Effects of High Dietary HEME Iron and Radiation on Cardiovascular Function

The radiation related health risks to astronauts is of particular concern to NASA. Data support that exposure to radiation is associated with a number of disorders including a heightened risk for cardiovascular diseases. Independent of radiation, altered nutrient status (e.g. high dietary iron) also increases ones risk for cardiovascular disease. However, it is unknown whether exposure to radiation in combination with high dietary iron further increases ones cardiovascular risk. The intent of our proposal is to generate compulsory data examining the combined effect of radiation exposure and iron overload on sensitivity to radiation injury to address HRP risks: 1) Risk Factor of Inadequate Nutrition; 2) Risk of Cardiac Rhythm Problems; and 3) Risk of Degenerative Tissue or other Health Effects from Space Radiation. Towards our goal we propose two distinct pilot studies using the following specific aims: Vascular Aim 1: To determine the short-term consequences of the independent and combined effects of exposure to gamma radiation and elevated body iron stores on measures of endothelial function and cell viability and integrity. We hypothesize that animals that have high body iron stores and are exposed to gamma radiation will show a greater reduction in endothelial dependent nitric oxid production and larger pathological changes in endothelial integrity than animals that have only 1 of those treatments (either high iron stores or exposure to gamma radiation). Vascular Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with endothelial cell function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with endothelial cell function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment. Cardiac Aim 1: To determine the short-term consequences of the independent and combined effects of gamma radiation and elevated body iron stores on measures of cardiac structure. We hypothesize that modifications to cardiac structure and function will be greater in rats with high body iron stores and exposed to gamma radiation than in rats that have only 1 of those treatments. Cardiac Aim 2: Identify and compare the effects of gamma radiation and elevated body iron stores on the genetic and epigenetic regulation of proteins associated with cardiac structure and function. We hypothesize that modifications of epigenetic control and posttranslational expression of proteins associated with cardiac contractile function will be differentially altered in rats with high body iron stores and exposed to gamma radiation compared to rats with only 1 type of treatment

Meteorological conditions during periods of low wind speed and insolation in Germany: The role of weather regimes

Renewable power generation from wind and solar energy is strongly dependent on the weather. To plan future sustainable energy systems that are robust to weather variability, a better understanding of why and when periods of low wind and solar power output occur is valuable. We call such periods of low wind speed and insolation “Dunkelflauten”, the German word for “dark wind lulls”. In this article, we analyse the meteorological conditions during Dunkelflauten in Germany by applying the concept of weather regimes. Weather regimes are quasi-stationary, recurrent and persistent large-scale circulation patterns that explain multi-day atmospheric variability (5–15 days). We use a regime definition that allows us to distinguish four different types of blocked regimes, characterized by high-pressure situations in the North Atlantic-European region. We find that Dunkelflauten in Germany occur mainly in winter when the solar power output is low due to the seasonal cycle of solar irradiance and wind power output drops for several consecutive days. A high-pressure system over Germany, associated with the European Blocking regime, is responsible for most of the Dunkelflauten. Dunkelflauten during the Greenland Blocking regime are associated with colder temperatures than usual, causing higher electricity demand, and would present a particular challenge as space heating becomes electrified in the future. Furthermore, we show that Dunkelflauten occur predominantly when a weather regime is well established and persists longer than usual. Our study provides novel insight into the occurrence and meteorological characteristics of Dunkelflauten, which is essential for planning resilient energy systems and supporting grid operators to prepare for potential shortages in supply

Meteorological conditions during Dunkelflauten in Germany: Characteristics, the role of weather regimes and impacts on demand

Renewable generation from wind and solar power is strongly weather-dependent. To plan future sustainable energy systems that are robust to this variability, a better understanding of why and when periods of low wind and solar power output occur is valuable. We call such periods of low wind and solar power output `Dunkelflauten', the German word for dark wind lulls. In this article, we analyse the meteorological conditions during Dunkelflauten in Germany by applying the concept of weather regimes. Weather regimes are quasi-stationary, recurrent, and persistent large-scale circulation patterns which explain multi-day atmospheric variability (5-15 days). We use a regime definition that allows us to distinguish four different types of blocked regimes, characterised by high pressure situations in the North Atlantic-European region. We find that in Germany, Dunkelflauten mainly occur in winter when the solar power output is anyway low and when the wind power output drops for several consecutive days. A high-pressure system over Germany, associated with the European Blocking regime, is responsible for most of the Dunkelflauten. Dunkelflauten during the Greenland Blocking regime are associated with colder temperatures than usual, causing higher electricity demand and presenting a particular challenge as space heating demand electrifies in future. Furthermore, we show that Dunkelflauten occur predominantly when a weather regime is well-established and persists longer than usual. Our study provides novel insight on the occurrence and meteorological characteristics of Dunkelflauten, which is essential for planning resilient energy systems and supporting grid operators to prepare for potential shortages in supply.Comment: 20pages, 11figures, submitted to "Meteorological Applications" by Royal Meteorological Society (https://rmets.onlinelibrary.wiley.com/journal/14698080

Surface induced magnetization reversal of MnP nanoclusters embedded in GaP

We investigate the quasi-static magnetic behavior of ensembles of non-interacting ferromagnetic nanoparticles consisting of MnP nanoclusters embedded in GaP(001) epilayers grown at 600, 650 and 700{\deg}C. We use a phenomenological model, in which surface effects are included, to reproduce the experimental hysteresis curves measured as a function of temperature (120-260 K) and direction of the applied field. The slope of the hysteresis curve during magnetization reversal is determined by the MnP nanoclusters size distribution, which is a function of the growth temperature. Our results show that the coercive field is very sensitive to the strength of the surface anisotropy, which reduces the energy barrier between the two states of opposite magnetization. Notably, this reduction in the energy barrier increases by a factor of 3 as the sample temperature is lowered from 260 to 120 K.Comment: 7 pages, 5 figure

Filaggrin-stratified transcriptomic analysis of pediatric skin identifies mechanistic pathways in patients with atopic dermatitis

BackgroundAtopic dermatitis (AD; eczema) is characterized by a widespread abnormality in cutaneous barrier function and propensity to inflammation. Filaggrin is a multifunctional protein and plays a key role in skin barrier formation. Loss-of-function mutations in the gene encoding filaggrin (FLG) are a highly significant risk factor for atopic disease, but the molecular mechanisms leading to dermatitis remain unclear.ObjectiveWe sought to interrogate tissue-specific variations in the expressed genome in the skin of children with AD and to investigate underlying pathomechanisms in atopic skin.MethodsWe applied single-molecule direct RNA sequencing to analyze the whole transcriptome using minimal tissue samples. Uninvolved skin biopsy specimens from 26 pediatric patients with AD were compared with site-matched samples from 10 nonatopic teenage control subjects. Cases and control subjects were screened for FLG genotype to stratify the data set.ResultsTwo thousand four hundred thirty differentially expressed genes (false discovery rate, P < .05) were identified, of which 211 were significantly upregulated and 490 downregulated by greater than 2-fold. Gene ontology terms for “extracellular space” and “defense response” were enriched, whereas “lipid metabolic processes” were downregulated. The subset of FLG wild-type cases showed dysregulation of genes involved with lipid metabolism, whereas filaggrin haploinsufficiency affected global gene expression and was characterized by a type 1 interferon–mediated stress response.ConclusionThese analyses demonstrate the importance of extracellular space and lipid metabolism in atopic skin pathology independent of FLG genotype, whereas an aberrant defense response is seen in subjects with FLG mutations. Genotype stratification of the large data set has facilitated functional interpretation and might guide future therapy development

Differential expression of microRNA-206 and its target genes in pre-eclampsia

Objectives: Pre-eclampsia is a multi-system disease that significantly contributes to maternal and fetal morbidity and mortality. In this study, we used a non-biased microarray approach to identify novel circulating miRNAs in maternal plasma that may be associated with pre-eclampsia. Methods: Plasma samples were obtained at 16 and 28 weeks of gestation from 18 women who later developed pre-eclampsia (cases) and 18 matched women with normotensive pregnancies (controls). We studied miRNA expression profiles in plasma and subsequently confirmed miRNA and target gene expression in placenta samples. Placental samples were obtained from an independent cohort of 19 women with pre-eclampsia matched with 19 women with normotensive pregnancies. Results: From the microarray, we identified 1 miRNA that was significantly differentially expressed between cases and controls at 16 weeks of gestation and 6 miRNAs that were significantly differentially expressed at 28 weeks. Following qPCR validation only one, miR-206, was found to be significantly increased in 28 week samples in women who later developed pre-eclampsia (1.4 fold change ± 0.2). The trend for increase in miR-206 expression was mirrored within placental tissue from women with pre-eclampsia. In parallel, IGF-1, a target gene of miR-206, was also found to be down-regulated (0.41 ± 0.04) in placental tissue from women with pre-eclampsia. miR-206 expression was also detectable in myometrium tissue and trophoblast cell lines. Conclusions: Our pilot study has identified miRNA-206 as a novel factor up-regulated in pre-eclampsia within the maternal circulation and in placental tissue

The Breast Cancer Microenvironment and Lipoprotein Lipase: Another Negative Notch for a Beneficial Enzyme?

The energy demand of breast cancers is in part met through the β-oxidation of exogenous fatty acids. Fatty acids may also be used to aid in cell signaling and toward the construction of new membranes for rapidly proliferating tumor cells. A significant quantity of fatty acids comes from the hydrolysis of lipoprotein triacylglycerols and phospholipids by lipoprotein lipase (LPL). The lipid obtained via LPL in the breast tumor microenvironment may thus promote breast tumor growth and development. In this hypothesis article, we introduce LPL, provide a meta-analysis of RNAseq data showing that LPL is associated with poor prognosis, and explain how LPL might play a role in breast cancer prognosis over time

Observation of a low-lying neutron-unbound state in 19C

Proton removal reactions from a secondary 22N beam were utilized to populate unbound states in neutron-rich carbon isotopes. Neutrons were measured with the Modular Neutron Array (MoNA) in coincidence with carbon fragments. A resonance with a decay energy of 76(14) keV was observed in the system 18C+n corresponding to a state in 19C at an excitation energy of 653(95)keV. This resonance could correspond to the first 5/2+ state which was recently speculated to be unbound in order to describe 1n and 2n removal cross section measurements from 20C.Comment: accepted for publication in Nucl. Phys.

Object detection networks and augmented reality for cellular detection in fluorescence microscopy

Object detection networks are high-performance algorithms famously applied to the task of identifying and localizing objects in photography images. We demonstrate their application for the classification and localization of cells in fluorescence microscopy by benchmarking four leading object detection algorithms across multiple challenging 2D microscopy datasets. Furthermore we develop and demonstrate an algorithm that can localize and image cells in 3D, in close to real time, at the microscope using widely available and inexpensive hardware. Furthermore, we exploit the fast processing of these networks and develop a simple and effective augmented reality (AR) system for fluorescence microscopy systems using a display screen and back-projection onto the eyepiece. We show that it is possible to achieve very high classification accuracy using datasets with as few as 26 images present. Using our approach, it is possible for relatively nonskilled users to automate detection of cell classes with a variety of appearances and enable new avenues for automation of fluorescence microscopy acquisition pipelines. © 2020 Waithe et al