Mechanistic origin of high retained strength in refractory BCC high entropy alloys up to 1900K

The body centered cubic (BCC) high entropy alloys MoNbTaW and MoNbTaVW show exceptional strength retention up to 1900K. The mechanistic origin of the retained strength is unknown yet is crucial for finding the best alloys across the immense space of BCC HEA compositions. Experiments on Nb-Mo, Fe-Si and Ti-Zr-Nb alloys report decreased mobility of edge dislocations, motivating a theory of strengthening of edge dislocations in BCC alloys. Unlike pure BCC metals and dilute alloys that are controlled by screw dislocation motion at low temperatures, the strength of BCC HEAs can be controlled by edge dislocations, and especially at high temperatures, due to the barriers created for edge glide through the random field of solutes. A parameter-free theory for edge motion in BCC alloys qualitatively and quantitatively captures the strength versus temperature for the MoNbTaW and MoNbTaVW alloys. A reduced analytic version of the theory then enables screening over >600,000 compositions in the Mo-Nb-Ta-V-W family, identifying promising new compositions with high retained strength and/or reduced mass density. Overall, the theory reveals an unexpected mechanism responsible for high temperature strength in BCC alloys and paves the way for theory-guided design of stronger high entropy alloys.Comment: This version corrects the theory and provides more extensive explanation

Molecular mechanisms behind inherited neurodegeneration of the optic nerve

Inherited neurodegeneration of the optic nerve is a paradigm in neurology, as many forms of isolated or syndromic optic atrophy are encountered in clinical practice. The retinal ganglion cells originate the axons that form the optic nerve. They are particularly vulnerable to mitochondrial dysfunction, as they present a peculiar cellular architecture, with axons that are not myelinated for a long intra-retinal segment, thus, very energy dependent. The genetic landscape of causative mutations and genes greatly enlarged in the last decade, pointing to common pathways. These mostly imply mitochondrial dysfunction, which leads to a similar outcome in terms of neurodegeneration. We here critically review these pathways, which include (1) complex I-related oxidative phosphor-ylation (OXPHOS) dysfunction, (2) mitochondrial dynamics, and (3) endoplasmic reticulum-mito-chondrial inter-organellar crosstalk. These major pathogenic mechanisms are in turn interconnected and represent the target for therapeutic strategies. Thus, their deep understanding is the basis to set and test new effective therapies, an urgent unmet need for these patients. New tools are now available to capture all interlinked mechanistic intricacies for the pathogenesis of optic nerve neuro-degeneration, casting hope for innovative therapies to be rapidly transferred into the clinic and effectively cure inherited optic neuropathies

Information Diversity in Coherent MIMO Radars

In this paper, the concept of information diversity in both the space and frequency domains is investigated for multiple-input multiple-output (MIMO) radars with widely separated antennas. Compared to phased-antenna arrays and multistatic radars, they can exploit more degrees of freedom, allowing them to maximize the information content upon centralized data fusion, thus granting unprecedented target detection and localization capabilities.This analysis proceeds in parallel with the running progresses of microwave photonics (MWP), which could represent, in the near future, a new paradigm for the development of centralized MIMO radar architectures.Thus, understanding the implications of information diversity becomes essential to foretell the system effectiveness in detecting and resolving closely spaced targets, as well as in suppressing sidelobes which may lead to false alarms. Performance metrics are proposed and evaluated to characterize the effects that information diversity has on centralized MIMO radars with widely separated antennas. On the other hand, the proposed methodology could reveal precious for designing the optimum system configuration

Update on Adverse Effects of HIV Integrase Inhibitors

PURPOSE OF REVIEW: The goal of this paper is to provide an up-to-date review of adverse events related to the class of integrase strand transfer inhibitors (INSTIs), which became the class of choice in few years. We sought answers specifically to issues pertaining to neuropsychiatric adverse events, as well as weight gain, which were the two most important categories of adverse events raised in recent studies based on real-life experience. The primary focus of this paper is on adults with a brief summary on pregnant women and children/adolescents. RECENT FINDINGS: Dolutegravir (DTG) bears the heaviest burden of neuropsychiatric side effects. Weight gain was reported with all INSTIs, although there are methodological caveats in the analyses and the findings need to be interpreted with caution. Moreover, due to recent findings on neural tube defects in infants exposed to dolutegravir during their peri-conception period, its use is not recommended for women of childbearing age without proper birth control method, while raltegravir remains the only drug which may be prescribed without caution. Given the importance of cognitive and metabolic co-morbidities in people living with HIV in regard to their quality of life, future research needs to focus on long-term effects of INSTIs in relation to these adverse events. Pharmacogenetics seems to be a promising tool. Safety during pregnancy is also another important issue to further clarify. SUMMARY: INSTIs are a generally well-tolerated class of antiretrovirals (ARV), and has a higher antiviral potency compared to other classes of ARV. Clinicians and patients need however to be aware of some red flags when starting with and monitoring patients on INSTIs. All INSTIs can lead to mild increases in creatinine levels, usually without clinical significance, but caution is needed in patients with low eGFR (<30ml/min), when using other nephrotoxic drugs, such as as tenofovir disoproxil. Neuro-psychiatric (NP) effects are to be monitored with INSTIs, especially with DTG (though reports are at times contradictory); clinicians might want to avoid DTG for patients with history of severe NP symptoms, until clarity is provided. Weight gain was reported with all INSTIs, especially with DTG, with possible differential effects according to sex and ethnicity (female and non-white patients being at increased risk). This is worrying since patients from African descent are at higher risk of cardio-vascular events and increased body mass index (BMI) can cause further increase metabolic risk. There is possibly an additional effect of tenofovir alafenamide (TAF) on weight increase. Discrepancies between clinical trials – with low rates of adverse events – and reports from real-life settings might be due partly to under-representation of some groups of patients in clinical trials, and/or the short duration of follow-up, since some adverse effects may only occur after prolonged exposure. Preliminary data on safety of bictegravir (BIC), from clinical trials and non-trial settings, are very reassuring and seem to show lower rates of adverse events compared to DTG. Elvitegravir/cobicistat (EVG/cobi) need to be used with caution in patients with other co-morbidities given potential for polypharmacy, as it is the case for aging patients, because of the high potential of drug-drug interactions due to effects of the cobicistat booster. We are awaiting the release of cabotegravir (CAB), which could represent a good option for patients struggling with adherence, despite injection site reactions. Pharmacogenetics is a promising way to explore adverse effects occurrence in the INSTI class

Author Correction: High energy barriers for edge dislocation motion in body-centered cubic high entropy alloys (npj Computational Materials, (2021), 7, 1, (112), 10.1038/s41524-021-00577-7)

The original version of this Article contained an error in the Acknowledgements: ‘Project 200021_18198/1’ should have read ‘Project 200021_181987/1’. This has now been corrected in both the PDF and HTML versions of the Article

Chromosome Biorientation Produces Hundreds of Piconewtons at a Metazoan Kinetochore

High-fidelity transmission of the genome through cell division requires that all sister kinetochores bind to dynamic microtubules (MTs) from opposite spindle poles. The application of opposing forces to this bioriented configuration produces tension that stabilizes kinetochore–microtubule (kt–MT) attachments. Defining the magnitude of force that is applied to kinetochores is central to understanding the mechano-molecular underpinnings of chromosome segregation; however, existing kinetochore force measurements span orders of magnitude. Here we measure kinetochore forces by engineering two calibrated force sensors into the Drosophila kinetochore protein centromere protein (CENP)-C. Measurements of both reporters indicate that they are, on average, under ∼1–2 piconewtons (pNs) of force at metaphase. Based on estimates of the number of CENP-C molecules and MTs per Drosophila kinetochore and envisioning kinetochore linkages arranged such that they distribute forces across them, we propose that kinetochore fibres (k-fibres) exert hundreds of pNs of poleward-directed force to bioriented kinetochores

Opioid-free anesthesia—dexmedetomidine as adjuvant in erector spinae plane block: a case series

Background: Laparoscopic pain is related to the stretching of the peritoneum and peritoneal irritation caused by insufflation of the parietal peritoneum with carbon dioxide. In 2017, erector spinae plane block (ESPB) was described for management of postoperative pain following open and laparoscopic abdominal surgery. The use of multimodal anesthesia reduces both intraoperative and postoperative opioid use and improves analgesia. The addition of dexmedetomidine to the anesthetic mixture significantly prolongs analgesia, without clinically significant side effects. Case Presentation: We describe a series of three Caucasian women cases that illustrate the efficacy of bilateral ESPB performed at the level of the T7 transverse process to provide intraoperative and postoperative analgesia for laparoscopic gynecological surgery. Conclusion: Further investigation is recommended to establish the potential for ESPB with dexmedetomidine as adjuvant as an opioid-free anesthetic modality in laparoscopic gynecological surgery

High energy barriers for edge dislocation motion in body-centered cubic high entropy alloys

Recent theory proposes that edge dislocations in random body-centered cubic (BCC) high entropy alloys have high barriers for motion, conveying high strengths up to high temperatures. Here, the energy barriers for edge motion are computed for two model alloys, NbTaV and MoNbTaW as represented by interatomic potentials, using the Nudged Elastic Band method and compared to theoretical predictions. The average magnitude of the barriers and the average spacing of the barriers along the glide direction agree well with the analytical theory, with no adjustable parameters. The evolution of the barriers versus applied stress is modeled, and the mean strength is in reasonable agreement with the predicted zero-temperature strength. These findings validate the analytic theory. A reduced analytic model based on solute misfit volumes is then applied to Hf-Mo-Nb-Ta-Ti-Zr and Mo-Nb-Ta-Ti-V-W alloys, rationalizing the observed significant strength increases at room temperature and 1000 C-circle upon addition of solutes with large misfit into a base alloy. The analytic theory for edge motion is thus a powerful validated tool for guiding alloy selection

Biological Responses to Cadmium Stress in Liverwort Conocephalum conicum (Marchantiales)

Oxidative damage (production and localization of reactive oxygen species) and related response mechanisms (activity of antioxidant enzymes), and induction of Heat Shock Protein 70 expression, have been studied in the toxi-tolerant liverwort Conocephalum conicum (Marchantiales) in response to cadmium stress using two concentrations (36 and 360 µM CdCl2). Cadmium dose-dependent production of reactive oxygen species (ROS) and related activity of antioxidant enzymes was observed. The expression level of heat shock protein (Hsp)70, instead, was higher at 36 µM CdCl2 in comparison with the value obtained after exposure to 360 µM CdCl2, suggesting a possible inhibition of the expression of this stress gene at higher cadmium exposure doses. Biological responses were related to cadmium bioaccumulation. Since C. conicum was able to respond to cadmium stress by modifying biological parameters, we discuss the data considering the possibility of using these biological changes as biomarkers of cadmium pollution