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Espressione del fibrinogeno nel carcinoma endometriale: analisi immunoistochimica e molecolare.
No full textmissin
Coordination between intrinsic and extrinsic mechanism in thoracic lymphatics.
No full textThe lymphatic system runs in parallel with the blood vasculature, it plays a key role in maintaining tissue fluid homeostasis, as a tissue-drainage system, and it contributes to the immunosurveillance by providing a route for migrating cells. The lymphatic system is a highly branched network of thin-walled blind-ended vessels, which drain fluid, macromolecules and cells from the extracellular spaces within most organs, carrying them into larger thicker-walled collectors running deeper in the body. Fluid and solutes extravasated from vascular capillaries into the interstitial space enter blind-ended initial lymphatics, which are anchored to the interstitial matrix via anchoring filaments and possess overlapping endothelial cell-cell junctions behaving like valve structures, only permitting unidirectional lymph entry into the lymphatic vessel lumen. Valves in collecting lymphatics consist of two modified adjacent endothelial cell leaflets which meet in the vessel lumen forming a funnel inside the vessel and separating adjacent lymphangions, the functional units of the lymphatic system. Lymph is formed along a hydraulic pressure gradient developing between the interstitial tissue and the lumen of initial lymphatics. This pressure gradient depends upon both extrinsic and intrinsic pump systems. Tissue movements provide the extrinsic factor affecting lymphatic function, causing cycles of external compression/expansion of the lymphatic vessels lumen.. Lymphangions, segments of lymphatic vessel delimited by unidirectional valves and surrounded by smooth muscle cells, represent the functional units of the intrinsic pump mechanism. Their rhythmic active contraction is essential to guarantee the correct lymph flow either as the only source of pressure gradient formation or along with the extrinsic pump, where the mechanical features of the surrounding tissue are able to generate such an external pump action. During active contraction, lymphatic smooth muscle cells create an increase in intraluminal pressure and generate a local positive pressure gradient which drives lymph propulsion. The subsequent relaxation of the smooth muscle layer generates a decrease in intraluminal pressure which drives lymph from the interstitial space into the vessel itself.
The aim of the present thesis was to study the interaction between the intrinsic and extrinsic mechanisms in a highly moving tissue such as the diaphragm. By in vivo fluorescence staining of diaphragmatic lymphatics we were able to identify vessels organized in loop structures and located both in the tendineous and in the peripheral muscle region. Lymphatic loops were classified into four groups (active, hybrid, passive and invariant) according to their functional behavior, forming functionally distinct regions. By whole mount immunostaining against smooth muscle actin we identified a dense smooth muscle mesh surrounding actively pumping sites, whereas in not contracting tracts smooth muscle fibers were more sparsely organized, showing a lot of large gaps around the vessel wall. Actively pumping lymphatic sites did not differ in diameter from all other classes of vessels. We found that their amplitude of contraction was independent on vessel size but strongly correlated to contraction frequency. By temporal analysis we were also able to identify trigger sites which controlled the diameter change of both other active and passive sites belonging to the same network.
We then made an extensive study on the temporal correlation of activity among active, hybrid and passive sites belonging to the same network, and were able to identify trigger regions and follower regions whose behavior was dependent upon their respective trigger sites
Lastly, we started an ongoing project in order to understand the extrinsic pump effect due to respiratory and cardiogenic movements on diaphragmatic lymphatic function. By locally injecting KCl into the interstitium next to invariant longitudinal and/or transverse lymphatics we tested diameter and/or length changes and then intraluminal pressure gradients due to extrinsic forces. Further analysis are required in order to define the actual contribution of intrinsic and extrinsic mechanisms in diaphragmatic lymphatics
Qualità di vita e alessitimia nel trattamento con antidepressivi.
No full textPremesse e obiettivi : Gli studi sull' impatto del trattamento con antidepressivi sulla qualità della vita hanno segnalato la necessità di non trascurare questo parametro nella valutazione a medio e lungo-termine dei disturbi ansioso-depressivi. La soddisfazione e il benessere sono esperienze soggettive che risultano fondamentali per comprendere l’atteggiamento del paziente verso la terapia. Scopo del progetto di ricerca è quello di valutare l’impatto del trattamento con antidepressivi sulla qualità della vita dei pazienti e di indagare l’eventuale influenza su tale parametro della presenza di alessitimia.
Metodi : Il presente progetto si configura come uno studio naturalistico osservazionale prospettico. I pazienti inclusi nello studio sono stati sottoposti ad una valutazione iniziale (T0), prima dell’introduzione del farmaco antidepressivo, e successivamente a 8 settimane (T1) e a 6 mesi (T2). In ciascuna valutazione sono state somministrate le seguenti scale: Hamilton Depression Rating Scale (HDRS); Toronto Alexythimia Scale 20 items (TAS-20); WHO Quality of Life versione breve di 26 items (WHOQOL-BREF).
Risultati : I pazienti che hanno accettato di partecipare allo studio sono 50, di cui 32 donne e 18 uomini con un’età media di 45.28 ± 12.16 anni. I pazienti che hanno effettuato la seconda valutazione sono 35 (70.0%) e quelli che ad oggi hanno completato lo studio sono 19 (38.0%).
Il punteggio medio della HDRS decresce (19±5,45 a T0 e 11.00 ± 8.69 a T2) evidenziando come l’introduzione della terapia farmacologica consenta di ottenere un miglioramento clinico. Invece il punteggio medio della scala TAS-20 rimane sostanzialmente stabile nel tempo (55,12±14,70 a T0 e 53.68 ± 13.52 a T2). Per quanto concerne la WHOQOL-BREF è possibile valutare un miglioramento di circa il 10% (cioè da 48,40% a 57.25%) da T0 a T2, in particolare nelle aree inerenti le componenti Fisica (da 48,56% a T0 a 61.44% a T2) e Psicologica (da 41,58% a T0 a 52.48 a T2).
Si è rilevata una correlazione negativa fra le scale HDRS e WHOQOL, che indica un miglioramento della QoL al ridursi della severità dei sintomi depressivi. Sia in acuto, che dopo parziale remissione della sintomatologia depressiva, i soggetti alessitimici tendono a percepire una peggiore QoL.
In base ai dati emersi dalla regressione logistica si può desumere che la presenza di HDRS <16 (p=0,040), l’assenza di tratti alessitimici (p=0,05) e l’assenza di patologie croniche (p=0,05) sono variabili in grado di influenzare positivamente la percezione della QoL.
Conclusioni: Il presente studio evidenzia come un corretto trattamento antidepressivo sia incisivo sulla QoL che rappresenta pertanto un paramentro indispensabile per una adeguata valutazione dell’esito a lungo termine dei disturbi dell’umore. La presenza di alessitimia sembra influenzare negativamente la QoL e potrebbe pertanto essere utile considerare anche tale variabile al fine di individuare strategie più mirate nel trattamento
Properties of the insect neutral amino acis cotransporter KAAT1 studied by alanine scanning mutagenesis and temperature.
No full textThe possibility of heterologous expression in Xenopus laevis oocytes has greatly expanded the knowledge of the properties of several cotransporters, membrane proteins that, combining features of pumps and channels, couple the movement of ions and substrates. Transport across the membrane guarantees the reuptake of neurotransmitters from the synaptic cleft, the absorption of nutrients, the regulation of osmolarity and ionic homeostasis. Some of these proteins are involved in neurological diseases and in drug abuse. All the Na+/Cl--dependent cotransporters share high homology and possess the structural topology of the procariotic prototype transporter, LeuT. The present research work was focused on the insect neutral amino acid contransporter KAAT1 (K+-coupled Amino Acid Transporter 1), cloned from the midgut of the larva of Manduca sexta (Castagna et al., 1998;Feldman et al., 2000) and homologous with amino acid transporters belonging to the solute carrier 6 (SLC6) gene family.
The functional role of an highly conserved sequence, consisting of three consecutive glycines (Gly85-Gly86-Gly87), has been investigated by alanine scanning mutagenesis; this sequence is located in the first extracellular loop of the protein, close to Arginine 76, the residue that participates to the external gate of the protein.
The functional characteristics, i.e. transport activity, apparent affinity, interaction with different cations, were derived from electrophysiological measurements (TEVC, Two Electrode Voltage Clamp), and uptake experiments. Additional informations about the correct targeting to the plasma membrane of the glycine mutants have been obtained performing optical measurement of the surface expression by the single oocyte chemiluminescence (SOC) technique pioneered by Zerangue (Zerangue et al., 1999) and used by others (Haerteis et al., 2009;Bossi et al., 2011).
Changes in the transport mechanisms observed for many of the analyzed mutants, indicated a relevant role of the glycine triplet in the transport function, that it was confirmed by the alterations of the uncoupled currents and the apparent affinity.
The second part of my PhD work, covered the analysis of the relationship between temperature and substrate affinity in the ion-coupled cotransporter KAAT1 (from a poikilotherm invertebrate) in comparison with rGAT1, the GABA neuronal transporter originating from a mammalian (homeotherm) animal. Observations based on the rate of transport, and the effects on the presteady-state currents, i.e. the electrical signal arising from the initial steps of the transport cycle (Parent et al., 1992;Parent et al., 1992;Mager et al., 1998;Bossi et al., 1999a) were studied in order to evaluate the kinetic properties of the cotransport system at more physiological temperatures. A strong increase of transmembrane currents was measured in both transporters at higher temperature (30°C); the increased maximal transport-associated current (Imax) was counterbalanced by a lower apparent substrate affinity (K05). The inverse relationship between affinity and current supports previous observations in the intestinal tranporter PepT1(Bossi et al., 2012)
Content based image indexing and retrieval using a textual approach in visual online shopping.
No full textIn this study a new Content-Based Image and Indexing Retrieval engine based on the textual representation of the extracted features is proposed. We discuss about the advantages in the use of the proposed method both from the point of view of the quality of the results than the efficiency and the ease in the integration of the visual features in a real context. Furthermore, one of the main aspects of the proposed method consists in the use of an object detection phase which is essential to extract the visual information only from
the Object of Interest within the image.
The main contributions of this work consist in the development of a new color feature based on the Human Visual Perception able to extract a limited set of representative colors from the whole RGB space, and the development of a new feature able to extract the Visual Attributes in the domain of fashion based on the Human Pose estimation. Moreover a prototype based on the results of this study has been proposed, which is designed as an engine for the online shopping, focusing on the fashion domain which is the most promising field to test the extraction of visual information.
As an additional contribution of this study, given the increasing amount of mobile devices and the consequently interest in the mobile shopping, an extension of the proposed prototype has been developed as a mobile application able to perform a simple query by similarity
Mappaggio ad alta densità dell'attività focale delle vene polmonari: analisi dell'innesco della fibrillazione atriale parossisitica nell'uomo.
No full textScopo: Analizzare le caratteristiche dell’attività focale originante dalle vene polmonari (VP) innescante la fibrillazione atriale (FA) nell’uomo, mediante mappaggio tridimensionale (3D) ad alta densità.
Metodi e risultati: L’attività focale della VP è stata registrata mediante catetere basket (64 elettrodi) ed il segnale endocavitario analizzato con sistema di mappaggio computerizzato (QMS2). Sono stati analizzati 40 pazienti e registrata attività focale in 23 VP. L’attività focale innescante la FA è stata registrata in 17 VP. La sequenza di acquisizioni nello stesso paziente e nella stessa VP mostra un pattern di attivazione riproducibile. Il pattern di attivazione più frequente risulta essere multifocale, prossimale alla giunzione atrio-venosa e breaktrough non correlata. La localizzazione dell’attività focale è prevalente in sede anteriore e inferiore della vena.
L’attività focale innescante la FA è caratterizzata da attività fibrillato ria nelle zone di più precoce attivazione seguita da potenziali discreti nelle zone più tardive. L’attività focale delle VP non innescante la FA presenta zone di minor precocità di attivazione con minore sincronizzazione dei foci aritmici.
Conclusioni: il mappaggio tridimensionale con catetere basket risulta essere un ottimo strumento di mappaggio endocavitario utile per la comprensione di aspetti anatomici e funzionali dell’attività focale delle VP innescanti la fibrillazione atriale nell’uomo
MYSCE, a new Monte Carlo code for star cluster simulations. Axion-like particles and very-high energy astrophysics
No full textThis thesis focuses on two different topics: (i) star clusters, as favourite environments for the formation of black holes of very high mass, and (ii) the implications of axionlike particles for very-high energy astrophysics by considering -ray observations from blazars.
In the first part of this thesis we develop a new Monte Carlo code MYSCE (Montecarlo Young Star Cluster Evolution) which improves and solves some problems of the original scheme presented by Hénon. We use our code to simulate star clusters and to inquire if an episode of gas infall during the cluster lifetime can lead to the formation of an intermediate mass black hole and/or a super massive black hole seed.
In the second part of this thesis we explore axion-like particles in an astrophysical context. We describe their origin and properties within extensions of the Standard Model of elementary particle physics. We show how axion-like particles can in principle solve the cosmic opacity problem for distant blazars and naturally explain the emission of very-high energy photons from at spectrum radio quasar
Optical Spectroscopy with Very Large Telescope: Instrumental Development and Data Interpretation. The case of the Rocky-Planets Finder ESPRESSO and Spectral Characterization of BL Lac Objects.
No full textThis PhD thesis is focused on one of the main research area in modern Astrophysics: the spectroscopy. Within the current framework of observational astronomy, I carried out the Thesis aiming at the figure of Instrument Scientist who acts as a junction between astronomer and design engineers joining the science and technology in order to contribute to a more consolidated and optimised design of new instrumentations for large experiments.
For this reason, in this Thesis I will present two main parts of my PhD activities that have characterised my entire doctoral training. In particular, I will first introduce ESPRESSO, the Echelle SPectrograph for Rocky Exoplanet and Stable Spectroscopic Observations, which will be a new generation extra stable spectrograph at the European Southern Observatory (ESO) Very Large Telescope (VLT). ESPRESSO will be a spectrograph mainly optimised for finding rocky planet orbiting main sequence G stars in the habitable zone through the Radial Velocity (RV) method. I will outline my contribution to ESPRESSO in Chapter 2 where I illustrate simulations on the expected performances of the detectors used by a main part of the instrument: the Front End Unit. This subsystem is responsible to stabilise the field and pupil of ESPRESSO through active optics and to collect the light from the four telescope and inject it through fiber feeding the spectrograph. I also outline the design of the Exposure Meter of the instrument which is in charge to continuously monitoring the exposure in order to evaluate a critical value, called Mean Time of Exposure (MTE), which is used in order to correct the measured Radial Velocity for the relative Earth motion at the time of observation. For the rst time, the exposure will be monitored chromatically allowing a better characterisation of the behaviour of the MTE and of the overall observation simultaneously.
In Chapter 3 I focus on pure astrophysical research based on spectroscopy of a particular class of Active Galatic Nuclei: the BL Lacertae Objects. These objects are characterised by a strong non-thermal emission which arises from the accreting nucleus. For this reason, spectral features (when present) are extremely diluted making the determination of their redshifts a challenging task. With the adoption of FORS2 spectrograph, in low resolution, at 10mt class VLT I completed a survey of these objects started few years ago and I derived from the complete sample a conspicuous number of properties of the class, including the characterisation of their line-of-sight Mg II absorber systems. Moreover, I will outline the results obtained from observation of a small subsample of strong FERMI gamma-rays (and in certain cases VHE emitters) source with ESO X-SHOOTER which combines medium resolution (R 4000) and large spectral range. In particular, for the source PKS 0048-097 the determination of its redshift for the first time allowed to deeply investigate its Spectral Energy Distribution and the close environment of the object. The spectra of the other sources in the sample are also illustrated and explicated for particular interesting objects