Dissecting the role of IGF2BP3 in the stress-adaptive response and in intercellular communication in Ewing Sarcoma.

Tumor microenvironment has emerged as key factor influencing tumor progression and metastatization. In this context, small vesicles produced by cancer cells can influence the fate of their surroundings via the horizontal transfer of specific molecular cargos. Ewing Sarcoma, the second most common bone tumor in young patients, presents early metastasis associated to worse prognosis. The RNA binding protein Insulin-like Growth Factor 2 mRNA Binding Protein 3 (IGF2BP3) exerts a pro-oncogenic role associated with metastasis formation and worse prognosis in Ewing Sarcoma. Our aim was to investigate the still unexplored role of IGF2BP3 in the stress-adaptive response to tumor microenvironment and in the interactions between Ewing Sarcoma cells. Hypoxia is a major feature of Ewing Sarcoma microenvironment and we demonstrated that IGF2BP3 can direct the CXCR4-mediated migratory response to CXCL12 in Ewing Sarcoma cells subjected to oxygen deprivation. We also discovered that the interaction between IGF2BP3 and CXCR4 is regulated through CD164 and which colocalize at plasma membrane level, upon CXCL12 exposure. Interestingly, high IGF2BP3 levels in Ewing Sarcoma metastatic lesions positively correlated with the expression of both CD164 and CXCR4, indicating the IGF2BP3/CD164/CXCR4 oncogenic axis as a critical modulator of Ewing Sarcoma metastatic progression. We demonstrated for the first time that IGF2BP3 is loaded into Ewing Sarcoma derived exosomes, accordingly to its cellular levels. We discovered that IGF2BP3+ exosomes carry high levels of IGF2BP3-client mRNAs involved in cellular migration, CD164 and IGF1R, and, by transferring this cargo, sustain the migratory abilities of receiving cells, induce a sharp up-regulation of CD164, CXCR4 and IGF1R and enhance the activation of AKT/mTOR and ERK down-stream signalling pathways. We demostrated that the pro-tumorigenic role of IGF2BP3 is not only exerted at cellular level, but that intercellular communication is crucial in the context of Ewing Sarcoma microenvironment.

Wind analysis of the Messina Strait Bridge design project proposal with stabilizing cables

A new study on suspension bridges has been prompted by the big disaster of the Tacoma Narrow Bridge at half its design speed. The aerodynamic instability of long-span bridges has been studied using wind tunnel tests. As a result of improved aerodynamic performance from the geometrical configuration of the bridge deck, the aerodynamic criteria for suspension and cable-stayed bridges have become well established in recent years, thereby allowing longer bridge spans to be developed. Although the Messina Strait Bridge has yet to be constructed, we are looking forward to evaluating the impact of different deck cross-sections on both aerodynamic stability and cost reduction. To further improve the aerodynamic characteristics of long-span suspension bridges, an optimized multi-box bridge deck model with two side decks for traffic lanes, two middle railway decks, and three gaps separating them has been proposed aerodynamic performance has been experimentally verified. 1:80 scale wind tunnel tests have been conducted. According to the current MIDAS Model, the first torsional and the first vertical frequency ratios are 1.27787 and 1.36[1] respectively. It is the torsional/vertical frequency ratio, combined with the deck aerodynamic properties, that determines the wind response properties of the bridge for the most dangerous possible form of aeroelastic instability. The classic flutter is caused by the coupling of torsional and vertical modes. Stabilizing cables to the deck could be a solution to this classic flutter by reducing lateral displacement of the deck and increasing frequency ratios. Stabilizing cables will be installed on the deck in three different orientations: vertical, inclined, and horizontal, with diameters of 80 cm, 60 cm, and 40 cm in each orientation respectively. An overview of the research undertaken on this topic will be presented, as well as the most important findings.

Investigating the origin of radio emission from the intra-cluster bridge A399-A401

Radio bridges are a newly observed class of phenomena, they are large scale filamentary structures that span between pairs of clusters in a pre-merger phase. In my Thesis, starting from the observed synchrotron emission in the bridge A399-A401, I apply a Fermi I shock re-acceleration model under different conditions to the bridge. The purpose of my work is to check the likelihood of the above mentioned model. In particular the Inverse Compton emission that the model predicts is above the current observational constraints on Inverse Compton for the bridge A399-A401, this means that a Fermi I re-acceleration model is unlikely to describe the emission from the bridge, while a Fermi II turbulent re-acceleration model could still explain the origin of the emission in the bridge.

Loading and damage modelling for an integrated SHM system of a prestressed concrete railway bridge in Naples

The thesis explores recent technology developments in the field of structural health monitoring and its application to railway bridge projects. It focuses on two main topics. First, service loads and effect of environmental actions are modelled. In particular, the train moving load and its interaction with rail track is considered with different degrees of detail. Hence, results are compared with real-time experimental measurements. Secondly, the work concerns the identification, definition and modelling process of damages for a prestressed concrete railway bridge, and their implementation inside FEM models. Along with a critical interpretation of the in-field measurements, this approach results in the development of undamaged and damaged databases for the AI-aided detection of anomalies and the definition of threshold levels to prompt automatic alert interventions. In conclusion, an innovative solution for the development of the railway weight-in-motion system is proposed.

Modeling and Design of Phase Shifted Full Bridge Isolated DC-DC ZVS Converter with Peak Current Mode Control

Nowadays, there is a boom in the use of electrification. Electric vehicles are gaining interest worldwide due to various factors, including climate and environmental awareness. In this thesis, a step-down isolated power supply for electric tractors is investigated, specifically the phase-shifted full-bridge (PSFB) DC-DC with synchronous rectification and zero-voltage switching (ZVS). This converter was selected for its high-power capacity with high efficiency. A 3500 W PSFB converter with peak current control (PCCM) is designed and modeled in MATLAB. The input voltage range is from 550 V to 820 V and the output voltage range is limited to 9 V to 16 V with a maximum output current of 250 A. All components were commercially designed and selected, including magnetics for the high-frequency transformer and inductors, taking into account loss calculations. Zero voltage switching for the lagging leg is achieved at 13% to 100% load. The proven efficiency of the converter is around 90

BIM-FEM model interoperability for the design of a prestressed concrete bridge deck

In questa tesi ho analizzato il passaggio dall'ambiente BIM a quello FEM di un impalcato da ponte a travata precompressa, identificando criteri e applicando una metodologia che hanno consentito lo sviluppo di un modello FEM utilizzabile per l'analisi strutturale. Nella tesi si descrive l'opera e il suo dimensionamento, con l'analisi statica e le verifiche strutturali eseguite sia a mano sia sul modello in ambiente FEM importato dall'ambiente BIM. Oltre a ciò, viene modellata l'opera nella sua interezza ed inserita in un contesto reale. La tesi discute l'interoperabilità tra i due software evidenziando vantaggi (modello geometrico di partenza in ambiente FEM, trasferimento di informazioni inserite in ambiente BIM, riduzione dei tempi di modellazione e inserimento proprietà dei materiali e caratteristiche degli oggetti, inserimento armature di precompressione) e criticità (implementazione manuale di alcuni elementi nel modello geometrico, perdita di alcune informazioni, definizione di alcuni parametri, limitata interoperabilità FEM-BIM) della metodologia applicata.

Analysis, Design, and Hardware-in-the-Loop Validation of Multi-Active Bridge Converters

This master's thesis investigates different aspects of Dual-Active-Bridge (DAB) Converter and extends aspects further to Multi-Active-Bridges (MAB). The thesis starts with an overview of the applications of the DAB and MAB and their importance. The analytical part of the thesis includes the derivation of the peak and RMS currents, which is required for finding the losses present in the system. The power converters, considered in this thesis are DAB, Triple-Active Bridge (TAB) and Quad-Active Bridge (QAB). All the theoretical calculations are compared with the simulation results from PLECS software for identifying the correctness of the reviewed and developed theory. The Hardware-in-the-Loop (HIL) simulation is conducted for checking the control operation in real-time with the help of the RT box from the Plexim. Additionally, as in real systems digital signal processor (DSP), system-on-chip or field programmable gate array is employed for the control of the power electronic systems, and the execution of the control in the real-time simulation (RTS) conducted is performed by DSP.

Un bridge tra sistemi di bordo e di terra per prevenire minacce informatiche alla sicurezza delle infrastrutture critiche dei trasporti ferroviari

Il progetto di tesi nasce dall’interesse e dalla passione verso il mondo della Cybersecurity, che da sempre segna il mio percorso accademico e di vita, ma che durante questo ultimo anno di università ha avuto particolare rilevanza. Il progetto è stato svolto con il supporto e la supervisione del team Railway dell’azienda ALTEN Italia presso la sede di Bologna. Il lavoro di tesi mira allo sviluppo di un componente software che rappresenta un livello aggiuntivo di sicurezza nella comunicazione tra sistemi di bordo e di terra. In particolare, il progetto si pone come obiettivo la creazione di un Bridge, ovvero un componente software indipendente e configurabile che si interfaccia sia con il client che con il server, con lo scopo di garantire autenticità e cifratura dei messaggi scambiati tra le due entità. Inoltre, la potenza del Bridge sta nel fatto che nasce come possibile soluzione ai problemi di sicurezza informatica in ambito ferroviario, ma la sua applicabilità può essere estesa anche ad altri settori in cui sia presente una comunicazione client/server da rendere sicura. Infatti, tale software risulta particolarmente flessibile e adattabile, attraverso l’impostazione a priori di parametri di configurazione, in base al tipo di comunicazione che si desidera implementare tra le due entità. Per questo motivo, si ritiene che la forza del progetto sia la possibilità di fornire una soluzione software per proteggere l’infrastruttura critica dei trasporti ferroviari da eventuali minacce informatiche, ma anche la capacità adattiva del Bridge, in grado di svolgere le sue funzioni di sicurezza in un ampio ventaglio di ambiti di applicazione.

RED-Bridge: A Multiprotocol Tool Prototype for IoT Sensors

The IoT is growing more and more each year and is becoming so ubiquitous that it includes heterogeneous devices with different hardware and software constraints leading to an highly fragmented ecosystem. Devices are using different protocols with different paradigms and they are not compatible with each other; some devices use request-response protocols like HTTP or CoAP while others use publish-subscribe protocols like MQTT. Integration in IoT is still an open research topic. When handling and testing IoT sensors there are some common task that people may be interested in: reading and visualizing the current value of the sensor; doing some aggregations on a set of values in order to compute statistical features; saving the history of the data to a time-series database; forecasting the future values to react in advance to a future condition; bridging the protocol of the sensor in order to integrate the device with other tools. In this work we will show the working implementation of a low-code and flow-based tool prototype which supports the common operations mentioned above, based on Node-RED and Python. Since this system is just a prototype, it has some issues and limitations that will be discussed in this work.

Minimal Invasive Ostheosintesis For Treatment Of Diaphiseal Transverse Humeral Shaft Fractures.

To evaluate patients with transverse fractures of the shaft of the humerus treated with indirect reduction and internal fixation with plate and screws through minimally invasive technique. Inclusion criteria were adult patients with transverse diaphyseal fractures of the humerus closed, isolated or not occurring within 15 days of the initial trauma. Exclusion criteria were patients with compound fractures. In two patients, proximal screw loosening occurred, however, the fractures consolidated in the same mean time as the rest of the series. Consolidation with up to 5 degrees of varus occurred in five cases and extension deficit was observed in the patient with olecranon fracture treated with tension band, which was not considered as a complication. There was no recurrence of infection or iatrogenic radial nerve injury. It can be concluded that minimally invasive osteosynthesis with bridge plate can be considered a safe and effective option for the treatment of transverse fractures of the humeral shaft. Level of Evidence III, Therapeutic Study.

Evidences Of Endocytosis Via Caveolae Following Blood-brain Barrier Breakdown By Phoneutria Nigriventer Spider Venom.

Spider venoms contain neurotoxic peptides aimed at paralyzing prey or for defense against predators; that is why they represent valuable tools for studies in neuroscience field. The present study aimed at identifying the process of internalization that occurs during the increased trafficking of vesicles caused by Phoneutria nigriventer spider venom (PNV)-induced blood-brain barrier (BBB) breakdown. Herein, we found that caveolin-1α is up-regulated in the cerebellar capillaries and Purkinje neurons of PNV-administered P14 (neonate) and 8- to 10-week-old (adult) rats. The white matter and granular layers were regions where caveolin-1α showed major upregulation. The variable age played a role in this effect. Caveolin-1 is the central protein that controls caveolae formation. Caveolar-specialized cholesterol- and sphingolipid-rich membrane sub-domains are involved in endocytosis, transcytosis, mechano-sensing, synapse formation and stabilization, signal transduction, intercellular communication, apoptosis, and various signaling events, including those related to calcium handling. PNV is extremely rich in neurotoxic peptides that affect glutamate handling and interferes with ion channels physiology. We suggest that the PNV-induced BBB opening is associated with a high expression of caveolae frame-forming caveolin-1α, and therefore in the process of internalization and enhanced transcytosis. Caveolin-1α up-regulation in Purkinje neurons could be related to a way of neurons to preserve, restore, and enhance function following PNV-induced excitotoxicity. The findings disclose interesting perspectives for further molecular studies of the interaction between PNV and caveolar specialized membrane domains. It proves PNV to be excellent tool for studies of transcytosis, the most common form of BBB-enhanced permeability.

Interplay Between Cell Growth And Cell Cycle In Plants.

The growth of organs and whole plants depends on both cell growth and cell-cycle progression, but the interaction between both processes is poorly understood. In plants, the balance between growth and cell-cycle progression requires coordinated regulation of four different processes: macromolecular synthesis (cytoplasmic growth), turgor-driven cell-wall extension, mitotic cycle, and endocycle. Potential feedbacks between these processes include a cell-size checkpoint operating before DNA synthesis and a link between DNA contents and maximum cell size. In addition, key intercellular signals and growth regulatory genes appear to target at the same time cell-cycle and cell-growth functions. For example, auxin, gibberellin, and brassinosteroid all have parallel links to cell-cycle progression (through S-phase Cyclin D-CDK and the anaphase-promoting complex) and cell-wall functions (through cell-wall extensibility or microtubule dynamics). Another intercellular signal mediated by microtubule dynamics is the mechanical stress caused by growth of interconnected cells. Superimposed on developmental controls, sugar signalling through the TOR pathway has recently emerged as a central control point linking cytoplasmic growth, cell-cycle and cell-wall functions. Recent progress in quantitative imaging and computational modelling will facilitate analysis of the multiple interconnections between plant cell growth and cell cycle and ultimately will be required for the predictive manipulation of plant growth.

Anatomical Study Of Minor Alterations In Neonate Vocal Folds.

Minor structural alterations of the vocal fold cover are frequent causes of voice abnormalities. They may be difficult to diagnose, and are expressed in different manners. Cases of intracordal cysts, sulcus vocalis, mucosal bridge, and laryngeal micro-diaphragm form the group of minor structural alterations of the vocal fold cover investigated in the present study. The etiopathogenesis and epidemiology of these alterations are poorly known. To evaluate the existence and anatomical characterization of minor structural alterations in the vocal folds of newborns. 56 larynxes excised from neonates of both genders were studied. They were examined fresh, or defrosted after conservation via freezing, under a microscope at magnifications of 25× and 40×. The vocal folds were inspected and palpated by two examiners, with the aim of finding minor structural alterations similar to those described classically, and other undetermined minor structural alterations. Larynges presenting abnormalities were submitted to histological examination. Six cases of abnormalities were found in different larynges: one (1.79%) compatible with a sulcus vocalis and five (8.93%) compatible with a laryngeal micro-diaphragm. No cases of cysts or mucosal bridges were found. The observed abnormalities had characteristics similar to those described in other age groups. Abnormalities similar to sulcus vocalis or micro-diaphragm may be present at birth.

Icam-1 Expression On Immune Cells In Chronic Villitis.

ICAM-1 expression on the villous syncytiotrophoblast (ST) is believed to participate in migration of maternal cells into the inflamed villi regardless of villitis etiology. However, its expression on immune cells in chronic villitis (CV) has yet to be analyzed. ICAM-1 induces cell-cell adhesion allowing intercellular communication, T cell-mediated defense mechanism, and inflammatory response. 21 cases of CV (all without an identifiable etiologic agent) and 3 control placentas were analyzed using ICAM-1, and for immune cells CD45, CD3 and CD68. These cells were subdivided according to their location in inflamed villi: a) within the inflamed villi and b) outside forming perivillous aggregates. Large amounts of CD45, CD3 and CD68 were found within the inflamed villi and forming perivillous aggregates attached to areas of trophoblastic loss. Inflamed villi usually showed ICAM-1+ ST. The majority of immune cells surrounding areas of trophoblastic rupture presented marked expression of ICAM-1. In contrast, a small number of immune cells within the inflamed villi exhibited ICAM-1 expression. Only some (<5%) inflamed villi without trophoblastic rupture and with ICAM-1+ ST presented adherence of immune cells. In inflamed villi of chronic villitis, the level of ICAM-1 expression on immune cells depends on their location: high in number of cells in the perivillous region and low within the villi. The strongest expression of ICAM-1 on immune cells attached to areas of trophoblastic rupture suggests that the loss of trophoblast can lead to an amplification of the inflammatory response.

Increased Circulating Pedf And Low Sicam-1 Are Associated With Sickle Cell Retinopathy.

Sickle cell retinopathy (SCR) develops in up to 30% of sickle cell disease patients (SCD) during the second decade of life. Treatment for this affection remains palliative, so studies on its pathophysiology may contribute to the future development of novel therapies. SCR is more frequently observed in hemoglobin SC disease and derives from vaso-occlusion in the microvasculature of the retina leading to neovascularization and, eventually, to blindness. Circulating inflammatory cytokines, angiogenic factors, and their interaction may contribute to the pathophysiology of this complication. Angiopoietin (Ang)-1, Ang-2, soluble vascular cell adhesion molecule-1, intercellular adhesion molecule (ICAM)-1, E-selectin, P-selectin, IL1-β, TNF-α, pigment epithelium derived factor (PEDF) and vascular endothelial growth factor plasmatic levels were determined in 37 SCD patients with retinopathy, 34 without retinopathy, and healthy controls. We observed that sICAM-1 is significantly decreased, whereas PEDF is elevated in HbSC patients with retinopathy (P=0.012 and P=0.031, respectively). Ang-1, Ang-2 and IL1-β levels were elevated in SCD patients (P=0.001, P<0.001 and P=0.001, respectively), compared to controls, and HbSS patients presented higher levels of Ang-2 compared to HbSC (P<0.001). Our study supports the possible influence of sICAM-1 and PEDF on the pathophysiology of retinal neovascularization in SCD patients.