Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

Polarised Photoluminescence from Surface-Passivated PbS Nanocrystals

Effective surface-passivation of PbS nanocrystals in aqueous colloidal solution has been achieved following treatment with CdS precursors. The resultant photoluminescent emission displays two distinct components, one originating from the absorption band-edge and the other from above the absorption band-edge. We show that both of these components are strongly polarised but display distinctly different behaviours. The polarisation arising from the band-edge shows little dependence on the excitation energy while the polarisation of the above-band-edge component is strongly dependent on the excitation energy. In addition, time resolved polarisation spectroscopy reveals that the above-band-edge polarisation is restricted to the first couple of nanoseconds, while the band-edge polarisation is nearly constant over hundreds of nanoseconds. We recognise an incompatibility between the two different polarisation behaviours, which enables us to identify two distinct types of surface-passivated PbS nanocrystal.Comment: Preprint, 19 pages, 4 figure

Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer

Lysine acetyltransferase 6A (KAT6A) and its paralog KAT6B form stoichiometric complexes with bromodomain- and PHD finger-containing protein 1 (BRPF1) for acetylation of histone H3 at lysine 23 (H3K23). We report that these complexes also catalyze H3K23 propionylati

Toward a next generation particle precipitation model: Mesoscale prediction through machine learning (a case study and framework for progress)

We advance the modeling capability of electron particle precipitation from the magnetosphere to the ionosphere through a new database and use of machine learning tools to gain utility from those data. We have compiled, curated, analyzed, and made available a new and more capable database of particle precipitation data that includes 51 satellite years of Defense Meteorological Satellite Program (DMSP) observations temporally aligned with solar wind and geomagnetic activity data. The new total electron energy flux particle precipitation nowcast model, a neural network called PrecipNet, takes advantage of increased expressive power afforded by machine learning approaches to appropriately utilize diverse information from the solar wind and geomagnetic activity and, importantly, their time histories. With a more capable representation of the organizing parameters and the target electron energy flux observations, PrecipNet achieves a $>$50\% reduction in errors from a current state-of-the-art model (OVATION Prime), better captures the dynamic changes of the auroral flux, and provides evidence that it can capably reconstruct mesoscale phenomena. We create and apply a new framework for space weather model evaluation that culminates previous guidance from across the solar-terrestrial research community. The research approach and results are representative of the `new frontier' of space weather research at the intersection of traditional and data science-driven discovery and provides a foundation for future efforts