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Metabolic reprogramming of oestrogen receptor positive breast cancer in endocrine therapy resistance
Get PDFThe majority of breast tumours express oestrogen receptor (ER) and are dependent on oestrogen (E2) for their growth and survival. Endocrine therapy is the standard of care for this breast cancer subset and acts by targeting ER pathway in different ways: selective ER modulators compete with E2 to bind ER (e.g. tamoxifen), selective ER downregulators promote ER degradation (e.g. fulvestrant) and aromatase inhibitors (AI) block E2 biosynthesis. Despite the efficacy of these endocrine agents, a large proportion of women relapse with endocrine-resistant disease. In this study, we investigated the link between altered breast cancer metabolism and endocrine therapy resistance. We found that AI-resistance cells can adapt to metabolic stress and switch ad hoc between OXPHOS and glycolysis. In particular, we identified the miR-155/hexokinase-2 (HK2) axis as an important regulator of this tumour plasticity. In addition to central carbon metabolism, we found a deregulated node between miR-23b-3p and the amino acid transporter SLC6A14 in endocrine therapy resistant cells, which leads to an impairment of amino acids metabolism in the resistant cells with subsequent activation of autophagy. Furthermore, the miRNA characterised have prognostic (miR-155 and miR-23b-3p) and predictive (miR155) value in ER positive breast cancer. These results suggest that high metabolic plasticity is involved in acquiring adaptive features that allow breast cancer cell survival even in the presence of endocrine therapy
I Poteri del giudice amministrativo in caso di annullamento dell'aggiudicazione e sorte del contratto
No full textThis thesis draws on the subject of the powers of the Administrative Judge when canceling the contract award and the outcome of the contract. The theme, falling within the scope of public contracts, is characterized by a discipline resulting from a constant mismatch between sources of national law and sources of Community law. The last major innovation in this matter was with Legislative Decree no. 53/2010 which has adopted the new "appeal directive" and that in the field of public procurement litigation has made a real revolution, extending considerably the powers of the administrative court, under exclusive jurisdiction. Powers that have placed various questions both substan- tially and procedurally. The present thesis analyzes the legal and jurisprudential evolution of this subject, as well as the various issues related to the nature of the court's ineffectiveness of the contract, whether declarative or constitutive, the possibility of a pronoun of the court, the substantial consequences of such pronouncement, or what kind of disability the contractor has
Contributo alla ricostruzione dei caratteri del "patrimonio culturale comune"
No full textThe international law lacks of a unique term to usefully describe all the aspects of the cultural heritage (tangible, intangible, underwater) and their relevance for the humanity as a whole.
To this end, the present study affirms the utility of the principle of the “common heritage of mankind”. It has been developed in the law of the sea to describe the areas outside the State's jurisdiction, where every State has the right to exploit the resources in a peaceful and rational way and to share the benefits; it could be applied also to the cultural heritage, although with some difference, especially the fact that cultural property stays under the sovereignty of the States.
Although the power to select the cultural properties that deserve an international protection is usually a prerogative of the State in whose territory they are located, the existence of the “common cultural heritage” is concretely testified from the possibility for some international institution to independently select, under certain circumstances, the properties to inscribe on the UNESCO’s lists for the interest of all the humanity. Another element which supports the principle of “common cultural heritage” is that, in the case of destruction of cultural properties (inscribed or not on the UNESCO’s lists), the international acts and the international organizations talk about “destruction of common heritage of mankind”
Biomedical applications of different nanomaterials: characterization and interaction with the immune system
Get PDFIn the field of nanotechnology, research is nowadays deeply focusing on the translational application of nanomaterials in medicine. Nanotechnology is expanding its legacy by implementing approaches aimed to delivering therapeutics and developing new diagnostic and imaging tools. However, before any effective application, a critical step to be done is represented by the assessment of their impact on the immune system, independently of their specific purpose. Following these aspects, this thesis focus on the immunological impact of some of the main promising nanomaterials for biomedical applications: Carbon based materials such as carbon nanotubes (CNTs) and graphene, lipid nanocapsules (NCs) and super paramagnetic iron oxide nanoparticles (SPIONs), in order to study their potential to be applied in therapy and diagnostic applications taking advantage from their intrinsic properties. The different studies presented explicitly demonstrate that the interactions between nanomaterials and the immune cells depend on many factors correlated to their physicochemical characteristics. A positive impact of nanomaterials on the immune system, able to trigger both immune suppression and immune activation, represent a new concept helpful in the development of new nanoscale platforms in medicine such as immunotherapy tools, vaccine carriers, adjuvants, and drug delivery systems
Boundaries: a study in the metaphysics of space
Get PDFThe dissertation is devoted to a study of the nature of spatial boundaries. Boundaries are what divide things from their surrounding, e.g. the surface of a table from the rest of the room.
Part one of my dissertation is about the nature of boundaries. In chapter 1 I present some formal theories I assume: mereology, mereotopology, and theories of location. In chapter 2 I set forth the main features of boundaries and I argue that things depend upon their boundaries, contrary to the mainstream view. In chapter 3 I face the problem of contact, i.e. the problem of how two discrete things can touch each other. I argue that things can never keep in touch, whatever the structure of space is.
In part two I defend the thesis according to which every boundary is of the fiat sort, i.e. it is mind independent. In chapter 4 I argue against bona fide boundaries, i.e. boundaries mind dependent. In chapter 5 I set forth a taxonomy of the various kinds of fiat boundaries in order to developing in details a general model of explanation of the fictional nature of boundaries and therefore of things.
In part three I show how fiat boundaries can be adopted by urban planners for their different purposes
Preventable proportion of intubation-associated pneumonia: role of adherence to a care bundle
No full textObjective: The aim of the present study was to estimate the preventable proportion of Intubation-Associated Pneumonia (IAP) in the Intensive Care Units (ICUs) participating in the Italian Nosocomial Infections Surveillance in ICUs (SPIN-UTI) network, taking into account differences in intrinsic patients’ risk factors, and additionally considering the compliance with the European bundle for IAP prevention.
Methods: A prospective patient-based survey was conducted and all patients staying in ICU for more than 2 days were enrolled in the surveillance. Compliance with the bundle was assessed using a questionnaire for each intubated patient. A twofold analysis by the parametric g-formula was used to compute the number of infections to be expected if the infection incidence in all ICUs could be reduced to that one of the top-tenth-percentile-ranked ICUs and to that one of the ICU with the highest compliance to all five bundle components.
Results: A total of 1,840 patients and of 17 ICUs were included in the first analysis showing a preventable proportion of 44% of IAP. In a second analysis on a subset of data, considering compliance with the European bundle, a preventable proportion of 40% of IAP was shown. A significant negative trend of IAP incidences was observed with increasing number of bundle components performed (p<0.001) and a strong negative correlation between these two factors was shown (r = -0.882; p = 0.048).
Conclusions: The g-formula controlled for time-varying factors is a valuable approach for estimating the preventable proportion of IAP and the impact of interventions, based entirely on an observed population in a real-world setting. However, both the study design that cannot definitively prove a causative relationship between bundle compliance and IAP risk, and the small number of patients included in the care bundle compliance analysis, may represent limits of the study and further and larger studies should be conducted
Phyto-toponyms of <i>Arbutus unedo</i> L. and their distribution in Sardinia (Italy)
No full textMediterranean species, widespread throughout Sardinia. The main aim was to compare the past distribution of place names, referring to the strawberry tree, to the current distribution of the species on the island. In addition, we investigated the meaning and the diversity of these local place names in the various communities. The result was a collection of 432 phyto-toponyms. 248 of them were used for an analysis of their distribution in the habitats, indicated on the Map of the Nature System in Sardinia, defined on the basis of the current vegetation typology. The persistence of the species in the various habitats was either confirmed or negated with in site investigations and interviews. 47.5% of municipalities have place names related to the strawberry tree. Of the 248 phyto-toponyms, 127 fall in the habitats where the species currently persists proving a correspondence between their regional distribution and the current distribution of the species. The remaining 121 phyto-toponyms fall in habitats where the strawberry tree is currently absent. Most of them are found in man-made habitats where man has transformed the forest cover which previously included the strawberry tree. This study also contributes to promoting and conserving the linguistic heritage of local communities
Epstein-Barr virus infection is associated to patients with multiple myeloma and monoclonal gammopathy of undetermined significance
No full textLetter to the editor
Aspetti della percezione della shelf-based scarcity nell'ambito del grocery
Get PDFThis study focuses on certain aspects of perception of the relative numerosity of item sets placed in contiguous displays. Previous studies have demonstrated that, ceteris paribus, perception of the relative numerosity of item sets in a display decreases as the amount of additional information (in polygonal form) placed in the panel behind the display increases. This result is attributed to a non-spatial type of clustering phenomenon exerted by the additional information. Unfortunately, however, the available literature does not address the perceptual mechanisms underlying the aforementioned effect. Our research is based on a laboratory study involving 200 participants. Using eye-tracking technology, we evidenced that upon augmenting the amount of additional information available in the decision-making context: a) there was an underestimation effect with regard to perceived item set numerosity; b) there was a significant decrease in number of total fixations per area of interest. In light of the available literature, we interpret these findings as evidence that strategically placed additional information generates “complex objects” (termed super-items), which tend to perceptually substitute entire item sets. Super-items appear to serve as “mediators” which facilitate cognitive processes elicited by approximate numeration tasks concerning item sets being compared. The results of our study presents some managerial implications in terms of merchandising and category management
Identificazione di fattori di virulenza nel fungo fitopatogeno <i>Fusarium culmorum</i>
Get PDFFusarium culmorum is a major fungal pathogen of wheat, causing foot and root rot (FRR) and fusarium head blight (FHB). Symptons include pre- and post-emergence death of the seedlings. It causes significant yield and quality losses. This study shows the importance to select mutants of F. culmorum altered in their metabolic or morphological processes and impaired in level of virulence and aggressiveness during the first step of interaction between this fungus with the host plant. The function of many genes that are implicated in FRR on durum wheat seedilings is as yet unknown. Therefore, the characterization and identification of pathogenicity-related genes is essential in the build-up of alternative control methods against this disease. The mutants of F. culmorum were obtained by random and targeted insertional mutagenesis methods using the transposon mimp1. The transposon insertion into a gene region allows to tag the gene of interest. In vitro bioassays to identify altered phenotypic characters of revertants growing in different metabolic conditions (osmotic stress, oxidative stress) were carried out. In vitro and in planta assays of pathogenicity were also performed by placing durum wheat seeds on mycelium discs in a Petri dish or covered by steril soil. The results showed the presence of F. culmorum revertants with altered phenotypic characters, including stunted vegetative growth and loss of pathogenicity towards wheat stem base/root tissue