The research investigates the use of innovative technologies for the documentation, analysis, cataloguing of tangible and intangible heritage within the historical urban landscape. The main objective ...is the implementation of knowledge for safeguarding the Heritage in a perspective of sustainable development based on the understanding and increasingly wide use of the cultural values of a territory. Within this frame, the contribution presents the case study of Ascoli Piceno, characterized by a rich and widespread architectural-cultural heritage, testimony of history and experiences and unique resource of memory. The heritage of Ascoli Piceno has been enhanced through an information management tool in GIS environment, proposing a new digital model to be applied to build thematic layers of knowledge/enhancement of historical-artistic stratifications. The different information levels are organized in a georeferenced database, then structured in itineraries, easily accessible according to the interests of the users. This approach allows to analyze and manage a lot of information, putting in synergy technologies, data and urban space.
Revelar el paisaje Luigi Coccia; Sara Cipolletti
A&P continuidad,
07/2024, Volume:
11, Issue:
20
Journal Article
Peer reviewed
Open access
Dentro de la debatida temática de las áreas interiores de Italia, los pueblos son asumidos como hitos en la construcción histórica del territorio; a ellos se les reconoce un valor patrimonial en ...cuanto son expresión de una relación entre asentamientos humanos y especificidades contextuales. En estos lugares la despoblación y el abandono son fenómenos recurrentes, acentuados por recientes eventos sísmicos que han dañado gravemente el patrimonio edilicio. La lectura y la interpretación de tales fenómenos requieren un cambio de mirada que lleve a atribuir a los pueblos nuevos valores con el fin de transformarlos en espacios de oportunidad y de potencial proyecto para el futuro, prefigurando economías alternativas como la turística. Una visión arquitectónica, basada en análisis y proyecto de obras edilicias y de las relaciones urbanas, puede estar integrada por una visión paisajística que revalorice los pueblos en la dimensión extensa del territorio antiguo y contemporáneo. El pueblo de Arquata del Tronto, considerado uno de los más bellos entre aquellos ubicados a lo largo de la cadena apenínica en el centro de Italia, ha sido arrasado por el terremoto del 2016-17. Aquello que permanece es su sedimento, la huella de una obra arquitectónica perfectamente adaptada a la geografía, terraplén desde el cual observar el paisaje. Al espolón de arenisca, figura geográfica, se asocia la idea de plataforma, figura arquitectónica, posible tema de una experimentación proyectual paisajística.
The article presents a design experiment conducted within the research PNRR VITALITY based on the issues of sustainability and the quality of living spaces. Considering the innovation opportunities ...expressed by the energy transition, also achieved through nature-based regenerative solutions, aimed at reducing consumption and CO2 emissions, the methodology leads to the conceptualisation of the multiscalar spatial device Green Room: a volumetric decrement action associated with vegetative infiltration applied to significant parts of buildings and open spaces in three sample areas of the Adriatic-Mediterranean region. Starting from morphological, typological, and climatic data and managing computational simulation processes, the experiment aims to update design tools at the architectural and urban scale, establishing a relationship between indoor and outdoor spaces to achieve benefits for the environment and people’s well-being. Article info Received: 18/03/2024; Revised: 20/04/2024; Accepted: 27/04/2024
The aim of this article is to offer a theoretical contribution to the organisation, design and significance of tourism spaces, at a time when tourist practices are experiencing both change and ...intensification. From an architectural perspective, the study seeks to understand the evolutionary link between holiday practices and spaces, interpreting tourism as a context of creative relations between people, aspects, things and the places in which practices take place.Based on this interpretation, the paper defines architectural and urban categories of tourism, briefly comparing various literature on tourist organisations. In the second part, through the examination of recent examples of tourist experiences, planning actions and their ability to generate new tourism landscapes are evaluated. For both places and tourist experiences, that which emerges and the fields of application involved constitute guidelines and development tools for a form of tourism design that is more knowledgeable about the encounter between tourists and residents, and more reliable given that it is founded on the distinctive features of territories. The study demonstrates that tourism spaces, if intended as contexts of creative relations between people, aspects, things and places in which practices take place, may now develop a certain potential that once again calls into question a series of much debated opposites, tourists - residents, free time - work time, holiday space - day-to-day space, attractive resources and their transformation into elements of tourism, which had otherwise previously been consolidated by the tourist phenomenon. In the end, tourism proves itself to be an imaginative impulse, which is capable of reinventing the qualities of places and successfully orientating urban events.
Casamondo Marco D’Annuntiis; Sara Cipolletti
Esili e esodi | Exiles and Exoduses,
05/2021
Book Chapter
L’intera penisola in cui viviamo e le sue grandi e piccole città sono inequivocabilmente segnate, nel tempo e nello spazio, dall’attraversamento di popoli e dall’intreccio di culture. Una condizione ...di per sé sufficiente a sgombrare il campo da ogni pregiudizio circa la disponibilità all’accoglienza delle nostre comunità e che permette di assumere, al di là di ogni retorica, la migrazione tra le categorie che maggiormente concorrono a definire la città contemporanea. Consente cioè, per quanto ci riguarda, di affrontare la questione delle migrazioni non solo come problema emergenziale1, ma quale enzima potente e ineludibile delle attuali trasformazioni urbane. Permette, inoltre,
Casamondo Marco D’Annuntiis; Sara Cipolletti
Esili e esodi | Exiles and Exoduses,
05/2021
Book Chapter
L’intera penisola in cui viviamo e le sue grandi e piccole città sono inequivocabilmente segnate, nel tempo e nello spazio, dall’attraversamento di popoli e dall’intreccio di culture. Una condizione ...di per sé sufficiente a sgombrare il campo da ogni pregiudizio circa la disponibilità all’accoglienza delle nostre comunità e che permette di assumere, al di là di ogni retorica, la migrazione tra le categorie che maggiormente concorrono a definire la città contemporanea. Consente cioè, per quanto ci riguarda, di affrontare la questione delle migrazioni non solo come problema emergenziale1, ma quale enzima potente e ineludibile delle attuali trasformazioni urbane. Permette, inoltre,
Breast cancer (BC) is a leading cause of global cancer-related mortality in women, necessitating accurate tumor classification for timely intervention. Molecular and histological factors, including ...PAM50 classification, estrogen receptor α (ERα), breast cancer type 1 susceptibility protein (BRCA1), progesterone receptor (PR), and HER2 expression, contribute to intricate BC subtyping. In this work, through a combination of bioinformatic and wet lab screenings, followed by classical signal transduction and cell proliferation methods, and employing multiple BC cell lines, we identified enhanced sensitivity of ERα-positive BC cell lines to ALK and MELK inhibitors, inducing ERα degradation and diminishing proliferation in specific BC subtypes. MELK inhibition attenuated ERα transcriptional activity, impeding E2-induced gene expression, and hampering proliferation in MCF-7 cells. Synergies between MELK inhibition with 4OH-tamoxifen (Tam) and ALK inhibition with HER2 inhibitors revealed potential therapeutic avenues for ERα-positive/PR-positive/HER2-negative and ERα-positive/PR-negative/HER2-positive tumors, respectively. Our findings propose MELK as a promising target for ERα-positive/PR-positive/HER2-negative BC and highlight ALK as a potential focus for ERα-positive/PR-negative/HER2-positive BC. The synergistic anti-proliferative effects of MELK with Tam and ALK with HER2 inhibitors underscore kinase inhibitors' potential for selective treatment in diverse BC subtypes, paving the way for personalized and effective therapeutic strategies in BC management.
Previously, we found that telaprevir (Tel), the inhibitor of hepatitis C virus NS3/4A serine protease, reduces estrogen receptor α (ERα) content at the transcriptional level without binding to the ...receptor, prevents ERα transcriptional activity, and inhibits basal and 17β‐estradiol (E2)‐dependent cell proliferation in different breast cancer (BC) cell lines. Here, we further characterize the Tel action mechanisms on ERα levels and function, identify a possible molecular target of Tel in BC cells, and evaluate Tel as an antiproliferative agent for BC treatment. Tel‐dependent reduction in ERα levels and function depends on a Tel‐dependent decrease in FOXA1 levels and activity. The effect of Tel is transduced by the IGF1‐R/AKT/FOXA1 pathway, with the antiviral compound interacting with IGF1‐R. Tel prevents the proliferation of several BC cell lines, while it does not affect the proliferation of normal nontransformed cell lines, and its antiproliferative effect is correlated with the ratio of FOXA1/IGF1‐R expression. In conclusion, Tel interferes with the IGF1‐R/AKT/FOXA1 pathway and induces cell death in ERα‐expressing BC cells. Thus, we propose that this antiviral could be repurposed for the treatment of ERα‐expressing BC.
Telaprevir prevents the growth of breast cancer cell lines by interfering with the IGF‐1R pathway leading to FOXA1 down‐regulation, ERα inhibition, and induction of apoptotic cell death.
Challenges exist in the clinical treatment of luminal estrogen receptor α (ERα)-positive breast cancers (BCs) both to prevent resistance to endocrine therapy (ET) and to treat ET-resistant metastatic ...BCs (MBC). Therefore, we evaluated if kinases could be new targets for the treatment of luminal primary and MBCs.
~ 170 kinase inhibitors were applied to MCF-7 cells either with adaptative or genetic resistance to ET drugs and both ERα levels and cell proliferation were measured. Robust-Z-score calculation identified AZD7762 (CHK1/CHK2 inhibitor) as a positive hit. Subsequently, Kaplan-Meier analyses of CHK1 and CHK2 impact on ERα-positive BC patients relapse-free-survival (RFS), bioinformatic evaluations of CHK1 and CHK2 expression and activation status as a function of ERα activation status as well as drug sensitivity studies in ERα-positive BC cell lines, validation of the impact of the ATR:CHK1 and ATM:CHK2 pathways on the control of ERα stability and BC cell proliferation via inhibitor- and siRNA-based approaches, identification of the molecular mechanism required for inhibitor-dependent ERα degradation in BC and the impact of CHK1 and CHK2 inhibition on the 17β-estradiol (E2):ERα signaling, synergy proliferation studies between ET-drugs and clinically relevant CHK1 inhibitors in different luminal BC cell lines, were performed.
A reduced CHK1 expression correlates with a longer RFS in women with ERα-positive BCs. Interestingly, women carrying luminal A BC display an extended RFS when expressing low CHK1 levels. Accordingly, CHK1 and ERα activations are correlated in ERα-positive BC cell lines, and the ATR:CHK1 pathway controls ERα stability and cell proliferation in luminal A BC cells. Mechanistically, the generation of DNA replication stress rather than DNA damage induced by ATR:CHK1 pathway inhibition is a prerequisite for ERα degradation. Furthermore, CHK1 inhibition interferes with E2:ERα signaling to cell proliferation, and drugs approved for clinical treatment of primary and MBC (4OH-tamoxifen and the CDK4/CDK6 inhibitors abemaciclib and palbociclib) exert synergic effects with the CHK1 inhibitors in clinical trials for the treatment of solid tumors (AZD7762, MK8776, prexasertib) in preventing the proliferation of cells modeling primary and MBC.
CHK1 could be considered as an appealing novel pharmacological target for the treatment of luminal primary and MBCs.
PDF
