Multiscale characterization of the micromechanics of pure Mg

An important limitation of wrought (rolled and extruded) Mg alloys is their inherent strong mechanical anisotropy, a consequence of their hexagonal closed- packed (hcp) lattice. Several reasons contribute to this effect. First, at room temperature, the critical resolved shear stresses (CRSSs) of basal and non-basal slip systems have very different values, spanning several orders of magnitude; second, twinning, a very common deformation mechanism in these materials, exhibits a pronounced polarity, i.e. its activation is dependent on the relative orientation between the c-axis and the applied stress; finally, both hot and cold deformation processing textures are often quite sharp and the way the activation of different slip systems is influenced by the local texture and grain boundary network is not clear. Together, these factors lead to a dependence of the dominant deformation mechanisms on the texture, grain size, testing mode (tension or compression) and the testing direction, resulting in large differences in yield stress values and strain-hardening responses. In this work, we adopt a multiscale characterization strategy to unravel the micromechanisms of pure Mg. First, we present a coupled experimental and simulation study on the nanoindentation of pure Mg at different temperatures to determine the critical resolved shear stress evolution of the different slip systems at the single crystal level [1-3]. For this, several indentations were performed at temperatures between RT and 300 °C in individual grains of a polycrystalline sheet of pure Mg with different crystallographic orientations. The deformation profile and the microstructure around the indents was analyzed by atomic force microscopy (AFM) and electron backscatter diffraction (EBSD), to determine the CRSS of the different slip systems without grain boundary effects. EBSD assisted trace analysis during in-situ SEM mechanical testing of cold-rolled polycrystalline Mg sheets was then used to account for the role of the local microstructure, such as the local texture and grain boundary network, on the activation of the different deformation modes, In particular, it was found that, with decreasing grain size, at room temperature, a clear transition from non-basal to basal-slip dominated flow takes place under tension [4] and a transition from twinning to basal slip takes place under compression [5]. On the other hand, a similar transition from twinning to basal slip takes place with increasing temperature and decreasing strain rate [6]. The emergence of basal slip as a dominant mechanism is shown to be due to increasing levels of connectivity between favorably oriented grains, which facilitate slip transfer across grain boundaries. This study emphasizes the complexity of the micromechanics of pure Mg, where the activation of different deformation modes is strongly affected, not only by their single crystal CRSS levels, but also by the local grain boundary networks and local texture emerging from processing

Entropic bonding of the type 1 pilus from experiment and simulation.

The type 1 pilus is a bacterial filament consisting of a long coiled proteic chain of subunits joined together by non-covalent bonding between complementing β -strands. Its strength and structural stability are critical for its anchoring function in uropathogenic Escherichia coli bacteria. The pulling and unravelling of the FimG subunit of the pilus was recently studied by atomic force microscopy experiments and steered molecular dynamics simulations (Alonso-Caballero et al. 2018 Nat. Commun. 9, 2758. (doi:10.1038/s41467-018-05107-6)). In this work, we perform a quantitative comparison between experiment and simulation, showing a good agreement in the underlying work values for the unfolding. The simulation results are then used to estimate the free energy difference for the detachment of FimG from the complementing strand of the neighbouring subunit in the chain, FimF. Finally, we show that the large free energy difference for the unravelling and detachment of the subunits which leads to the high stability of the chain is entirely entropic in nature

High Trait Anger, Interpersonal Context, and the Recognition of Anger Problems

Background: High trait anger is usually destructive for individuals and their relationships. This proneness to anger is reflected in frequent angry feelings, for longer periods of time, and with higher levels of physical arousal and negative expressions (e.g., insulting or arguing with others). Unfortunately, not all individuals with high trait anger recognize the problem. Objective: This research assessed the contribution of the interpersonal context (e.g., family members, friends, and boyfriend/girlfriend) to recognize anger problems. Methods: We recruited 192 individuals with high trait anger who completed questionnaires about 1) recognition of anger problems, 2) how they are perceived by others in terms of anger (i.e., “being irascible”), and 3) if they care about what others think about their anger. Research Design: Cross-sectional. Results: Individuals who recognized their anger problems perceived they have received more messages of “You are very irascible” from their social contexts, while those who do not recognize anger problems, have received these messages less often. Moreover, the higher the extent to which the individuals care about what other people think or say about their anger (i.e., higher importance attached to messages from others), the more it contributed to a higher recognition of anger problems. In addition, a lower importance attached to such messages was related to a lower recognition of such problems. Recognition of anger problems was higher in participants who had a boyfriend/girlfriend (versus those who did not have one), and in female (versus male) participants

Cloud Computing en salud: Sistema para Administrar Imagenes Biomedicas

En el campo de la biomedicina se genera una inmensa cantidad de imágenes diariamente. Para administrarlas es necesaria la creación de sistemas informáticos robustos y ágiles, que necesitan gran cantidad de recursos computacionales. El presente artículo presenta un servicio de cloud computing capaz de manejar grandes colecciones de imágenes biomédicas. Gracias a este servicio organizaciones y usuarios podrían administrar sus imágenes biomédicas sin necesidad de poseer grandes recursos informáticos. El servicio usa un sistema distribuido multi agente donde las imágenes son procesadas y se extraen y almacenan en una estructura de datos las regiones que contiene junto con sus características. Una característica novedosa del sistema es que una misma imagen puede ser dividida, y las sub-imágenes resultantes pueden ser almacenadas por separado por distintos agentes. Esta característica ayuda a mejorar el rendimiento del sistema a la hora de buscar y recuperar las imágenes almacenadas

The Complete Star Formation History of the Universe

The determination of the star-formation history of the Universe is a key goal of modern cosmology, as it is crucial to our understanding of how structure in the Universe forms and evolves. A picture has built up over recent years, piece-by-piece, by observing young stars in distant galaxies at different times in the past. These studies indicated that the stellar birthrate peaked some 8 billion years ago, and then declined by a factor of around ten to its present value. Here we report on a new study which obtains the complete star formation history by analysing the fossil record of the stellar populations of 96545 nearby galaxies. Broadly, our results support those derived from high-redshift galaxies elsewhere in the Universe. We find, however, that the peak of star formation was more recent - around 5 billion years ago. Our study also shows that the bigger the stellar mass of the galaxy, the earlier the stars were formed. This striking result indicates a very different formation history for high- and low-mass formation.Comment: Accepted by Nature. Press embargo until publishe

First reported double drug–drug interaction in a cancer renal patient under everolimus treatment: therapeutic drug monitoring and review of literature

Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) used in both transplantation and cancer treatment (breast, renal and neuroendocrine). In transplantation, therapeutic drug monitoring (TDM) is recommended due to the potential drug-drug interactions with chronic medications, which can affect everolimus pharmacokinetics. In cancer treatment, everolimus is used at higher doses than in transplantation and without a systematic drug monitoring.We present a case report of a 72-year-old woman with epilepsy history to whom everolimus 10 mg QD was prescribed as third line of treatment for renal cell carcinoma (RCC). The potential drug interactions between everolimus and the patient's chronic medications, carbamazepine and phenytoin, are significant as both are known as strong inducers CYP3A4 metabolism, potentially leading to underexposure to everolimus.TDM of everolimus was recommended by the pharmacist. The literature suggests that a minimum plasma concentration (Cminss) of everolimus over 10 ng/ml is associated with better response to treatment and progression-free survival (PFS). The patient's everolimus dose had to be increased until 10 mg BID, and regular monitoring of everolimus levels showed an increase in Cminss from 3.7 ng/ml to 10.8 ng/ml.This case highlights the importance of checking for potential drug interactions and monitoring everolimus levels in patients on chronic medication, especially those with several inducers or inhibitors of CYP3A4 metabolism. TDM can help to ensure that patients are treated with their optimal dose, which can improve the effectiveness of the treatment or minimize the risk of toxicities

Role of conservative mutations in protein multi-property adaptation

Protein physicochemical properties must undergo complex changes during evolution, as a response to modifications in the organism environment, the result of the proteins taking up new roles or because of the need to cope with the evolution of molecular interacting partners. Recent work has emphasized the role of stability and stability–function trade-offs in these protein adaptation processes. In the present study, on the other hand, we report that combinations of a few conservative, high-frequency-of-fixation mutations in the thioredoxin molecule lead to largely independent changes in both stability and the diversity of catalytic mechanisms, as revealed by single-molecule atomic force spectroscopy. Furthermore, the changes found are evolutionarily significant, as they combine typically hyperthermophilic stability enhancements with modulations in function that span the ranges defined by the quite different catalytic patterns of thioredoxins from bacterial and eukaryotic origin. These results suggest that evolutionary protein adaptation may use, in some cases at least, the potential of conservative mutations to originate a multiplicity of evolutionarily allowed mutational paths leading to a variety of protein modulation patterns. In addition the results support the feasibility of using evolutionary information to achieve protein multi-feature optimization, an important biotechnological goal

Lymphocyte Profile and Immune Checkpoint Expression in Drug-Induced Liver Injury: An Immunophenotyping Study

The identification of specific HLA risk alleles in drug-induced liver injury (DILI) points toward an important role of the adaptive immune system in DILI development. In this study, we aimed to corroborate the role of an adaptive immune response in DILI through immunophenotyping of leukocyte populations and immune checkpoint expressions. Blood samples were collected from adjudicated DILI (n = 12), acute viral hepatitis (VH; n = 13), acute autoimmune hepatitis (AIH; n = 9), and acute liver injury of unknown etiology (n = 15) at day 1 (recognition), day 7, and day >30. Blood samples from patients with nonalcoholic fatty liver disease (NAFLD; n = 20) and healthy liver controls (HLCs; n = 54) were extracted at one time point. Leukocyte populations and immune checkpoint expressions were determined based on cell surface receptors, except for CTLA-4 that was determined intracellularly, using flow cytometry. At recognition, DILI demonstrated significantly higher levels of activated helper T-cell (P < 0.0001), activated cytotoxic T-cells (P = 0.0003), Th1 (P = 0.0358), intracellular CTLA-4 level in helper T-cells (P = 0.0192), and PD-L1 presenting monocytes (P = 0.0452) than HLC. These levels approached those of HLC over time. No significant differences were found between DILI and VH. However, DILI presented higher level of activated helper T-cells and CTLA-4 than NAFLD and lower PD-L1 level than AIH. Our findings suggest that an adaptive immune response is involved in DILI in which activated CD4+ and CD8+ play an important role. Increased expression of negative immune checkpoints is likely the effect of peripheral tolerance regulation.The present study has been supported by grants of Instituto de Salud Carlos III cofounded by Fondo Europeo de Desarrollo Regional – FEDER (contract numbers: PI19/00883, PI16/01748, P18-RT-3364-2020, and PT20/000127). CIBERehd and Plataforma ISCiii Ensayos Clínicos are funded by Instituto de Salud Carlos III. Funding for open access charge: Universidad de Málaga/CBUA. The funding sources had no involvement in the study design; in the collection, analysis, and interpretation of data; in the writing of the report, or in the decision to submit the manuscript for publication