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Radiation-induced embrittlement of nuclear steels is one of the main limiting factors for safe long-term operation of nuclear power plants. In support of accurate and safe reactor pressure vessel (RPV) lifetime assessments, we developed a physics-based model that predicts RPV steel hardening and subsequent embrittlement as a consequence of the formation of nano-sized clusters of minor alloying elements. This model is shown to provide reliable assessments of embrittlement for a very wide range of materials, with higher accuracy than industrial correlations. The core of our model is a multiscale modelling tool that predicts the kinetics of solute clustering, given the steel chemical composition and its irradiation conditions. It is based on the observation that the formation of solute clusters ensues from atomic transport driven by radiation-induced mechanisms, differently from classical nucleation-and-growth theories. We then show that the predicted information about solute clustering can be translated into a reliable estimate for radiation-induced embrittlement, via standard hardening laws based on the dispersed barrier model. We demonstrate the validity of our approach by applying it to hundreds of nuclear reactors vessels from all over the world.

The formation of nano-sized, coherent, solute-rich clusters (NSRC) is known to be an important factor causing the degradation of the macroscopic properties of steels under irradiation. The mechanisms driving their formation are still debated. This work focuses on low-Cu reactor pressure vessel (RPV) steels, where solute species are generally not expected to precipitate. We rationalize the processes that take place at the nanometer scale under irradiation, relying on the latest theoretical and experimental evidence on atomic-level diffusion and transport processes. These are compiled in a new model, based on the object kinetic Monte Carlo (OKMC) technique. We evaluate the relevance of the underlying physical assumptions by applying the model to a large variety of irradiation experiments. Our model predictions are compared with new experimental data obtained with atom probe tomography and small angle neutron scattering, complemented with information from the literature. The results of this study reveal that the role of immobilized self-interstitial atoms (SIA) loops dominates the nucleation process of NSRC.

Early and long-term outcomes in elderly patients who underwent isolated aortic valve replacement (iAVR) are well defined. Conflicting data exist in elderly patients who underwent AVR plus coronary artery bypass grafting (CABG). We sought to evaluate the early and long-term outcomes of combined AVR + CABG in patients older than 75 years of age. From June 1999 to June 2018, 402 patients ≥ 75 years who underwent iAVR (n = 200; 49.7%) or combined AVR plus CABG (n = 202; 50.3%) were retrospectively analysed. AVR + CABG patients were older than iAVR patients (78.5 ± 2.5 vs 77.6 ± 2.8 years; p < 0.0001), with greater co-morbidities and more urgent/emergency surgery. 30-day mortality was 6.5% in the AVR + CABG and 4.5% in the iAVR group (p = 0.38). Multivariate analysis identified EuroSCORE II [odd ratio (OR) 1.13] postoperative stroke (OR 12.53), postoperative low cardiac output syndrome (OR 8.72) and postoperative mechanical ventilation > 48 h (OR 8.92) as independent predictors of 30-day mortality; preoperative cerebrovascular events (OR 3.43), creatinine (OR 7.27) and extracorporeal circulation time (OR 1.01) were independent predictors of in-hospital major adverse cardiovascular and cerebral events (MACCE). Treatment was not an independent predictor of 30-day mortality and in-hospital MACCE. Survival at 1, 5 and 10 years was 94.7 ± 1.6%, 72.6 ± 3.6% and 31.7 ± 4.8% for iAVR patients and 89.1 ± 2.3%, 73.9 ± 3.5% and 37.2 ± 4.8% for AVR + CABG subjects (p = 0.99). Using adjusted Cox regression model, creatinine [hazard ration (HR) 1.50; p = 0.018], COPD (HR 1.97; p = 0.003) and NYHA class (HR 1.39; p < 0.0001) were independent predictors of late mortality; the combined AVR + CABG was not associated with increased risk of late mortality (HR 0.83; p = 0.30). In patients aged ≥ 75 years, combined AVR + CABG was not associated with increased 30-day mortality, in-hospital MACCE and long-term mortality. Surgical revascularization can be s

The formation of nano-sized, coherent, solute-rich clusters (NSRC) is known to be an important factor causing the degradation of the macroscopic properties of steels under irradiation. The mechanisms driving their formation are still debated. This work focuses on low-Cu reactor pressure vessel (RPV) steels, where solute species are generally not expected to precipitate. We rationalize the processes that take place at the nanometer scale under irradiation, relying on the latest theoretical and experimental evidence on atomic-level diffusion and transport processes. These are compiled in a new model, based on the object kinetic Monte Carlo (OKMC) technique. We evaluate the relevance of the underlying physical assumptions by applying the model to a large variety of irradiation experiments. Our model predictions are compared with new experimental data obtained with atom probe tomography and small angle neutron scattering, complemented with information from the literature. The results of this study reveal that the role of immobilized self-interstitial atoms (SIA) loops dominates the nucleation process of NSRC.

The formation of nano-sized, coherent, solute-rich clusters (NSRC) is known to be an important factor causing the degradation of the macroscopic properties of steels under irradiation. The mechanisms driving their formation are still debated. This work focuses on low-Cu reactor pressure vessel (RPV) steels, where solute species are generally not expected to precipitate. We rationalize the processes that take place at the nanometer scale under irradiation, relying on the latest theoretical and experimental evidence on atomic-level diffusion and transport processes. These are compiled in a new model, based on the object kinetic Monte Carlo (OKMC) technique. We evaluate the relevance of the underlying physical assumptions by applying the model to a large variety of irradiation experiments. Our model predictions are compared with new experimental data obtained with atom probe tomography and small angle neutron scattering, complemented with information from the literature. The results of this study reveal that the role of immobilized self-interstitial atoms (SIA) loops dominates the nucleation process of NSRC.

The formation of nano-sized, coherent, solute-rich clusters (NSRC) is known to be an important factor causing the degradation of the macroscopic properties of steels under irradiation. The mechanisms driving their formation are still debated. This work focuses on low-Cu reactor pressure vessel (RPV) steels, where solute species are generally not expected to precipitate. We rationalize the processes that take place at the nanometer scale under irradiation, relying on the latest theoretical and experimental evidence on atomic-level diffusion and transport processes. These are compiled in a new model, based on the object kinetic Monte Carlo (OKMC) technique. We evaluate the relevance of the underlying physical assumptions by applying the model to a large variety of irradiation experiments. Our model predictions are compared with new experimental data obtained with atom probe tomography and small angle neutron scattering, complemented with information from the literature. The results of this study reveal that the role of immobilized self-interstitial atoms (SIA) loops dominates the nucleation process of NSRC.

Background: Long-term survival benefits of full arterial revascularization with radial artery (RA) used in addition to bilateral internal mammary arteries (BIMA) compared with saphenous vein (SV) used in addition to BIMA has not been clearly defined. Methods: We retrospectively analyzed 660 3-vessel coronary artery disease subjects who received BIMA in addition to either RA (n = 206) or SV (n = 454) grafting in a period between June 1999 and November 2017. After propensity score matching, we obtained 190 matched pairs for analysis. Results: In the matched population, in-hospital mortality occurred in 4 patients (1%), with 2 deaths (1.1%) in the BIMA + RA group and 2 deaths (1.1%) in BIMA + SV group (P >.99). The median follow-up time was 9.2 years (interquartile range, 5.6-13 years) with a maximum follow-up time of 18.5 years. There was not a significant difference in long-term survival between the 2 groups over the follow-up period. Survival at 5, 10, and 15 years were 94.8 ± 1.7%, 83.7 ± 3.1%, and 78.6 ± 3.9% in the BIMA + RA group and 96.2 ± 1.4%, 85.1 ± 2.9%, and 80.4 ± 3.6% in the BIMA + SV group (stratified log-rank P =.78). Cox proportional hazard regression model was used to estimate that the use of RA in addition to BIMA did not affect the late mortality (propensity score adjusted hazard ratio, 1.05; 95% confidence interval, 0.62-1.79; P =.83). Conclusions: In a relatively small population of triple-vessel coronary artery disease, the use of RA as a third arterial conduit with BIMA did not confer a long-term survival benefit.

OBJECTIVES: Left ventricular free wall rupture (LVFWR) is a catastrophic complication following acute myocardial infarction with an estimated incidence of 0.2–7.6% and mortality can be as high as 60%. This study aimed to identify the risk factors for morbidity and mortality in patients affected by LVFWR. METHODS: This is a retrospective study of 35 patients who underwent surgery for LVFWR between January 2000 and December 2016 at our institution. RESULTS: The mean age of patients was 68.3 years. The in-hospital survival was 65.7% (n = 23), and 13% of survived patients presented with cardiac arrest. The following characteristics were associated with in-hospital mortality at univariable analysis: pre-existing hypertension (P = 0.02), need for inotropes (P = 0.02) and cardiac arrest (P < 0.0001) at presentation, cardiopulmonary resuscitation (P = 0.004), preoperative extracorporeal membrane oxygenation (P = 0.004), technique of LVFWR repair (P = 0.013), operation on extracorporeal membrane oxygenation (P = 0.005) and postoperative extracorporeal membrane oxygenation (P = 0.001). In the multivariable analysis, cardiac arrest at presentation was an independent predictor of in-hospital mortality (odds ratio 11.7, 95% confidence interval 2.352–59.063; P = 0.003). The overall mean postoperative follow-up was 8.3 ± 1.3 years. Overall survival rates at 5 and 10 years were 53.2 ± 8.6% and 49.1 ± 8.9%, respectively. Among the survivors, only 6 (26.1%) patients died during follow-up with a 5-year and 10-year overall survival rate of 80.9 ± 8.7% and 74.7 ± 10%, respectively. CONCLUSIONS: These data suggest a trend towards long-term benefit in patients surviving high-risk surgery for LVFWR repair. Considering the high lethality of LVFWR, the urgency and complexity of the primary surgical intervention early diagnosis and prompt surgery play a key role in the management of this complication

This study aimed to assess if clampless off-pump coronary artery bypass grafting (OPCAB) decreases the incidence of perioperative stroke (POS) rate and in-hospital mortality. The secondary aim was to evaluate 12-year rates of overall mortality. Between January 2003 to December 2015, data of 645 consecutive patients undergoing isolated CABG were retrospectively collected. 363 underwent aortic no-touch OPCAB (No-touch group) and 282 underwent OPCAB with the Heartstring device (HS group). In-hospital mortality and perioperative stroke rate as primary endpoint, as well as long-term follow-up outcome were analysed. In-hospital mortality was lower into No-touch group compared with HS group but without significant statistical difference (1.7 vs. 3.2%, p = 0.19, respectively); the rate of postoperative stroke was higher in No-touch group compared with HS group, although this difference did not reach statistically significance. Delirium was reported with higher presentation rate in HS group (3.9 vs. 0.8%, p = 0.01). Blood transfusions rate was higher in HS subjects (23.4 vs. 16.1%, p = 0.01). Intubation time, ICU, and hospital length of stay were increased in the HS group (p = 0.008, p = 0.001 and p = 0.003, respectively). Over a 12-year follow-up period, survival probabilities at 1, 5, and 10 years were 93.6 ± 1.3 vs. 93.2 ± 1.5, 80.4 ± 2.6 vs. 80.3 ± 2.2, and 57.9 ± 5 vs. 58.4 ± 3.8% in the No-touch and HS group, respectively (p = 0.97). In this retrospective study, clampless off-pump CABG lowers perioperative stroke rate whose incidence is, however, not inferior compared with No-touch technique, and no statistically significance was detected. Delirium has a higher presentation rate in clampless off-pump CABG.

We significantly improve the physical models underlying atomistic Monte Carlo (MC) simulations, through the use of ab initio fitted high-dimensional neural network potentials (NNPs). In this way, we can incorporate energetics derived from density functional theory (DFT) in MC, and avoid using empirical potentials that are very challenging to design for complex alloys. We take significant steps forward from a recent work where artificial neural networks (ANNs), exclusively trained on DFT vacancy migration energies, were used to perform kinetic MC simulations of Cu precipitation in Fe. Here, a more extensive transfer of knowledge from DFT to our cohesive model is achieved via the fitting of NNPs, aimed at accurately mimicking the most important aspects of the ab initio predictions. Rigid-lattice potentials are designed to monitor the evolution during the simulation of the system energy, thus taking care of the thermodynamic aspects of the model. In addition, other ANNs are designed to evaluate the activation energies associated with the MC events (migration towards first-nearest-neighbor positions of single point defects), thereby providing an accurate kinetic modeling. Because our methodology inherently requires the calculation of a substantial amount of reference data, we design as well lattice-free potentials, aimed at replacing the very costly DFT method with an approximate, yet accurate and considerably more computationally efficient, potential. The binary FeCu and FeCr alloys are taken as sample applications considering the extensive literature covering these systems., QC 20171208

The release of RNA-containing extracellular vesicles (EV) into the extracellular milieu has been demonstrated in a multitude of different in vitro cell systems and in a variety of body fluids. RNA-containing EV are in the limelight for their capacity to communicate genetically encoded messages to other cells, their suitability as candidate biomarkers for diseases, and their use as therapeutic agents. Although EV-RNA has attracted enormous interest from basic researchers, clinicians, and industry, we currently have limited knowledge on which mechanisms drive and regulate RNA incorporation into EV and on how RNA-encoded messages affect signalling processes in EV-targeted cells. Moreover, EV-RNA research faces various technical challenges, such as standardisation of EV isolation methods, optimisation of methodologies to isolate and characterise minute quantities of RNA found in EV, and development of approaches to demonstrate functional transfer of EV-RNA in vivo. These topics were discussed at the 2015 EV-RNA workshop of the International Society for Extracellular Vesicles. This position paper was written by the participants of the workshop not only to give an overview of the current state of knowledge in the field, but also to clarify that our incomplete knowledge - of the nature of EV(-RNA)s and of how to effectively and reliably study them - currently prohibits the implementation of gold standards in EV-RNA research. In addition, this paper creates awareness of possibilities and limitations of currently used strategies to investigate EV-RNA and calls for caution in interpretation of the obtained data.

The expression of NKG2D ligands (NKG2D-L) flag stressed cells for immune recognition and destruction. A precise control of the cell surface expression of these proteins is therefore required to ensure an appropriate immune response and it is becoming clear that NKG2D ligand expression is regulated at multiple levels. We now report that the surface stability of the human glycosyl-phosphatidyl-inositol (GPI)-anchored ligand ULBP1 (UL16-binding protein) at the plasma membrane is lower than other ULBP molecules. This difference in stability is due neither to shedding nor to a higher internalization rate of ULBP1 but rather occurs because of a rapid degradation of ULBP1 protein after internalization from the cell surface that is blocked by proteasome inhibition. These data indicate that, in addition to the known transcriptional and post-translational mechanisms, surface expression of human NKG2D-L is also regulated by protein turnover and that the brief residence of ULBP1 could contribute to the fine tuning of immune responses.

La biblioteca di Ateneo dell’Università di Milano-Bicocca riporta la propria esperienza di formazione digitale. Parallelamente allo sviluppo delle collezioni digitali sta sviluppando la propria offerta formativa in e-learning, sia attraverso uno spazio per l’autoformazione (chiamato Biblio E-learning) che con seminari in e-learning curati da bibliotecari. Il Learning Management System utilizzato è Moodle.

La biblioteca di Ateneo dell’Università di Milano-Bicocca riporta la propria esperienza di formazione digitale. Parallelamente allo sviluppo delle collezioni digitali sta sviluppando la propria offerta formativa in e-learning, sia attraverso uno spazio per l’autoformazione (chiamato Biblio E-learning) che con seminari in e-learning curati da bibliotecari. Il Learning Management System utilizzato è Moodle.

L’obiettivo della sperimentazione del learning object “Le radici” realizzato dal nostro gruppo di ricerca in Didattica della biologia è quello di indagare la sua validità pedagogico-didattica e la possibilità di utilizzarlo in contesti di apprendimento diversi. A tale scopo abbiamo raccolto e analizzato i prodotti realizzati dagli studenti e somministrato un questionario finale di valutazione. I risultati ottenuti portano a ritenere che il learning object realizzato costituisca una risorsa didattica valida, anche quando è utilizzato in autoapprendimento. Risulta tuttavia particolarmente efficace se inserito in un contesto ricco di scambi e confronto tra pari. La sperimentazione del learning object proseguirà nell'ottica di raccogliere ulteriori dati per integrare i risultati ottenuti fino ad ora. Sarà interessante, inoltre, valutare l’utilizzo del dispositivo in altri contesti educativi

In questo contributo verranno presentati e discussi i risultati relativi all’utilizzo delle tecnologie da parte degli studenti dell’Università degli Studi di Milano-Bicocca ottenuti grazie all’indagine sulla dieta mediale e sui profili di utilizzo delle nuove tecnologie di rete condotta dall’Osservatorio sui Nuovi Media dell’Università di Milano-Bicocca NuMediaBiOs e verranno esposte alcune riflessioni sull’uso dei new media in ambito educativo alla luce dei risultati della survey e della letteratura scientifica internazionale. L’indagine in oggetto, che è alla sua quarta edizione (Ferri et al. 2010, 2012, 2014) ed è stata realizzata nell’anno accademico 2014-2015, in linea anche con le rilevazioni effettuate negli anni precedenti (Ferri et al. 2010, 2012, 2014), si è basata su una indagine quantitativa su 4937 studenti iscritti alle lauree triennali dell’Università degli Studi di Milano-Bicocca. Lo strumento utilizzato è stato un questionario composto di 29 domande, divise in 6 parti: 1. rilevazione dei dati socio-anagrafici generali, 2. rapporto con la tecnologia, 3. consumi culturali, 4. ruolo di Internet all’interno della vita quotidiana, 5. utilizzo di piattaforme e servizi Web 2.0 e 6. Internet per la vita universitaria.

Immune recognition mediated by the activating receptor NKG2D plays an important role for the elimination of stressed cells, including tumors and virus-infected cells. On the other hand, the ligands for NKG2D can also be shed into the sera of cancer patients where they weaken the immune response by downmodulating the receptor on effector cells, mainly NK and T cells. Although both families of NKG2D-ligands, major histocompatibility complex class I-related chain (MIC) A/B and UL16 binding proteins (ULBPs), are related to MHC molecules and their expression is increased after stress, many differences are observed in terms of their biochemical properties and cell trafficking. In this paper, we summarize the variety of NKG2D-ligands and propose that selection pressure has driven evolution of diversity in their trafficking and shedding, but not receptor binding affinity. However, it is also possible to identify functional properties common to individual ULBP molecules and MICA/B alleles, but not generally conserved within the MIC or ULBP families. These characteristics likely represent examples of convergent evolution for efficient immune recognition, but are also attractive targets for pathogen immune evasion strategies. Categorization of NKG2D-ligands according to their biological features, rather than their genetic family, may help to achieve a better understanding of NKG2D-ligand association with disease.

MICA and MICB (MHC-class-I-related chain A/B) are transmembrane proteins expressed in pathological conditions that are ligands for NKG2D, an activating receptor found on cytotoxic lymphocytes. The recognition on target cells of NKG2D ligands leads to the activation of lysis and cytokine secretion by NK cells and T cells. Besides being expressed at the cell surface, MICA/B can be released as soluble proteins. Soluble NKG2D ligands downmodulate expression of the NKG2D receptor on lymphocytes, leading to a diminished cytotoxic response. Prior studies suggested that recruitment of MICA/B molecules to cholesterol-enriched microdomains was an important factor regulating the proteolytic release of these molecules. We now show that recruitment of MICA to these microdomains depends on palmitoylation of two cysteine residues that allow MICA molecules to reside in the membrane in the same domains as caveolin-1. Compared with WT molecules, nonpalmitoylated mutant MICA molecules were shed to the supernatant with low efficiency; however, both WT and mutant MICA were able to trigger NK cell cytotoxicity. These data suggest that the presence of NKG2D ligands at the plasma membrane is sufficient to activate cytotoxicity and reflect the need of different ligands to exploit different cellular pathways to reach the cell surface upon different stress situations.