MicroRNA expression profile in head and neck cancer: HOX-cluster embedded microRNA-196a and microRNA-10b dysregulation implicated in cell proliferation

Abstract Background Current evidence implicates aberrant microRNA expression patterns in human malignancies; measurement of microRNA expression may have diagnostic and prognostic applications. Roles for microRNAs in head and neck squamous cell carcinomas (HNSCC) are largely unknown. HNSCC, a smoking-related cancer, is one of the most common malignancies worldwide but reliable diagnostic and prognostic markers have not been discovered so far. Some studies have evaluated the potential use of microRNA as biomarkers with clinical application in HNSCC. Methods MicroRNA expression profile of oral squamous cell carcinoma samples was determined by means of DNA microarrays. We also performed gain-of-function assays for two differentially expressed microRNA using two squamous cell carcinoma cell lines and normal oral keratinocytes. The effect of the over-expression of these molecules was evaluated by means of global gene expression profiling and cell proliferation assessment. Results Altered microRNA expression was detected for a total of 72 microRNAs. Among these we found well studied molecules, such as the miR-17-92 cluster, comprising potent oncogenic microRNA, and miR-34, recently found to interact with p53. HOX-cluster embedded miR-196a/b and miR-10b were up- and down-regulated, respectively, in tumor samples. Since validated HOX gene targets for these microRNAs are not consistently deregulated in HNSCC, we performed gain-of-function experiments, in an attempt to outline their possible role. Our results suggest that both molecules interfere in cell proliferation through distinct processes, possibly targeting a small set of genes involved in cell cycle progression. Conclusions Functional data on miRNAs in HNSCC is still scarce. Our data corroborate current literature and brings new insights into the role of microRNAs in HNSCC. We also show that miR-196a and miR-10b, not previously associated with HNSCC, may play an oncogenic role in this disease through the deregulation of cell proliferation. The study of microRNA alterations in HNSCC is an essential step to the mechanistic understanding of tumor formation and could lead to the discovery of clinically relevant biomarkers.

Tecnologie ad agenti e sistemi embedded

Information technology (IT) is on the verge of another revolution. Driven by the increasing capabilities and ever declining costs of computing and communications devices, IT is being embedded into a growing range of physical devices linked together through networks and will become ever more pervasive as the component technologies become smaller, faster, and cheaper. [..] These networked systems of embedded computers, referred to as EmNets throughout this report, have the potential to change radically the way people interact with their environment by linking together a range of devices and sensors that will allow information to be collected, shared, and processed in unprecedented ways.[..] The use of EmNets throughout society could well dwarf previous milestones in the information revolution.[..] IT will eventually become \textbf{an invisible component of almost everything} in everyone`s surroundings. Con il ridursi dei costi e l'aumentare della capacità di computazione dei componenti elettronici sono proliferate piattaforme che permettono al bambino come all'ingegnere di sviluppare un'idea che trasversalmente taglia il mondo reale e quello virtuale. Una collisione tra due mondi che fino a poco tempo fa era consentita esclusivamente a professionisti. Oggetti che possono acquisire o estendere funzionalità, che ci permettono di estendere la nostra percezione del mondo e di rivalutarne i suoi limiti. Oggetti connessi alla 'rete delle reti' che condividono ed elaborano dati per un nuovo utilizzo delle informazioni. Con questa tesi si vuole andare ad esplorare l'applicazione degli agenti software alle nuove piattaforme dei sistemi embedded e dell'Internet of Things, tecnologie abbastanza mature eppure non ancora esplorate a fondo. Ha senso modellare un sistema embedded con gli agenti?

Simple superposition approach for dynamic analysis of piled embedded footings.

[EN]The effectiveness and accuracy of the superposition method in assessing the dynamic stiffness and damping functions of embedded footings supported by vertical piles in homogeneous viscoelastic soil is addressed. To the end, the impedances of piled embedded footings are compared to those obtained by suporposing the impedance functions of the corresponding pile groups and embedded footing treated separately.

Importance of footing-soil separation on dynamic stiffness of piled embedded footings

[EN]Different phenomena such a soil consolidation, erosion, and scour beneath an embedded footing supported on piles may lead to loss of contact between soil and the pile cap underside. The importance of this separation on the dynamic stiffness and damping of the foundation is assessed in this work.

Active fibre-reinforced composites with embedded shape memory alloys

This dissertation concerns active fibre-reinforced composites with embedded shape memory alloy wires. The structural application of active materials allows to develop adaptive structures which actively respond to changes in the environment, such as morphing structures, self-healing structures and power harvesting devices. In particular, shape memory alloy actuators integrated within a composite actively control the structural shape or stiffness, thus influencing the composite static and dynamic properties. Envisaged applications include, among others, the prevention of thermal buckling of the outer skin of air vehicles, shape changes in panels for improved aerodynamic characteristics and the deployment of large space structures. The study and design of active composites is a complex and multidisciplinary topic, requiring in-depth understanding of both the coupled behaviour of active materials and the interaction between the different composite constituents. Both fibre-reinforced composites and shape memory alloys are extremely active research topics, whose modelling and experimental characterisation still present a number of open problems. Thus, while this dissertation focuses on active composites, some of the research results presented here can be usefully applied to traditional fibre-reinforced composites or other shape memory alloy applications. The dissertation is composed of four chapters. In the first chapter, active fibre-reinforced composites are introduced by giving an overview of the most common choices available for the reinforcement, matrix and production process, together with a brief introduction and classification of active materials. The second chapter presents a number of original contributions regarding the modelling of fibre-reinforced composites. Different two-dimensional laminate theories are derived from a parent three-dimensional theory, introducing a procedure for the a posteriori reconstruction of transverse stresses along the laminate thickness. Accurate through the thickness stresses are crucial for the composite modelling as they are responsible for some common failure mechanisms. A new finite element based on the First-order Shear Deformation Theory and a hybrid stress approach is proposed for the numerical solution of the two-dimensional laminate problem. The element is simple and computationally efficient. The transverse stresses through the laminate thickness are reconstructed starting from a general finite element solution. A two stages procedure is devised, based on Recovery by Compatibility in Patches and three-dimensional equilibrium. Finally, the determination of the elastic parameters of laminated structures via numerical-experimental Bayesian techniques is investigated. Two different estimators are analysed and compared, leading to the definition of an alternative procedure to improve convergence of the estimation process. The third chapter focuses on shape memory alloys, describing their properties and applications. A number of constitutive models proposed in the literature, both one-dimensional and three-dimensional, are critically discussed and compared, underlining their potential and limitations, which are mainly related to the definition of the phase diagram and the choice of internal variables. Some new experimental results on shape memory alloy material characterisation are also presented. These experimental observations display some features of the shape memory alloy behaviour which are generally not included in the current models, thus some ideas are proposed for the development of a new constitutive model. The fourth chapter, finally, focuses on active composite plates with embedded shape memory alloy wires. A number of di®erent approaches can be used to predict the behaviour of such structures, each model presenting different advantages and drawbacks related to complexity and versatility. A simple model able to describe both shape and stiffness control configurations within the same context is proposed and implemented. The model is then validated considering the shape control configuration, which is the most sensitive to model parameters. The experimental work is divided in two parts. In the first part, an active composite is built by gluing prestrained shape memory alloy wires on a carbon fibre laminate strip. This structure is relatively simple to build, however it is useful in order to experimentally demonstrate the feasibility of the concept proposed in the first part of the chapter. In the second part, the making of a fibre-reinforced composite with embedded shape memory alloy wires is investigated, considering different possible choices of materials and manufacturing processes. Although a number of technological issues still need to be faced, the experimental results allow to demonstrate the mechanism of shape control via embedded shape memory alloy wires, while showing a good agreement with the proposed model predictions.

Sistemi embedded open source: Arduino come caso di studio

Il lavoro svolto in questa tesi è stato quello di introdurre alcuni concetti importanti dei sistemi embedded, in particolare ci si è soffermati su quelli open source. È stato trattato nello specifico Arduino come esempio di sistema embedded open source a basso costo.

Hardware/Software Design of Dynamic Real-Time Schedulers for Embedded Multiprocessor Systems

The new generation of multicore processors opens new perspectives for the design of embedded systems. Multiprocessing, however, poses new challenges to the scheduling of real-time applications, in which the ever-increasing computational demands are constantly flanked by the need of meeting critical time constraints. Many research works have contributed to this field introducing new advanced scheduling algorithms. However, despite many of these works have solidly demonstrated their effectiveness, the actual support for multiprocessor real-time scheduling offered by current operating systems is still very limited. This dissertation deals with implementative aspects of real-time schedulers in modern embedded multiprocessor systems. The first contribution is represented by an open-source scheduling framework, which is capable of realizing complex multiprocessor scheduling policies, such as G-EDF, on conventional operating systems exploiting only their native scheduler from user-space. A set of experimental evaluations compare the proposed solution to other research projects that pursue the same goals by means of kernel modifications, highlighting comparable scheduling performances. The principles that underpin the operation of the framework, originally designed for symmetric multiprocessors, have been further extended first to asymmetric ones, which are subjected to major restrictions such as the lack of support for task migrations, and later to re-programmable hardware architectures (FPGAs). In the latter case, this work introduces a scheduling accelerator, which offloads most of the scheduling operations to the hardware and exhibits extremely low scheduling jitter. The realization of a portable scheduling framework presented many interesting software challenges. One of these has been represented by timekeeping. In this regard, a further contribution is represented by a novel data structure, called addressable binary heap (ABH). Such ABH, which is conceptually a pointer-based implementation of a binary heap, shows very interesting average and worst-case performances when addressing the problem of tick-less timekeeping of high-resolution timers.

Use of shared memory in the context of embedded multi-core processors: exploration of the technology and its limits

Modern embedded systems embrace many-core shared-memory designs. Due to constrained power and area budgets, most of them feature software-managed scratchpad memories instead of data caches to increase the data locality. It is therefore programmers’ responsibility to explicitly manage the memory transfers, and this make programming these platform cumbersome. Moreover, complex modern applications must be adequately parallelized before they can the parallel potential of the platform into actual performance. To support this, programming languages were proposed, which work at a high level of abstraction, and rely on a runtime whose cost hinders performance, especially in embedded systems, where resources and power budget are constrained. This dissertation explores the applicability of the shared-memory paradigm on modern many-core systems, focusing on the ease-of-programming. It focuses on OpenMP, the de-facto standard for shared memory programming. In a first part, the cost of algorithms for synchronization and data partitioning are analyzed, and they are adapted to modern embedded many-cores. Then, the original design of an OpenMP runtime library is presented, which supports complex forms of parallelism such as multi-level and irregular parallelism. In the second part of the thesis, the focus is on heterogeneous systems, where hardware accelerators are coupled to (many-)cores to implement key functional kernels with orders-of-magnitude of speedup and energy efficiency compared to the “pure software” version. However, three main issues rise, namely i) platform design complexity, ii) architectural scalability and iii) programmability. To tackle them, a template for a generic hardware processing unit (HWPU) is proposed, which share the memory banks with cores, and the template for a scalable architecture is shown, which integrates them through the shared-memory system. Then, a full software stack and toolchain are developed to support platform design and to let programmers exploiting the accelerators of the platform. The OpenMP frontend is extended to interact with it.

Model driven design for embedded systems

Questo lavoro di tesi si focalizza sulla modellazione di sistemi software in grado far interagire piattaforme elettroniche differenti tra loro.

Discovery di dispositivi embedded e raccolta di dati con bluetooth e bluetooth smart

L'obbiettivo di questa tesi è la produzione del prototipo di un sistema che sia in grado di ottenere dati da un insieme di sensori per poterli poi trasmettere all’utente, in modo che esso sia maggiormente cosciente del mondo che lo circonda. Affronteremo la sfida in uno scenario medico / di soccorso, dove un operatore si avvicinerà ad un gruppo di pazienti con l’intenzione di ottenere i parametri vitali di uno di essi. All'interno del documento saranno descritte le tecnologie sfruttate per la realizzazione del prototipo: Bluetooth e Bluetooth Smart, il sistema operativo Linux in esecuzione su un Raspberry Pi dotato di sensori, il sistema operativo Android in esecuzione su smartphone o tablet e iBeacon. Verranno poi analizzati i requisiti del sistema da realizzare. Infine verrà descritta l'implementazione utilizzata nel prototipo e analizzato il suo comportamento.

Middleware per Internet of Things: Java Embedded come caso di studio

Grazie al progresso dell'elettronica, ai giorni nostri, è possibile costruire dispositivi elettronici molto piccoli, che col passare del tempo lo sono sempre più. Questo ci permette di poter imboccare nuove strade nel mondo dell'informatica, sfruttando proprio questo fatto. Le dimensioni ridotte dei dispositivi in commercio, come sensori, attuatori, tag e tanto altro, sono particolarmente adatte a nuovi scenari applicativi. Internet of Things è una visione in cui Internet viene esteso alle cose. Facendo largo uso di dispositivi come sensori e tag è possibile realizzare sistemi intelligenti che possono avere riscontri positivi nella vita di tutti i giorni. Tracciare la posizione degli oggetti, monitorare pazienti da remoto, rilevare dati sull'ambiente per realizzare sistemi automatici (ad esempio regolare automaticamente la luce o la temperatura di una stanza) sono solo alcuni esempi. Internet of Things è la naturale evoluzione di Internet, ed è destinato a cambiare radicalmente la nostra vita futura, poichè la tecnologia sarà sempre più parte integrante della nostra vita, aumentando sempre più il nostro benessere e riducendo sempre più il numero delle azioni quotidiane da compiere. Sempre più sono middleware, le piattaforme e i sistemi operativi che nascono per cercare di eliminare o ridurre le problematiche relative allo sviluppo di sistemi di questo genere, e lo scopo di questa tesi è proprio sottolinearne l'importanza e di analizzare gli aspetti che questi middleware devono affrontare. La tesi è strutturata in questo modo: nel capitolo uno verrà fatta una introduzione a Internet of Things, analizzando alcuni degli innumerevoli scenari applicativi che ne derivano, insieme però alle inevitabili problematiche di tipo tecnologico e sociale. Nel secondo capitolo verranno illustrate le tecnologie abilitanti di Internet of Things, grazie alle quali è possibile realizzare sistemi intelligenti. Nel terzo capitolo verranno analizzati gli aspetti relativi ai middleware, sottolineandone l'importanza e prestando attenzione alle funzioni che devono svolgere, il tutto riportando anche degli esempi di middleware esistenti. Nel quarto capitolo verrà approfondito il middleware Java Embedded di Oracle.

Swarm constructability: designing through embedded tectonic behaviors in swarm robotic systems

Con questa tesi di laurea si muovono i primi passi di una ricerca applicata finalizzata alla costruzione-deposizione di materiale da parte di sciami di mini-robot dal comportamento indipendente che si coordinano tramite segnali lasciati e rilevati nell’ambiente in cui si muovono. Lo sviluppo di tecniche di progettazione e fabbricazione digitale ha prodotto un aumento nel grado di interconnessione tra tecnologia e design, dunque, di nuove possibilità tettoniche. Le relazioni tettoniche tradizionali stanno infatti subendo una trasformazione radicale, potendo essere esplicitamente informate e dunque mediate attraverso gli strumenti digitali dall’ideazione alla produzione. Questa mediazione informata del contenuto tettonico (che opera costantemente) è distintivo di un approccio material-based alla progettazione che aumenta l’integrazione tra struttura, materia e forma entro le tecnologie di fabbricazione (R.Oxman). Dei numerosi processi di fabbricazione per l’architettura che si servono di tecnologia robotica, pochi sono capaci di superare la logica gerarchica, rigida e lineare-sequenziale che serve di fatto agli obiettivi di automazione ed ottimizzazione. La distribuzione di forme di intelligenza semplificata ad un numero elevato di unità robot è quindi qui proposta come alternativa al modello appena descritto. Incorporando semplici decisioni di carattere architettonico negli agenti-robot che costituiscono il sistema distribuito di entità autonome, la loro interazione e le decisioni prese individualmente producono comportamento collettivo e l’integrazione delle suddette relazioni tettoniche. Nello sviluppo del progetto, si è fatto così riferimento a modelli comportamentali collettivi (di sciame) osservabili in specie comunitarie che organizzano strutture materiali -come termiti e vespe- ed in organismi semplici -come le muffe cellulari della specie Physarum polycephalum. Per queste specie biologiche il processo di costruzione non dipende da un ‘piano generale’ ma è guidato esclusivamente da azioni dei singoli individui che comunicano lasciando tracce chimiche nell’ambiente e modificano il loro comportamento rilevando le tracce lasciate dagli altri individui. A questo scopo, oltre alle simulazioni in digitale, è stato indispensabile sviluppare dei prototipi funzionali di tipo fisico, ovvero la realizzazione di mini-robot dal movimento indipendente, in grado di coordinarsi tra loro tramite segnali lasciati nell’ambiente e capaci di depositare materiale.