Efforts to identify the genetic underpinnings of rare undiagnosed diseases increasingly involve the use of next-generation sequencing and comparative genomic hybridization methods. These efforts are ...limited by a lack of knowledge regarding gene function, and an inability to predict the impact of genetic variation on the encoded protein function. Diagnostic challenges posed by undiagnosed diseases have solutions in model organism research, which provides a wealth of detailed biological information. Model organism geneticists are by necessity experts in particular genes, gene families, specific organs, and biological functions. Here, we review the current state of research into undiagnosed diseases, highlighting large efforts in North America and internationally, including the Undiagnosed Diseases Network (UDN) (Supplemental Material, File S1) and UDN International (UDNI), the Centers for Mendelian Genomics (CMG), and the Canadian Rare Diseases Models and Mechanisms Network (RDMM). We discuss how merging human genetics with model organism research guides experimental studies to solve these medical mysteries, gain new insights into disease pathogenesis, and uncover new therapeutic strategies.
This paper presents a new physics-based model for understanding the basic mechanism of single-event gate rupture (SEGR) in analog devices. This model accounts for the different competing physics ...mechanisms, such as carrier drift, diffusion, recombination in the drift diffusion, and Poisson's equations, to explain the dependence of SEGR on biasing voltage, cross section, and critical electric field strength. Hence, the model provides a more accurate method of understanding and predicting the breakdown of oxides from heavy-ion strikes.
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