1,721,004 research outputs found
Development of a novel Polymer-based delivery system for siRNAs to hepatocellular carcinoma cells
No full textFor Hepatocellular carcinoma (HCC) there are no effective treatments thus, the individuation of novel therapeutic approaches and molecular targets are urgent. Small interference RNA (siRNAs) are small double stranded RNAs able to induce gene silencing thus, representing an attractive therapeutic strategy. The main impediment in using siRNAs is the fast degradation rate in the biological environment. To protect siRNAs from degradation, we developed a novel delivery system based on the polymer α,β-poly-(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) derivatized with diethylene triamine (DETA) linked via a polyethylene glycol (PEG) to galactose (GAL) molecules (PDPG). The GAL residue has been introduced to target to the asialoglycoprotein receptor (ASGPR), overexpressed in HCC cells.
Using a fluorescently labelled PDPG (PDPG-BodipyTRX) carrying a model siRNA, we demonstrated that the PDPG polymer can specifically deliver the siRNA to HuH7 cells, a cellular model of HCC. Notably, the elimination of the Gal residue from the PDPG (PDP) or the chemical block of ASGPR, resulted in an evident reduction of PDPG targeting effectiveness. These data have been confirmed in HuH7 constitutively expressing the enhanced green fluorescence protein (EGFP) using a functional siRNA against EGFP. Finally, PDPG delivery specificity and effectiveness was proved also in vivo in a mouse dorsal skinfold window chamber assay. Together, our data support the remarkable targeting ability of the developed PDPG.
When PDPG was loaded by siRNAs targeting HCC proliferative factors (eEF1A1, eEF1A2 and E2F1), we observed a clear decrease of HuH7 cell vitality and cell number. These phenomena were paralleled by the reduction of targeted mRNAs and relative proteins levels. Interestingly, siRNAs-PDP, lacking the Gal residue was poorly effective in reducing HuH7 vitality and number. Finally, in vivo experiments performed in a subcutaneous xenograft mouse model of HCC, revealed the ability of siRNAs-PDGP to reduce HCC tumor growth compared to controls. Notably, PDPG did not show significant polymer-related toxic effects as evaluated by monitoring animal weight and the levels of markers of organs function.
In conclusion, our study demonstrates the priceless potentials of PDPG as a novel delivery system for siRNA paving the way for innovative anti-HCC treatments
Exploring Approaches to Define Cultural Ecosystem Services in Planning Support System
No full textCultural ecosystem services (CES) play a crucial role in enhancing human well-being by providing intangible benefits such as spiritual enrichment, aesthetic enjoyment, and cultural identity. However, defining and categorizing CES presents a significant challenge due to their subjective nature and multifaceted dimensions. This paper critically examines various approaches adopted in defining and conceptualizing CES within the realm of ecosystem services research. Through a review of existing literature, we explore the diversity of perspectives and methodologies used to identify, assess, and classify cultural services provided by ecosystems. Various approaches exist for spatial identification of CES, ranging from territorial indicator-based methods to philosophical theories. However, literature analysis reveals the difficulty in universally defining evaluation methods applicable to all cases. While macrolevel guidelines aid in recognizing potential CES, contextual analysis of structural elements is necessary. Integrating a system for assessing immaterial values can track both material and non-material benefits of CES within the territory. This suggests a context-based approach for both identification and evaluation of CES, essential for effective planning processes. By synthesizing diverse conceptualizations and methodological approaches, this paper aims to contribute to a deeper comprehension of the complexities inherent in defining and valuing cultural ecosystem services, ultimately fostering more effective conservation and sustainable management strategies
“Ecomuseo dell’Acqua”: An Indivisible Unit of Strategic Sustainable Planning
No full textThe paper introduces an experimental approach aimed at delineating strategies for urban regeneration with a focus on nature-based leisure, recreational, and outdoor activities within the framework of downscaling the New Urban Agenda 2030. The objective of this research project is to develop and implement practical tools for applying the principles outlined in the New Urban Agenda (NUA) within diverse territorial components. These components encompass not only anthropic elements, such as urban infrastructure and built environments, but also natural elements, including ecological systems and landscapes. This approach is pivotal in guiding the programming and execution of the sustainable project proposals, which is deeply rooted in addressing the specific needs of the locality and its residents. A core emphasis of the project lies in ensuring equitable access for all individuals, considering factors such as proximity to populated areas, availability of parking, clearly identifiable access points, and accessible restroom facilities during the selection of project areas. Furthermore, the design of these routes aims to offer diverse options in terms of length and accessibility. Ultimately, the project seeks to generate public value and potential benefits for the local community. This comprehensive approach strives to harmonize efforts towards heritage conservation, enhancement, and effective management, all while ensuring the appropriate allocation and investment of public resources
Regole per l'abitare sostenibile
No full textIl presente contributo intende proporre una riflessione a sostegno di una rinnovata centralità per il ruolo che lo strumento del Regolamento Edilizio (RE) può assumere nell’agevolare interventi orientati al conseguimento di obiettivi di qualità diffusa per il patrimonio edilizio non solo rispetto al singolo edificio, ma nell’ambiente urbano nel suo complesso. Si ritiene, infatti, che tale strumento collocandosi, nella geografia del quadro pianificatorio, come elemento nodale tra le previsioni del piano e la pratica degli interventi e quale espressione dell’autonomia normativa delle amministrazioni locali, goda di una vocazione intrinsecamente strategica non solo per il presidio dei fattori di sintassi dell’edificato, ma anche per esplicare le molteplici dimensioni del contesto di riferimento – quella ambientale, quella geomorfologica, quella storico-culturale, quella climatica, quella sociale etc. – nelle quali si articolano i requisiti della qualità. Il Regolamento Edilizio, a partire dalla fine degli anni novanta, in occasione delle riforme messe in atto dalle leggi regionali di seconda generazione e dalle emergenti istanze per il contenimento degli impatti ambientali delle trasformazioni, è stato oggetto di una generale revisione variamente orientata ad uniformarne il linguaggio, a dare rilievo a principi di sostenibilità, a favorire regole prestazionali etc. Non solo. Alcuni dei provvedimenti analizzati avanzano una riformulazione del nome proprio dello strumento: da ‘regolamento edilizio’ a ‘prontuario’, ‘regolamento sostenibile’ etc. Un cambiamento lessicale che si intende cogliere per tentare, seppure in maniera essenziale, di dare una risposta in merito all’adeguatezza dei ‘nuovi’ strumenti, delle loro capacità di accogliere le molteplici dimensioni dei contesti e le istanze della qualità, in una visione di sostenibilità per l’abitare contemporaneo
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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