Differential expression analysis for sequence count data via mixtures of negative binomials

The recent advent of Next-generation sequencing technologies has revolutionized the way of analyzing the genome. This innovation allows to get deeper information at a lower cost and in less time, and provides data that are discrete measurements. One of the most important applications with these data is the differential analysis, that is investigating if one gene exhibit a different expression level in correspondence of two (or more) biological conditions (such as disease states, treatments received and so on). As for the statistical analysis, the final aim will be statistical testing and for modeling these data the Negative Binomial distribution is considered the most adequate one especially because it allows for "over dispersion". However, the estimation of the dispersion parameter is a very delicate issue because few information are usually available for estimating it. Many strategies have been proposed, but they often result in procedures based on plug-in estimates, and in this thesis we show that this discrepancy between the estimation and the testing framework can lead to uncontrolled first-type errors. We propose a mixture model that allows each gene to share information with other genes that exhibit similar variability. Afterwards, three consistent statistical tests are developed for differential expression analysis. We show that the proposed method improves the sensitivity of detecting differentially expressed genes with respect to the common procedures, since it is the best one in reaching the nominal value for the first-type error, while keeping elevate power. The method is finally illustrated on prostate cancer RNA-seq data.

Dynamics of coastal aquifers: data-driven forecasting and risk analysis

This work is focused on the study of saltwater intrusion in coastal aquifers, and in particular on the realization of conceptual schemes to evaluate the risk associated with it. Saltwater intrusion depends on different natural and anthropic factors, both presenting a strong aleatory behaviour, that should be considered for an optimal management of the territory and water resources. Given the uncertainty of problem parameters, the risk associated with salinization needs to be cast in a probabilistic framework. On the basis of a widely adopted sharp interface formulation, key hydrogeological problem parameters are modeled as random variables, and global sensitivity analysis is used to determine their influence on the position of saltwater interface. The analyses presented in this work rely on an efficient model reduction technique, based on Polynomial Chaos Expansion, able to combine the best description of the model without great computational burden. When the assumptions of classical analytical models are not respected, and this occurs several times in the applications to real cases of study, as in the area analyzed in the present work, one can adopt data-driven techniques, based on the analysis of the data characterizing the system under study. It follows that a model can be defined on the basis of connections between the system state variables, with only a limited number of assumptions about the "physical" behaviour of the system.

Chirale effektive Feldtheorie mit Vektormesonen : vom elektromagnetischen Formfaktor zur virtuellen Compton-Streuung

Die vorliegende Arbeit beschäftigt sich mit der Modellierung niederenergetischer elektromagnetischer und hadronischer Prozesse im Rahmen einer manifest lorentzinvarianten, chiralen effektiven Feldtheorie unter expliziter, dynamischer Berücksichtigung resonanter, das heißt vektormesonischer Freiheitsgrade. Diese effektive Theorie kann daher als Approximation der grundlegenden Quantenchromodynamik bei kleinen Energien verstanden werden. Besonderes Augenmerk wird dabei auf das verwendete Zähl- sowie Renormierungschema gelegt, wodurch eine konsistente Beschreibung mesonischer Prozesse bis zu Energien von etwa 1GeV ermöglicht wird. Das verwendete Zählschema beruht dabei im Wesentlichen auf einem Argument für großes N_c (Anzahl der Farbfreiheitsgrade) und lässt eine äquivalente Behandlung von Goldstonebosonen (Pionen) und Resonanzen (Rho- und Omegamesonen) zu. Als Renormierungsschema wird das für (bezüglich der starken Wechselwirkung) instabile Teilchen besonders geeignete complex-mass scheme als Erweiterung des extended on-mass-shell scheme verwendet, welches in Kombination mit dem BPHZ-Renormierungsverfahren (benannt nach Bogoliubov, Parasiuk, Hepp und Zimmermann) ein leistungsfähiges Konzept zur Berechnung von Quantenkorrekturen in dieser chiralen effektiven Feldtheorie darstellt. Sämtliche vorgenommenen Rechnungen schließen Terme der chiralen Ordnung vier sowie einfache Schleifen in Feynman-Diagrammen ein. Betrachtet werden unter anderem der Vektorformfaktor des Pions im zeitartigen Bereich, die reelle Compton-Streuung (beziehungsweise Photonenfusion) im neutralen und geladenen Kanal sowie die virtuelle Compton-Streuung, eingebettet in die Elektron-Positron-Annihilation. Zur Extraktion der Niederenergiekopplungskonstanten der Theorie wird letztendlich eine Reihe experimenteller Datensätze verschiedenartiger Observablen verwendet. Die hier entwickelten Methoden und Prozeduren - und insbesondere deren technische Implementierung - sind sehr allgemeiner Natur und können daher auch an weitere Problemstellungen aus diesem Gebiet der niederenergetischen Quantenchromodynamik angepasst werden.

A new information fusion method for land-use classification using high resolution satellite imagery

Satellite image classification involves designing and developing efficient image classifiers. With satellite image data and image analysis methods multiplying rapidly, selecting the right mix of data sources and data analysis approaches has become critical to the generation of quality land-use maps. In this study, a new postprocessing information fusion algorithm for the extraction and representation of land-use information based on high-resolution satellite imagery is presented. This approach can produce land-use maps with sharp interregional boundaries and homogeneous regions. The proposed approach is conducted in five steps. First, a GIS layer - ATKIS data - was used to generate two coarse homogeneous regions, i.e. urban and rural areas. Second, a thematic (class) map was generated by use of a hybrid spectral classifier combining Gaussian Maximum Likelihood algorithm (GML) and ISODATA classifier. Third, a probabilistic relaxation algorithm was performed on the thematic map, resulting in a smoothed thematic map. Fourth, edge detection and edge thinning techniques were used to generate a contour map with pixel-width interclass boundaries. Fifth, the contour map was superimposed on the thematic map by use of a region-growing algorithm with the contour map and the smoothed thematic map as two constraints. For the operation of the proposed method, a software package is developed using programming language C. This software package comprises the GML algorithm, a probabilistic relaxation algorithm, TBL edge detector, an edge thresholding algorithm, a fast parallel thinning algorithm, and a region-growing information fusion algorithm. The county of Landau of the State Rheinland-Pfalz, Germany was selected as a test site. The high-resolution IRS-1C imagery was used as the principal input data.

Progettazione e implementazione di una piattaforma per la localizzazione indoor basata su tecniche di radio fingerprinting e data-crowdsourcing

Questa tesi ha come scopo principale l'analisi delle diverse tecnologie di localizzazione in ambito indoor, analizzando in particolare l'utilizzo del Wifi RSS Fingerprinting. La tecnica del Wifi RSS Fingerprinting è una tecnica per la localizzazione all'interno di ambienti chiusi, che consiste nella definizione di un 'impronta'(fingerprint) in un punto preciso dell'ambiente(definito reference point), andando a inserire in un database i valori di potenza del segnale ricevuto(RSS) da ogni access point rilevato all'interno di quel determinato reference point. Per l'implementazione di questa tecnica è stato sviluppato un applicativo con un architettura client-server. Il client è stato sviluppato in ambiente Android, realizzando una applicazione per la gestione della fase di salvataggio di nuovi fingerprint e per la fase di localizzazione della posizione corrente, tramite l'utilizzo dei vari fingerprint precedentemente inseriti all'interno del DB. Il server, sviluppato in Node.js(framework Javascript), gestirà le diverse richieste ricevute dal client tramite delle chiamate AJAX, prelevando le informazioni richieste direttamente dal database. All'interno delle applicativo sono stati implementati diversi algoritmi per la localizzazione indoor, in modo da poter verificare l'applicabilità di questo sistema in un ambito reale. Questi algoritmi sono stati in seguito testati per valutare l'accuratezza e la precisione di ciascuno, andando ad individuare gli algoritmi migliori da utilizzare in base a scenari diversi.

Sviluppo di applicazioni mobile platform-independent: Un caso di studio basato sul framework sencha

Negli ultimi anni si è imposto il concetto di Ubiquitous Computing, ovvero la possibilità di accedere al web e di usare applicazioni per divertimento o lavoro in qualsiasi momento e in qualsiasi luogo. Questo fenomeno sta cambiando notevolmente le abitudini delle persone e ciò è testimoniato anche dal fatto che il mercato mobile è in forte ascesa: da fine 2014 sono 45 milioni gli smartphone e 12 milioni i tablet in circolazione in Italia. Sembra quasi impossibile, dunque, rinunciare al mobile, soprattutto per le aziende: il nuovo modo di comunicare ha reso necessaria l’introduzione del Mobile Marketing e per raggiungere i propri clienti ora uno degli strumenti più efficaci e diretti sono le applicazioni. Esse si definiscono native se si pongono come traguardo un determinato smartphone e possono funzionare solo per quel sistema operativo. Infatti un’app costruita, per esempio, per Android non può funzionare su dispositivi Apple o Windows Phone a meno che non si ricorra al processo di porting. Ultimamente però è richiesto un numero sempre maggiore di app per piattaforma e i dispositivi presenti attualmente sul mercato presentano differenze tra le CPU, le interfacce (Application Programming Interface), i sistemi operativi, l’hardware, etc. Nasce quindi la necessità di creare applicazioni che possano funzionare su più sistemi operativi, ovvero le applicazioni platform-independent. Per facilitare e supportare questo genere di lavoro sono stati definiti nuovi ambienti di sviluppo tra i quali Sencha Touch e Apache Cordova. Il risultato finale dello sviluppo di un’app attraverso questi framework è proprio quello di ottenere un oggetto che possa essere eseguito su qualsiasi dispositivo. Naturalmente la resa non sarà la stessa di un’app nativa, la quale ha libero accesso a tutte le funzionalità del dispositivo (rubrica, messaggi, notifiche, geolocalizzazione, fotocamera, accelerometro, etc.), però con questa nuova app vi è la garanzia di un costo di sviluppo minore e di una richiesta considerevole sul mercato. L’obiettivo della tesi è quello di analizzare questo scenario attraverso un caso di studio proveniente da una realtà aziendale che presenta proprio la necessità di sviluppare un’applicazione per più piattaforme. Nella prima parte della tesi viene affrontata la tematica del mobile computing e quella del dualismo tra la programmazione nativa e le web app: verranno analizzate le caratteristiche delle due diverse tipologie cercando di capire quale delle due risulti essere la migliore. Nella seconda parte sarà data luce a uno dei più importanti framework per la costruzione di app multi-piattaforma: Sencha Touch. Ne verranno analizzate le caratteristiche, soffermandosi in particolare sul pattern MVC e si potrà vedere un confronto con altri framework. Nella terza parte si tratterà il caso di studio, un app mobile per Retail basata su Sencha Touch e Apache Cordova. Nella parte finale si troveranno alcune riflessioni e conclusioni sul mobile platform-independent e sui vantaggi e gli svantaggi dell’utilizzo di JavaScript per sviluppare app.

Progettazione e sviluppo di una soluzione Hadoop per il calcolo di Big Data Analytics

Il presente elaborato ha come oggetto la progettazione e lo sviluppo di una soluzione Hadoop per il Calcolo di Big Data Analytics. Nell'ambito del progetto di monitoraggio dei bottle cooler, le necessità emerse dall'elaborazione di dati in continua crescita, ha richiesto lo sviluppo di una soluzione in grado di sostituire le tradizionali tecniche di ETL, non pi�ù su�fficienti per l'elaborazione di Big Data. L'obiettivo del presente elaborato consiste nel valutare e confrontare le perfomance di elaborazione ottenute, da un lato, dal flusso di ETL tradizionale, e dall'altro dalla soluzione Hadoop implementata sulla base del framework MapReduce.

Big Data: applicazione di una λ-Architecture alla gestione batch di dati climatici

L’avanzamento tecnologico degli ultimi anni ha portato ad un aumento sostanziale dei dati generati giornalmente. L’analisi di queste ingenti quantità di dati si è rivelata essere troppo complessa per i sistemi tradizionali ed è stato pertanto necessario sviluppare nuovi approcci basati sul calcolo distribuito. I nuovi strumenti sviluppati in seguito a queste nuove necessità sono framework di calcolo parallelo basati sul paradigma del MapReduce, un modello di programmazione sviluppato da Google, e sistemi di gestione di basi di dati fluidi, in grado di trattare rapidamente grandi quantità di dati non strutturati. Lo scopo alla base di entrambi è quello di costruire sistemi scalabili orizzontalmente e utilizzabili su hardware di largo consumo. L’utilizzo di questi nuovi strumenti può comunque portare alla creazione di sistemi poco ottimizzati e di difficile gestione. Nathan Marz propone un’architettura a livelli che utilizza i nuovi strumenti in maniera congiunta per creare sistemi semplici e robusti: questa prende il nome di Lambda-Architecture. In questa tesi viene introdotto brevemente il concetto di Big Data e delle nuove problematiche ad esso associate, si procede poi ad illustrare i principi su cui si basano i nuovi strumenti di calcolo distribuito sviluppati per affrontarle. Viene poi definita l’Architettura Lambda di Nathan Marz, ponendo particolare attenzione su uno dei livelli che la compone, chiamato Batch Layer. I principi della Lambda Architecture sono infine applicati nella costruzione di un Batch Layer, utilizzato per l’analisi e la gestione di dati climatici con fini statistici.

Elaborazione di Big Data: un’applicazione dello Speed Layer di Lambda Architecture

I Big Data hanno forgiato nuove tecnologie che migliorano la qualità della vita utilizzando la combinazione di rappresentazioni eterogenee di dati in varie discipline. Occorre, quindi, un sistema realtime in grado di computare i dati in tempo reale. Tale sistema viene denominato speed layer, come si evince dal nome si è pensato a garantire che i nuovi dati siano restituiti dalle query funcions con la rapidità in cui essi arrivano. Il lavoro di tesi verte sulla realizzazione di un’architettura che si rifaccia allo Speed Layer della Lambda Architecture e che sia in grado di ricevere dati metereologici pubblicati su una coda MQTT, elaborarli in tempo reale e memorizzarli in un database per renderli disponibili ai Data Scientist. L’ambiente di programmazione utilizzato è JAVA, il progetto è stato installato sulla piattaforma Hortonworks che si basa sul framework Hadoop e sul sistema di computazione Storm, che permette di lavorare con flussi di dati illimitati, effettuando l’elaborazione in tempo reale. A differenza dei tradizionali approcci di stream-processing con reti di code e workers, Storm è fault-tolerance e scalabile. Gli sforzi dedicati al suo sviluppo da parte della Apache Software Foundation, il crescente utilizzo in ambito di produzione di importanti aziende, il supporto da parte delle compagnie di cloud hosting sono segnali che questa tecnologia prenderà sempre più piede come soluzione per la gestione di computazioni distribuite orientate agli eventi. Per poter memorizzare e analizzare queste moli di dati, che da sempre hanno costituito una problematica non superabile con i database tradizionali, è stato utilizzato un database non relazionale: HBase.

Toward optimal display of physiologic status in critical care: I. Recreating bedside displays from archived physiologic data

BACKGROUND: Physiologic data display is essential to decision making in critical care. Current displays echo first-generation hemodynamic monitors dating to the 1970s and have not kept pace with new insights into physiology or the needs of clinicians who must make progressively more complex decisions about their patients. The effectiveness of any redesign must be tested before deployment. Tools that compare current displays with novel presentations of processed physiologic data are required. Regenerating conventional physiologic displays from archived physiologic data is an essential first step. OBJECTIVES: The purposes of the study were to (1) describe the SSSI (single sensor single indicator) paradigm that is currently used for physiologic signal displays, (2) identify and discuss possible extensions and enhancements of the SSSI paradigm, and (3) develop a general approach and a software prototype to construct such "extended SSSI displays" from raw data. RESULTS: We present Multi Wave Animator (MWA) framework-a set of open source MATLAB (MathWorks, Inc., Natick, MA, USA) scripts aimed to create dynamic visualizations (eg, video files in AVI format) of patient vital signs recorded from bedside (intensive care unit or operating room) monitors. Multi Wave Animator creates animations in which vital signs are displayed to mimic their appearance on current bedside monitors. The source code of MWA is freely available online together with a detailed tutorial and sample data sets.

A Fully Automatic Calibration Framework for Navigated Ultrasound Imaging

Navigated ultrasound (US) imaging is used for the intra-operative acquisition of 3D image data during imageguided surgery. The presented approach includes the design of a compact and easy to use US calibration device and its integration into a software application for navigated liver surgery. User interaction during the calibration process is minimized through automatic detection of the calibration process followed by automatic image segmentation, calculation of the calibration transform and validation of the obtained result. This leads to a fast, interaction-free and fully automatic calibration procedure enabling intra-operative

Rapid fusion and syncytium formation of heterologous cells upon expression of the FGFRL1 receptor

The fusion of mammalian cells into syncytia is a developmental process that is tightly restricted to a limited subset of cells. Besides gamete and placental trophoblast fusion, only macrophages and myogenic stem cells fuse into multinucleated syncytia. In contrast to viral cell fusion, which is mediated by fusogenic glycoproteins that actively merge membranes, mammalian cell fusion is poorly understood at the molecular level. A variety of mammalian transmembrane proteins, among them many of the immunoglobulin superfamily, have been implicated in cell-cell fusion, but none has been shown to actively fuse cells in vitro. Here we report that the FGFRL1 receptor, which is up-regulated during the differentiation of myoblasts into myotubes, fuses cultured cells into large, multinucleated syncytia. We used luciferase and GFP-based reporter assays to confirm cytoplasmic mixing and to identify the fusion inducing domain of FGFRL1. These assays revealed that Ig-like domain III and the transmembrane domain are both necessary and sufficient to rapidly fuse CHO cells into multinucleated syncytia comprising several hundred nuclei. Moreover, FGFRL1 also fused HEK293 and HeLa cells with untransfected CHO cells. Our data show that FGFRL1 is the first mammalian protein that is capable of inducing syncytium formation of heterologous cells in vitro.

Mondrian: An Agile Visualization Framework

Data visualization is the process of representing data as pictures to support reasoning about the underlying data. For the interpretation to be as easy as possible, we need to be as close as possible to the original data. As most visualization tools have an internal meta-model, which is different from the one for the presented data, they usually need to duplicate the original data to conform to their meta-model. This leads to an increase in the resources needed, increase which is not always justified. In this work we argue for the need of having an engine that is as close as possible to the data and we present our solution of moving the visualization tool to the data, instead of moving the data to the visualization tool. Our solution also emphasizes the necessity of reusing basic blocks to express complex visualizations and allowing the programmer to script the visualization using his preferred tools, rather than a third party format. As a validation of the expressiveness of our framework, we show how we express several already published visualizations and describe the pros and cons of the approach.

Study design, baseline patient characteristics and intervention in a cross-cultural framework: results from the ADORE study

OBJECTIVE : To describe the methodology and to present the baseline findings of the Attention-deficit/hyperactivity Disorder Observational Research in Europe (ADORE) study, the primary objective of which is to describe the relationship between treatment regimen prescribed and quality of life of children with ADHD in actual practice. METHODS : In this 2-year prospective observational study, data on diagnosis, prescribed treatment and outcomes of ADHD were collected at seven time points by paediatricians and child psychiatrists on 1,573 children recruited in 10 European countries. The data presented here from the 1,478 patients included in the analyses describe the baseline condition, initial treatment regimen prescribed and quality of life of families with children with ADHD. RESULTS : Patients had a mean age of 9.0 years (SD 2.5) and 84% were male. Physicians diagnoses were made using DSM-IV (43 %), ICD-10 (32%) and both DSM-IV and ICD-10 (12 %). Mean age of awareness of a problem was 5.1 years, suggesting an average delay of approximately 4 years between awareness and diagnosis of ADHD. Baseline ADHD rating scale scores (physicianrated) indicated moderate to severe ADHD. Parent-rated SDQ scores were in agreement and suggested significant levels of co-existing problems. CGI-S, CGAS and CHIPCE scores also indicated significant impairment. Patients were offered the following treatments after the initial assessment: pharmacotherapy (25 %), psychotherapy (19 %), combination of pharmacotherapy and psychotherapy (25 %), other therapy (10 %) and no treatment (21 %). CONCLUSION : The ADORE study shows that ADHD is similarly recognised across 10 European countries and that the children are significantly impaired across a wide range of domains. In this respect, they resemble children described in previous ADHD samples.

Harvesting local cylinder autograft from adjacent vertebral body for anterior lumbar interbody fusion: surgical technique, operative feasibility and preliminary clinical results

Autogenous iliac crest has long served as the gold standard for anterior lumbar arthrodesis although added morbidity results from the bone graft harvest. Therefore, femoral ring allograft, or cages, have been used to decrease the morbidity of iliac crest bone harvesting. More recently, an experimental study in the animal showed that harvesting local bone from the anterior vertebral body and replacing the void by a radio-opaque beta-tricalcium phosphate plug was a valid concept. However, such a concept precludes theoretically the use of posterior pedicle screw fixation. At one institution a consecutive series of 21 patients underwent single- or multiple-level circumferential lumbar fusion with anterior cages and posterior pedicle screws. All cages were filled with cancellous bone harvested from the adjacent vertebral body, and the vertebral body defect was filled with a beta-tricalcium phosphate plug. The indications for surgery were failed conservative treatment of a lumbar degenerative disc disease or spondylolisthesis. The purpose of this study, therefore, was to report on the surgical technique, operative feasibility, safety, benefits, and drawbacks of this technique with our primary clinical experience. An independent researcher reviewed all data that had been collected prospectively from the onset of the study. The average age of the patients was 39.9 (26-57) years. Bone grafts were successfully harvested from 28 vertebral bodies in all but one patient whose anterior procedure was aborted due to difficulty in freeing the left common iliac vein. This case was converted to a transforaminal interbody fusion (TLIF). There was no major vascular injury. Blood loss of the anterior procedure averaged 250 ml (50-350 ml). One tricalcium phosphate bone plug was broken during its insertion, and one endplate was broken because of wrong surgical technique, which did not affect the final outcome. One patient had a right lumbar plexopathy that was not related to this special technique. There was no retrograde ejaculation, infection or pseudoarthrosis. One patient experienced a deep venous thrombosis. At the last follow up (mean 28 months) all patients had a solid lumbar spine fusion. At the 6-month follow up, the pain as assessed on the visual analog scale (VAS) decreased from 6.9 to 4.5 (33% decrease), and the Oswestry disability index (ODI) reduced from 48.0 to 31.7 with a 34% reduction. However, at 2 years follow up there was a trend for increase in the ODI (35) and VAS (5). The data in this study suggest that harvesting a cylinder of autograft from the adjacent vertebral body is safe and efficient. Filling of the void defect with a beta-tricalcium phosphate plug does not preclude the use of posterior pedicle screw stabilization.