726 research outputs found

    Contribution of non-canonical DNA G-quadruplex structures to premature ageing

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    Previous studies have identified Cockayne Syndrome B (CSB) as a helicase that can resolve non-canonical DNA structures, called G-quadruplexes (G4s). The aim of this study is to investigate the properties of CSB as a G4-binder and -resolvase, and examine the correlation between the G4-helicase activity of CSB and premature ageing phenotype observed in CSB-deficient cells. Accordingly, the recombinant CSB full-length protein (FL) and its helicase- “like" domain (HD) were respectively expressed from insect and bacterial cells, and their resolvase and binding activities were tested over a large panel of DNA substrates. Native gel analysis and biophysical characterisations revealed that ribosomal DNA (rDNA) sequences, that typically act as CSB substrate, can form intermolecular G4s. We discovered that intermolecular G4s were strongly bound by CSB with picomolar affinity, whilst negligible binding to intramolecular G4s was observed. In vitro and cellular data demonstrated that G4-ligands can compete with CSB for binding to intermolecular rDNA G4, which results in CSB being displaced off the nucleoli of cells upon treatment with G4-ligands. Immunostaining with the selective G4-antibody BG4 revealed a lack of BG4-staining in the nucleoli of CSB-deficient cells after exogenous expression of recombinant CSB, further corroborating the hypothesis that CSB can bind intermolecular rDNA G4s in the nucleoli and compete with BG4 for the binding of such DNA-substrate. The work presented in this thesis allowed us to observe that (I) intermolecular G4s are likely to form from long-range distant rDNA sequences within the nucleoli of cells, and (II) CSB specifically binds and resolves these structures. Our results provide the first evidence of an endogenous protein that specifically interacts with intermolecular G4s, suggesting potential biological significance of these structures. The biological relevance of intermolecular rDNA G4s could be key in rare genetic disorders like Cockayne Syndrome, where senescence and premature ageing is observed when CSB is functionally mutated.Open Acces

    The Internationalization of Real Estate Research

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    The contributions of international researchers and institutions to real estate literature for the 1990 to 2006 period are assessed. Both the Asia-Pacific and European regions increase their influence on the top tier of real estate literature. The North American region, while still the dominant source of real estate research, sees its weighted share of publications in the top tier of academic real estate journals decline. Universities from Singapore, Hong Kong, Australia, the United Kingdom, Sweden, and the Netherlands are leaders in their respective regions. Individual researchers domiciled outside of North America are also gaining influence, but few individuals rank high when compared to North American authors. It is anticipated that these trends will continue given the global growth in real estate as an asset class, the importance of real estate investment in countries posting substantial economic growth, and the allocation of resources and human capital within these growing regions to real estate research.

    The Apulian Territory and the Typical Local Farmhouses: A Case of Study Through Landscape Analysis

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    The Apulian territory is strongly characterized by a rural architectural heritage with many historical features. Rural and agro-industrial buildings, their reuse or degradation, are the testimony of a history whose investigation is complex and varied over time. The Regional Territorial Landscape Plan, which entered into force in 2015, promotes the realization of a self-sustainable and lasting socio-economic development and education for an appropriate use of the regional territory. The knowledge, conservation, use and promotion of the Traditional Apulian Architectural Heritage are among its aims. This in fact constitutes the memory of a place, culturally identifies a local community and the territory. In-depth knowledge of the identifying characteristics of the rural heritage is essential before any recovery intervention specifically aimed at protecting and enhancing the buildings, the landscape and the environmental context. A recovery activity, mindful of these issues, can generate strategic resources for reaching wider objectives of regional development. This study aims to analyze the current relationship between ancient Apulian farmhouses that have been subject to functional restoration interventions and the landscape in which they are located, in order to outline strategies for the development and promotion of the related rural area

    The medieval pilgrims routes in the Apulian settlements and their relationship with Rome and Santiago de Compostela

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    The medieval pilgrims routes in the Apulian settlements and their relationship with Rome and Santiago de Compostela The Medieval cave settlements and cave churches in the Apulia region, in southern Itlay, created with their frescoes, along the pilgrims roads and the Ancient Appia route, a connection with the grave of Saint James in Santiago de Compostela. Indeed during the Middle Age the Church and the local nobles and feudatories used the Apulian medieval pilgrims’ routes for religious and marketing purposes linking Apulian Cave frescoes churches with Santiago de Compostela, therefore one of the aim of the research is to retrace the pilgrims routes basing on the images of the Saints painted in some frescoes and to create a veritable virtual link of the Apulian medieval cave churches with Saint James’ tomb in Santiago de Compostela thanks to the representation of the Saint bringing the pecten iacobeus (shell of St. James) and the Pilgrim’s bagshow. Aim of the research, applied to the proposed study area of the ravines and cave churches of Apulia, is to analyse, plan and restructure the ancient routes and livestock trail paths of the area by means of the files found in the archives in order to “redraw” the historical, social and environmental landscape and present it as paths with strong touristic interest with reference to the Apulian ravines area, the agricultural and forest landscapes and the traditional farmhouses

    FUERA DEL CANON

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    El artículo comienza con una definición del canon y con una consideración sobre cómo se establece. Luego, habla de algunos escritores canónicos de Centro América, como Sergio Ramírez o Gioconda Belli. Después, se refieren a escritores “fuera del canon”: la poesía feminista, la generación “x”, el grupo de Marco Antonio Flores, la literatura escrita por mujeres, la escrita por indígenas, la literatura póstuma. Al final, trata de establecer características generales, estilo, temas y motivos

    Faire avec – Genet Cixous Dustan - Pour une réévaluation négative de l'échec littéraire

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    My dissertation offers a reevaluation of the role of failure in a selection of contemporary French literary works. Dealing with the concept of faire avec (making do with) as a form of inconclusive literary bricolage, it draws link between the queer theorisation that David Caron offers of it and two other concepts that directly influence it: the concept of être-avec (being with) as defined by Jean-Luc Nancy in Être singulier pluriel, and the concept of faire sans (making do without) taken from Adorno’s reevaluation of the negative, in his Negative Dialectics. Drawing on the recent multidisciplinary body of theories around failure, it gives an (obviously non-exhaustive) overview of the variety of ways contemporary French literature creatively makes do with failure. To do so, it provides three independent case studies based on works from Genet, Cixous and Dustan. The first one, focusing on the last novel from Jean Genet, Un captif amoureux (Prisoner of Love), explores the impact on his work of his political attempt to faire avec the Palestinian movements, and to write about it, without doing them violence. The second is centred on three recent books by Hélène Cixous, all part of a project called le “Livre-Que-Je-N’écris-Pas” (the “Book-I-Do-Not-Write”); it deals with the evolution of Cixous ethical positioning towards those close to her, as they are now dying and yet still a central part of her literary work. The third case study focuses on the fourth novel by the HIV positive French writer Guillaume Dustan, Nicolas Pages; it analyses how the discovery of the tritherapies (a then new treatment that strongly reduced the impact of the virus on people living with HIV) forced the narrator, realising suddenly that he will not be dying soon, to make do with the life (vivre avec) he newly got back, and to find something to do with (faire avec) it

    MODELPEMELIHARAAN BERBASIS LIFE CYCLE COST UNTUK INFRASTRUKTUR BENDUNG KARET (Studi Kasus: Proyek Bendung Gerak Kanal Banjir Barat Semarang)

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    Teknologi infrastruktur di Indonesia terus berkembang oleh karena itu perlu dilakukannya penilaian atau evaluasi kelayakan terhadap inplementasi teknologi tersebut juga harus dilakukan. Penelitian terhadap bendung karet dengan teknologi gate panel ini merupakan salah satu bentuk evaluasi atas aspek biaya dari penerapan teknologi baru yang diimplementasikan. Penekanan pada rencana pembiayaannya menggunakan metode Life Cycle Costing dipilih untuk dapat memberikan gambaran kedepan bagaimana konsekuensi pembiayaan yang mungkin terjadi selama umur hidup bendung karet ini. Penelitian untuk mendapatkan model pemeliharaan bendung dengan metode Life Cycle Cost ini diterapkan dalam cycle periode 35 tahun. Diketahui terdapat tiga komponen utama dalam yang disusun dalam penelitian ini adalah perencanaan biaya Initial Cost, Maintanance Cost dan Operational Cost. Proporsi perencanaan pembiayaan dari Proyek Bendung Gerak Kanal Banjir Barat Semarang adalah senilai Rp. 292.155.995.351,25. Nilai tersebut terbagi dalam persentase menjadi biaya awal (Initial Cost) sebesar 67,06%; diikuti dengan maintenance cost sebesar 26,31% dan Operational Cost sebesar 6,62

    Enhancement of the Roman Bridge of Canosa in the Ofanto Valley Rural Landscape

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    The ancient Roman Bridge, 2,000 years old, is located on the old Via Traiana route, three kilometers far from the town of Canosa (Apulia Region), and for many centuries it was the connection between northern and southern part of the Apulia Region along the Adriatic coast. It has an imposing structure stonework, with a donkey back shape, built with five round arches supported by piers sustained by rostrums. During the Second World War, a concrete access way was realized in order to let the British and American army tank pass through the bridge. The “Municipal Plan of the Tratturi” qualifies the area as “sheep trails or path” that preserves the original consistency or that can be at the same renovated. Aim of the research is the requalification of the study area through analyses, plan and restructuring the ancient routes. In this study, the current status of the area is analyzed in detail and the inconsistency of the interventions is highlighted. The project proposal provides for new tourism paths equipped with cycle/pedestrian tracks and small resting and refreshment areas, intermodal exchange car parks and management structures, allowing the creation of a green tourist-cultural route

    Experimental Analysis of Noise and Vibration for Large Brushless Doubly Fed Machines

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    In this work, a large-scale Brushless Doubly Fed Machine (BDFM) built in frame size D400 is tested at different operating conditions in order to examine its noise and vibration levels. A series of measurements were conducted on the machine to establish the main modes of excitation of vibration and noise developed by the machine. The harmonic spectrums of the vibration amplitudes are presented at two different rotor speeds at which the vibration level is highest, in order to determine the vibration components frequencies existed in the vibration spectrum. A harmonic analysis of the BDFM is then proposed in order to assess the sources of vibration in the machine
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