Probes and monitors for the study of solidification of molten semiconductors

The purpose is to examine solidification in the LiCl-KCl system to determine if phenomena such as solute rejection can be obseved by laser schlieren imaging. Molten salts have attributes that make them attractive as physical models in solidification studies. With optical techniques of investigation such as schlieren imaging, it is possible to study fluid flow phenomena in molten salts and to watch the trajectory of the solid-liquid interface

Phase separation kinetics in immiscible liquids

The kinetics of phase separation in the succinonitrile-water system are being investigated. Experiments involve initial physical mixing of the two immiscible liquids at a temperature above the consolute, decreasing the temperature into the miscibility gap, followed by imaging of the resultant microstructure as it evolves with time. Refractive index differences allow documentation of the changing microstructures by noninvasive optical techniques without the need to quench the liquid structures for analysis

A new anode material for oxygen evolution in molten oxide electrolysis

Molten oxide electrolysis (MOE) is an electrometallurgical technique that enables the direct production of metal in the liquid state from oxide feedstock and compared with traditional methods of extractive metallurgy offers both a substantial simplification of the process and a significant reduction in energy consumption. MOE is also considered a promising route for mitigation of CO[subscript 2] emissions in steelmaking, production of metals free of carbon, and generation of oxygen for extra-terrestrial exploration. Until now, MOE has been demonstrated using anode materials that are consumable (graphite for use with ferro-alloys and titanium) or unaffordable for terrestrial applications (iridium for use with iron). To enable metal production without process carbon, MOE requires an anode material that resists depletion while sustaining oxygen evolution. The challenges for iron production are threefold. First, the process temperature is in excess of 1,538 degrees Celsius. Second, under anodic polarization most metals inevitably corrode in such conditions. Third, iron oxide undergoes spontaneous reduction on contact with most refractory metals and even carbon. Here we show that anodes comprising chromium-based alloys exhibit limited consumption during iron extraction and oxygen evolution by MOE. The anode stability is due to the formation of an electronically conductive solid solution of chromium(iii) and aluminium oxides in the corundum structure. These findings make practicable larger-scale evaluation of MOE for the production of steel, and potentially provide a key material component enabling mitigation of greenhouse-gas emissions while producing metal of superior metallurgical quality.American Iron and Steel Institut

Process Demonstration For Lunar In Situ Resource Utilization-Molten Oxide Electrolysis (MSFC Independent Research and Development Project No. 5-81)

The purpose of this Focus Area Independent Research and Development project was to conduct, at Marshall Space Flight Center, an experimental demonstration of the processing of simulated lunar resources by the molten oxide electrolysis process to produce oxygen and metal. In essence, the vision was to develop two key technologies, the first to produce materials (oxygen, metals, and silicon) from lunar resources and the second to produce energy by photocell production on the Moon using these materials. Together, these two technologies have the potential to greatly reduce the costs and risks of NASA s human exploration program. Further, it is believed that these technologies are the key first step toward harvesting abundant materials and energy independent of Earth s resources

Integrating genomic information and productivity and climate-adaptability traits into a regional white spruce breeding program

Tree improvement programs often focus on improving productivity-related traits; however, under present climate change scenarios, climate change-related (adaptive) traits should also be incorporated into such programs. Therefore, quantifying the genetic variation and correlations among productivity and adaptability traits, and the importance of genotype by environment interactions, including defense compounds involved in biotic and abiotic resistance, is essential for selecting parents for the production of resilient and sustainable forests. Here, we estimated quantitative genetic parameters for 15 growth, wood quality, drought resilience, and monoterpene traits for Picea glauca (Moench) Voss (white spruce). We sampled 1,540 trees from three open-pollinated progeny trials, genotyped with 467,224 SNP markers using genotyping-by-sequencing (GBS). We used the pedigree and SNP information to calculate, respectively, the average numerator and genomic relationship matrices, and univariate and multivariate individual-tree models to obtain estimates of (co)variance components. With few site-specific exceptions, all traits examined were under genetic control. Overall, higher heritability estimates were derived from the genomic- than their counterpart pedigree-based relationship matrix. Selection for height, generally, improved diameter and water use efficiency, but decreased wood density, microfibril angle, and drought resistance. Genome-based correlations between traits reaffirmed the pedigree-based correlations for most trait pairs. High and positive genetic correlations between sites were observed (average 0.68), except for those pairs involving the highest elevation, warmer, and moister site, specifically for growth and microfibril angle. These results illustrate the advantage of using genomic information jointly with productivity and adaptability traits, and defense compounds to enhance tree breeding selection for changing climate.Instituto de Recursos BiológicosFil: Cappa, Eduardo Pablo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Recursos Biológicos; ArgentinaFil: Cappa, Eduardo Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Klutsch, Jenifer G. University of Alberta; Department of Renewable Resources; CanadaFil: Sebastian-Azcona, Jaime. University of Alberta; Department of Renewable Resources; CanadaFil: Ratchiffe, Blaise. University of British Columbia. Faculty of Forestry. Department of Forest and Conservation Sciences; CanadáFil: Xiaojing, Wei. University of Alberta; Department of Renewable Resources; CanadaFil: Da Ros, Letitia. University of British Columbia. Faculty of Forestry. Department of Wood Science; CanadáFil: Yang, Liu. University of British Columbia. Faculty of Forestry. Department of Forest and Conservation Sciences; CanadáFil: Chen, Charles. Oklahoma State University. Department of Biochemistry and Molecular Biology; Estados UnidosFil: Benowicz, Andy. Alberta Agriculture and Forestry. Forest Stewardship and Trade Branch; CanadáFil: Sadoway, Shane. Blue Ridge Lumber Inc.; CanadáFil: Mansfield, Shawn D. University of British Columbia. Faculty of Forestry. Department of Wood Science; CanadáFil: Erbilgin, Nadir. University of Alberta; Department of Renewable Resources; CanadaFil: Thomas, Barb R. University of Alberta; Department of Renewable Resources; CanadaFil: El-Kassaby, Yousry A. University of British Columbia. Faculty of Forestry. Department of Forest and Conservation Sciences; Canad

NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns

Purpose: Pathogenic variants in the X-linked gene NEXMIF (previously KIAA2022) are associated with intellectual disability (ID), autism spectrum disorder, and epilepsy. We aimed to delineate the female and male phenotypic spectrum of NEXMIF encephalopathy. / Methods: Through an international collaboration, we analyzed the phenotypes and genotypes of 87 patients with NEXMIF encephalopathy. / Results: Sixty-three females and 24 males (46 new patients) with NEXMIF encephalopathy were studied, with 30 novel variants. Phenotypic features included developmental delay/ID in 86/87 (99%), seizures in 71/86 (83%) and multiple comorbidities. Generalized seizures predominated including myoclonic seizures and absence seizures (both 46/70, 66%), absence with eyelid myoclonia (17/70, 24%), and atonic seizures (30/70, 43%). Males had more severe developmental impairment; females had epilepsy more frequently, and varied from unaffected to severely affected. All NEXMIF pathogenic variants led to a premature stop codon or were deleterious structural variants. Most arose de novo, although X-linked segregation occurred for both sexes. Somatic mosaicism occurred in two males and a family with suspected parental mosaicism. / Conclusion: NEXMIF encephalopathy is an X-linked, generalized developmental and epileptic encephalopathy characterized by myoclonic–atonic epilepsy overlapping with eyelid myoclonia with absence. Some patients have developmental encephalopathy without epilepsy. Males have more severe developmental impairment. NEXMIF encephalopathy arises due to loss-of-function variants

Polygenic burden in focal and generalized epilepsies

Rare genetic variants can cause epilepsy, and genetic testing has been widely adopted for severe, paediatric-onset epilepsies. The phenotypic consequences of common genetic risk burden for epilepsies and their potential future clinical applications have not yet been determined. Using polygenic risk scores (PRS) from a European-ancestry genome-wide association study in generalized and focal epilepsy, we quantified common genetic burden in patients with generalized epilepsy (GE-PRS) or focal epilepsy (FE-PRS) from two independent non-Finnish European cohorts (Epi25 Consortium, n = 5705; Cleveland Clinic Epilepsy Center, n = 620; both compared to 20 435 controls). One Finnish-ancestry population isolate (Finnish-ancestry Epi25, n = 449; compared to 1559 controls), two European-ancestry biobanks (UK Biobank, n = 383 656; Vanderbilt biorepository, n = 49 494), and one Japaneseancestry biobank (BioBank Japan, n = 168 680) were used for additional replications. Across 8386 patients with epilepsy and 622 212 population controls, we found and replicated significantly higher GE-PRS in patients with generalized epilepsy of European-ancestry compared to patients with focal epilepsy (Epi25: P = 1.64 710-15; Cleveland: P = 2.85 710-4; Finnish-ancestry Epi25: P = 1.80 710-4) or population controls (Epi25: P = 2.35 710-70; Cleveland: P = 1.43 710-7; Finnish-ancestry Epi25: P = 3.11 710-4; UK Biobank and Vanderbilt biorepository meta-analysis: P = 7.99 710-4). FE-PRS were significantly higher in patients with focal epilepsy compared to controls in the non-Finnish, non-biobank cohorts (Epi25: P = 5.74 710-19; Cleveland: P = 1.69 710-6). European ancestry-derived PRS did not predict generalized epilepsy or focal epilepsy in Japanese-ancestry individuals. Finally, we observed a significant 4.6-fold and a 4.5-fold enrichment of patients with generalized epilepsy compared to controls in the top 0.5% highest GE-PRS of the two non-Finnish European cohorts (Epi25: P = 2.60 710-15; Cleveland: P = 1.39 710-2). We conclude that common variant risk associated with epilepsy is significantly enriched in multiple cohorts of patients with epilepsy compared to controls-in particular for generalized epilepsy. As sample sizes and PRS accuracy continue to increase with further common variant discovery, PRS could complement established clinical biomarkers and augment genetic testing for patient classification, comorbidity research, and potentially targeted treatment

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12- q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

Ultra-Rare Genetic Variation in the Epilepsies : A Whole-Exome Sequencing Study of 17,606 Individuals

Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,436 controls of European ancestry. We focused on three phenotypic groups: severe developmental and epileptic encephalopathies (DEEs), genetic generalized epilepsy (GGE), and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy; we saw the strongest enrichment in individuals with DEEs and the least strong in individuals with NAFE. Moreover, we found that inhibitory GABA(A) receptor genes were enriched for missense variants across all three classes of epilepsy, whereas no enrichment was seen in excitatory receptor genes. The larger gene groups for the GABAergic pathway or cation channels also showed a significant mutational burden in DEEs and GGE. Although no single gene surpassed exome-wide significance among individuals with GGE or NAFE, highly constrained genes and genes encoding ion channels were among the lead associations; such genes included CACNAIG, EEF1A2, and GABRG2 for GGE and LGI1, TRIM3, and GABRG2 for NAFE. Our study, the largest epilepsy WES study to date, confirms a convergence in the genetics of severe and less-severe epilepsies associated with ultra-rare coding variation, and it highlights a ubiquitous role for GABAergic inhibition in epilepsy etiology.Peer reviewe

Sub-genic intolerance, ClinVar, and the epilepsies: A whole-exome sequencing study of 29,165 individuals

Both mild and severe epilepsies are influenced by variants in the same genes, yet an explanation for the resulting phenotypic variation is unknown. As part of the ongoing Epi25 Collaboration, we performed a whole-exome sequencing analysis of 13,487 epilepsy-affected individuals and 15,678 control individuals. While prior Epi25 studies focused on gene-based collapsing analyses, we asked how the pattern of variation within genes differs by epilepsy type. Specifically, we compared the genetic architectures of severe developmental and epileptic encephalopathies (DEEs) and two generally less severe epilepsies, genetic generalized epilepsy and non-acquired focal epilepsy (NAFE). Our gene-based rare variant collapsing analysis used geographic ancestry-based clustering that included broader ancestries than previously possible and revealed novel associations. Using the missense intolerance ratio (MTR), we found that variants in DEE-affected individuals are in significantly more intolerant genic sub-regions than those in NAFE-affected individuals. Only previously reported pathogenic variants absent in available genomic datasets showed a significant burden in epilepsy-affected individuals compared with control individuals, and the ultra-rare pathogenic variants associated with DEE were located in more intolerant genic sub-regions than variants associated with non-DEE epilepsies. MTR filtering improved the yield of ultra-rare pathogenic variants in affected individuals compared with control individuals. Finally, analysis of variants in genes without a disease association revealed a significant burden of loss-of-function variants in the genes most intolerant to such variation, indicating additional epilepsy-risk genes yet to be discovered. Taken together, our study suggests that genic and sub-genic intolerance are critical characteristics for interpreting the effects of variation in genes that influence epilepsy