Thermal Radiometer Signal Processing Using Radiation Hard CMOS Application Specific Integrated Circuits for Use in Harsh Planetary Environments

Thermal radiometers such as proposed for the Europa Clipper flyby mission require low noise signal processing for thermal imaging with immunity to Total Ionizing Dose (TID) and Single Event Latchup (SEL). Described is a second generation Multi- Channel Digitizer (MCD2G) Application Specific Integrated Circuit (ASIC) that accurately digitizes up to 40 thermopile pixels with greater than 50 Mrad (Si) immunity TID and 174 MeV-sq cm/mg SEL. The MCD2G ASIC uses Radiation Hardened By Design (RHBD) techniques with a 180 nm CMOS process node

Single Event Transients in Low Voltage Dropout (LVDO) Voltage Regulators

This viewgraph presentation reviews the use of Low Voltage Dropout (LVDO) Voltage Regulators in environments where heavy ion induced Single Event Transients are a concern to the designers.Included in the presentation are results of tests of voltage regulators

Truncating Variants in NAA15 Are Associated with Variable Levels of Intellectual Disability, Autism Spectrum Disorder, and Congenital Anomalies

Genetics of disease, diagnosis and treatmen

System-on-Chip Data Processing and Data Handling Spaceflight Electronics

This paper presents a methodology and a tool set which implements automated generation of moderate-size blocks of customized intellectual property (IP), thus effectively reusing prior work and minimizing the labor intensive, error-prone parts of the design process. Customization of components allows for optimization for smaller area and lower power consumption, which is an important factor given the limitations of resources available in radiation-hardened devices. The effects of variations in HDL coding style on the efficiency of synthesized code for various commercial synthesis tools are also discussed

Paralog Studies Augment Gene Discovery: DDX and DHX Genes

PubMedID: 31256877Members of a paralogous gene family in which variation in one gene is known to cause disease are eight times more likely to also be associated with human disease. Recent studies have elucidated DHX30 and DDX3X as genes for which pathogenic variant alleles are involved in neurodevelopmental disorders. We hypothesized that variants in paralogous genes encoding members of the DExD/H-box RNA helicase superfamily might also underlie developmental delay and/or intellectual disability (DD and/or ID) disease phenotypes. Here we describe 15 unrelated individuals who have DD and/or ID, central nervous system (CNS) dysfunction, vertebral anomalies, and dysmorphic features and were found to have probably damaging variants in DExD/H-box RNA helicase genes. In addition, these individuals exhibit a variety of other tissue and organ system involvement including ocular, outer ear, hearing, cardiac, and kidney tissues. Five individuals with homozygous (one), compound-heterozygous (two), or de novo (two) missense variants in DHX37 were identified by exome sequencing. We identified ten total individuals with missense variants in three other DDX/DHX paralogs: DHX16 (four individuals), DDX54 (three individuals), and DHX34 (three individuals). Most identified variants are rare, predicted to be damaging, and occur at conserved amino acid residues. Taken together, these 15 individuals implicate the DExD/H-box helicases in both dominantly and recessively inherited neurodevelopmental phenotypes and highlight the potential for more than one disease mechanism underlying these disorders. © 2019 American Society of Human GeneticsNational Heart, Lung, and Blood Institute Aicardi Syndrome Foundation: 2T32NS043124-16 National Institute on Drug Abuse National Institute of Diabetes and Digestive and Kidney Diseases: K12 DK083014 National Heart, Lung, and Blood Institute Fondazione Telethon National Institute of Neurological Disorders and Stroke: U54-HG003273 GSP15001 Deutsche Forschungsgemeinschaft California Department of Fish and Game: LE 4223/1 National Human Genome Research Institute National Institutes of Health: K08 HG008986, DK088767 National Cancer Institute R01 NS058529, R35 NS105078 National Institute of Mental Health National Institute of Neurological Disorders and StrokeThis work was supported in part by grants UM1 HG006542 (J.R.L) and UM1 HG006493 (M.B.) from the National Human Genome Research Institute (NHGRI) and the National Heart, Lung, and Blood Institute (NHLBI) to the Baylor Hopkins Center for Mendelian Genomics and the University of Washington Center for Mendelian Genomics, R01 NS058529 and R35 NS105078 (J.R.L.) from the National Institute of Neurological Disorders and Stroke (NINDS), U54-HG003273 (R.A.G.) from NHGRI , and Telethon Undiagnosed Diseases Program (TUDP) GSP15001 (N.B.-P.) from the Telethon Foundation , and also by the Aicardi Syndrome Foundation. I.P. was supported by 2T32NS043124-16 through the National Institutes of Health . J.E.P. was supported by NHGRI K08 HG008986 . F.H. was supported by the National Institutes of Health ( DK088767 ). M.R.B. was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) K12 DK083014 . D.L was supported by the Werner Otto Stiftung and the German Research Foundation ( DFG; LE 4223/1 ). The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health , and by the National Cancer Institute , NHGRI , NHLBI , the National Institute on Drug Abuse , the National Institute of Mental Health , and NINDS . The data used for the analyses described in this manuscript were obtained from the GTEx Portal on 10/29/18. The authors would like to thank Hans-Jurgen Kreienkamp for the help in identifying helicase core motifs and the Genome Aggregation Database (gnomAD) and the groups that provided exome and genome variant data to this resource. A full list of contributing groups can be found at https://gnomad.broadinstitute.org/about

Paralog Studies Augment Gene Discovery: DDX and DHX Genes

Members of a paralogous gene family in which variation in one gene is known to cause disease are eight times more likely to also be associated with human disease. Recent studies have elucidated DHX30 and DDX3X as genes for which pathogenic variant alleles are involved in neurodevelopmental disorders. We hypothesized that variants in paralogous genes encoding members of the DExD/H-box RNA helicase superfamily might also underlie developmental delay and/or intellectual disability (DD and/or ID) disease phenotypes. Here we describe 15 unrelated individuals who have DD and/or ID, central nervous system (CNS) dysfunction, vertebral anomalies, and dysmorphic features and were found to have probably damaging variants in DExD/H-box RNA helicase genes. In addition, these individuals exhibit a variety of other tissue and organ system involvement including ocular, outer ear, hearing, cardiac, and kidney tissues. Five individuals with homozygous (one), compound-heterozygous (two), or de novo (two) missense variants in DHX37 were identified by exome sequencing. We identified ten total individuals with missense variants in three other DDX/DHX paralogs: DHX16 (four individuals), DDX54 (three individuals), and DHX34 (three individuals). Most identified variants are rare, predicted to be damaging, and occur at conserved amino acid residues. Taken together, these 15 individuals implicate the DExD/H-box helicases in both dominantly and recessively inherited neurodevelopmental phenotypes and highlight the potential for more than one disease mechanism underlying these disorders.National Human Genome Research Institute (NHGRI)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [UM1 HG006542, UM1 HG006493]; National Heart, Lung, and Blood Institute (NHLBI)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI); University of Washington Center for Mendelian Genomics [R01 NS058529, R35 NS105078]; National Institute of Neurological Disorders and Stroke (NINDS)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS); NHGRIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [K08 HG008986]; Telethon Undiagnosed Diseases Program [GSP15001]; Telethon FoundationFondazione Telethon; Aicardi Syndrome Foundation [2T32NS043124-16]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [DK088767]; Werner Otto Stiftung [K12 DK083014]; German Research Foundation (DFG)German Research Foundation (DFG) [LE 4223/1]; Common Fund of the Office of the Director of the National Institutes of Health; National Cancer Institute, NHGRI; NHLBIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI); National Institute on Drug AbuseUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA)European Commission; National Institute of Mental HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH); NINDSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS); NATIONAL HUMAN GENOME RESEARCH INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [K08HG008986, UM1HG006542] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [T32GM008307] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R35NS105078] Funding Source: NIH RePORTERThis work was supported in part by grants UM1 HG006542 (J.R.L) and UM1 HG006493 (M.B.) from the National Human Genome Research Institute (NHGRI) and the National Heart, Lung, and Blood Institute (NHLBI) to the Baylor Hopkins Center for Mendelian Genomics and the University of Washington Center for Mendelian Genomics, R01 NS058529 and R35 NS105078(J.R.L.) from the National Institute of Neurological Disorders and Stroke (NINDS), U54-HG003273 (R.A.G.) from NHGRI, and Telethon Undiagnosed Diseases Program (TUDP) GSP15001 (N.B.-P.) from the Telethon Foundation, and also by the Aicardi Syndrome Foundation. I.P. was supported by 2T32NS043124-16 through the National Institutes of Health. J.E.P. was supported by NHGRI K08 HG008986. F.H. was supported by the National Institutes of Health (DK088767). M.R.B. was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) K12 DK083014. D.L was supported by the Werner Otto Stiftung and the German Research Foundation (DFG; LE 4223/1). The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by the National Cancer Institute, NHGRI, NHLBI, the National Institute on Drug Abuse, the National Institute of Mental Health, and NINDS. The data used for the analyses described in this manuscript were obtained from the GTEx Portal on 10/29/18. The authors would like to thank Hans-Jurgen Kreienkamp for the help in identifying helicase core motifs and the Genome Aggregation Database (gnomAD) and the groups that provided exome and genome variant data to this resource. A full list of contributing groups can be found at https://gnomad.broadinstitute.org/about

KBG syndrome involving a single-nucleotide duplication in ANKRD11

KBG syndrome is a rare autosomal dominant genetic condition characterized by neurological involvement and distinct facial, hand, and skeletal features. More than 70 cases have been reported; however, it is likely that KBG syndrome is underdiagnosed because of lack of comprehensive characterization of the heterogeneous phenotypic features. We describe the clinical manifestations in a male currently 13 years of age, who exhibited symptoms including epilepsy, severe developmental delay, distinct facial features, and hand anomalies, without a positive genetic diagnosis. Subsequent exome sequencing identified a novel de novo heterozygous single base pair duplication (c.6015dupA) in ANKRD11, which was validated by Sanger sequencing. This single-nucleotide duplication is predicted to lead to a premature stop codon and loss of function in ANKRD11, thereby implicating it as contributing to the proband's symptoms and yielding a molecular diagnosis of KBG syndrome. Before molecular diagnosis, this syndrome was not recognized in the proband, as several key features of the disorder were mild and were not recognized by clinicians, further supporting the concept of variable expressivity in many disorders. Although a diagnosis of cerebral folate deficiency has also been given, its significance for the proband's condition remains uncertain

The Effects of Architecture and Process on the Hardness of Programmable Technologies

Architecture and process, combined, significantly affect the hardness of programmable technologies. The effects of high energy ions, ferroelectric memory architectures, and shallow trench isolation are investigated. A detailed single event latchup (SEL) study has been performed