264 research outputs found
Exploring the Importance of Dynamics in Materials from the Atomic to the Supramolecular Scale Using Advanced Computational Methods
L'abstract è presente nell'allegato / the abstract is in the attachmen
Francesco d'Antonio di Francesco (documentato dal 1439 al 1480) e compagni. Reliquiario del braccio destro di San Giovanni Battista, 1465-1466.
Il contributo analizza il reliquiario destinato a custodire la preziosa reliquia del braccio destro del Battista commissionato a Francesco d'Antonio nella sua piena maturità artistica. Si sottolinea l'interesse dell'artista per le novità rinascimentali che traspare in tutti gli aspetti formali dell'opera, molto diversa nella concezione dal reliquiario della cappa di San Bernardino portato a compimento dall'orafo appena quattro anni prima di questo importante incarico. Si sottolinea tuttavia come l'adesione di Francesco d'Antonio alle novità rinascimentali sia alquanto peculiare. Si mette in evidenza come Francesco d'Antonio abbia osservato con interesse sia la produzione pittorica di Domenico di Bartolo, sia quella del giovane Matteo di Giovanni
Francesco d'Antonio di Francesco (documentato dal 1439 al 1480). Croce astile, sesto-settimo decennio del XV secolo (ante agosto 1470).
Il contributo analizza la croce, purtroppo gravemente depauperata, proveniente dalla chiesa di Sant'Agostino di Asciano e conservata nel Museo d'Arte Sacra (Palazzo Corboli). Si ricostruiscono le vicende dell'opera donata dal mercante Jacopo Scotti - che nel 1453 risultava tra i più ricchi cittadini di Siena - alla chiesa di Sant'Agostino di Asciano dove egli aveva ottenuto lo ius patronatus di ben due altari, corredandoli entrambi con dipinti di Matteo di Giovanni. Si propne per la prima volta di inserire quanto ancora resta della croce donata dallo Scotti alla chiesa di Sant'Agostino, nel corpus di Francesco d'Antonio in base ai caratteri stilistici delle immagini a sbalzo dei Dolenti che si prestano a confronti quanto mai convincenti con le figurazioni, ugualmente a sbalzo, nel basamento del reliquiario del Battista realizzato dall'orafo tra il 1465 e il 1466. Su questa base, e in mancanza di altri riscontri, si avanza per l'opera una datazione nello stesso giro di anni
Unsupervised tracking of local and collective defects dynamics in metals under deformation
Metals owe their unique mechanical properties to how defects emerge and propagate within their crystal structure under stress. However, the mechanisms leading from the early emerging (local) defects to the amplification of dislocations (collective plastic events) are not easy to track. Here, using tensile-stress atomistic simulations of a copper lattice as a case study, we revisit this classical problem under a new perspective based on local dynamics rather than on purely structural arguments. We use a data-driven approach that allows tracking how local fluctuations emerge and accumulate in the atomic lattice in space and time, anticipating/determining the emergence of local or collective structural defects during deformation. Building solely on the general concepts of local fluctuations and spatiotemporal fluctuation correlations, this approach allows characterizing in a unique way the evolution through the elastic, plastic, and fracture phases, describing metals as complex systems where collective phenomena originate from local dynamical triggering events
Appunti per una storia dell'oreficeria a Siena nella seconda metà del Trecento. La croce del Cleveland Museum of Art.
Il contributo si articola in due parti. Nella prima si delineano alcuni aspetti della produzione di oreficeria a Siena nella seconda metà del Trecento sottolineando come in questo periodo - e anche nel primo Quattrocento - si configuri una sorta di 'devozione' nei confronti di quanto era stato realizzato nella prima metà del secolo quando gli orafi avevano espresso tutte le loro grandi potenzialità. Le novità che vengono introdotte non sono mai veramente tali: sono piuttosto dei rinnovamenti da leggere nel solco della tradizione e da interpretare quindi come una rimeditazione su tipologie, caratteri e tecniche che già avevano fatto la loro comparsa da moltissimo tempo. Si osserva come i principali orafi della seconda metà del Trecento siano tutti quanti impegnati nella realizzazione di sculture di grandi dimensioni. Per quanto riguarda le tecniche si accenna al largo uso che si continua a fare dello smalto champlevé e alla rivalutazione di questo tipo di smalto che si verifica nel periodo preso in esame. La seconda parte è dedicata ad un'approfondita analisi della croce processionale proveniente dalla prepositura di Trequanda (Siena) a lungo conservata nel Cleveland Museum of Art. Si mette in evidenza come, per la croce, i riferimenti più significativi e stringenti siano da cogliere nelle opere di oreficeria uscite dalle botteghe degli orafi-scultori attivi nella cappella di Piazza: il reliquiario a busto di San Marco papa che non è firmato, ma che in base ai caratteri stilistici può essere considerato di Mariano d'Agnolo Romanelli, il calice sottoscritto da Bartolomeo di Tommè detto Pizzino del Musée des Beaux Arts di Lione, e anche, ma decisamente in minor misura, il calice con la firma di Matteo d'Ambrogio detto Sapa del Louvre. Si propone una datazione dell'opera intorno agli anni ottanta del Trecento
sj-docx-1-anp-10.1177_00048674221106669 – Supplemental material for Clinical correlates of comorbid attention deficit hyperactivity disorder in adults suffering from bipolar disorder: A meta-analysis
Supplemental material, sj-docx-1-anp-10.1177_00048674221106669 for Clinical correlates of comorbid attention deficit hyperactivity disorder in adults suffering from bipolar disorder: A meta-analysis by Francesco Bartoli, Tommaso Callovini, Daniele Cavaleri, Riccardo Matteo Cioni, Bianca Bachi, Angela Calabrese, Federico Moretti, Aurelia Canestro, Marco Morreale, Christian Nasti, Dario Palpella, Susanna Piacenti, Renata Nacinovich, Ilaria Riboldi, Cristina Crocamo and Giuseppe Carrà in Australian & New Zealand Journal of Psychiatry</p
Concurrent and predictive validity of the infant motor profile in infants at risk of neurodevelopmental disorders
BACKGROUND: Preterm infants and infants with perinatal brain injury show a higher incidence of neurodevelopmental disorders (NDD). The Infant Motor Profile (IMP) is a clinical assessment which evaluates the complexity of early motor behaviour. More data are needed to confirm its predictive ability and concurrent validity with other common and valid assessments such as the Alberta Infant Motor Scale (AIMS) and Prechtl's General Movement Assessment (GMA). The present study aims to evaluate the concurrent validity of the IMP with the AIMS, to assess its association with the GMA, to evaluate how the IMP reflects the severity of the brain injury and to compare the ability of the IMP and the AIMS to predict an abnormal outcome in 5-month-old infants at risk of NDD.METHODS: 86 infants at risk of NDD were retrospectively recruited among the participants of two clinical trials. Preterm infants with or without perinatal brain injury and term infants with brain injury were assessed at 3months corrected age (CA) using the GMA and at 5months CA using the IMP and the AIMS. The neurodevelopmental outcome was established at 18months.RESULTS: Results confirm a solid concurrent validity between the IMP Total Score and the AIMS (Spearman's rho 0.76; p<.001) and a significant association between IMP Total Score and the GMA. Unlike the AIMS, the IMP Total score accurately reflects the severity of neonatal brain injury (p<.001) and proves to be the strongest predictor of NDD (p<.001). The comparison of areas under receiver operating characteristic curves (AUC) confirms that the IMP Total score has the highest diagnostic accuracy at 5months (AUC 0.92). For an optimal IMP Total Score cut-off value of 70, the assessment shows high sensitivity (93%) and specificity (81%) (PPV 84%; NPV 90%).CONCLUSIONS: Early motor behaviour assessed with the IMP is strongly associated with middle-term neurodevelopmental outcome. The present study confirms the concurrent validity of the IMP with the AIMS, its association with the GMA and its ability to reflect brain lesion load, hence contributing to the construct validity of the assessment.TRIAL REGISTRATION: NCT01990183 and NCT03234959 (clinicaltrials.gov)
Characterizing determinants of BK Polyomavirus-specific immune response
BK polyomavirus (BKPyV) is one of now 13 human polyomavirus (HPyV) species detected in humans. BKPyV is only known to infect humans and seroprevalence rates of more than 90% have been reported in adult populations around the world. Following primary infection, BKPyV persists in the renourinary tract without causing any disease as evidenced by urinary shedding in 5% - 10% of healthy immunocompetent blood donors.
In immunocompromised persons, however, BKPyV can cause significant diseases whereby uncontrolled high-level replication may lead to organ invasive pathologies in kidneys, bladder, lungs, vasculature, and the central nervous system. The most consistently found diseases are BKPyV-associated hemorrhagic cystitis (BKPyVHC) in 5%-20% allogeneic hematopoietic stem cells transplant patients, and BKPyV-associated nephropathy (BKPyVAN) in 1%-15% of kidney transplant patients. BKPyVHC is highly symptomatic with pain, anemic bleeding, and increased mortality. BKPyVAN is asymptomatic except for progressive renal failure and premature return to dialysis. Both entities are characterized by high-level viral replication i.e. with urine BKPyV loads of 8-10 log10 Geq/mL, plasma BKPyV loads often above 4 log10 Geq/mL, and an allogeneic constellation between the virus-infected host cell and the available T-cell effectors. Despite these similarities, the clinical manifestations are strikingly different suggesting relevant, but experimentally undefined differences in pathogenesis. Thus, BKPyVHC typically occurs within 4 weeks after allogeneic HSCT and is confined to the bladder, and typically without kidney involvement. By contrast, BKPyVAN is diagnosed around 3-6 months after kidney transplantation and confined to the kidney allograft without causing cystitis. Although high-level BKPyV replication should be formally amenable to antiviral drug treatment, no effective and BKPyV-specific antiviral therapy is currently available. Therefore, a better understanding of the immune alteration in both diseases has been deemed essential to identify patients at risk and to develop prophylactic, preemptive and therapeutic strategies.
The currently recommended strategy for BKPyVAN is to screen kidney transplant patients for BKPyV replication and to promptly reduce immunosuppressive therapy in those with significant replication to facilitate mounting of BKPyV-specific T cell responses and thereby preventing progression to disease. This manoeuver has been linked to expanding BKPyV-specific T cell responses in the peripheral blood of kidney transplant patients. However, this approach may place patients at risk for acute rejection episodes that predispose equally well to premature kidney transplant failure. Although the clinical feasibility of reducing immunosuppression and curtailing BKPyV replication has been shown to be effective in prospective cohort studies for many, but not all of kidney transplant patients, this approach has not been possible in allogeneic HSCT patients because of concurrent or imminent graft-versus host disease. Thus, there are significant gaps in the current understanding of the BKPyV– host interaction in the normal host and in the allogeneic setting, which need to be investigated for a more effective and safer management of these significant viral complications.
In this thesis, the interaction of BKPyV and the immune response has been approached from two different angles. In the first project, potential mechanisms of BKPyV immune evasion were studied. Here, we focused on a small accessory protein called agnoprotein encoded as a leader protein in the late viral early region (LVGR). Although HPyV genomes overall show a very similar genome organization, agnoproteins are only found in the genomes of BKPyV and JCPyV that have a kidney tropisms, but not in any of the other 11 presumably non-renotropic HPyVs. We hypothesized that agnoprotein could play a role in immune evasion by downregulating HLA expression. The effects of agnoprotein were studied on HLA class I and II expression in vitro by flow cytometry following transfection of primary human renal tubular epithelial cells, which are the viral target of BKPyV-associated nephropathy. In addition, transfected human UTA-6 cells were studied as well as UTA-6 cells bearing a tetracycline-regulated agnoprotein. As control, the effects were compared with the ICP47 protein of Herpes simplex virus-1, which has been previously reported to effectively down-regulate HLA class I. Although both viral proteins share some similarities at the protein level, our results showed that BKPyV agnoprotein did not down-regulate HLA class I or class II molecules. Also, there was not inhibitory effect on the increase of HLA-class I or class-II surface expression following exposure to interferon-. By contrast, ICP47 reduced HLA class I surface expression, but not class II. We also evaluated effects of agnoprotein on virus epitope-specific T-cell killing by 51Chromium release assay, however no interference could be observed. We concluded that agnoprotein did not contribute to these types of HLA-dependent immune evasion processes. However, further investigations are needed to understand if agnoprotein could contribute to viral immune escape by other mechanisms.
In the second project, we aimed at better characterizing BKPyV-specific CD8 T cell immunity targeting epitopes encoded in the early viral gene region (EVGR). Selected coding sequences of the BKPyV EVGR were submitted to two web-based computer algorithms (SYFPEITHI, IEDB) in order to predict immunodominant 9mer epitopes presented by 14 frequent HLA-class I molecules. For an experimental confirmation, 97 different 9mer epitopes were chemically synthesized and tested in 42 healthy individuals. A total of 39 epitopes could be confirmed by interferon- ELISpot assay in at least 30% of healthy individuals. Interestingly, most of the 9mer epitopes appeared to cluster in short amino acid stretches, and some 9mer could be presented by more than one HLA class I allele as expected for immunodominant domains. HLA-specific presentation was demonstrated by 9mer- MHC-I streptamers for 21/39 (54%) epitopes. The 9mer dependent T-cell killing by 51Chromium release assay and the CD107a surface detection indicated that the 9mer epitopes could be recognized by cytotoxic T-cells. Moving to a clinically relevant situation, 13 9mer epitopes could be validated in 19 kidney transplant patients protected from, or recovering from, BKPyV viremia. The results suggest that, pending further corroboration in larger patient populations, novel 9mer epitopes can be identified, which are associated with CD8 T cell control of BKPyV replication. Thus the identified immunodominant 9mer T-cell epitopes could be further developed for clinical assays to better predict the risk and the recovery of BKPyV diseases, help guiding immunosuppression reduction, and to develop specific adoptive T-cell therapy or vaccine responses to prevent or treat BKPyV-associated disease
Machine learning of atomic dynamics and statistical surface identities in gold nanoparticles
Abstract It is known that metal nanoparticles (NPs) may be dynamic and atoms may move within them even at fairly low temperatures. Characterizing such complex dynamics is key for understanding NPs’ properties in realistic regimes, but detailed information on, e.g., the stability, survival, and interconversion rates of the atomic environments (AEs) populating them are non-trivial to attain. In this study, we decode the intricate atomic dynamics of metal NPs by using a machine learning approach analyzing high-dimensional data obtained from molecular dynamics simulations. Using different-shape gold NPs as a representative example, an AEs’ dictionary allows us to label step-by-step the individual atoms in the NPs, identifying the native and non-native AEs and populating them along the MD simulations at various temperatures. By tracking the emergence, annihilation, lifetime, and dynamic interconversion of the AEs, our approach permits estimating a “statistical equivalent identity” for metal NPs, providing a comprehensive picture of the intrinsic atomic dynamics that shape their properties
Innate dynamics and identity crisis of a metal surface unveiled by machine learning of atomic environments
Metals are traditionally considered hard matter. However, it is well known that their atomic lattices may become dynamic and undergo reconfigurations even well below the melting temperature. The innate atomic dynamics of metals is directly related to their bulk and surface properties. Understanding their complex structural dynamics is, thus, important for many applications but is not easy. Here, we report deep-potential molecular dynamics simulations allowing to resolve at an atomic resolution the complex dynamics of various types of copper (Cu) surfaces, used as an example, near the Hüttig (∼1/3
of melting) temperature. The development of deep neural network potential trained on density functional theory calculations provides a dynamically accurate force field that we use to simulate large atomistic models of different Cu surface types. A combination of high-dimensional structural descriptors and unsupervized machine learning allows identifying and tracking all the atomic environments (AEs) emerging in the surfaces at finite temperatures. We can directly observe how AEs that are non-native in a specific (ideal) surface, but that are, instead, typical of other surface types, continuously emerge/disappear in that surface in relevant regimes in dynamic equilibrium with the native ones. Our analyses allow estimating the lifetime of all the AEs populating these Cu surfaces and to reconstruct their dynamic interconversions networks. This reveals the elusive identity of these metal surfaces, which preserve their identity only in part and in part transform into something else under relevant conditions. This also proposes a concept of “statistical identity” for metal surfaces, which is key to understanding their behaviors and properties
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