Calcolo degli effetti di gravità quantistica sull'evoluzione degli spettri inflazionari

Lo scopo di questa tesi è di calcolare l'approssimazione al primo ordine in M_p^{-2} dell'equazione di evoluzione della funzione di correlazione a due punti in presenza di effetti quantistici gravitazionali. La forma di questa funzione di correlazione determina le proprietà degli spettri inflazionari. Gli effetti studiati sono la conseguenza della quantizzazione dei gradi di libertà gravitazionali che descrivono il background (fattore di scala) e sono valutati per lo stato di vuoto e per una serie di stati eccitati. L'equazione di evoluzione trovata per la funzione di correlazione verrà quindi risolta assumendo un'evoluzione tipo De Sitter. Inoltre le conseguenze dell'ordinamento nella procedura di quantizzazione che conduce all'equazione di Wheeler-DeWitt verranno studiate

[Beyond] posthuman violence : epic rewritings of ethics in the contemporary novel

My research will consist of a literary investigation into changing representations of violence in the contemporary novel in the context of the paradigm shift from humanism to posthumanism, from reality to fiction. The core of my work, developed through the reading of some research in neuroscience, will concern the examination of the brain as metaphor machine. From here, I will argue that the problem of violence in relation to fiction today is due to the struggle in the human body between transcendence and immanence. The individual has a tendency to transcend reality and in so doing lives violence as fiction even when inflicting pain to the other. I will observe how this transcendence is translated in contemporary narrative forms and I will shape a rhetoric of contemporary literary violence. My intention is to conduct comparative research across British, American, French and Italian literary fiction of the past 20 years, with a few exceptions. I will explore whether and how, in a globalizing world, it is both possible and necessary to develop a comparative literary analysis of the forms of contemporary violence. I will observe how the advent of posthumanity or of the fictional man has generated a crisis in the definition of identity and reality in a context in which fiction has taken its place. I will show how the individual re-acts to this condition through violence in order to find authenticity. References will include the works of Deleuze, Badiou, Bauman, Baudrillard, De Man, Agamben, Hayles et alii. In order to explore the different ramifications of the substitution of fiction to reality and its connection to violence, I will focus on what I consider the main three tools for the creation of simulation today: language, desire and information, through the works of Wallace, McCarthy, Miéville, Ballard, Gibson, Palahniuk et alii. Finally, the work will focus on the new emphasis given by contemporary writers to literary responsibility after the irresponsible writing (after the death of the author) of postmodernism through the analysis of the New Italian Epic postulated by Wu Ming but applied to the English Weird Fiction writer China Miéville. I will suggest that an attempt to overcome postmodernism is taking place in contemporary global fiction based on a more ‘serious’ approach (as Wallace would have said), a new ethics of literature, which endeavours to depict the reasons for contemporary violence in fiction and advocates for a balance between the transcendence of fiction and the immanence of reality

Functional exploration of colorectal cancer genomes using Drosophila

The multigenic nature of human tumours presents a fundamental challenge for cancer drug discovery. Here we use Drosophila to generate 32 multigenic models of colon cancer using patient data from The Cancer Genome Atlas. These models recapitulate key features of human cancer, often as emergent properties of multigenic combinations. Multigenic models such as ras p53 pten apc exhibit emergent resistance to a panel of cancer-relevant drugs. Exploring one drug in detail, we identify a mechanism of resistance for the PI3K pathway inhibitor BEZ235. We use this data to identify a combinatorial therapy that circumvents this resistance through a two-step process of emergent pathway dependence and sensitivity we term ‘induced dependence’. This approach is effective in cultured human tumour cells, xenografts and mouse models of colorectal cancer. These data demonstrate how multigenic animal models that reference cancer genomes can provide an effective approach for developing novel targeted therapies

Physiological, biochemical, and biophysical characterization of the lung-lavaged spontaneously-breathing rabbit as a model for respiratory distress syndrome

Nasal continuous positive airway pressure (nCPAP) is a widely accepted technique of non-invasive respiratory support in spontaneously-breathing premature infants with respiratory distress syndrome (RDS). Surfactant administration techniques compatible with nCPAP ventilation strategy are actively investigated. Our aim is to set up and validate a respiratory distress animal model that can be managed on nCPAP suitable for surfactant administration techniques studies. Surfactant depletion was induced by bronchoalveolar lavages (BALs) on 18 adult rabbits. Full depletion was assessed by surfactant component analysis on the BALs samples. Animals were randomized into two groups: Control group (nCPAP only) and InSurE group, consisting of a bolus of surfactant (Poractant alfa, 200 mg/kg) followed by nCPAP. Arterial blood gases were monitored until animal sacrifice, 3 hours post treatment. Lung mechanics were evaluated just before and after BALs, at the time of treatment, and at the end of the procedure. Surfactant phospholipids and protein analysis as well as surface tension measurements on sequential BALs confirmed the efficacy of the surfactant depletion procedure. The InSurE group showed a significant improvement of blood oxygenation and lung mechanics. On the contrary, no signs of recovery were appreciated in animals treated with just nCPAP. The surfactant-depleted adult rabbit RDS model proved to be a valuable and efficient preclinical tool for mimicking the clinical scenario of preterm infants affected by mild/moderate RDS who spontaneously breathe and do not require mechanical ventilation. This population is of particular interest as potential target for the non-invasive administration of surfactant

Athletic Performance and Recovery-Stress Factors in Cycling: An Ever Changing Balance

We sought to examine whether the relationship between recovery-stress factors and performance would differ at the beginning (Stage 1) and the end (Final Stage) of a multi-stage cycling competition. Sixty-seven cyclists with a mean age of 21.90 years (SD = 1.60) and extensive international experience participated in the study. The cyclists responded to the Recovery-Stress Questionnaire for Athletes (RESTQ-Sport) and rated their performance (1 = extremely poor to 10 = excellent) in respect to the first and last stage. Two step-down multiple regression models were used to estimate the relationship among recovery (nine factors; e.g., Physical Recovery, Sleep Quality) and stress factors (10 factors; e.g., Lack of Energy, Physical Complaints), as assessed by the RESTQ and in relation to performance. Model-1 pertained to Stage 1, whereas Model-2 used data from the Final Stage. The final Model-1 revealed that Physical Recovery (β = .46, p = .01), Injury (β = -.31, p = .01) and General Well-being (β = -.26, p = .04) predicted performance in Stage 1 (R2 = .21). The final Model-2 revealed a different relationship between recovery-stress factors and performance. Specifically, being a climber (β = .28, p = .01), Conflicts/Pressure (β = .33, p = .01), and Lack of Energy (β = -.37, p = .01) were associated with performance at the Final Stage (R2 = .19). Collectively, these results suggest that the relationship among recovery and stress factors changes greatly over a relatively short period of time, and dynamically influences performance in multi-stage competitions

MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer

MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment

Schmallenberg virus pathogenesis, tropism and interaction with the innate immune system of the host

Schmallenberg virus (SBV) is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals. Since its discovery in November 2011, SBV has spread very rapidly to many European countries. Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV. We showed that SBV has a wide tropism in cell culture and “synthetic” SBV replicates in vitro as efficiently as wild type virus. We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex. These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases. Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage. Finally, we investigated the molecular determinants of SBV virulence. Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice. We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs) is less virulent in mice than wild type SBV. Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells. In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV

Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer

A real-time KLT implementation for radio-SETI applications

SETI, the Search for ExtraTerrestrial Intelligence, is the search for radio signals emitted by alien civilizations living in the Galaxy. Narrow-band FFT-based approaches have been preferred in SETI, since their computation time only grows like N*lnN, where N is the number of time samples. On the contrary, a wide-band approach based on the Kahrunen-Lo`eve Transform (KLT) algorithm would be preferable, but it would scale like N*N. In this paper, we describe a hardware-software infrastructure based on FPGA boards and GPU-based PCs that circumvents this computation-time problem allowing for a real-time KLT