Analisi e sperimentazione della piattaforma Cloud Dataflow

In questa trattazione si è interessati a sperimentare le possibilità offerte nel campo dell’elaborazione di Big Data da parte di una piattaforma di Cloud Computing sviluppata da Google, chiamata Cloud Dataflow. In particolare l’obiettivo è quello di analizzare e confrontare in modo sperimentale le caratteristiche e le performance di Cloud Dataflow con le piattaforme Apache Hadoop e Apache Spark tramite l’esecuzione di programmi di WordCount basati sul modello MapReduce

Multifocal gastrointestinal angiosarcoma: A challenging diagnosis?

Angiosarcoma rarely involves the gastrointestinal tract. Herein, we describe the case of a 68-year-old man with haemoptysis and melena who was eventually diagnosed with multifocal angiosarcoma of the stomach, small bowel, lungs, and thyroid. The peculiarity was that the histological feature of the polypoid lesions removed at endoscopy was initially misinterpreted as benign hyperplastic polyps, whilst their neoplastic nature was clinically suspected only when the videocapsule endoscopy revealed the presence of multiple variable-sized nodules with apical erosion or active bleeding in the small bowel. Based on the very low incidence, diagnosis of angiosarcoma involving the gastrointestinal tract may be misinterpreted by both the endoscopist and pathologist

Numerical and experimental characterization of a novel modular passive micromixer

This paper reports a new low-cost passive microfluidic mixer design, based on a replication of identical mixing units composed of microchannels with variable curvature (clothoid) geometry. The micromixer presents a compact and modular architecture that can be easily fabricated using a simple and reliable fabrication process. The particular clothoid-based geometry enhances the mixing by inducing transversal secondary flows and recirculation effects. The role of the relevant fluid mechanics mechanisms promoting the mixing in this geometry were analysed using computational fluid dynamics (CFD) for Reynolds numbers ranging from 1 to 110. A measure of mixing potency was quantitatively evaluated by calculating mixing efficiency, while a measure of particle dispersion was assessed through the lacunarity index. The results show that the secondary flow arrangement and recirculation effects are able to provide a mixing efficiency equal to 80 % at Reynolds number above 70. In addition, the analysis of particles distribution promotes the lacunarity as powerful tool to quantify the dispersion of fluid particles and, in turn, the overall mixing. On fabricated micromixer prototypes the microscopic-Laser-Induced-Fluorescence (μLIF) technique was applied to characterize mixing. The experimental results confirmed the mixing potency of the microdevice

Image-Based Three-Dimensional Analysis to Characterize the Texture of Porous Scaffolds

The aim of the present study is to characterize the microstructure of composite scaffolds for bone tissue regeneration containing different ratios of chitosan/gelatin blend and bioactive glasses. Starting from realistic 3D models of the scaffolds reconstructed from micro-CT images, the level of heterogeneity of scaffold architecture is evaluated performing a lacunarity analysis. The results demonstrate that the presence of the bioactive glass component affects not only macroscopic features such as porosity, but mainly scaffold microarchitecture giving rise to structural heterogeneity, which could have an impact on the local cell-scaffold interaction and scaffold performances. The adopted approach allows to investigate the scale-dependent pore distribution within the scaffold and the related structural heterogeneity features, providing a comprehensive characterization of the scaffold texture

RAS/BRAF mutational status in familial non‑medullary thyroid carcinomas: A retrospective study

There are contrasting views on whether familial non‑medullary thyroid carcinomas (FNMTCs) are characterized by aggressive behavior, and limited evidence exists on the prognostic value of BRAF and RAS mutations in these tumors. Thus, in the present study, clinicopathological features were analyzed in 386 non‑medullary thyroid carcinomas (NMTCs), subdivided in 82 familial and 304 sporadic cases. Furthermore, the RAS and BRAF mutational statuses were investigated in a subgroup of 34 FNMTCs to address their clinical and biological significance. The results demonstrated that, compared with sporadic NMTCs, FNMTCs are characterized by significantly higher rates of multicentricity and bilaterality and are more frequently associated with chronic autoimmune thyroiditis. Notably, a statistically significant difference in the rates of multicentricity was observed by subgrouping familial tumors according to the number of relatives involved; those with ≥3 affected relatives were more likely to be multicentric. Furthermore, the FNMTC cohort exhibited higher rates of tumors >4 cm in size with extrathyroidal or lymph node involvement. However, no significant difference was observed. Similarly, no differences were observed with respect to the age of onset or the patient outcome. The mutational profiling exhibited a rate of 58.8% for BRAF V600E mutations in familial tumors, which is at the upper limit of the mutational frequency observed in historical series of sporadic thyroid cancer. A high rate of NRAS mutations (17.6%) was also observed, mostly in the follicular variant histotype. Notably, compared with BRAF/RAS‑wild type FNMTCs, the familial carcinomas bearing BRAF or NRAS mutations exhibited slightly higher rates of bilaterality and multicentricity, in addition to increased frequency of locally advanced stage or lymph node involvement. The present data support the theory that FNMTCs are characterized by clinicopathological features that resemble a more aggressive phenotype and suggest that RAS/BRAF mutational analysis deserves to be further evaluated as a tool for the identification of FNMTCs with a potentially unfavorable prognosis

Automated Analysis of Proliferating Cells Spatial Organisation Predicts Prognosis in Lung Neuroendocrine Neoplasms

SIMPLE SUMMARY: Lung neuroendocrine neoplasms (lung NENs) are categorised by morphology, defining a classification sometimes unable to reflect ultimate clinical outcome, particularly for the intermediate domains of adenocarcinomas and large-cell neuroendocrine carcinomas. Moreover, subjectivity and poor reproducibility characterise diagnosis and prognosis assessment of all NENs. The aim of this study was to design and evaluate an objective and reproducible approach to the grading of lung NENs, potentially extendable to other NENs, by exploring a completely new perspective of interpreting the well-recognised proliferation marker Ki-67. We designed an automated pipeline to harvest quantitative information from the spatial distribution of Ki-67-positive cells, analysing its heterogeneity in the entire extent of tumour tissue—which currently represents the main weakness of Ki-67—and employed machine learning techniques to predict prognosis based on this information. Demonstrating the efficacy of the proposed framework would hint at a possible path for the future of grading and classification of NENs. ABSTRACT: Lung neuroendocrine neoplasms (lung NENs) are categorised by morphology, defining a classification sometimes unable to reflect ultimate clinical outcome. Subjectivity and poor reproducibility characterise diagnosis and prognosis assessment of all NENs. Here, we propose a machine learning framework for tumour prognosis assessment based on a quantitative, automated and repeatable evaluation of the spatial distribution of cells immunohistochemically positive for the proliferation marker Ki-67, performed on the entire extent of high-resolution whole slide images. Combining features from the fields of graph theory, fractality analysis, stochastic geometry and information theory, we describe the topology of replicating cells and predict prognosis in a histology-independent way. We demonstrate how our approach outperforms the well-recognised prognostic role of Ki-67 Labelling Index on a multi-centre dataset comprising the most controversial lung NENs. Moreover, we show that our system identifies arrangement patterns in the cells positive for Ki-67 that appear independently of tumour subtyping. Strikingly, the subset of these features whose presence is also independent of the value of the Labelling Index and the density of Ki-67-positive cells prove to be especially relevant in discerning prognostic classes. These findings disclose a possible path for the future of grading and classification of NENs

Sperimentazione di una Soluzione Edge Computing Applicata alla Manutenzione Predittiva su Piattaforma MindSphere

In questa trattazione si è interessati a studiare e analizzare quali sono le reali funzionalità messe a disposizione da MindSphere, la piattaforma cloud per l’Industrial IoT sviluppata da Siemens, e successivamente sperimentare le potenzialità della sua infrastruttura in generale. In particolare, l'obiettivo è quello di approcciarsi allo sviluppo di una soluzione Edge Computing che si possa integrare con la piattaforma stessa, in modo tale da separare l’elaborazione dei dati sul cloud da quella svolta sui dispositivi edge. Tale soluzione potrebbe applicarsi ad un caso d’uso di interesse pratico, come ad esempio quello della Manutenzione Predittiva, per poter analizzare anche quali sono le reali implicazioni, i vantaggi e i risultati ottenuti con l’adozione di una soluzione di questo tipo in ambito enterprise

Analysis of microscale flows in tissue engineering systems and microfluidic devices

The doctoral research summarized in this thesis has focused on the study of microflows in Tissue Engineering (TE) scaffolds and microdevices. The thesis is organized in two parts. In the first part, the properties influencing mass transport through scaffold are investigated both experimentally and in silico. In detail: (1) an acoustic measurement system suitable for the evaluation of TE porous scaffolds and based on a single (pressure) transducer is developed; (2) realistic models of irregular porous scaffolds were reconstructed from micro-CT images and fluid transport through them is simulated by applying the Lattice Boltzmann method. In the second part, the issue of mixing of species in microdevices is investigated in depth and a novel low-cost passive microfluidic mixer design is proposed and its performance evaluated both in silico and in vitro. PART I: The performance of porous scaffold for tissue engineering (TE) applications are generally evaluated in terms of porosity, pore size and distribution, and pore tortuosity. However these descriptors are often confounding when they are applied to characterize the mass transport within porous scaffolds. On the contrary, permeability is a more effective parameter in (1) estimating mass and species transport through the scaffold and (2) describing its topological features. Therefore, this first part has focused on the study of TE porous scaffold permeability and on its dependence on the microscopic features of the scaffold. Firstly, an overview of methods applied to evaluate TE scaffold permeability is provided, with an emphasis on both experimental and computational approaches. In detail, after a discussion on the most relevant scaffolds features to be considered in the evaluation of the permeability, the presentation of the theoretical background and the introduction of semi-empirical models relating scaffolds features to permeability, the most widely applied experimental setup for the direct measurement of tissue engineered scaffold permeability are presented. Then, the focus is put on the application of computational methods, useful to verify and compare the experimental measurements of permeability, and to integrate experimental data with a more quantitative analysis which is very effective in supporting the design process of TE porous scaffolds. In conclusion, limitations of the methods and future challenges are pointed out. Successively, an acoustic permeability measurement system to quantify the inter-pore connectivity structure of tissue-engineering scaffolds by using a single (pressure) transducer is presented. The proposed method has been developed keeping in mind the limitations of the permeability measurement system in TE field. Technically, this system uses a slow alternating airflow as a fluid medium and allows at the same time a simple and accurate measurement procedure. The intrinsic permeability has been determined in the linear Darcy's region, and deviation from linearity due to inertial losses has been also quantified. The structural parameters of a scaffold, such as effective porosity, tortuosity and effective length of cylindrical pores, have been estimated using the modified Ergun's equation. From this relation, it is possible to achieve a well-defined range of data and associated uncertainties for characterizing the structure/architecture of tissue-engineering scaffolds. This quantitative analysis is of paramount importance in tissue engineering, where scaffold topological features are strongly related to their biological performance. In the last investigation of this part, the permeability of three bioactive glass/polymer composite scaffolds for bone tissue regeneration is evaluated. Structural features such as porosity, specific surface area and tortuosity, and lacunarity have been measured as well. Concerning lacunarity analysis, results confirmed its potential in providing insights into (i) self-similarity, (ii) random structure at some scale (i.e. heterogeneity) and (iii) Representative Elementary Volume (REV) identification. Permeability is evaluated both experimentally and computationally using the novel acoustic permeability system and Lattice Boltzmann Method (LBM), respectively. The advantage of LBM approach is due to their geometric versatility in simulating flows in irregular porous media. Results of the LBM models are in good agreement with the experimental results, even if the permeability values estimated in silico overestimate experimental data. This discrepancy is due to the influence of grid resolution and sample size on permeability calculations. In addition, the lower permeability values obtained in this study than the permeability data of different bone tissue reported in literature confirms the need to optimize the design of these scaffolds in terms of mass transport. PART II: Microfluidic deals with the control and manipulation of fluids at the microscale. A typical microfluidic platform is characterized by several components. One of the most important is the micromixer. Mixing of species is often critical to be achieved, since microfluidics is characterized mainly by very low Reynolds flows, and cannot take advantage of turbulence in order to enhance mixing. A good understanding of the dynamic of mixing becomes crucial to i) improve the effectiveness of and ii) speed up chemical reactions. In order to enhance mixing, several techniques have been developed. In general, mixing strategies can be classified as either active or passive, according to the operational mechanism. Active mixers employ external forces in order to perform mixing, so that actuation system must be embedded into the microchips. On the contrary, passive mixers avoid resorting to external electrical or mechanical sources by exploiting characteristics of specific flow fields in microchannel geometries to mix species, offering the advantage to be easy to be produced and integrated. The aim of this investigation was to develop a new low-cost passive microfluidic mixer design. First, a survey of the passive micromixing solutions currently adopted is provided. In detail, the most widely used microchannel geometries and the metrics used to quantify mixing effectiveness in microfluidic applications has been discussed. Then, a new low-cost passive microfluidic mixer design, based on a replication of identical mixing units composed of microchannels with variable curvature (clothoid) geometry, is shown. The micromixer presents a compact and modular architecture that can be easily fabricated using a simple and reliable fabrication process. The particular clothoid-based geometry enhances the mixing by inducing transversal secondary flows and recirculation effects. The role of the relevant fluid mechanics mechanisms promoting the mixing in this geometry have been analysed using computational fluid dynamics (CFD) for Reynolds numbers ranging from 1 to 110. A measure of mixing potency has been quantitatively evaluated by calculating mixing efficiency, while a measure of particle dispersion has been assessed through the lacunarity index. The results showed that the secondary flow arrangement and recirculation effects are able to provide a mixing efficiency equal to 80% at Reynolds number above 70. In addition, the analysis of particles distribution promotes the lacunarity as powerful tool to quantify the dispersion of fluid particles and, in turn, the overall mixing. On fabricated micromixer prototypes the microscopic-Laser-Induced-Fluorescence (µLIF) technique has been applied to characterize mixing. The experimental results confirmed the mixing potency of the microdevice. In conclusion, the proposed design (i) assures a good mixing efficiency (i.e. comparable, if not superior, to other passive micromixer, (ii) is easy to fabricate (i.e. single layer microfluidic devices) and (iii) is easy to integrate (i.e. high modularity

Application of Structural Topology Optimization to Couple Thin-Walled Stiffened Box-Beams

Future generations of civil aircrafts and unconventional unmanned configurations demand for innovative structural concepts to improve the structural performance, and thus reduce the structural weight, but also to allow possible material couplings to be made. Static and dynamic aeroelastic stability can be altered by these couplings. It is therefore necessary to use an accurate and computationally efficient beam model during the preliminary design phase. A stiffened box, made of isotropic material, but with the stiffeners oriented so that they originate the expected bending/torsion coupling, is considered in the present work. The overall equivalent bending, torsional and coupled stiffness is derived by means of homogenization of the shell skin and of the stiffener plate stiffness. A new equivalent homogeneous orthotropic material is determined and introduced into the equivalent plate configuration. The accuracy of the simplified beam model is demonstrated by the application of structural topology optimization technique by means of Altair Optistruct. Good agreement has been found between the theoretical simplified beam model and numerical analysis