Dynamics of Laterally Propagating Flames in X-Ray Bursts. I. Burning Front Structure

We investigate the structure of laterally propagating flames through the highly stratified burning layer in an X-ray burst. Two-dimensional hydrodynamics simulations of flame propagation are performed through a rotating plane-parallel atmosphere, exploring the structure of the flame. We discuss the approximations needed to capture the length and timescales at play in an X-ray burst and describe the flame acceleration observed. Our studies complement other multidimensional studies of burning in X-ray bursts

Additive drug-specific and sex-specific risks associated with co-use of marijuana and tobacco during pregnancy: Evidence from 3 recent developmental cohorts (2003-2015).

BACKGROUND: Methodologic challenges related to the concomitant use (co-use) of substances and changes in policy and potency of marijuana contribute to ongoing uncertainty about risks to fetal neurodevelopment associated with prenatal marijuana use. In this study, we examined two biomarkers of fetal neurodevelopmental risk-birth weight and length of gestation-associated with prenatal marijuana use, independent of tobacco (TOB), alcohol (ALC), other drug use (OTH), and socioeconomic risk (SES), in a pooled sample (N = 1191) derived from 3 recent developmental cohorts (2003-2015) with state-of-the-art substance use measures. We examined differential associations by infant sex, and multiplicative effects associated with co-use of MJ and TOB. METHODS: Participants were mother-infant dyads with complete data on all study variables derived from Growing Up Healthy (n = 251), Behavior and Mood in Babies and Mothers (Cohorts 1 and 2; n = 315), and the Early Growth and Development Study (N = 625). We estimated direct effects on birth weight and length of gestation associated with MJ, TOB, and co-use (MJ x TOB), using linear regression analysis in the full sample, and in male (n = 654) and female (n = 537) infants, separately. RESULTS: Mean birth weight and length of gestation were 3277 g (SD = 543) and 37.8 weeks (SD = 2.0), respectively. Rates of prenatal use were as follows: any use, n = 748 (62.8%); MJ use, n = 273 (22.9%); TOB use, n = 608 (51.0%); co-use of MJ and TOB, n = 230 (19.3%); ALC use, n = 464 (39.0%); and OTH use n = 115 (9.7%.) For all infants, unique effects on birth weight were observed for any MJ use [B(SE) = -84.367(38.271), 95% C.I. -159.453 to -9.281, p = .028], any TOB use [B(SE) = -0.99.416(34.418), 95% C.I. -166.942 to -31.889, p = .004], and each cigarette/day in mean TOB use [B(SE) = -12.233(3.427), 95% C.I. -18.995 to -5.510, p \u3c .001]. Additional effects of co-use on birth weight, beyond these drug-specific effects, were not supported. In analyses stratified by sex, while TOB use was associated with lower birth weight in both sexes, MJ use during pregnancy was associated with lower birth weight of male infants [B(SE) = -153.1 (54.20); 95% C.I. -259.5 to -46.7, p = .005], but not female infants [B(SE) = 8.3(53.1), 95% C.I. -96.024 to 112.551, p = .876]. TOB, MJ, and their co-use were not associated with length of gestation. CONCLUSIONS: In this sample, intrauterine co-exposure to MJ and TOB was associated with an estimated 18% reduction in birth weight not attributable to earlier delivery, exposure to ALC or OTH drugs, nor to maternal SES. We found evidence for greater susceptibility of male fetuses to any prenatal MJ exposure. Examination of dose-dependence in relationships found in this study, using continuous measures of exposure, is an important next step. Finally, we underscore the need to consider (a) the potential moderating influence of fetal sex on exposure-related neurodevelopmental risks; and (b) the importance of quantifying expressions of risk through subtle alterations, rather than dichotomous outcomes

The Castro AMR Simulation Code: Current and Future Developments

We describe recent developments to the Castro astrophysics simulation code, focusing on new features that enable our simulations of X-ray bursts. Two highlights of Castro's ongoing development are the new integration technique to couple hydrodynamics and reactions to high order and GPU offloading. We discuss how these features will help offset some of the computational expense in X-ray burst models

Mechanistic insights revealed by lipid profiling in monogenic insulin resistance syndromes.

BACKGROUND: Evidence from several recent metabolomic studies suggests that increased concentrations of triacylglycerols with shorter (14-16 carbon atoms), saturated fatty acids are associated with insulin resistance and the risk of type 2 diabetes. Although causality cannot be inferred from association studies, patients in whom the primary cause of insulin resistance can be genetically defined offer unique opportunities to address this challenge. METHODS: We compared metabolite profiles in patients with congenital lipodystrophy or loss-of-function insulin resistance (INSR gene) mutations with healthy controls. RESULTS: The absence of significant differences in triacylglycerol species in the INSR group suggest that changes previously observed in epidemiological studies are not purely a consequence of insulin resistance. The presence of triacylglycerols with lower carbon numbers and high saturation in patients with lipodystrophy suggests that these metabolite changes may be associated with primary adipose tissue dysfunction. The observed pattern of triacylglycerol species is indicative of increased de novo lipogenesis in the liver. To test this we investigated the distribution of these triacylglycerols in lipoprotein fractions using size exclusion chromatography prior to mass spectrometry. This associated these triacylglycerols with very low-density lipoprotein particles, and hence release of triacylglycerols into the blood from the liver. To test further the hepatic origin of these triacylglycerols we induced de novo lipogenesis in the mouse, comparing ob/ob and wild-type mice on a chow or high fat diet, confirming that de novo lipogenesis induced an increase in relatively shorter, more saturated fatty acids. CONCLUSIONS: Overall, these studies highlight hepatic de novo lipogenesis in the pathogenesis of metabolic dyslipidaemia in states where energy intake exceeds the capacity of adipose tissue

Impact of Chromogranin A deficiency on catecholamine storage, catecholamine granule morphology and chromaffin cell energy metabolism in vivo

Chromogranin A (CgA) is a prohormone and granulogenic factor in neuroendocrine tissues with a regulated secretory pathway. The impact of CgA depletion on secretory granule formation has been previously demonstrated in cell culture. However, studies linking the structural effects of CgA deficiency with secretory performance and cell metabolism in the adrenomedullary chromaffin cells in vivo have not previously been reported. Adrenomedullary content of the secreted adrenal catecholamines norepinephrine (NE) and epinephrine (EPI) was decreased 30–40 % in Chga-KO mice. Quantification of NE and EPI-storing dense core (DC) vesicles (DCV) revealed decreased DCV numbers in chromaffin cells in Chga-KO mice. For both cell types, the DCV diameter in Chga-KO mice was less (100–200 nm) than in WT mice (200–350 nm). The volume density of the vesicle and vesicle number was also lower in Chga-KO mice. Chga-KO mice showed an ~47 % increase in DCV/DC ratio, implying vesicle swelling due to increased osmotically active free catecholamines. Upon challenge with 2 U/kg insulin, there was a diminution in adrenomedullary EPI, no change in NE and a very large increase in the EPI and NE precursor dopamine (DA), consistent with increased catecholamine biosynthesis during prolonged secretion. We found dilated mitochondrial cristae, endoplasmic reticulum and Golgi complex, as well as increased synaptic mitochondria, synaptic vesicles and glycogen granules in Chga-KO mice compared to WT mice, suggesting that decreased granulogenesis and catecholamine storage in CgA-deficient mouse adrenal medulla is compensated by increased VMAT-dependent catecholamine update into storage vesicles, at the expense of enhanced energy expenditure by the chromaffin cell

A GABAergic cell type in the lateral habenula links hypothalamic homeostatic and midbrain motivation circuits with sex steroid signaling

Abstract The lateral habenula (LHb) has a key role in integrating a variety of neural circuits associated with reward and aversive behaviors. There is limited information about how the different cell types and neuronal circuits within the LHb coordinate physiological and motivational states. Here, we report a cell type in the medial division of the LHb (LHbM) in male rats that is distinguished by: (1) a molecular signature for GABAergic neurotransmission (Slc32a1/VGAT) and estrogen receptor (Esr1/ERα) expression, at both mRNA and protein levels, as well as the mRNA for vesicular glutamate transporter Slc17a6/VGLUT2, which we term the GABAergic estrogen-receptive neuron (GERN); (2) its axonal projection patterns, identified by in vivo juxtacellular labeling, to both local LHb and to midbrain modulatory systems; and (3) its somatic expression of receptors for vasopressin, serotonin and dopamine, and mRNA for orexin receptor 2. This cell type is anatomically located to receive afferents from midbrain reward (dopamine and serotonin) and hypothalamic water and energy homeostasis (vasopressin and orexin) circuits. These afferents shared the expression of estrogen synthase (aromatase) and VGLUT2, both in their somata and axon terminals. We demonstrate dynamic changes in LHbM VGAT+ cell density, dependent upon gonadal functional status, that closely correlate with motivational behavior in response to predator and forced swim stressors. The findings suggest that the homeostasis and reward-related glutamatergic convergent projecting pathways to LHbMC employ a localized neurosteroid signaling mechanism via axonal expression of aromatase, to act as a switch for GERN excitation/inhibition output prevalence, influencing depressive or motivated behavior

Laser ablation loading of a radiofrequency ion trap

The production of ions via laser ablation for the loading of radiofrequency (RF) ion traps is investigated using a nitrogen laser with a maximum pulse energy of 0.17 mJ and a peak intensity of about 250 MW/cm^2. A time-of-flight mass spectrometer is used to measure the ion yield and the distribution of the charge states. Singly charged ions of elements that are presently considered for the use in optical clocks or quantum logic applications could be produced from metallic samples at a rate of the order of magnitude 10^5 ions per pulse. A linear Paul trap was loaded with Th+ ions produced by laser ablation. An overall ion production and trapping efficiency of 10^-7 to 10^-6 was attained. For ions injected individually, a dependence of the capture probability on the phase of the RF field has been predicted. In the experiment this was not observed, presumably because of collective effects within the ablation plume.Comment: submitted to Appl. Phys. B., special issue on ion trappin

A randomized phase I study of the safety and immunogenicity of three ascending dose levels of a 3-antigen Staphylococcus aureus vaccine (SA3Ag) in healthy adults

Background: Staphylococcus aureus is a common cause of healthcare-acquired morbidity and mortalityand increased healthcare resource utilization. A prophylactic vaccine is being developed that may reducethis disease burden.Methods: Volunteers in good general health aged 50–85 (n = 312) and 18–24 (n = 96) years were random-ized to receive a single intramuscular dose of one of three dose levels of a non-adjuvanted, 3-antigen S.aureus vaccine (SA3Ag) or placebo. SA3Ag antigens included capsular polysaccharides 5 and 8 (CP5 andCP8), each conjugated to cross-reactive material 197 (CRM197), and recombinant clumping factor A (ClfA).Safety, tolerability, and immunogenicity were evaluated.Results: At day 29 post-vaccination, robust immune responses were observed in both age cohorts at allthree SA3Ag dose levels. In the primary analysis population, the 50- to 85-year age stratum, geometricmean-fold-rises in competitive Luminex® immunoassay antibody titers from baseline ranged from 29.2to 83.7 (CP5), 14.1 to 31.0 (CP8), and 37.1 to 42.9 (ClfA), all (P < 0.001) exceeding the pre-defined two-fold rise criteria. Similar rises in opsonophagocytic activity assay titers demonstrated functionality ofthe immune response. Most injection-site reactions were mild in severity and there were no substantial differences (SA3Ag vs. placebo) with regard to systemic or adverse events.Conclusions: In this study of healthy adults aged 50–85 and 18–24 years, SA3Ag elicited a rapid and robustimmune response and was well tolerated, with no notable safety concerns.Michael Nissen, Helen Marshall, Peter Richmond, Sepehr Shakib, Qin Jiang, David Cooper, Denise Rill, James Baber, Joseph Eiden, William Gruber, Kathrin U. Jansen, Emilio A. Emini, Annaliesa S. Anderson, Edward T. Zito, Douglas Girgent