisi della letteratura esistente all'intersezione dell'innovazione guidata dai dati e dal pensiero progettuale. Infine viene riportato un caso aziendale che è stato condotto presso la realtà ospedaliero-sanitaria di Parma in cui, a fronte di una problematica relativa al rapporto tra clinici dell’ospedale e clinici del territorio, si è progettato un sistema innovativo attraverso l’utilizzo del Design Thinking. Inoltre, si cercherà di sviluppare un’analisi critica di tipo “what-if” al fine di elaborare un possibile scenario di integrazione di metodi o tecniche provenienti anche dal mondo del Data Science e applicarlo al caso studio in oggetto.

Structural behaviour of three-pile caps subjected to axial compressive loading

This work presents a comparative analysis about the behaviour of pile caps supported by 3 piles subjected to axial loading. Piles with 20 cm and 30 cm diameters were analysed. The main reinforcement was maintained in all the specimens, however, the arrangement of the secondary reinforcement varied. The main reinforcement consisted of steel bars connecting the piles. The secondary reinforcement was made up of: (a) bars going through the piles and through the projection of the column, (b) bars forming a network, and (c) vertical and horizontal stirrups. The main objective was the observation of the pile cap behaviour regarding the cracks and the modes of rupture. The real scale specimens were subjected to experimental tests until failure by rupture. Instruments were placed with the aim to obtain the displacement of the bases, the strains in the main and secondary reinforcement bars, in the compression struts, in the lower and upper nodal zones and in the sides of the caps. None of the caps reached failure by rupture with a load less than 1.12 times the theoretical load. The specimens ruptured due to the cracking of the compression strut and/or the yielding of the reinforcement bars in one direction.

A calibration approach based on Takagi-Sugeno fuzzy inference system for digital electronic compasses

Recently, the development of industrial processes brought on the outbreak of technologically complex systems. This development generated the necessity of research relative to the mathematical techniques that have the capacity to deal with project complexities and validation. Fuzzy models have been receiving particular attention in the area of nonlinear systems identification and analysis due to it is capacity to approximate nonlinear behavior and deal with uncertainty. A fuzzy rule-based model suitable for the approximation of many systems and functions is the Takagi-Sugeno (TS) fuzzy model. IS fuzzy models are nonlinear systems described by a set of if then rules which gives local linear representations of an underlying system. Such models can approximate a wide class of nonlinear systems. In this paper a performance analysis of a system based on IS fuzzy inference system for the calibration of electronic compass devices is considered. The contribution of the evaluated IS fuzzy inference system is to reduce the error obtained in data acquisition from a digital electronic compass. For the reliable operation of the TS fuzzy inference system, adequate error measurements must be taken. The error noise must be filtered before the application of the IS fuzzy inference system. The proposed method demonstrated an effectiveness of 57% at reducing the total error based on considered tests. (C) 2011 Elsevier Ltd. All rights reserved.

Advantages of graded-channel SOI nMOSFETs for application as source-follower analog buffer

In this work the performance of graded-channel (CC) SOI MOSFETs operating as source-follower buffers is presented. The experimental analysis is performed by comparing the gain and linearity of buffers implemented with CC and standard SOI MOS devices considering the same mask dimensions. It is shown that by using CC devices, buffer gain very close to the theoretical limit can be achieved, with improved linearity, while for standard devices the gain departs from the theoretical value depending on the inversion level imposed by the bias current and input voltage. Two-dimensional numerical simulations were performed in order to confirm some hypotheses proposed to explain the gain behavior observed in the experimental data. By using numerical simulations the channel length has been varied, showing that the gain of buffers implemented with CC devices remains close to the theoretical limit even when short-channel devices are adopted. It has also been shown that the length of a source-follower buffer using CC devices can be reduced by a factor of 5, in comparison with a standard Sol MOSFET, without gain loss or linearity degradation. (C) 2008 Elsevier Ltd. All rights reserved.

Quantitative Trait Loci Mapping and The Genetic Basis of Heterosis in Maize and Rice

Despite its importance to agriculture, the genetic basis of heterosis is still not well understood. The main competing hypotheses include dominance, overdominance, and epistasis. NC design III is an experimental design that. has been used for estimating the average degree of dominance of quantitative trait 106 (QTL) and also for studying heterosis. In this study, we first develop a multiple-interval mapping (MIM) model for design III that provides a platform to estimate the number, genomic positions, augmented additive and dominance effects, and epistatic interactions of QTL. The model can be used for parents with any generation of selling. We apply the method to two data sets, one for maize and one for rice. Our results show that heterosis in maize is mainly due to dominant gene action, although overdominance of individual QTL could not completely be ruled out due to the mapping resolution and limitations of NC design III. For rice, the estimated QTL dominant effects could not explain the observed heterosis. There is evidence that additive X additive epistatic effects of QTL could be the main cause for the heterosis in rice. The difference in the genetic basis of heterosis seems to be related to open or self pollination of the two species. The MIM model for NC design III is implemented in Windows QTL Cartographer, a freely distributed software.