Obstruction to movement in edge dislocations ½ <111> {110} by Cu, Mn and Ni solutes

El principal mecanismo de fragilización de los aceros bainíticos por la irradiación es la obstrucción al movimiento de las dislocaciones. Los defectos estructurales responsables de esta obstrucción son producto de la irradiación a la que está sometido el material. En particular los precipitados de Cu, Ni y Mn son considerados como los principales contribuyentes a la fragilización y la evidencia experimental indica que se ubican preferentemente en la zona de la línea de dislocación. En este trabajo se estudia el efecto de la segregación alrededor de las dislocaciones de borde con vector de Burgers b = 1/2[111] y la tensión necesaria para el movimiento. Para redistribuir los átomos de soluto minimizando la energía se aplica un algoritmo de Monte Carlo en el ensamble semi-gran-canónico. La tensión de corte crítica se estudia mediante la técnica de dinámica molecular y se analiza como afecta la presencia de Cu en una matriz de Fe con 1%Ni-1%Mn. Los resultados muestran que la tensión requerida para mover las dislocaciones aumenta sustancialmente con la presencia de solutos segregados.The main mechanism of embrittlement of bainitic steels by irradiation is the impediment of dislocation movement. Structural defects responsible for this obstruction are a product of irradiation. In particular, Cu, Ni and Mn precipitates are considered as major contributors to embrittlement and experimental evidence indicates that preferentially locate in the area of the dislocation line. In this paper we study the effect of this segregation around edge dislocations with Burgers vector b = 1/2 [111] and the stress required for the movement. A Monte Carlo algorithm in the semi-grand canonical ensemble is used to study the alloying elements segregation to the dislocation core. The critical resolved shear stress is studied by molecular dynamics to analyze the effect of Cu atoms in a Fe-matrix containing 1%Ni-1%Mn. The results show that the stress required for the dislocation to break-away substantially increases with the presence of segregated solutes.Fil: Pascuet, Maria Ines Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: E. Martínez. Los Alamos National Laboratory; Estados Unido

Solute effects on edge dislocation pinning in complex alpha-Fe alloys

Reactor pressure vessel steels are well-known to harden and embrittle under neutron irradiation, mainly because of the formation of obstacles to the motion of dislocations, in particular, precipitates and clusters composed of Cu, Ni, Mn, Si and P. In this paper, we employ two complementary atomistic modelling techniques to study the heterogeneous precipitation and segregation of these elements and their effects on the edge dislocations in BCC iron. We use a special and highly computationally efficient Monte Carlo algorithm in a constrained semi-grand canonical ensemble to compute the equilibrium configurations for solute clusters around the dislocation core. Next, we use standard molecular dynamics to predict and analyze the effect of this segregation on the dislocation mobility. Consistently with expectations our results confirm that the required stress for dislocation unpinning from the precipitates formed on top of it is quite large. The identification of the precipitate resistance allows a quantitative treatment of atomistic results, enabling scale transition towards larger scale simulations, such as dislocation dynamics or phase field.Fil: Pascuet, Maria Ines Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comision Nacional de Energia Atomica. Centro Atomico Constituyentes. Departamento de Materiales; ArgentinaFil: Martínez, E.. Los Alamos National High Magnetic Field Laboratory; Estados UnidosFil: Monnet, G.. EDF–R&D; FranciaFil: Malerba, L.. SCK•CEN. Structural Materials Expert Group. Nuclear Materials Institute; Bélgic

Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding: Sanofi and Regeneron Pharmaceuticals

Solute precipitation on a screw dislocation and its effects on dislocation mobility in bcc Fe

Reactor pressure vessel steels are well-known to harden and embrittle under neutron irradiation. The primary mechanism of radiation embrittlement for these bainitic steels is the obstruction of dislocation motion, mainly due to clusters or precipitates of solute atoms such as Cu, Ni, Mn, Si and P. Microstructural examinations reveal that these clusters or precipitates are often preferentially formed at dislocation lines, which are sometimes completely surrounded by segregated solute clusters. Evidence of this is provided in this work, too, which extends a previous one dedicated to edge dislocations, by studying the effect of this segregation around screw dislocations (Burgers vector b = 1/2 [111]) on the critical stress for dislocation motion. A Monte Carlo algorithm in a variance-constrained semi-grand canonical (VC-SGC) ensemble is applied to study the decoration of atoms around dislocations, by minimizing the free energy. Next, the critical stress for dislocation unpinning from the clusters is evaluated by standard molecular dynamics to analyze the effect of Cu, Ni, Mn, and P segregation in the Fe matrix. Consistently with expectations and in agreement with previous work, our results highlight that the required stress for triggering dislocation motion drastically increases due to the presence of segregated solutes. Our finding is that solute-decorated screw dislocations may be considered as practically immobile because of the strong segregation around them.Fil: Pascuet, Maria Ines Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica; ArgentinaFil: Monnet, G.. No especifíca;Fil: Bonny, G.. No especifíca;Fil: Martínez, E.. Los Alamos National Laboratory; Estados UnidosFil: Lim, J.J.H.. United Kingdom Atomic Energy Authority; Reino UnidoFil: Burke, M.G.. University of Manchester; Reino UnidoFil: Malerba, L.. No especifíca