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Serverless middlewares to integrate heterogeneous and distributed services in cloud continuum environments
Get PDFThe application of modern ICT technologies is radically changing many fields pushing toward more open and dynamic value chains fostering the cooperation and integration of many connected partners, sensors, and devices. As a valuable example, the emerging Smart Tourism field derived from the application of ICT to Tourism so to create richer and more integrated experiences, making them more accessible and sustainable. From a technological viewpoint, a recurring challenge in these decentralized environments is the integration of heterogeneous services and data spanning multiple administrative domains, each possibly applying different security/privacy policies, device and process control mechanisms, service access, and provisioning schemes, etc. The distribution and heterogeneity of those sources exacerbate the complexity in the development of integrating solutions with consequent high effort and costs for partners seeking them.
Taking a step towards addressing these issues, we propose APERTO, a decentralized and distributed architecture that aims at facilitating the blending of data and services. At its core, APERTO relies on APERTO FaaS, a Serverless platform allowing fast prototyping of the business logic, lowering the barrier of entry and development costs to newcomers, (zero) fine-grained scaling of resources servicing end-users, and reduced management overhead. APERTO FaaS infrastructure is based on asynchronous and transparent communications between the components of the architecture, allowing the development of optimized solutions that exploit the peculiarities of distributed and heterogeneous environments.
In particular, APERTO addresses the provisioning of scalable and cost-efficient mechanisms targeting: i) function composition allowing the definition of complex workloads from simple, ready-to-use functions, enabling smarter management of complex tasks and improved multiplexing capabilities; ii) the creation of end-to-end differentiated QoS slices minimizing interfaces among application/service running on a shared infrastructure; i) an abstraction providing uniform and optimized access to heterogeneous data sources, iv) a decentralized approach for the verification of access rights to resources
Understanding the role of microglial extracellular vesicles (EVs) in neuroinflammation spreading: an in vitro study
Get PDFNeuroinflammation is a crucial pathogenic mechanism that commonly underlies most neurodegenerative diseases. Microglia, the immune cells of the brain, play a critical role that changes depending on the stage of neuropathology: at early phases of brain diseases microglia display the neuroprotective phenotype which is switched to the classically activated pro-inflammatory subtype at later stages, contributing to neurodegeneration. The microglial phenotypic shift is characterized by a change in the release of bioactive molecules both soluble and through extracellular vesicles. Our in vitro studies aim to understand whether different types of activation could determine change in vesicles content, in particular miRNAs, and whether this could influence the activation state of control microglial cells. Microglial polarization has been induced in two different in vitro models: N9, microglial murine cell line, have been treated by using LPS towards a proinflammatory/neurotoxic phenotype or ATP towards antinflammatory/neuroprotective status; HMC3, human microglial cell line, have been activated using IFN-+ATP. We demonstrated that conditioned media/exosomes obtained from donor microglia were able to promote a pro-inflammatory phenotype in control cells, leading us to prove the existence of a neuroinflammation spreading process mediated by extracellular vesicles of microglia with a crucial role of miRNAs. Increased expression of miRNA-34a observed in N9 model underlines a possible contribution in the diffusion of proinflammatory activation of microglia. Thus, we tried to downregulate miR-34a expression using cleaving sequences of anti-mir-34a DNAzyme delivered by DNA nanostructures aimed to confirm the involvement of miR-34a in microglia polarization towards the neurotoxic phenotype. In conclusion, this thesis work reveal a new inflammation spreading mechanism that involves release of vesicles containing specific cargos by donor polarized microglia, particularly miRNAs, able to influence the phenotypic shift in unpolarized microglia: this process deserves to be deeply investigated as potential therapeutic target to counteract neurodegenerative diseases
A hydrodynamical view on the mass accretion onto massive halos
Get PDFThis Thesis presents the results of my work on how galaxy clusters form by the
accretion of sub-clumps and diffuse materials, and how the accreted energy is distributed in the X-ray emitting plasma. Indeed, on scales larger than tens of millions of light years, the Universe is self-organised by gravity into a spiderweb, the Cosmic Web. Galaxy clusters are the knots of this Cosmic Web, but a strong definition of filaments (which link different knots) and their physical proprieties, is still uncertain. Even if this pattern was determined by studying the spatial distribution of galaxies in the optical band, recently, also in the X-rays probes of filamentary structures around galaxy clusters were obtained. Therefore, given these observational facilities, the galaxy clusters’ outskirts are the best candidate regions to detect filaments and study their physical characteristics. However, from X-rays observations, we have only a few detections of cosmic filaments to date.
On the other hand, it is crucial to understand how the accreted energy is dissipated
in the baryon content of galaxy clusters and groups. Indeed, it is well known
that in the central region of galaxy clusters and groups, the baryon fraction increases with the halo mass. On the outer region, the lack of X-rays constraints influences our understanding of the evolution of baryons in the halos volume. The standard assumption of “closed-box” system, for which the baryon fraction should approach the cosmological ratio Omega_bar/Omega_m, for galaxy clusters and groups seems to be too strong, especially for less massive objects. Moreover, a complete redshift evolution of baryons in galaxy clusters and groups is still missing
Role of next generation sequencing technology in the management of patients with metastatic colorectal cancer
Get PDFL'utilità clinica dell’uso routinario delle tecniche di sequenziamento di nuova generazione (NGS) nei pazienti con cancro colorettale metastatico andrebbe approfondita.
In questo studio, è stato valutato l'impatto di un pannello NGS da 52 geni utilizzato nella pratica clinica di routine. Abbiamo analizzato i risultati dei test molecolari multigenici in pazienti con carcinoma colorettale metastatico (mCRC) in uno studio osservazionale, retrospettivo e monocentrico su pazienti affetti da carcinoma colorettale metastatico consecutivamente testati presso un centro oncologico italiano tra giugno 2019 e dicembre 2020. Le analisi di sopravvivenza sono state effettuate con il metodo Kaplan-Meier, test log-rank e modello di Cox.
Complessivamente sono stati inclusi 179 pazienti con mCRC. Il follow-up mediano è stato di 33 mesi (IQR: 28,45–NR). I quattro geni più frequentemente mutati sono stati: KRAS (48,6%), PIK3CA (22,4%), BRAF (14,5%) e APC (8,4%). È stata trovata un'associazione positiva tra la sopravvivenza globale (OS) e le mutazioni KRAS con un'alta frequenza allelica variante (VAF) [HR: 0,60 (0.36 – 0.99), P=0.047]. La mutazione BRAF era associata a OS inferiore [HR: 2,62 (1,59-4,32), P <0,001]. Il panello NGS ha consentito a otto pazienti di accedere a terapie a bersaglio molecolare non ancora registrate per il cancro colorettale.
In conclusione, i pannelli NGS in mCRC sono fattibili nella pratica clinica in laboratori di riferimento per consentire un impatto inferiore sui costi e un aggiornamento regolare. La mutazione di BRAF risulta associata a una prognosi peggiore. Le mutazioni di KRAS con un’elevata variazione di frequenza allelica erano associate a una sopravvivenza globale superiore rispetto ai pazienti KRAS non mutati. Sono necessari studi più approfonditi per analizzare meglio i fattori prognostici.The clinical impact of targeted next-generation sequencing (NGS) in routine practice should be addressed in metastatic colorectal cancers.
In this work, we studied the impact of a 52-gene amplicon-based NGS panel performed in routine practice. We analyzed the results of multigene molecular testing in metastatic colorectal cancer (mCRC) patients in a single-center, retrospective, observational study of consecutive mCRC patients tested at an Italian cancer centre between June 2019 and December 2020. Outcome was evaluated by the Kaplan–Meier method, log-rank tests and Cox models.
Overall, 179 patients with mCRC were included. Median follow-up was 33 months (IQR: 28.45–NR). The four most frequently mutated genes were: KRAS (48.6%), PIK3CA (22.4%), BRAF (14.5%) and APC (8.4%). A positive association was found between overall survival and KRAS mutations with a high variant allele frequency (VAF) [HR: 0,60 (0.36 – 0.99), P=0.047]. BRAF mutation was associated with inferior overall survival (OS) [HR: 2.62 (1.59–4.32), P < 0.001]. The NGS panel enabled eight patients to access a targeted therapy not currently registered for mCRC.
In conclusion, NGS panels in mCRC are feasible in reference laboratories for routine practice to allow for lower cost impact and regular updating. BRAF mutation is associated with a worse prognosis. Mutations in KRAS with a high VAF were associated with superior OS of mCRC patients compared with patients with KRAS wild-type tumors. In-depth studies are needed to better analyze the prognostic factors
The alchemical work of the Christian Philosopher. Edition, translation, and notes
Get PDFQuesta tesi è l’edizione critica, con traduzione italiana e note di commento, dell’opera alchemica di un autore bizantino, detto il Filosofo Cristiano. Nella parte introduttiva si esaminano le testimonianze dirette e indirette dell’opera, senza tralasciare l’analisi di alcuni problemi storici concernenti il nome e la datazione del nostro autore. L’edizione critica, con traduzione a fronte in italiano, è il nucleo della tesi. Seguono alcuni capitoli sulle varianti recenziori e le note di commento più estese, concernenti specifici punti dell’opera.
Concludono il presente lavoro le appendici e le tabelle riguardanti l’ordinamento dei capitoli del Cristiano e la posizione dell’opera all’interno del corpus alchemico greco, secondo i principali manoscritti.This thesis is the critical edition, with Italian translation and commentary notes, of the alchemical work of a Byzantine author, known as the Christian Philosopher. In the introductory part, direct and indirect witnesses are examined, without neglecting the analysis of some historical problems concerning the name and dating of our author. The critical edition, with a translation into Italian, is the core of the thesis. This part is followed by a few chapters on the later variants and more extensive commentary notes on specific points of the work. This thesis concludes with appendices and tables on the ordering of the chapters of the Christian Philosopher and the position of his work within the Greek alchemical corpus, according to the main manuscripts
Numerical simulations of the spine for patient-specific models of severe scoliosis
Get PDFIn silico methods, such as musculoskeletal modelling, may aid the selection of the optimal surgical treatment for highly complex pathologies such as scoliosis. Many musculoskeletal models use a generic, simplified representation of the intervertebral joints, which are fundamental to the flexibility of the spine. Therefore, to model and simulate the spine, a suitable representation of the intervertebral joint is crucial. The aim of this PhD was to characterise specimen-specific models of the intervertebral joint for multi-body models from experimental datasets. First, the project investigated the characterisation of a specimen-specific lumped parameter model of the intervertebral joint from an experimental dataset of a four-vertebra lumbar spine segment. Specimen-specific stiffnesses were determined with an optimisation method. The sensitivity of the parameters to the joint pose was investigate. Results showed the stiffnesses and predicted motions were highly depended on both the joint pose. Following the first study, the method was reapplied to another dataset that included six complete lumbar spine segments under three different loading conditions. Specimen-specific uniform stiffnesses across joint levels and level-dependent stiffnesses were calculated by optimisation. Specimen-specific stiffness show high inter-specimen variability and were also specific to the loading condition. Level-dependent stiffnesses are necessary for accurate kinematic predictions and should be determined independently of one another. Secondly, a framework to create subject-specific musculoskeletal models of individuals with severe scoliosis was developed. This resulted in a robust codified pipeline for creating subject-specific, severely scoliotic spine models from CT data. In conclusion, this thesis showed that specimen-specific intervertebral joint stiffnesses were highly sensitive to joint pose definition and the importance of level-dependent optimisation. Further, an open-source codified pipeline to create patient-specific scoliotic spine models from CT data was released. These studies and this pipeline can facilitate the specimen-specific characterisation of the scoliotic intervertebral joint and its incorporation into scoliotic musculoskeletal spine models
Colic surgery in the equine patient: novel biomarkers, postoperative management, microbiotal influence and epidemiological analysis on the italian territory
Get PDFThe aim of this work was to investigate novel diagnostic and prognostic tools, postoperative treatments and epidemiologic factors impacting the outcome of surgical cases of colic.
To make a more accurate diagnosis and establish a prognosis, several biomarkers have been investigated in colic patients. In this study we evaluated peritoneal PCT and blood ADMA and SDMA in SIRS positive and negative colic patients to be used as prognostic biomarkers. Our results highlighted the limits of these biomarkers in detection and
the lack of specificity. In fact PCT was not detectable and even if ADMA and SDMA significantly increased in colic horses, they are not diagnostic nor prognostic markers for SIRS.
Fluid therapy has been described to be crucial for the outcome of colic patients, nevertheless no guidelines have been established. Overhydration was the common practice in post surgical management. We compared cases with an extended fluid therapy protocol and cases with a restricted protocol. Results showed that survival rate and postoperative complications were similar between the groups, despite costs being significantly lower in the restricted group.
The possible correlation between intestinal microbiota and colics has gained interest. In this study, cecal and colonic content from horses undergoing laparotomy were collected, and the microbiota analized. Results showed some differences in microbiota between discharged and non discharged patients, and between strangulating and non strangulating types of colic, that might suggest some influence of hind gut microbiota on the disease.
A multicentric study involving three veterinary teaching hospitals on the italian territory was conducted investigating factors affecting postoperative survival and complications in colics. Results showed that the influence of age, PCV, TPP, blood lactate, reflux, type of disease, type of lesion, presence of anastomosis, duration of surgery and surgeons, were in line with literature. Amount of crystalloids used could affected the outcome
Exploring the white dwarf cooling sequence in Globular Clusters
Get PDFWhite dwarfs (WDs) are electron-degenerate structures that are commonly assumed to evolve via a pure cooling process, with no stable thermonuclear activity at work. Their cooling rate is adopted as a cosmic chronometer to constrain the age of several Galactic populations, including the disk, Globular Clusters (GCs) and open clusters.
This thesis work is aimed at the study of the WD populations in globular clusters and is articulated in two branches.
The first was focused on the study of the bright portion of the WD cooling sequence. By analyzing high resolution UV data acquired with the Hubble Space Telescope (HST), we compared the WD luminosity functions (LFs) in four Galactic GCs (namely M13, M3, NGC6752, and M5) finding an unexpected over-abundance of WDs in M13 and NGC6752 with respect to M3 and M5. Theoretical models suggest that, consistently with the blue-tail horizontal branch (HB) morphology of M13 and NGC6752, this overabundance is due to a population of slowly cooling WDs, i.e., WDs fading more slowly than in a pure cooling process thanks to an extra-energy source provided by stable thermonuclear burning in their residual hydrogen-rich envelope. This is the first empirical evidence of WDs fading at a slower rate than usually assumed, and has a crucial impact on the use of the cooling sequence as a cosmic chronometer.
The second branch was focused on the search for the companion star to binary millisecond Pulsars (MSP) in the globular clusters M13 and NGC 6652: the identified companions turned out to be helium-core WDs, and provided a invaluable constraints on the mass of the neutron star and the epoch of the MSP formation
Acoustic backscatter of small pelagic fish species in the Adriatic Sea
Get PDFThe aim of the present study is to apply a broad range of techniques to increase the knowledge of acoustic properties of Sprattus sprattus, Scomber colias and Trachurus mediterraneus in the Adriatic Sea.
A novel study using tethered live fish but not involving hooks and anesthetic was tested on T. mediterraneus and S. colias through several ex situ experiments using a split-beam scientific echosounder operating at 38, 120, and 200 kHz. The mean TS was estimated for 29 live specimens, resulting in a conversion factor b20 value of -71.4 dB re 1 m2 and -71.6 dB re 1 m2 respectively which is ~3 dB lower than the current one in use in the Mediterranean Sea.
Successively, two monospecific trawl hauls were analyzed through the application of in situ approach for the computation of TS values of S. sprattus which led to six b20 values for sprat (range, -68.8 dB re 1 m2 to -65.6 dB re 1 m2), all higher than the current known value of -71.7 dB re 1 m2. The high difference up to 4.2 dB compared to the current value translates in a significant decrease of absolute sprat biomass along the time series un to 20%. Finally, 149 specimens of the three species were collected for backscattering model application(i.e. Kirchhoff-ray mode model (KRM) and Finite Element Method (FEM)) from digital images of the fish body and swimbladder obtained from Computer Tomography (CT) and X-Ray scans. The values resulting from the application of KRM and FEM are in agreement with empirical results. In general terms the present work proposes the acoustic backscatter characterization of S. colias, S. sprattus and T. mediterraneus in the Mediterranean Sea
What do rendering options tell us about the translating mind? Testing the choice network analysis hypothesis
Get PDFFrame. Assessing the difficulty of source texts and parts thereof is important in CTIS, whether for research comparability, for didactic purposes or setting price differences in the market. In order to empirically measure it, Campbell & Hale (1999) and Campbell (2000) developed the Choice Network Analysis (CNA) framework. Basically, the CNA’s main hypothesis is that the more translation options (a group of) translators have to render a given source text stretch, the higher the difficulty of that text stretch will be. We will call this the CNA hypothesis. In a nutshell, this research project puts the CNA hypothesis to the test and studies whether it does actually measure difficulty.
Data collection. Two groups of participants (n=29) of different profiles and from two universities in different countries had three translation tasks keylogged with Inputlog, and filled pre- and post-translation questionnaires. Participants translated from English (L2) into their L1s (Spanish or Italian), and worked—first in class and then at home—using their own computers, on texts ca. 800–1000 words long. Each text was translated in approximately equal halves in two 1-hour sessions, in three consecutive weeks. Only the parts translated at home were considered in the study.
Results. A very different picture emerged from data than that which the CNA hypothesis might predict: there was no prevalence of disfluent task segments when there were many translation options, nor was a prevalence of fluent task segments associated to fewer translation options. Indeed, there was no correlation between the number of translation options (many and few) and behavioral fluency. Additionally, there was no correlation between pauses and both behavioral fluency and typing speed. The discussed theoretical flaws and the empirical evidence lead to the conclusion that the CNA framework does not and cannot measure text and translation difficulty.Stato dell'arte. La valutazione della difficoltà dei testi di partenza e di parti di essi ricopre un ruolo centrale nel campo degli studi cognitivi sulla traduzione e l'interpretazione (CTIS). Per misurarla a livello empirico, Campbell & Hale (1999) e Campbell (2000) hanno sviluppato la Choice Network Analysis (CNA). L'ipotesi principale della CNA è che quante più opzioni di traduzione un gruppo di traduttori ha per tradurre una porzione di testo, più alta sarà la sua difficoltà. Questo progetto di ricerca mette alla prova l'ipotesi della CNA per verificarne la validità come strumento per misurare la difficoltà.
Raccolta dei dati. Due gruppi di partecipanti (n=29) di profili diversi e provenienti da due università di paesi diversi hanno svolto tre prove di traduzione usando Inputlog, ognuna preceduta e seguita da un questionario. I partecipanti hanno tradotto dall'inglese (L2) alla loro L1 (spagnolo o italiano) e hanno lavorato prima in classe e poi a casa con i propri computer su testi di circa 800-1000 parole. Ogni testo è stato suddiviso in metà pressoché uguali e tradotto in due sessioni da un'ora l'una, in tre settimane consecutive.
Risultati. Dai dati è emerso un quadro molto diverso da quello suggerito dall'ipotesi della CNA: non è stata riscontrata alcuna prevalenza di segmenti con minore fluidità relativi a un maggior numero di opzioni di traduzione, né una prevalenza di segmenti con maggiore fluidità associati a un minor numero di opzioni di traduzione. Al contrario, in entrambi i casi la fluidità dei segmenti è rimasta tendenzialmente nella media. Infine, non è stata riscontrata alcuna correlazione tra le pause e fluidità comportamentale o la velocità di batttitura. Le inesattezze teoriche precedentemente discusse e le prove empiriche portano alla conclusione che la CNA non misura e non può misurare la difficoltà del testo e della traduzione