8 research outputs found
Sonification of quantum spectra
ABSTRACT Quantum spectra provide an interesting field for auditory display due to the richness of their data sets. Here, we are concerned with the sonification of quantum-mechanical spectra of baryons, the most fundamental particles of subatomic physics observed in nature. The data under investigation stem from different competing theoretical models designed for the description of baryon properties. We report on first attempts towards finding valid and useful strategies for displaying, comparing and exploring various model predictions in relation to experimentally measured data by means of sonification. The aim is to investigate the possibilities of sonification in order to develop them as a tool for classifying and explaining baryon properties in the context of present particle theory
Homicide as Infectious Disease: Using Public Health Methods to Investigate the Diffusion of Homicide
Studying Implementation Quality of a School-Based Prevention Curriculum in Frontier Alaska: Application of Video-Recorded Observations and Expert Panel Judgment
De Novo Variants in CNOT1, a Central Component of the CCR4-NOT Complex Involved in Gene Expression and RNA and Protein Stability, Cause Neurodevelopmental Delay.
CNOT1 is a member of the CCR4-NOT complex, which is a master regulator, orchestrating gene expression, RNA deadenylation, and protein ubiquitination. We report on 39 individuals with heterozygous de novo CNOT1 variants, including missense, splice site, and nonsense variants, who present with a clinical spectrum of intellectual disability, motor delay, speech delay, seizures, hypotonia, and behavioral problems. To link CNOT1 dysfunction to the neurodevelopmental phenotype observed, we generated variant-specific Drosophila models, which showed learning and memory defects upon CNOT1 knockdown. Introduction of human wild-type CNOT1 was able to rescue this phenotype, whereas mutants could not or only partially, supporting our hypothesis that CNOT1 impairment results in neurodevelopmental delay. Furthermore, the genetic interaction with autism-spectrum genes, such as ASH1L, DYRK1A, MED13, and SHANK3, was impaired in our Drosophila models. Molecular characterization of CNOT1 variants revealed normal CNOT1 expression levels, with both mutant and wild-type alleles expressed at similar levels. Analysis of protein-protein interactions with other members indicated that the CCR4-NOT complex remained intact. An integrated omics approach of patient-derived genomics and transcriptomics data suggested only minimal effects on endonucleolytic nonsense-mediated mRNA decay components, suggesting that de novo CNOT1 variants are likely haploinsufficient hypomorph or neomorph, rather than dominant negative. In summary, we provide strong evidence that de novo CNOT1 variants cause neurodevelopmental delay with a wide range of additional co-morbidities. Whereas the underlying pathophysiological mechanism warrants further analysis, our data demonstrate an essential and central role of the CCR4-NOT complex in human brain development