Terrace grading of SiGe for high-quality virtual substrates

Silicon germanium (SiGe) virtual substrates of final germanium composition x = 0.50 have been fabricated using solid-source molecular beam epitaxy with a thickness of 2 µm. A layer structure that helps limit the size of dislocation pileups associated with the modified Frank–Read dislocation multiplication mechanism has been studied. It is shown that this structure can produce lower threading dislocation densities than conventional linearly graded virtual substrates. Cross-sectional transmission electron microscopy shows the superior quality of the dislocation network in the graded regions with a lower rms roughness shown by atomic force microscopy. X-ray diffractometry shows these layers to be highly relaxed. This method of Ge grading suggests that high-quality virtual substrates can be grown considerably thinner than with conventional grading methods

Misfit strain relaxation and dislocation formation in supercritical strained silicon on virtual substrates

Relaxation of strained silicon on 20% linear graded virtual substrates was quantified using high resolution x-ray diffraction and a defect etching technique. The thickness of strained silicon was varied between 10 and 180 nm. Relaxation was observed in layers below the critical thickness but increased to only 2% relaxation in the thickest layers even with annealings up to 950 °C. Cross-sectional transmission electron microscopy revealed stacking faults present in layers thicker than 25 nm, and nucleated 90° Shockley partial dislocations forming microtwins in the thickest layer. These features are implicated in the impediment of the relaxation process

Technique for producing highly planar Si/SiO0.64Ge0.36/Si metal–oxide–semiconductor field effect transistor channels

Si/Si0.64Ge0.36/Si heterostructures have been grown at low temperature (450 °C) to avoid the strain-induced roughening observed for growth temperatures of 550 °C and above. The electrical properties of these structures are poor, and thought to be associated with grown-in point defects as indicated in positron annihilation spectroscopy. However, after an in situ annealing procedure (800 °C for 30 min) the electrical properties dramatically improve, giving an optimum 4 K mobility of 2500 cm2 V – 1 s – 1 for a sheet density of 6.2 × 1011 cm – 2. The low temperature growth yields highly planar interfaces, which are maintained after anneal as evidenced from transmission electron microscopy. This and secondary ion mass spectroscopy measurements demonstrate that the metastably strained alloy layer can endure the in situ anneal procedure necessary for enhanced electrical properties. Further studies have shown that the layers can also withstand a 120 min thermal oxidation at 800 °C, commensurate with metal–oxide–semiconductor device fabrication

Effective mobilities in pseudomorphic Si/SiGe/Si p-channel metal-oxide-semiconductor field-effect transistors with thin silicon capping layers

The room-temperature effective mobilities of pseudomorphic Si/Si0.64Ge0.36/Si p-metal-oxidesemiconductor field effect transistors are reported. The peak mobility in the buried SiGe channel increases with silicon cap thickness. It is argued that SiO2/Si interface roughness is a major source of scattering in these devices, which is attenuated for thicker silicon caps. It is also suggested that segregated Ge in the silicon cap interferes with the oxidation process, leading to increased SiO2/Si interface roughness in the case of thin silicon caps

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Genetic determinants of cortical structure (thickness, surface area and volumes) among disease free adults in the CHARGE Consortium

Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging

Cellular Active N-Hydroxyurea FEN1 Inhibitors Block Substrate Entry to the Active Site

The structure-specific nuclease human flap endonuclease-1 (hFEN1) plays a key role in DNA replication and repair and may be of interest as an oncology target. We present the first crystal structure of inhibitor-bound hFEN1 and show a cyclic N-hydroxyurea bound in the active site coordinated to two magnesium ions. Three such compounds had similar IC50 values but differed subtly in mode of action. One had comparable affinity for protein and protein– substrate complex and prevented reaction by binding to active site catalytic metal ions, blocking the unpairing of substrate DNA necessary for reaction. Other compounds were more competitive with substrate. Cellular thermal shift data showed engagement of both inhibitor types with hFEN1 in cells with activation of the DNA damage response evident upon treatment. However, cellular EC50s were significantly higher than in vitro inhibition constants and the implications of this for exploitation of hFEN1 as a drug target are discussed

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

A genomic catalog of Earth’s microbiomes

The reconstruction of bacterial and archaeal genomes from shotgun metagenomes has enabled insights into the ecology and evolution of environmental and host-associated microbiomes. Here we applied this approach to >10,000 metagenomes collected from diverse habitats covering all of Earth’s continents and oceans, including metagenomes from human and animal hosts, engineered environments, and natural and agricultural soils, to capture extant microbial, metabolic and functional potential. This comprehensive catalog includes 52,515 metagenome-assembled genomes representing 12,556 novel candidate species-level operational taxonomic units spanning 135 phyla. The catalog expands the known phylogenetic diversity of bacteria and archaea by 44% and is broadly available for streamlined comparative analyses, interactive exploration, metabolic modeling and bulk download. We demonstrate the utility of this collection for understanding secondary-metabolite biosynthetic potential and for resolving thousands of new host linkages to uncultivated viruses. This resource underscores the value of genome-centric approaches for revealing genomic properties of uncultivated microorganisms that affect ecosystem processes