A New Four‐Component L*‐Dependent Model for Radial Diffusion Based on Solar Wind and Magnetospheric Drivers of ULF Waves

The outer radiation belt is a region of space comprising highly energetic electrons. During periods of extreme space weather, the number and energy of these electrons can rapidly vary. During these periods as the electron energies and numbers become enhanced, they can pose a threat to satellite and space infrastructure. While we have an excellent understanding of the physical processes which drive radiation belt electron dynamics, we still have a limited ability to model and forecast radiation belt dynamics; this is a result of the complexity of Earth's radiation belt system. One of the key processes controlling radiation belt dynamics is Ultra Low Frequency (ULF) wave radial diffusion. In this work we detail the development a new model quantifying the strength of ULF wave radial diffusion in the outer radiation belt utilizing space base observations of the electric and magnetic fields in Earth's magnetosphere. Accurately quantifying ULF wave radial diffusion is fundamental to understanding radiation belt dynamics and any improvement or refinements in radial diffusion models can help to provide a better understanding of the complex radiation belt system and importantly improve hindcasts, nowcasts, and forecasts

Genetic basis of a cognitive complexity metric

Relational complexity (RC) is a metric reflecting capacity limitation in relational processing. It plays a crucial role in higher cognitive processes and is an endophenotype for several disorders. However, the genetic underpinnings of complex relational processing have not been investigated. Using the classical twin model, we estimated the heritability of RC and genetic overlap with intelligence (IQ), reasoning, and working memory in a twin and sibling sample aged 15-29 years (N = 787). Further, in an exploratory search for genetic loci contributing to RC, we examined associated genetic markers and genes in our Discovery sample and selected loci for replication in four independent samples (ALSPAC, LBC1936, NTR, NCNG), followed by meta-analysis (N>6500) at the single marker level. Twin modelling showed RC is highly heritable (67%), has considerable genetic overlap with IQ (59%), and is a major component of genetic covariation between reasoning and working memory (72%). At the molecular level, we found preliminary support for four single-marker loci (one in the gene DGKB), and at a gene-based level for the NPS gene, having influence on cognition. These results indicate that genetic sources influencing relational processing are a key component of the genetic architecture of broader cognitive abilities. Further, they suggest a genetic cascade, whereby genetic factors influencing capacity limitation in relational processing have a flow-on effect to more complex cognitive traits, including reasoning and working memory, and ultimately, IQ

Germline Mutations but Not Somatic Changes at the MYH Locus Contribute to the Pathogenesis of Unselected Colorectal Cancers

MYH-associated polyposis is a recently described, autosomal recessive condition comprising multiple colorectal adenomas and cancer. This disease is caused by germline mutations in the base excision repair (BER) gene MYH. Genes involved in the BER pathway are thus good candidates for involvement in the pathogenesis of sporadic tumors of the large bowel. We have screened a set of 75 sporadic colorectal cancers for mutations in MYH, MTH1, and OGG1. Allelic loss at MYH was also assessed. Selected samples were screened for mutations and allele loss at APC and mutations in p53, K-ras, and β-catenin. A panel of 35 colorectal cancer cell lines was screened for MYH mRNA and protein expression. One of 75 cancers had bi-allelic germline mutations in MYH and on retrospective analysis of medical records this patient was found to have synchronous multiple small adenomas in addition to carcinoma. No somatic MYH mutations were found and mRNA and protein were expressed in all of our cell lines. There were no clearly pathogenic mutations in MTH1 or OGG1 in any tumor. Bi-allelic germline MYH mutations cause ∼1 to 3% of unselected colorectal cancers, but appear always to be associated with multiple adenomas. Somatic inactivation of the DNA glycosylases involved in the BER pathway however does not appear to be involved in colorectal tumorigenesis