1359 research outputs found
Sort by
Fattori prognostici nel melanoma cutaneo e nel tumore mammario associati a caratteristiche molecolari simil-staminali
Get PDFNestin (a neuronal stem cell/progenitor cell marker of central nervous system development), vimentin (which is ubiquitously expressed in mesenchymal cells), and the glucocorticoid receptor (GR, which is involved in the immune response, cell proliferation, and apoptosis) have been shown to interact in embryonic and undifferentiated tissues in modulating cell proliferation. In recent years, expression of nestin has shown to be associated with general proliferation of progenitor cell populations within neoplasms. The aim of this study was to analyse nestin, vimentin and GR expression in tumour tissue (melanoma), and their association with clinicopathological variables, to evaluate any effect on tumour progression. There is no reported study addressing nestin expression in T4 breast cancer patients. Thus, the aim of the present study was also to investigate, through immunohistochemistry, the expression and distribution of nestin in T4 breast cancer, in order to determine its association with clinical and pathological parameters as well as with patients’ outcome. Immunohistochemistry, double label immunofluorescence and confocal laser scanning microscopy were performed on biopsy specimens of cutaneous melanoma from 81 patients and in breast carcinomas from 53 patients. In melanoma, Fisher’s and Pearson’s tests showed a correlation between nestin, vimentin and subcellular GR location (P = 0.008). Their concomitant expression also correlated with Clark level and thickness (P = 0.02 and P = 0.029, respectively). Kaplan–Meier analysis revealed a poorer outcome for stage III and IV patients with associated expression of nestin, vimentin and cytoplasmic GR in tumour tissue (P = 0.02). Nestin was detectable in tumoral cells and in endothelial cells of blood microvessels, and it is significantly expressed in triple-negative and in inflammatory breast cancer (IBC) subgroups of T4 breast tumours. The Kaplan-Meier analysis showed that the presence of nestin in tumoral cells significantly predicted poor prognosis at 5 years survival (P=0.02) and with borderline significance at 10-years of survival (P=0.05) in T4 breast cancer patients. These results suggest the presence in melanoma of growth mechanisms involving nestin, vimentin, and GR, similarly to that occurring in embryonic and undifferentiated cells, and may help in understanding tumour biology to provide a molecular basis for clinical therapies. In breast cancer the presence of nestin in tumoral cells and vessels suggest that this protein may be considered an important factor that leads to a poor prognosis. On the basis of these observations, we speculate that the stem cell marker nestin may characterize tumours with an aggressive clinical behavior
Ruolo dell’acetaldeide nelle proprietà motivazionali dell’etanolo: studio di Self-administration orale nel ratto
Get PDFOur line of research was focused on the study of the motivational and rewarding properties of ethanol. Particularly, our research activity examined the role of acetaldehyde, in mediating the reinforcing properties of ethanol. We show that acetaldehyde is orally self-administered by Wistar rats and possesses its own motivational and reinforcing effects. Interestingly, we have observed that acetaldehyde reinforcing effects are reduced by L-Cysteine, a not essential amino acid, which was
previously shown to reduce ethanol self-administration. Furthermore, acetaldehyde selfadministration was reduced by the pre-treatment with the nonselective opioid receptor antagonist, naltrexone, and with the μ1-selective opioid receptor antagonist, naloxonazine. This suggests an
involvement of the endogenous opioid system in the central actions of acetaldehyde as an ethanol metabolite. In order to further our understanding on the role of centrally formed acetaldehyde in the mechanism of action of alcoholic beverages, we studied the role of catalase, the main enzymatic system that oxidizes ethanol to acetaldehyde in the central nervous system. In this phase we studied
the effect of alpha-lipoic acid, an antioxidant agent which is able to reduce H2O2 concentrations in the brain, on ethanol oral self-administration. These experiments show that alpha-lipoic acid intraperitoneal administration reduced all self-administration phases in a dose-dependent manner. These studies underscore the role of acetaldehyde in the motivational properties of ethanol and suggest that acetaldehyde may be a pharmacological “target” for devising new therapeutic strategies in alcoholism
Synthesis of different series of small molecules targeting HIV-1 RT, Candida albicans, MAO and G-Quadruplex
Get PDFMy PhD work has been focused towards four different targets: HIV-1 RT, Candida albicans, Monoamine oxidase, and G-Quadruplex. Thus in order to give the reader a clearer exposition this report has been divided in four different chapters. Each of the chapters has his own figures, schemes, tables and references. The main part of my work has been dedicated to HIV-1 RT, thus this chapter is the major and first one
Dissimilarity-based people re-identification and search for intelligent video surveillance
Get PDFIntelligent video-surveillance is at present one of the most active research fields in computer science. It brings together a wide variety of computer vision and machine learning techniques to provide useful tools for surveillance operators and forensic video analytics. Person
re-identification is among these tools; it consists of recognising whether an individual has already been observed over a network of cameras. Person re-identification has various possible applications, e.g., off-line retrieval of all the video-sequences showing an individual of interest whose image is given as query, or on-line pedestrian tracking overmultiple cameras. The task is typically achieved by exploiting the clothing appearance, as classical biometric traits like the face are impractical in real-world video surveillance scenarios. Clothing appearance
is represented by means of low-level local and global features of the images, usually extracted according to some part-based body model to treat different body parts (e.g.
torso and legs) independently. The use of novel sensor technologies, e.g. RGB-D cameras like the MS Kinect, could also allow for the extraction of anthropometric measures from a reconstructed 3D model of the body, that can be used in combination with the clothing appearance to increase recognition accuracy. This thesis presents a novel framework, namedMultipleComponentDissimilarity (MCD),
to construct descriptors of images of persons, using dissimilarity representations, a recent paradigm in machine learning in which the objects of interest are described as vectors of dissimilarities to a set of predefined prototypes. MCD extends the original dissimilarity
paradigm to objects decomposable in multiple parts and with localised characteristics, to better deal with the peculiarities of the human body. The use of MCD has at least three important advantages:
(i) a drastic reduction of computational needs, mostly due to the compactness of dissimilarity
representations (basically, small vectors of real numbers, easy to store and very fast to be matched);
(ii) a totally generic formulation of the underlying low-level representation, that allows
one to combine different descriptors, even if they are heterogeneous in terms of the
model and features used, into a single dissimilarity vector;
(iii) it provides a natural way to learn high-level concepts from low-level representations. Building on its above salient features, MCD is used in this thesis to achieve several objectives:
(i) develop an approach to speed up existing person re-identification methods;
iii
(ii) implement a novel person re-identification method based on the combination of different
local and global features into a single dissimilarity vector, able to attain state-ofthe-
art performance;
(iv) develop a multi-modal approach to person re-identification (a novelty in the literature),
by combining the clothing appearance with anthropometric measures extracted
through the use of novel RGB-D sensors, into a single dissimilarity vector;
(v) develop a method to perform a novel task, proposed for the first time in this thesis,
consisting in finding, among a set of images of individuals, those relevant to a textual, semantic query describing clothing appearance of an individual of interest. This task has been named appearance-based people search and can be useful in applications like
forensics video analysis, where a textual description of the individual of interest given by a witness can be available, instead of an image. Person re-identification and appearance-based people search are different tasks, aimed at addressing different problems. Still, they can be seen as instances of the more general problem of searching and matching people on multi-media data, e.g., video footages, rangedepth data, speech audio data. Building on the commonalities with Information Retrieval, in the final part of the thesis, a possible formulation of the task of people search on multimedia data will be proposed, with some suggestions and guidelines on how to exploit the
MCD framework for addressing this novel class of problems
La visione delle città delle Fiandre negli scrittori fiamminghi di lingua francese (1881-1922)
Get PDFThis research aims to investigate the vision of the cities of Flanders, given by writers who belong to the same region but, for cultural reasons, wrote in a different language such as French. This language was the used language of the culture in the period that we analyzed, which is the great revival of Belgian literature of the 1880s up to the beginning of the First World War. This temporal distinction is due to the partial, but steady decline in the use of the French language by Flemish writers, and above all to a radical change of the thematic references by those writers who lived in a brutally occupied territory.
It is necessary to present more precisely the corpus of the writers chosen for the proposed investigation. We analyzed different works by Georges Eekhoud, Max Elskamp, Camille Lemonnier, Maurice Maeterlinck, Georges Rodenbach and Émile Verhaeren. Cities involved in our analysis are the main cities of Flanders: Bruges, Antwerp, Ghent, Brussels, Leuven and Furnes. Our attention is focused on the cities of Bruges and Antwerp above all, because of their main presence in the Belgian literature in authors like Georges Rodenbach and Georges Eekhoud. They dedicated their entire works to these cities instead of offering precedence to cities like Ghent, Brussels, Leuven and Furnes which are regarded as young sisters cities to Bruges and Antwerp.
We aim to analyze how these cities were seen by the writers chosen, which kind of relationship they have to each other and what role these cities play in the poetics of each author
Models and algorithms for the empty container repositioning and its integration with routing problems
Get PDFThe introduction of containers has fostered intermodal freight transportation. A definition of intermodality was provided by the European Commission as “a characteristic
of a transport system whereby at least two different modes are used in an integrated manner in order to complete a door-to-door transport sequence”. The intermodal container transportation leads to several benefits, such as higher
productivity during handling phases and advantages in terms of security, losses and damages. However, the distribution of containers comes with a drawback: due to directional imbalances in freight flows, some areas tend to accumulate unnecessary empty containers, while others face container shortages. Several planning models were developed for carriers in order to manage both loaded and empty containers profitably. However, they were built to operate under normal circumstances, neglecting the fact that networks are increasingly affected by both uncertainty and vulnerability, which may result in disruptions. The thesis aims to survey whether the impact of uncertainty can be mitigated by a stochastic programming approach, in which disruptions and normal operations are both foreseen as possible futures or scenarios. This approach is carried out by a multi-scenario optimization model in which scenarios are linked by non-anticipativity conditions. The empty container repositioning becomes even more challenging and difficult when integrated with routing problems. In fact, carriers often face problems in which they must determine simultaneously how many empty containers are carried by a
fleet of vehicles and which routes must be followed by these vehicles. These problems typically arise in inland networks, in which one must plan the distribution by trucks
of loaded and empty containers to customers.
The thesis addresses this type of vehicle routing problems, which are motivated by a real case study occurred during the collaboration with a carrier that operates in the Mediterranean Sea in door-to-door modality. The carrier manages a fleet of trucks based at the port. Trucks and containers are used to service two types of transportation requests, the delivery of container loads from the port to import customers, and the shipment of container loads from export customers to the port. The thesis addresses two problems which differ in the composition of the fleet
of trucks. The first problem involves a heterogeneous fleet of trucks that can carry one or two containers. We present a Vehicle Routing Problem with backhauls, load
splits into multiple visits, and the impossibility to separate trucks and containers during customer service. Then, we formalize the problem by an Integer Linear
Programming formulation and propose an efficient meta-heuristic algorithm able to solve it. The meta-heuristic determines the initial solution by a variant of the Clarkeand-Wright algorithm, and improves it by several local search phases, in which both node movements and truck swaps are implemented. The second problem involves a homogeneous fleet of trucks that can carry more than a container. As a consequence, the identification of routes can be more difficult. We present and formalize the associated Vehicle Routing Problem by an Integer Linear Programming formulation. Then we propose an efficient adaptive guidance meta-heuristic algorithm able to solve
it. The meta-heuristic determines an initial feasible solution by a Tabu Search step, and next improves this solution by appropriate adaptive guidance mechanisms
Seed germination requirements and salt stress tolerance of coastal rare species in Sardinia
Get PDFTo survive to adverse factors that characterize coastal environments, plant species often require special physiological or metabolic adaptations to overcome environmental stresses. Stress may be physical (e.g.
temperature) or chemical (e.g. salinity). Many communities comprise highly specialized species, which have comparatively restricted geographical distributions. The coastal species investigated in this Ph.D. program were chosen accordingly to their habitat: Phleum sardoum (Hackel) Hackel and Rouya polygama (Desf.) Coincy for sandy dunes; Brassica insularis Moris and Lavatera triloba L. ssp. pallescens (Moris) Nyman for coastal cliffs; Lavatera triloba L. ssp. triloba and Halopeplis amplexicaulis (Vahl) Ces., Pass. & Gibelli for ultra-saline environments. Moreover, seed germination ecology of L. agrigentina Tineo, a species growing in clayey-chalky plains of South Italy, was also investigated for a comparative study within the Lavatera genus. For all the studied species, light and temperature requirements for seed germination were
evaluated; their germination responses to salt stress (NaCl) and their germination recovery. Interpopulation
variability on germination patterns was also evaluated for R. polygama, B. insularis and L. triloba ssp. triloba. Salt spray tolerance on the vegetative growth and biomass production during the early seedling developmental stages was evaluated for B. insularis, L. triloba ssp. pallescens, L. triloba ssp. triloba and H. amplexicaulis. Light did not affect germination percentages in any of the studied species enabling seed germination also under soil surface and highlighting that seeds were not photo-inhibited for germination. Seed germination of P. sardoum and R. polygama, as well as that of L. agrigentina, L. triloba ssp. pallescens and L. triloba ssp. triloba, reflected the optimal range of temperatures of “typical” Mediterranean species, suggesting germination in autumn-winter, when water availability, soil moisture and rainfalls are high, and temperatures are not excessively prohibitive for germination and consequent seedlings establishment. B.
insularis differed from other “typical” Mediterranean plants, for which germination at low temperatures is
a widely extended trait, demonstrating that germination of this species may occur in a wide time window during the year. H. amplexicaulis seed germination was highly promoted by the daily fluctuation of temperatures, while germination at constant temperatures was sensibly lower. Salinity tests showed higher germination percentages in the non-saline conditions, with seed mortality increasing proportionally with NaCl concentrations and temperatures. Salt tolerance limits varied among species, from a minimum of 100 mM NaCl for P. sardoum to 600 mM for H. amplexicaulis and L.
triloba ssp. pallescens, without a clear habitat related pattern. The species for which salt spray experiments were conducted showed different responses on seedling growth to salt aerosol tolerance, with these differences being related to the habitat of each species and their distance from the sea. Populations of B. insularis and L. triloba ssp. pallescens, growing in coastal cliffs highly influenced by wind and salt spray, showed the lowest seedling mortality. High interpopulation variability in salt spray tolerance was detected for B. insularis, between a coastal and an inland population, with the latter resulting not adapted to this abiotic environmental factor. Seedling survival of the two inland species (L. triloba ssp. triloba and H. amplexicaulis) was inversely proportional to the increase of nebulization frequency, demonstrating a low adaptation to salt spray, likely due to their distance from the sea coast and/or to interposed vegetation that may determine a lower impact of marine
aerosol. The results of this study lead to a better knowledge on the autoecology of the investigated species and to their limits of tolerance to abiotic factors such as temperature, soil salinity and salt spray
Spectral Comparisons of Neutron Star Low-Mass X-Ray Binaries with Black Hole X-Ray Binaries
Get PDFThe study of high-resolution X-ray spectra of neutron star low-mass X-ray binaries (LMXBs) allows the investigation of the innermost parts of the accretion disk and immediate surroundings of the compact object. The weak magnetic eld of old neutron stars present in such systems allows the
accretion disk to approach very close to the compact object, like in black hole X-ray binaries. Using data from X-ray satellites such as XMM-Newton, RXTE, and BeppoSAX, I studied the reection component in two neutron star LMXBs:
MXB 1728-34 and 4U 1735-44. I showed that the iron line at 6:
Innovatives liposomes for overcoming biological barriers
Get PDFIn this thesis work were prepared and characterized liposomes and liposomes modified with a coating of chitosan called chitosomes. Through these structures were conveyed drugs of natural origin with anti-inflammatory and antioxidant properties: quercetin,phycocyanin and curcumin. The liposomes loading quercetin and phycocyanin are designed for a topical application and were tested on new born pig skin. Liposomes and chitosomes loading curcumin are designed for pulmonary delivery as a cure for cystic fibrosis. In this case, has been tested the toxicity of the system using a model of lung tissue using Calu-3 cells.
The drug delivery via liposomes and chitosomes improves the retention time of the drug and increases its stability. Studies continue with biocompatibility and in vivo tests
Analisi integrata dell'espressione di geni/microrna in un modello di epatocancerogenesi sperimentale
Get PDFHepatocellular carcinoma (HCC) is the fifth most common cancer in the world, accounting for an estimated half million deaths annually, and represents one of the major health problems.
Although much is known about the cellular changes that lead to HCC, the molecular pathogenesis of HCC is not yet well understood.
Gene expression studies conducted with microarray techniques and real-time PCR, suggest that tumors are characterized by an aberrant activation of signal transduction pathways involved in proliferation, survival, cell differentiation and angiogenesis. However, for HCC, these studies don’t allow the identification of a "signature" or a single specific pathway that is predominantly involved in the development and prognosis of the malignancy.
Recently it has become clear that the classification and stratification of cancer can be performed not only through the analysis of gene expression, but also by analyzing the expression of microRNAs, small non-coding RNA molecules that negatively control gene expression and protein synthesis.
In the present study we performed an integrated analysis of genome-wide mRNA and microRNA (miR) expression profiles to characterize the molecular events involved in the step-by-step progression (preneoplastic nodules-adenoma-early HCC-advanced HCC) of hepatocellular carcinoma (HCC) in the rat Resistant-Hepatocyte (R-H) model.
Interestingly, while analysis of the transcriptome clustered together preneoplastic lesions and advanced HCC, suggesting that the majority of the genes dysregulated in HCC are already aberrantly expressed in early lesions, miRNome analysis did not co-cluster the two populations but, very interestingly, stratified the lesions according to their stage of progression to HCC. The results also unveiled specific genes/miRs, altered in the very early steps of the carcinogenic process, in the transition from adenoma to early HCC or in the progression to advanced HCC. By assessing the correlation between the expression of each miRNA and its targets, we determined that distinct pathways are aberrantly activated in different stages of the carcinogenic process. This integrated approach was also able to identify molecular events discriminating the preneoplastic lesions that will progress to HCC from those that spontaneously regress. Finally, 110 orthologous genes were almost super imposable between rat and human HCC signatures, supporting the value of the R-H model in recapitulating human liver cancer.
Conclusions: This systematic analysis deciphered the molecular phenotypes of the several steps involved in the onset and progression of HCC and investigated their variations at mRNA and miR levels. In view of the striking similarity between mRNA and miRs commonly dysregulated in rat and human HCC, our results provide a valuable source for future studies and highlight promising genes, miRNAs, pathways and processes which may be useful for diagnostic or therapeutic applications