The effects of dynamical substructure on Milky Way mass estimates from the high-velocity tail of the local stellar halo

We investigate the impact of dynamical streams and substructure on estimates of the local escape speed and total mass of Milky-Way-mass galaxies from modelling the high-velocity tail of local halo stars. We use a suite of high-resolution magnetohydrodynamical cosmological zoom-in simulations that resolve phase space substructure in local volumes around solar-like positions. We show that phase space structure varies significantly between positions in individual galaxies and across the suite. Substructure populates the high-velocity tail unevenly and leads to discrepancies in the mass estimates. We show that a combination of streams, sample noise, and truncation of the high-velocity tail below the escape speed leads to a distribution of mass estimates with a median that falls below the true value by ∼20 per cent ∼20 per cent ⁠, and a spread of a factor of 2 across the suite. Correcting for these biases, we derive a revised value for the Milky Way mass presented in Deason et al. of 1.29 +0.37 −0.47 × 10 12 M ⊙ 1.29−0.47+0.37×1012M⊙ ⁠

Subhalo destruction in the Apostle and Auriga simulations

N-body simulations make unambiguous predictions for the abundance of substructures within dark matter halos. However, the inclusion of baryons in the simulations changes the picture because processes associated with the presence of a large galaxy in the halo can destroy subhalos and substantially alter the mass function and velocity distribution of subhalos. We compare the effect of galaxy formation on subhalo populations in two state-of-the-art sets of hydrodynamical ΛCDM simulations of Milky Way mass halos, APOSTLE and AURIGA. We introduce a new method for tracking the orbits of subhalos between simulation snapshots that gives accurate results down to a few kiloparsecs from the centre of the halo. Relative to a dark matter-only simulation, the abundance of subhalos in APOSTLE is reduced by 50% near the centre and by 10% within r200. In AURIGA the corresponding numbers are 80% and 40%. The velocity distributions of subhalos are also affected by the presence of the galaxy, much more so in AURIGA than in APOSTLE. The differences on subhalo properties in the two simulations can be traced back to the mass of the central galaxies, which in AURIGA are typically twice as massive as those in APOSTLE. We show that some of the results from previous studies are inaccurate due to systematic errors in the modelling of subhalo orbits near the centre of halos

Simulating cosmological substructure in the solar neighbourhood

We explore the predictive power of cosmological, hydrodynamical simulations for stellar phase-space substructure and velocity correlations with the AURIGA simulations and AURIGAIA mock Gaia catalogues. We show that at the solar circle the AURIGA simulations commonly host phase-space structures in the stellar component that have constant orbital energies and arise from accreted subhaloes. These structures can persist for a few Gyr, even after coherent streams in position space have been erased. We also explore velocity two-point correlation functions and find this diagnostic is not deterministic for particular clustering patterns in phase space. Finally, we explore these structure diagnostics with the AURIGAIA catalogues and show that current catalogues have the ability to recover some structures in phase space but careful consideration is required to separate physical structures from numerical structures arising from catalogue generation methods

Prenatal and Postnatal Tobacco Exposure and Behavioral Problems in 10-Year-Old Children: Results from the GINI-plus Prospective Birth Cohort Study

BACKGROUND: Prenatal and postnatal tobacco exposure have been reported to be associated with behavioral problems. However, the magnitude of the association with tobacco exposure at specific periods of exposure is unclear. OBJECTIVE: We assessed the relative risk of behavioral problems in children who had been exposed to tobacco smoke in utero and postnatally. METHODS: We analyzed data from a prospective birth cohort study in two cities in Germany: the German Infant Nutrition Intervention. Our sample included 5,991 children born between 1995 and 1998 as well as their parents. We measured behavioral problems using the Strength and Difficulties Questionnaire (SDQ) at follow-up 10 years after birth. According to prespecified SDQ cutoff values, children were classified as "normal," "borderline," or "abnormal" according to the subscales "emotional symptoms," "conduct problems," "hyperactivity/inattention," "peer-relationship problems," and a total difficulties score. Smoke exposure and further covariates were assessed using parent questionnaires. RESULTS: Compared with children not exposed to tobacco smoke, children exposed both pre- and postnatally to tobacco smoke had twice the estimated risk [95% confidence interval (CI), 1.4-3.1] of being classified as abnormal according to the total difficulties score of the SDQ at 10 years of age. Children who were only prenatally exposed had a 90% higher relative risk (95% CI, 0.9-4.0), whereas children who were only postnatally exposed had a 30% higher relative risk (95% CI, 0.9-1.9). These results could not be explained by confounding by parental education, father's employment, child's time spent in front of computer or television screen, being a single father or mother, or mother's age. CONCLUSIONS: Prenatal exposure to tobacco smoke is associated with behavioral problems in school-age children. Although our findings do not preclude the influence of postnatal exposure, prenatal exposure seems to be more important

Effect of exogenous surfactants on viability and DNA synthesis in A549, immortalized mouse type II and isolated rat alveolar type II cells

<p>Abstract</p> <p>Background</p> <p>In mechanically ventilated preterm infants with respiratory distress syndrome (RDS), exogenous surfactant application has been demonstrated both to decrease DNA-synthesis but also and paradoxically to increase epithelial cell proliferation. However, the effect of exogenous surfactant has not been studied directly on alveolar type II cells (ATII cells), a key cell type responsible for alveolar function and repair.</p> <p>Objective</p> <p>The aim of this study was to investigate the effects of two commercially available surfactant preparations on ATII cell viability and DNA synthesis.</p> <p>Methods</p> <p>Curosurf^®and Alveofact^®were applied to two ATII cell lines (human A549 and mouse iMATII cells) and to primary rat ATII cells for periods of up to 24 h. Cell viability was measured using the redox indicator resazurin and DNA synthesis was measured using BrdU incorporation.</p> <p>Results</p> <p>Curosurf^®resulted in slightly decreased cell viability in all cell culture models. However, DNA synthesis was increased in A549 and rat ATII cells but decreased in iMATII cells. Alveofact^®exhibited the opposite effects on A549 cells and had very mild effects on the other two cell models.</p> <p>Conclusion</p> <p>This study showed that commercially available exogenous surfactants used to treat preterm infants with RDS can have profound effects on cell viability and DNA synthesis.</p

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

What Happens in Between? Human Oscillatory Brain Activity Related to Crossmodal Spatial Cueing

Previous studies investigated the effects of crossmodal spatial attention by comparing the responses to validly versus invalidly cued target stimuli. Dynamics of cortical rhythms in the time interval between cue and target might contribute to cue effects on performance. Here, we studied the influence of spatial attention on ongoing oscillatory brain activity in the interval between cue and target onset. In a first experiment, subjects underwent periods of tactile stimulation (cue) followed by visual stimulation (target) in a spatial cueing task as well as tactile stimulation as a control. In a second experiment, cue validity was modified to be 50%, 75%, or else 25%, to separate effects of exogenous shifts of attention caused by tactile stimuli from that of endogenous shifts. Tactile stimuli produced: 1) a stronger lateralization of the sensorimotor beta-rhythm rebound (15–22 Hz) after tactile stimuli serving as cues versus not serving as cues; 2) a suppression of the occipital alpha-rhythm (7–13 Hz) appearing only in the cueing task (this suppression was stronger contralateral to the endogenously attended side and was predictive of behavioral success); 3) an increase of prefrontal gamma-activity (25–35 Hz) specifically in the cueing task. We measured cue-related modulations of cortical rhythms which may accompany crossmodal spatial attention, expectation or decision, and therefore contribute to cue validity effects. The clearly lateralized alpha suppression after tactile cues in our data indicates its dependence on endogenous rather than exogenous shifts of visuo-spatial attention following a cue independent of its modality

DMF inhibits PDGF-BB induced airway smooth muscle cell proliferation through induction of heme-oxygenase-1

Airway wall remodelling is an important pathology of asthma. Growth factor induced airway smooth muscle cell (ASMC) proliferation is thought to be the major cause of airway wall thickening in asthma. Earlier we reported that Dimethylfumarate (DMF) inhibits platelet-derived growth factor (PDGF)-BB induced mitogen and stress activated kinase (MSK)-1 and CREB activity as well as IL-6 secretion by ASMC. In addition, DMF altered intracellular glutathione levels and thereby reduced proliferation of other cell types

Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids.

Altered daily patterns of hormone action are suspected to contribute to metabolic disease. It is poorly understood how the adrenal glucocorticoid hormones contribute to the coordination of daily global patterns of transcription and metabolism. Here, we examined diurnal metabolite and transcriptome patterns in a zebrafish glucocorticoid deficiency model by RNA-Seq, NMR spectroscopy and liquid chromatography-based methods. We observed dysregulation of metabolic pathways including glutaminolysis, the citrate and urea cycles and glyoxylate detoxification. Constant, non-rhythmic glucocorticoid treatment rescued many of these changes, with some notable exceptions among the amino acid related pathways. Surprisingly, the non-rhythmic glucocorticoid treatment rescued almost half of the entire dysregulated diurnal transcriptome patterns. A combination of E-box and glucocorticoid response elements is enriched in the rescued genes. This simple enhancer element combination is sufficient to drive rhythmic circadian reporter gene expression under non-rhythmic glucocorticoid exposure, revealing a permissive function for the hormones in glucocorticoid-dependent circadian transcription. Our work highlights metabolic pathways potentially contributing to morbidity in patients with glucocorticoid deficiency, even under glucocorticoid replacement therapy. Moreover, we provide mechanistic insight into the interaction between the circadian clock and glucocorticoids in the transcriptional regulation of metabolism