A Re-examination of the Portevin-Le Chatelier Effect in Alloy 718 in Connection with Oxidation-Assisted Intergranular Cracking

In Alloy 718, a sharp transition exists in the fracture path changing from an intergranular brittle mode to a transgranular ductile mode which is associated with a transition of flow behavior from smooth in the dynamic strain aging regime to a serrated one in the Portevin-Le Chatelier (PLC) regime. In order to better understand both deformation and rupture behavior, PLC phenomenon in a precipitation-hardened nickel-base superalloy was carefully investigated in a wide range of temperatures [573 K to 973 K (300°C to 700°C)] and strain rates (109^-5 to 3.2910^-2 s^-1 ). Distinction was made between two PLC domains characterized by different evolutions of the critical strain to the onset of the first serration namely normal and inverse behavior. The apparent activation energies associated with both domains were determined using different methods. Results showed that normal and inverse behavior domains are related to dynamic interaction of dislocations with, respectively, interstitial and substitutional solutes atoms. This analysis confirms that normal PLC regime may be associated to the diffusion of carbon atoms, whereas the substitutional species involves in the inverse regime is discussed with an emphasis on the role of Nb and Mo

Multi-system neurological disease is common in patients with OPA1 mutations

Additional neurological features have recently been described in seven families transmitting pathogenic mutations in OPA1, the most common cause of autosomal dominant optic atrophy. However, the frequency of these syndromal 'dominant optic atrophy plus' variants and the extent of neurological involvement have not been established. In this large multi-centre study of 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular neurological complications are common in OPA1 disease, and affect up to 20% of all mutational carriers. Bilateral sensorineural deafness beginning in late childhood and early adulthood was a prominent manifestation, followed by a combination of ataxia, myopathy, peripheral neuropathy and progressive external ophthalmoplegia from the third decade of life onwards. We also identified novel clinical presentations with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple sclerosis-like illness. In contrast to initial reports, multi-system neurological disease was associated with all mutational subtypes, although there was an increased risk with missense mutations [odds ratio = 3.06, 95% confidence interval = 1.44-6.49; P = 0.0027], and mutations located within the guanosine triphosphate-ase region (odds ratio = 2.29, 95% confidence interval = 1.08-4.82; P = 0.0271). Histochemical and molecular characterization of skeletal muscle biopsies revealed the presence of cytochrome c oxidase-deficient fibres and multiple mitochondrial DNA deletions in the majority of patients harbouring OPA1 mutations, even in those with isolated optic nerve involvement. However, the cytochrome c oxidase-deficient load was over four times higher in the dominant optic atrophy + group compared to the pure optic neuropathy group, implicating a causal role for these secondary mitochondrial DNA defects in disease pathophysiology. Individuals with dominant optic atrophy plus phenotypes also had significantly worse visual outcomes, and careful surveillance is therefore mandatory to optimize the detection and management of neurological disability in a group of patients who already have significant visual impairment

DigiTranScope: some key findings

Digitranscope originated from the JRC Strategy 20301. The strategy identified ten strategic topics on which the JRC should concentrate to anticipate future policy requests. One of these topics was ‘Data and Digital Transformation’, to which the JRC set up two initiatives: the first being a transversal project on ‘Artificial Intelligence and Digital Transformation’, the second being a CAS research project on digital transformation, which was to be more exploratory in nature. The CAS project originally proposed to address two key issues: i) how the information glut triggered by digital transformation reverses the cognitive balance between humans and machines, and ii) the impact of digital information technology on the rules and institutions that guide modern societies. This proposal therefore led to the establishment of two projects in 2017: ‘Human behaviour and machine intelligence’ (HUMAINT)2 and our project, ‘Digital transformation and the governance of human society’ (Digitranscope)

DigiTranScope: some key findings

Digitranscope originated from the JRC Strategy 20301. The strategy identified ten strategic topics on which the JRC should concentrate to anticipate future policy requests. One of these topics was ‘Data and Digital Transformation’, to which the JRC set up two initiatives: the first being a transversal project on ‘Artificial Intelligence and Digital Transformation’, the second being a CAS research project on digital transformation, which was to be more exploratory in nature. The CAS project originally proposed to address two key issues: i) how the information glut triggered by digital transformation reverses the cognitive balance between humans and machines, and ii) the impact of digital information technology on the rules and institutions that guide modern societies. This proposal therefore led to the establishment of two projects in 2017: ‘Human behaviour and machine intelligence’ (HUMAINT)2 and our project, ‘Digital transformation and the governance of human society’ (Digitranscope)

Multi-dimensional modeling and simulation of semiconductor nanophotonic devices

Self-consistent modeling and multi-dimensional simulation of semiconductor nanophotonic devices is an important tool in the development of future integrated light sources and quantum devices. Simulations can guide important technological decisions by revealing performance bottlenecks in new device concepts, contribute to their understanding and help to theoretically explore their optimization potential. The efficient implementation of multi-dimensional numerical simulations for computer-aided design tasks requires sophisticated numerical methods and modeling techniques. We review recent advances in device-scale modeling of quantum dot based single-photon sources and laser diodes by self-consistently coupling the optical Maxwell equations with semiclassical carrier transport models using semi-classical and fully quantum mechanical descriptions of the optically active region, respectively. For the simulation of realistic devices with complex, multi-dimensional geometries, we have developed a novel hp-adaptive finite element approach for the optical Maxwell equations, using mixed meshes adapted to the multi-scale properties of the photonic structures. For electrically driven devices, we introduced novel discretization and parameter-embedding techniques to solve the drift-diffusion system for strongly degenerate semiconductors at cryogenic temperature. Our methodical advances are demonstrated on various applications, including vertical-cavity surface-emitting lasers, grating couplers and single-photon sources

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Genetic mechanisms of critical illness in Covid-19.

Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by Covid-19. Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study(GWAS) in 2244 critically ill Covid-19 patients from 208 UK intensive care units (ICUs). We identify and replicate novel genome-wide significant associations, on chr12q24.13 (rs10735079, p=1.65 [Formula: see text] 10-8) in a gene cluster encoding antiviral restriction enzyme activators (OAS1, OAS2, OAS3), on chr19p13.2 (rs2109069, p=2.3 [Formula: see text] 10-12) near the gene encoding tyrosine kinase 2 (TYK2), on chr19p13.3 (rs2109069, p=3.98 [Formula: see text] 10-12) within the gene encoding dipeptidyl peptidase 9 (DPP9), and on chr21q22.1 (rs2236757, p=4.99 [Formula: see text] 10-8) in the interferon receptor gene IFNAR2. We identify potential targets for repurposing of licensed medications: using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease; transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe Covid-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms, and mediators of inflammatory organ damage in Covid-19. Both mechanisms may be amenable to targeted treatment with existing drugs. Large-scale randomised clinical trials will be essential before any change to clinical practice

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Wood and fibre properties of dryland conifers A report for the RIRDC/Land & Water Australia/FWPRDC/MDB