513225 research outputs found
Sort by
The effective running Hubble constant in SNe Ia as a marker for the dark energy nature
No full textWe propose a new method that reveal the nature of dark energy (DE) evolution. Specifically, the method consists of studying the evolving trend regarding the effective running Hubble constant: when it increases, it indicates a quintessence nature, and when it decreases, it reveals a phantom behavior. Within the framework of the dark energy models we analyze three parameterizations: the wCDM model, a reduced Chevallier-Polarski-Linder (CPL) model and a new theoretical model based on the possible creation of dark energy by the time-varying gravitational field of the expanding Universe. For each DE model, we construct a theoretical effective running Hubble constant, i.e. a function of the redshift, which highlights the difference between modified dynamics and the ΛCDM-one. Furthermore, these dark energy models are compared to a phenomenological model, called the power-law model (PL), that assumes a decreasing trend of the Hubble constant with redshift, and to the ΛCDM one. These three theoretical functions for DE are fitted against the binned Type Ia Supernovae (SNe Ia) data samples, i.e. the Pantheon and the Master samples, the latter being a collection of SNe Ia from 4 catalogs: Dark Energy Survey (DES), PantheonPlus, Pantheon and Joint Lightcurve Analysis (JLA), without duplicated SNe Ia, called the Master sample. The main result of our study is that the phenomenological PL model is statistically favored compared to the other proposed scenarios, both for the Pantheon and the Master samples. At this stage, the SNe Ia data do not indicate that the evolution of dark energy models among the studied ones is favored respect to the ΛCDM. Nevertheless, the binned Pantheon sample allows for a discrimination of the nature of dark energy at least at the 1σ level via the fit of the effective running Hubble constant
Césare Peeren – Superuse on Site, Villa Maggiore, Como (2017–2019). Heritage, harvesting and superuse. ARCò Architecture and Cooperation, Casa Chiaravalle, Milan (2018). Earthbags and Earthship: a Manifesto Building
No full textThe two essays examine two relevant case studies relating to circular design with superuse and upcycling of different kinds of materials. The first one is Villa Maggiore, Como (2017–2019), by Césare Peeren – Superuse on Site, a best practice of materials' harvesting and superuse in a heritage building. The second one, Casa Chiaravalle, Milan (2018) by ARCò Architecture and Cooperation, is a Manifesto Building for upcycling, using Earthbags and Earthship
“La dextérité des mains sert avec avantage le génie”: Jacques Fabien Gautier-Dagoty (1716–1785) tra scienza e arte
No full textIl contributo analizza la produzione di incisioni a colori di Jacques Fabien Gautier-Dagoty in una prospettiva inedita, mettendolo a confronto con il dibattito sull'arte e sulle incisioni d'après durante il Settecento, evidenziando come questo dibattito abbia influito sulle scelte dell'incisore, spingendolo verso il mondo della scienza e delle grandi imprese tipografiche di carattere anatomico
La struttura dei sistemi educativi e le aspettative di istruzione: il complesso intreccio tra disuguaglianze scolastiche e di contesto
No full textIl capitolo analizza come la struttura dei sistemi educativi europei – in particolare il loro grado di differenziazione/selettività – influenzi non solo le performance scolastiche, ma anche le aspettative di istruzione degli studenti. Attraverso dati comparativi di 17 paesi e indicatori costruiti tramite Analisi delle Componenti Principali, gli autori mostrano che i sistemi più selettivi anticipano le scelte scolastiche, aumentano la segregazione sociale e accademica e amplificano gli effetti dell’origine sociale.
Le aspettative educative non dipendono però esclusivamente dalla struttura scolastica: emergono dall’interazione tra caratteristiche istituzionali, contesto socio-economico, mercato del lavoro e disuguaglianze di reddito. Nei sistemi altamente differenziati, gli studenti svantaggiati tendono ad adattare le proprie aspirazioni verso percorsi brevi e professionalizzanti, mentre nei paesi con mercati del lavoro più inclusivi l’università appare meno necessaria. Al contrario, nei contesti più diseguali e con scarse opportunità occupazionali, la laurea assume un valore protettivo e simbolico, generando aspettative elevate anche tra gli studenti con meno risorse.
Il capitolo conclude che le aspettative educative sono un prodotto ecologico e stratificato: riflettono la combinazione di struttura scolastica, condizioni economiche, opportunità percepite e meccanismi di riproduzione sociale. Per questo, comprendere le aspettative significa comprendere come i sistemi educativi contribuiscono – o potrebbero contribuire meno – alla riproduzione delle disuguaglianze
EXPLORING THE ENDONUCLEASE MUS81 AS A NEW FACTOR IMPACTING ON CANCER CHEMOSENSITIVITY
No full textThe MUS81 complex is a crucial factor for genome stability maintenance. It is often overexpressed in breast and ovarian cancer and has been proposed as cancer predisposition gene. The complex is regulated by Casein Kinase 2 (CK2) through phosphorylation at serine 87 (S87), which is essential for resolving branched intermediates during mitosis. Our previous findings show that the phosphomimetic MUS81S87D mutant confers PARP inhibitor (PARPi) resistance in BRCA2-deficient backgrounds, possibly because replication-related double-strand breaks (DSBs), induced by deregulated MUS81 function during the S-phase, can be completely resolved through alternative end-joining (Alt-EJ). Thus, deregulated function of the MUS81 complex in S-phase emerged as a potential modifier of the response to PARPi when BRCA2 is mutated or absent.
In this study, we investigate why the MUS81S87D mutant aberrantly targets DNA replication forks. We found that MUS81S87D is hyper-recruited at ongoing replication forks and that the characteristic phenotype of S87D-MUS81 mutant cells is reversed by depletion of the protein scaffold SLX4 by siRNA transfection. This indicates that the unscheduled cleavage function conferred to MUS81 by the S87D mutation and excessive recruitment at DNA replication forks depend on SLX4. We confirm these findings also using a set of mutations that abrogate the binding of MUS81 to SLX4. Finally, we assessed if counteracting the association between SLX4 and MUS81 in S-phase affects PARPi resistance in BRCA2-deficient cells. Consistent with the DNA damage and localization data, abrogation or reduction of the S87D-MUS81/SLX4 association was sufficient to largely restore normal PARPi sensitivity of BRCA2-deficient cells.
These findings could lead to a better understanding of the relationship between MUS81 status, PARPi chemosensitivity and a possible MUS81 exploitation in target therapy.
Moreover, this study investigates the hypothesis that MUS81 loss creates a synthetic lethal vulnerability with PARP inhibition, particularly in the context of oncogene-induced replication stress. Using CRISPR/Cas9, MUS81 was knocked out in a panel of human cell lines. We demonstrate that MUS81 loss induces a clear sensitivity to the PARPi Olaparib in HR-proficient breast (MCF7) and ovarian (OVCAR-3) cancer cells, but not in a non-cancerous mammary epithelial model cell line (HMEC). This sensitivity directly correlates with a significant accumulation of DNA double-strand breaks (DSBs). Interestingly, the triple-negative breast cancer cell line MDA-MB-231 remained resistant to Olaparib even after MUS81 knockout. We identified MYC oncogene amplification, which is present in the sensitive MCF7 and OVCAR-3 lines but not in the resistant MDA-MB-231 line, as the key differentiating factor. Moreover, we found that the increased PARPi sensitivity is also linked with a metabolic shift occurring upon MUS81 loss.
These findings reveal a novel, cancer-specific synthetic lethality between MUS81 and PARP that seems to be conditional upon MYC overexpression. Our results suggest that high MYC levels create an intense state of RS, making cancer cells critically dependent on MUS81 for survival. We propose that MYC amplification could serve as a key biomarker to identify patients with HR-proficient tumours who may benefit from a combination therapy involving PARP inhibitors and potential future MUS81-targeting agents, thereby expanding the utility of PARPis beyond their current application.
Furthermore, the metabolic rewiring conferred by MUS81 KO could be studied to identify novel vulnerabilities and to find novel therapeutic targets
Perceiving in time: see, understand, remember
No full textRooted in the remarkable capability of human visual cognition to navigate the real world effortlessly, this thesis spans from perception to memory, to theoretically and empirically examine the
fundamental concepts needed to realize the vision of an artificial visual intelligence: a machine with the capacity to autonomously perceive the world, understand semantics, reason in time, and remember.
The journey begins with perception. Vision Transformers, despite their success, suffer from feature collapse—a loss of spatial structures in deeper layers caused by over-globalized attention. ReViT addresses this through a simple yet effective residual attention mechanism that preserves spatial awareness, the very foundation of visual perception.
However, understanding perception alone is insufficient. The real world unfolds through interconnected events defined by motion, interactions and semantic patterns. This brings our journey towards S-GEAR, which tackles semantic understanding and temporal intelligence in the context of action anticipation —a challenge that goes beyond isolated actions and explores sequences, aiming to understand what has happened in order to predict what is next. S-GEAR tackles this by explicitly embedding semantic relationships and temporal co-occurrence patterns into visual representations. Where existing anticipation methods treat events in isolation, S-GEAR recognizes that semantics constrain what can happen next, dramatically reducing future uncertainty.
The final piece is memory—the mechanism that enables us to recall past experiences when needed most. ReWind introduces a query-guided memory system that determines not just how to compress information, but what to remember and what to forget. By coordinating reading, writing, and selection mechanisms, ReWind enables visual models to process long videos efficiently while maintaining coherent and relevant information.
Together, these contributions advance the path toward machines that not only see, but also understand and remember
Shaken politics. The electoral outcomes of disasters and social capital
No full textWe study the electoral repercussions of the L'Aquila earthquake in 2009, one of Italy's most catastrophic post‐WWII seismic events. We construct a unique municipality‐level dataset, combining high‐resolution data on the ground acceleration recorded during the earthquake with European election results and social capital metrics. Our findings indicate that the intensity of the shock positively influenced support for the incumbent national government but provided no electoral advantage to local incumbents. Analyzing potential transmission mechanisms, we find that relief measures did not automatically translate into political rewards. Instead, turnout dynamics and what we term emergency social capital—the density of civic organizations involved in social assistance, volunteering, and disaster management—played a pivotal role in shaping post‐disaster electoral outcomes. In left‐leaning municipalities, greater exposure to the shock was associated with both a decline in turnout and an improved performance of the incumbent government. Moreover, the incumbent's electoral gains increased with the ground acceleration only in municipalities with low emergency social capital, where citizens relied primarily on political institutions for assistance. Individual‐level evidence from survey data further supports our findings. Nonetheless, the impact of the earthquake was not enduring. In the subsequent elections, the incumbent government experienced a decline in support in the very municipalities where it had initially gained favor following the disaster. Overall, our evidence paints a picture of disillusionment with the incumbent's response and promises
Prediction of High School Study Outcome through Clustering and Embedding
No full textWe investigate the integration of semantic analysis techniques and machine learning models, to identify and predict academic success patterns for high school students. Starting from an existing dataset, we generated summary notes for teachers based on key academic indicators, and transformed them into embeddings using a lightweight transformer model (DistilBERT). Principal component analysis was applied to reduce the dimensionality of the embeddings, to be then used for K-Means clustering. A decision tree classifier was trained to predict student success, leveraging both classical features (such as grades, non-attendance, and failures) and semantic embeddings. The results show the great potential of combining structured and unstructured data for early detection of students at-risk
Probabilistic Safety Bounds for Discrete-Time High Relative Degree Systems with Unknown Dynamics
No full textThis paper develops a theoretical framework for the construction and analysis of high-order discrete-time control barrier functions (CBFs). Two main results are presented. First, we show that the difference between the true and nominal auxiliary functions associated with a high-order discrete-time CBF is linear if and only if the class– functions satisfy for some . Second, we prove that if a corresponding optimization problem admits a solution at each time step, then the resulting control law renders a prescribed safe set forward invariant, thereby guaranteeing system safety. The theoretical results are numerically demonstrated on a discrete-time nonlinear system representing a type-1 diabetic patient, showing that the proposed control framework ensures safety in the regulation of blood glucose levels while respecting safety constraints
Il rischio interpretativo nel regime dell’adempimento collaborativo
No full textIl contributo affronta le questioni collegate alla gestione del rischio interpretativo nella specifica prospettiva del regime dell'adempimento collaborativo di cui al D.l.gs. n. 128 del 2015