Gene repositioning within the cell nucleus is not random and is determined by its genomic neighborhood

Background: Heterochromatin has been reported to be a major silencing compartment during development and differentiation. Prominent heterochromatin compartments are located at the nuclear periphery and inside the nucleus (e.g., pericentric heterochromatin). Whether the position of a gene in relation to some or all heterochromatin compartments matters remains a matter of debate, which we have addressed in this study. Answering this question demanded solving the technical challenges of 3D measurements and the large-scale morphological changes accompanying cellular differentiation. Results: Here, we investigated the proximity effects of the nuclear periphery and pericentric heterochromatin on gene expression and additionally considered the effect of neighboring genomic features on a gene's nuclear position. Using a well-established myogenic in vitro differentiation system and a differentiation-independent heterochromatin remodeling system dependent on ectopic MeCP2 expression, we first identified genes with statistically significant expression changes by transcriptional profiling. We identified nuclear gene positions by 3D fluorescence in situ hybridization followed by 3D distance measurements toward constitutive and facultative heterochromatin domains. Single-cell-based normalization enabled us to acquire morphologically unbiased data and we finally correlated changes in gene positioning to changes in transcriptional profiles. We found no significant correlation of gene silencing and proximity to constitutive heterochromatin and a rather unexpected inverse correlation of gene activity and position relative to facultative heterochromatin at the nuclear periphery. Conclusion: In summary, our data question the hypothesis of heterochromatin as a general silencing compartment. Nonetheless, compared to a simulated random distribution, we found that genes are not randomly located within the nucleus. An analysis of neighboring genomic context revealed that gene location within the nucleus is rather dependent on CpG islands, GC content, gene density, and short and long interspersed nuclear elements, collectively known as RIDGE (regions of increased gene expression) properties. Although genes do not move away/to the heterochromatin upon up-/down-regulation, genomic regions with RIDGE properties are generally excluded from peripheral heterochromatin. Hence, we suggest that individual gene activity does not influence gene positioning, but rather chromosomal context matters for sub-nuclear location

Finite Element Convergence for the Joule Heating Problem with Mixed Boundary Conditions

We prove strong convergence of conforming finite element approximations to the stationary Joule heating problem with mixed boundary conditions on Lipschitz domains in three spatial dimensions. We show optimal global regularity estimates on creased domains and prove a priori and a posteriori bounds for shape regular meshes.Comment: Keywords: Joule heating problem, thermistors, a posteriori error analysis, a priori error analysis, finite element metho

Evaluating health facility access using Bayesian spatial models and location analysis methods

Background Floating catchment methods have recently been applied to identify priority regions for Automated External Defibrillator (AED) deployment, to aid in improving Out of Hospital Cardiac Arrest (OHCA) survival. This approach models access as a supply-to-demand ratio for each area, targeting areas with high demand and low supply for AED placement. These methods incorporate spatial covariates on OHCA occurrence, but do not provide precise AED locations, which are critical to the initial intent of such location analysis research. Exact AED locations can be determined using optimisation methods, but they do not incorporate known spatial risk factors for OHCA, such as income and demographics. Combining these two approaches would evaluate AED placement impact, describe drivers of OHCA occurrence, and identify areas that may not be appropriately covered by AED placement strategies. There are two aims in this paper. First, to develop geospatial models of OHCA that account for and display uncertainty. Second, to evaluate the AED placement methods using geospatial models of accessibility. We first identify communities with the greatest gap between demand and supply for allocating AEDs. We then use this information to evaluate models for precise AED location deployment. Methods Case study data set consisted of 2802 OHCA events and 719 AEDs. Spatial OHCA occurrence was described using a geospatial model, with possible spatial correlation accommodated by introducing a conditional autoregressive (CAR) prior on the municipality-level spatial random effect. This model was fit with Integrated Nested Laplacian Approximation (INLA), using covariates for population density, proportion male, proportion over 65 years, financial strength, and the proportion of land used for transport, commercial, buildings, recreation, and urban areas. Optimisation methods for AED locations were applied to find the top 100 AED placement locations. AED access was calculated for current access and 100 AED placements. Priority rankings were then given for each area based on their access score and predicted number of OHCA events. Results Of the 2802 OHCA events, 64.28% occurred in rural areas, and 35.72% in urban areas. Additionally, over 70% of individuals were aged over 65. Supply of AEDs was less than demand in most areas. Priority regions for AED placement were identified, and access scores were evaluated for AED placement methodology by ranking the access scores and the predicted OHCA count. AED placement methodology placed AEDs in areas with the highest priority, but placed more AEDs in areas with more predicted OHCA events in each grid cell. Conclusion The methods in this paper incorporate OHCA spatial risk factors and OHCA coverage to identify spatial regions most in need of resources. These methods can be used to help understand how AED allocation methods affect OHCA accessibility, which is of significant practical value for communities when deciding AED placements

Identifying chemical aerosol signatures using optical suborbital observations: How much can optical properties tell us about aerosol composition?

Improvements in air quality and Earth's climate predictions require improvements of the aerosol speciation in chemical transport models, using observational constraints. Aerosol speciation (e.g., organic aerosols, black carbon, sulfate, nitrate, ammonium, dust or sea salt) is typically determined using in situ instrumentation. Continuous, routine aerosol composition measurements from ground-based networks are not uniformly widespread over the globe. Satellites, on the other hand, can provide a maximum coverage of the horizontal and vertical atmosphere but observe aerosol optical properties (and not aerosol speciation) based on remote sensing instrumentation. Combinations of satellite-derived aerosol optical properties can inform on air mass aerosol types (AMTs). However, these AMTs are subjectively defined, might often be misclassified and are hard to relate to the critical parameters that need to be refined in models. In this paper, we derive AMTs that are more directly related to sources and hence to speciation. They are defined, characterized and derived using simultaneous in situ gas-phase, chemical and optical instruments on the same aircraft during the Study of Emissions and Atmospheric Composition, Clouds, and Climate Coupling by Regional Surveys (SEAC4RS, an airborne field campaign carried out over the US during the summer of 2013). We find distinct optical signatures for AMTs such as biomass burning (from agricultural or wildfires), biogenic and polluted dust. We find that all four AMTs, studied when prescribed using mostly airborne in situ gas measurements, can be successfully extracted from a few combinations of airborne in situ aerosol optical properties (e.g., extinction Ångström exponent, absorption Ångström exponent and real refractive index). However, we find that the optically based classifications for biomass burning from agricultural fires and polluted dust include a large percentage of misclassifications that limit the usefulness of results related to those classes. The technique and results presented in this study are suitable to develop a representative, robust and diverse source-based AMT database. This database could then be used for widespread retrievals of AMTs using existing and future remote sensing suborbital instruments/networks. Ultimately, it has the potential to provide a much broader observational aerosol dataset to evaluate chemical transport and air quality models than is currently available by direct in situ measurements. This study illustrates how essential it is to explore existing airborne datasets to bridge chemical and optical signatures of different AMTs, before the implementation of future spaceborne missions (e.g., the next generation of Earth Observing System (EOS) satellites addressing Aerosols, Cloud, Convection and Precipitation (ACCP) designated observables). © 2022 Copernicus GmbH. All rights reserved.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Angle- and spin-resolved photoelectron spectroscopy in rotationally resolved photoionization of HI

Mank A, Drescher M, Brockhinke A, Böwering N, Heinzmann U. Angle- and spin-resolved photoelectron spectroscopy in rotationally resolved photoionization of HI. Zeitschrift für Physik D: Atoms, Molecules and Clusters. 1994;29(4):275-289