102,450 research outputs found
Investigating the Piaggio Avanti design using CEASIOM
No full textIn early steps of aircraft design the unification of configuration definition is important to avoid user–input errors. Also coupling with each other can strengthen different tools with different specifications simultaneously provided that the geometry definition is transferred with minimum data loss. This is vitally useful especially when geometry data is transferred in order to perform high–fidelity analysis. This paper reports the analysis for the pitch control of a three–lifting–surface aircraft Piaggio Avanti using CEASIOM, a tool–chain software for aircraft preliminary design, with the baseline configuration coming from the conceptual design code AAA, linked by a common name–space CPACS for the means of data collaboratio
Targeting Hedgehog pathway in medulloblastoma: identification of SALL4A as a new activator and isoflavone c22 as multitarget inhibitor
No full textHedgehog (Hh) pathway is essential for embryonal development and tissues homeostasis; its alteration causes several human cancers, including medulloblastoma (MB), the most common brain malignancy in childhood. Because of its crucial role in tumorigenesis, the regulation of the Hh pathway and the identification of new Hh modulators emerged as a field of great interest in tumor biology.
My Ph. D. project was focused on two main goals:
Aim 1 | Identification of new molecular mechanisms involved in Hh signalling pathway regulation and MB tumorigenesis. To address this aim, we focused on the identification of new interactors of the known Hh negative regulator and tumor suppressor RENKCTD11. Through mass spectrometry analysis, we identified the transcription factor SALL4A. SALL4A plays a key role in maintaining pluripotency and self-renewal of embryonic stem cells, regulating different signalling pathway. SALL4A expression is inhibited in the post-natal period in many adult tissues, but it is reactivated in different tumors and is often related to worse prognosis and lower survival rate. Our data demonstrate that SALL4A is a substrate of RENKCTD11, that induces its poly-ubiquitylation and its consequent proteasome-mediated degradation. In order to investigate its biological role in Hh signalling, we demonstrated that SALL4A enhances GLI1 activity working in complex with HDAC1, a well known Hh activator. Of note, we observed that the proliferation ability of human MB cell lines increases in presence of SALL4A, whereas their migration rate is reduced after its genetic depletion; in vivo, SALL4A genetic depletion leads to a reduction of Hh-dependent tumor growth. Our findings identify SALL4A as a previously unknown regulator of Hh pathway able to promote, in complex with HDAC1, GLI1 activity and to contribute to Hh-dependent tumorigenesis. Hence, SALL4A stands as a new molecular target involved in the onset and progression of Hh-dependent tumors and represents an interesting focus in cancer research.
Aim 2 | Pharmacological targeting of Hedgehog pathway. Given the primary role of Hh signalling in tumorigenesis and in the maintenance of cancer stem cell niches, this pathway is now considered an attractive therapeutic target in cancer. In recent years, many efforts have focused on the development of drugs that can block the activating effect of SMO receptor. However, several studies underlined some limitations of the inhibitors identified so far, linked in particular to the poor selectivity, the onset of drug resistance events and the activation of GLI1 mediated by other oncogenic pathways. These evidences raise the need to identify new and more effective Hh inhibitors able to overcome drug resistance and to counteract tumor growth. To this end, my research activity was aimed at identifying, characterizing and optimizing new molecules able to block the oncogenic potential of Hh. In particular, by combining the most profitable pharmacophores for targeting SMO and GLI1 by synthetic isoflavones, we designed and synthesized the isoflavone 22, a small molecule that acts as a multitarget Hh inhibitor blocking both SMO and GLI1 activity at the same time. Compound 22 is able to inhibit Hh-dependent tumor growth in human and murine MB cells at sub-micromolar concentration, as a consequence of the reduction in GLI1 expression levels. Isoflavone 22 remarkably shows a strong anti-tumor effect also in vivo by suppressing cell proliferation and promoting apoptosis. Molecular modeling further corroborated the multitarget mechanism of action of compound 22, showing that the drug is able to fit the ligand binding site in both SMO and GLI1. Overall, these results reveal a valuable form of targeted therapy to increase the efficacy and to decrease the toxicity of individual anticancer agents; our findings discover the first multitarget Hh inhibitor that impinges Hh-dependent tumor growth and stands as new potential weapons against Hh-driven tumors
Gli aerei Piaggio, prendere al volo un secolo di storia.
No full textStoria della Piaggio aeronautica di Finale Ligure e della sua eredità culturale e architettonic
The post-genomic era: workshop on chromatin immunoprecipitation-related techniques
No full text[No abstract available
Swelling Rocks Investigation on Hydro Tunnels – A Comprehensive Characterization based on Laboratory Tests and Constitutive Models
No full textSwelling of rocks is a common phenomenon in the Andean Region, due to the presence of volcano-sedimentary units containing clays, typically from the smectite group as part of the rock matrix. Hence, a comprehensive rock mass characterization has to be made in order to evaluate the risk of underground works located in this kind of geological environment. For hydro tunnels in South America, a set of swelling pressure tests of different type (on intact rock discs, ground rock powder, cyclic loading and triaxial tests) were executed for swelling potential evaluation. The results show that obtained values are highly dependent on test procedures, suggesting that swelling pressure test has to be considered as an index, instead of a definitive value of pressure (especially when using ground rock powder). A result comparison and discussion is included in this paper and recommendations for engineering design are provided based on numerical modelling
A study of the conformational analysis and intermolecular hydrogen-bonding in solid malonaldeyde by infrared specra
No full textLa storia della Piaggio attraverso l'analisi dei bilanci (1920-1950)
No full textIl presente contributo tratta dell'evoluzione storica delle vicende aziendali della Piaggio, VE S.p.A., dal 1920 al 1950. In particolare, la storia dell'azienda in oggetto viene ricostruita attraverso l'analisi dei suoi bilanci
Optical, electrical and ESR characterization of poly(p-phenylenesulfide) during electrochemical doping
No full textElectrochemical doping of poly(p-phenylenesulfide) (pPPS) in concentrated sulfuric acid offers a promising way for studying electrical properties of this material because an accurate control of the doping level is possible. We have performed an extensive investigation of the electrochemical behaviour of pPPS in 96% H2SO4 and, hence, measured in situ optical spectra, conductivity and ESR data of samples at different values of the injected charge; in this paper the results are presented and discussed in relation to data of pPPS and oligomers chemically doped
Optical, electrical and ESR characterization of poly(p-phenylenesulfide) (pPPS) in concentrated sulfuric acid offers a during electrochemical doping
No full textElectrochemical doping of poly(p-phenylenesulfide) (pPPS) in concentrated sulfuring acid offers a promising way for studying electrical properties of this material because an accurate control of the doping level is possible. We have performed an extensive investigation of the electrochemical behaviour of pPPS in 96% H2SO4 and, hence, measured in situ optical spectra, conductivity and ESR data of samples at different values of the injected charge; in this paper the results are presented and discussed in relation to data of pPPS and oligomers chemically doped. © 1993
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