57 research outputs found
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
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
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
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 propionylation in vitro and in vivo. Immunofluorescence microscopy and ATAC-See revealed the association of this modification with active chromatin. Brpf1 deletion obliterates the acylation in mouse embryos and fibroblasts. Moreover, we identify BRPF1 variants in 12 previously unidentified cases of syndromic intellectual disability and demonstrate that these cases and known BRPF1 variants impair H3K23 propionylation. Cardiac anomalies are present in a subset of the cases. H3K23 acylation is also impaired by cancer-derived somatic BRPF1 mutations. Valproate, vorinostat, propionate and butyrate promote H3K23 acylation. These results reveal the dual functionality of BRPF1-KAT6 complexes, shed light on mechanisms underlying related developmental disorders and various cancers, and suggest mutation-based therapy for medical conditions with deficient histone acylation
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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
Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome
Background: Genomics enables individualized diagnosis and treatment, but large challenges remain to functionally interpret rare variants. To date, only one causative variant has been described for KCNK9 imprinting syndrome (KIS). The genotypic and phenotypic spectrum of KIS has yet to be described and the precise mechanism of disease fully understood.
Methods: This study discovers mechanisms underlying KCNK9 imprinting syndrome (KIS) by describing 15 novel KCNK9 alterations from 47 KIS-affected individuals. We use clinical genetics and computer-assisted facial phenotyping to describe the phenotypic spectrum of KIS. We then interrogate the functional effects of the variants in the encoded TASK3 channel using sequence-based analysis, 3D molecular mechanic and dynamic protein modeling, and in vitro electrophysiological and functional methodologies.
Results: We describe the broader genetic and phenotypic variability for KIS in a cohort of individuals identifying an additional mutational hotspot at p.Arg131 and demonstrating the common features of this neurodevelopmental disorder to include motor and speech delay, intellectual disability, early feeding difficulties, muscular hypotonia, behavioral abnormalities, and dysmorphic features. The computational protein modeling and in vitro electrophysiological studies discover variability of the impact of KCNK9 variants on TASK3 channel function identifying variants causing gain and others causing loss of conductance. The most consistent functional impact of KCNK9 genetic variants, however, was altered channel regulation.
Conclusions: This study extends our understanding of KIS mechanisms demonstrating its complex etiology including gain and loss of channel function and consistent loss of channel regulation. These data are rapidly applicable to diagnostic strategies, as KIS is not identifiable from clinical features alone and thus should be molecularly diagnosed. Furthermore, our data suggests unique therapeutic strategies may be needed to address the specific functional consequences of KCNK9 variation on channel function and regulation
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Evaluation of tropospheric water vapor profiling using eye-safe, infrared differential absorption lidar
Continuous, high quality profiles of water vapor, free of systematic bias, and of moderate temporal and spatial resolution are fundamental to the success of the ARM CART program. In addition, these should be acquired over long periods at low operational and maintenance cost. The development and verification of realistic climate model parameterizations for clouds and net radiation balance, and the correction of other CART site sensor observations for interferences due to the presence of water vapor are critically dependent on water vapor profile measurements. To date, application of profiles have been limited by vertical resolution and uniqueness and high operating cost, or diminished daytime performance, lack of eye-safety, and high maintenance cost. Recent developments in infrared laser and detector technology make possible compact IR differential absorption lidar (DIAL) systems at eye-safe wavelengths. In the studies reported here, we develop DIAL system performance models and examine the potential of solving some of the shortcomings of previous methods using parameters representative of current technologies. These simulations are also applied to determine the strengths and weaknesses unique to the DIAL method for this application
Observation of a Flare and Filament Eruption in Lyman- α on 8 September 2011 by the PRoject for OnBoard Autonomy/Large Yield Radiometer (PROBA2/LYRA)
International audienceThe Large Yield Radiometer (LYRA) instrument onboard the PRoject for OnBoard Autonomy (PROBA2) observes the solar irradiance in four channels in the UVâEUV. One of these channels is centered around the hydrogen line at 121.6 nm. The solar Lyman-α emission line is an optically thick line mostly formed in the chromosphere. Although it is one of the strongest lines of the solar spectrum, only a limited number of instruments provided observations of solar flares in Lyman-α, and those observations differ significantly in shape, durations, and amplitude. We focus on an event that happened on 8 September 2011 (SOL2011-09-08T15:46). This event, an M6.7 flare, was associated with a filament eruption that happened during the decaying phase of the flare. Most of the irradiance fluctuations observed in the Lyman-α time series are synchronized with nonthermal emission fluctuations, as is predicted by flare models. However, there is a late-phase peak in Lyman-α observations that rather correlates with the timing of the filament eruption. We demonstrate that the eruption of the filament is at the origin of this peak
Correction to: Observation of a Flare and Filament Eruption in Lyman-α on 8 September 2011 by the PRoject for OnBoard Autonomy/Large Yield Radiometer (PROBA2/LYRA)
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