Systoles of Arithmetic Hyperbolic Surfaces and 3-manifolds

Our main result is that for all sufficiently large $x_0>0$, the set of commensurability classes of arithmetic hyperbolic 2- or 3-orbifolds with fixed invariant trace field $k$ and systole bounded below by $x_0$ has density one within the set of all commensurability classes of arithmetic hyperbolic 2- or 3-orbifolds with invariant trace field $k$. The proof relies upon bounds for the absolute logarithmic Weil height of algebraic integers due to Silverman, Brindza and Hajdu, as well as precise estimates for the number of rational quaternion algebras not admitting embeddings of any quadratic field having small discriminant. When the trace field is $\mathbf{Q}$, using work of Granville and Soundararajan, we establish a stronger result that allows our constant lower bound $x_0$ to grow with the area. As an application, we establish a systolic bound for arithmetic hyperbolic surfaces that is related to prior work of Buser-Sarnak and Katz-Schaps-Vishne. Finally, we establish an analogous density result for commensurability classes of arithmetic hyperbolic 3-orbifolds with small area totally geodesic $2$-orbifolds.Comment: v4: 17 pages. Revised according to referee report. Final version. To appear in Math. Res. Let

Quantifying the Origin and Distribution of Intracluster Light in a Fornax-like Cluster

Using a cosmological $N$-body simulation, we investigate the origin and distribution of stars in the intracluster light (ICL) of a Fornax-like cluster. In a dark matter only simulation we identify a halo which, at $z=0$, has $M_200 \simeq 4.1 \times 10^{13}M_{sun}$ and $r_{200} = 700kpc$, and replace infalling subhalos with models that include spheroid and disc components. As they fall into the cluster, the stars in some of these galaxies are stripped from their hosts, and form the ICL. We consider the separate contributions to the ICL from stars which originate in the haloes and the discs of the galaxies. We find that disc ICL stars are more centrally concentrated than halo ICL stars. The majority of the disc ICL stars are associated with one initially disc-dominated galaxy that falls to the centre of the cluster and is heavily disrupted, producing part of the cD galaxy. At radial distances greater than 200kpc, well beyond the stellar envelope of the cD galaxy, stars formerly from the stellar haloes of galaxies dominate the ICL. Therefore at large distances, the ICL population is dominated by older stars.Comment: Paper published as MNRAS , 2017, 467, 4501 This version corrects a small typo in the authors fiel

Hemodynamic and ADH responses to central blood volume shifts in cardiac-denervated humans

Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes designed to induce blood volume shifts in ten cardiac transplant recipients to assess the contribution of cardiac and vascular volume receptors in the control of ADH secretion. Each subject underwent 15 min of a control period in the seated posture, then assumed a lying posture for 30 min at 6 deg head down tilt (HDT) followed by 20 min of seated recovery. Venous blood samples and cardiac dimensions (echocardiography) were taken at 0 and 15 min before HDT, 5, 15, and 30 min of HDT, and 5, 15, and 30 min of seated recovery. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Resting plasma volume (PV) was measured by Evans blue dye and percent changes in PV during posture changes were calculated from changes in hematocrit. Heart rate (HR) and blood pressure (BP) were recorded every 2 min. Results indicate that cardiac volume receptors are not the only mechanism for the control of ADH release during acute blood volume shifts in man

Neuroplasticity of the extended amygdala in opioid withdrawal and prolonged opioid abstinence

Opioid use disorder is characterized by excessive use of opioids, inability to control its use, a withdrawal syndrome upon discontinuation of opioids, and long-term likelihood of relapse. The behavioral stages of opioid addiction correspond with affective experiences that characterize the opponent process view of motivation. In this framework, active involvement is accompanied by positive affective experiences which gives rise to “reward craving,” whereas the opponent process, abstinence, is associated with the negative affective experiences that produce “relief craving.” Relief craving develops along with a hypersensitization to the negatively reinforcing aspects of withdrawal during abstinence from opioids. These negative affective experiences are hypothesized to stem from neuroadaptations to a network of affective processing called the “extended amygdala.” This negative valence network includes the three core structures of the central nucleus of the amygdala (CeA), the bed nucleus of the stria terminalis (BNST), and the nucleus accumbens shell (NAc shell), in addition to major inputs from the basolateral amygdala (BLA). To better understand the major components of this system, we have reviewed their functions, inputs and outputs, along with the associated neural plasticity in animal models of opioid withdrawal. These models demonstrate the somatic, motivational, affective, and learning related models of opioid withdrawal and abstinence. Neuroadaptations in these stress and motivational systems are accompanied by negative affective and aversive experiences that commonly give rise to relapse. CeA neuroplasticity accounts for many of the aversive and fear-related effects of opioid withdrawal via glutamatergic plasticity and changes to corticotrophin-releasing factor (CRF)-containing neurons. Neuroadaptations in BNST pre-and post-synaptic GABA-containing neurons, as well as their noradrenergic modulation, may be responsible for a variety of aversive affective experiences and maladaptive behaviors. Opioid withdrawal yields a hypodopaminergic and amotivational state and results in neuroadaptive increases in excitability of the NAc shell, both of which are associated with increased vulnerability to relapse. Finally, BLA transmission to hippocampal and cortical regions impacts the perception of conditioned aversive effects of opioid withdrawal by higher executive systems. The prevention or reversal of these varied neuroadaptations in the extended amygdala during opioid withdrawal could lead to promising new interventions for this life-threatening condition

Variable expression and silencing of CRISPR-Cas9 targeted transgenes identifies the AAVS1 locus as not an entirely safe harbour

Background: Diseases such as hypertrophic cardiomyopathy (HCM) can lead to severe outcomes including sudden death. The generation of human induced pluripotent stem cell (hiPSC) reporter lines can be useful for disease modelling and drug screening by providing physiologically relevant in vitro models of disease. The AAVS1 locus is cited as a safe harbour that is permissive for stable transgene expression, and hence is favoured for creating gene targeted reporter lines. Methods: We generated hiPSC reporters using a plasmid-based CRISPR/Cas9 nickase strategy. The first intron of PPP1R12C, the AAVS1 locus, was targeted with constructs expressing a genetically encoded calcium indicator (R-GECO1.0) or HOXA9-T2A-mScarlet reporter under the control of a pCAG or inducible pTRE promoter, respectively. Transgene expression was compared between clones before, during and/or after directed differentiation to mesodermal lineages. Results: Successful targeting to AAVS1 was confirmed by PCR and sequencing. Of 24 hiPSC clones targeted with pCAG-R-GECO1.0, only 20 expressed the transgene and in these, the percentage of positive cells ranged from 0% to 99.5%. Differentiation of a subset of clones produced cardiomyocytes, wherein the percentage of cells positive for R-GECO1.0 ranged from 2.1% to 93.1%. In the highest expressing R-GECO1.0 clones, transgene silencing occurred during cardiomyocyte differentiation causing a decrease in expression from 98.93% to 1.3%. In HOXA9-T2A-mScarlet hiPSC reporter lines directed towards mesoderm lineages, doxycycline induced a peak in transgene expression after two days but this reduced by up to ten-thousand-fold over the next 8-10 days. Nevertheless, for R-GECO1.0 lines differentiated into cardiomyocytes, transgene expression was rescued by continuous puromycin drug selection, which allowed the Ca 2+ responses associated with HCM to be investigated in vitro using single cell analysis. Conclusions: Targeted knock-ins to AAVS1 can be used to create reporter lines but variability between clones and transgene silencing requires careful attention by researchers seeking robust reporter gene expression

Variable expression and silencing of CRISPR-Cas9 targeted transgenes identifies the AAVS1 locus as not an entirely safe harbour

Background: Diseases such as hypertrophic cardiomyopathy (HCM) can lead to severe outcomes including sudden death. The generation of human induced pluripotent stem cell (hiPSC) reporter lines can be useful for disease modelling and drug screening by providing physiologically relevant in vitro models of disease. The AAVS1 locus is cited as a safe harbour that is permissive for stable transgene expression, and hence is favoured for creating gene targeted reporter lines.Methods: We generated hiPSC reporters using a plasmid-based CRISPR/Cas9 nickase strategy. The first intron of PPP1R12C, the AAVS1 locus, was targeted with constructs expressing a genetically encoded calcium indicator (R-GECO1.0) or HOXA9-T2A-mScarlet reporter under the control of a pCAG or inducible pTRE promoter, respectively. Transgene expression was compared between clones before, during and/or after directed differentiation to mesodermal lineages.Results: Successful targeting to AAVS1 was confirmed by PCR and sequencing. Of 24 hiPSC clones targeted with pCAG-R-GECO1.0, only 20 expressed the transgene and in these, the percentage of positive cells ranged from 0% to 99.5%. Differentiation of a subset of clones produced cardiomyocytes, wherein the percentage of cells positive for R-GECO1.0 ranged from 2.1% to 93.1%. In the highest expressing R-GECO1.0 clones, transgene silencing occurred during cardiomyocyte differentiation causing a decrease in expression from 98.93% to 1.3%. In HOXA9-T2A-mScarlet hiPSC reporter lines directed towards mesoderm lineages, doxycycline induced a peak in transgene expression after two days but this reduced by up to ten-thousand-fold over the next 8-10 days. Nevertheless, for R-GECO1.0 lines differentiated into cardiomyocytes, transgene expression was rescued by continuous puromycin drug selection, which allowed the Ca2+ responses associated with HCM to be investigated in vitro using single cell analysis.Conclusions: Targeted knock-ins to AAVS1 can be used to create reporter lines but variability between clones and transgene silencing requires careful attention by researchers seeking robust reporter gene expression

A third red supergiant rich cluster in the Scutum-Crux arm

Aims. We aim to characterise the properties of a third massive, red supergiant dominated galactic cluster. Methods. To accomplish this we utilised a combination of near/mid-IR photometry and spectroscopy to identify and classify the properties of cluster members, and statistical arguments to determine the mass of the cluster. Results. We found a total of 16 strong candidates for cluster membership, for which formal classification of a subset yields spectral types from K3-M4 Ia and luminosities between log(L/L-circle dot) similar to 4.5-4.8 for an adopted distance of 6 +/- 1 kpc. For an age in the range of 16-20 Myr, the implied mass is 2-4 x 10(4) M-circle dot, making it one of the most massive young clusters in the Galaxy. This discovery supports the hypothesis that a significant burst of star formation occurred at the base of Scutum-Crux arm between 10-20 Myr ago, yielding a stellar complex comprising at least similar to 10(5) M-circle dot of stars (noting that since the cluster identification criteria rely on the presence of RSGs, we suspect that the true stellar yield will be significantly higher). We highlight the apparent absence of X-ray binaries within the star formation complex and finally, given the physical association of at least two pulsars with this region, discuss the implications of this finding for stellar evolution and the production and properties of neutron stars

The dominant global modes of recent internal sea level variability

Author Posting. © American Geophysical Union, 2019. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research-Oceans 124(4), (2019):2750-2768, doi: 10.1029/2018JC014635.The advances in the modern sea level observing system have allowed for a new level of knowledge of regional and global sea level in recent years. The combination of data from satellite altimeters, Gravity Recovery and Climate Experiment (GRACE) satellites, and Argo profiling floats has provided a clearer picture of the different contributors to sea level change, leading to an improved understanding of how sea level has changed in the present and, by extension, may change in the future. As the overlap between these records has recently extended past a decade in length, it is worth examining the extent to which internal variability on timescales from intraseasonal to decadal can be separated from long‐term trends that may be expected to continue into the future. To do so, a combined modal decomposition based on cyclostationary empirical orthogonal functions is performed simultaneously on the three data sets, and the dominant shared modes of variability are analyzed. Modes associated with the trend, seasonal signal, El Niño–Southern Oscillation, and Pacific decadal oscillation are extracted and discussed, and the relationship between regional patterns of sea level change and their associated global signature is highlighted.The satellite altimetry grids are available from NASA JPL/PO.DAAC at the following location: https://podaac.jpl.nasa.gov/dataset. GRACE land water storage data are available at http://grace.jpl.nasa.gov, supported by the NASA MEaSUREs Program. The gridded fields based on Argo data used to compute the steric sea level data are available at http://www.argo.ucsd.edu/Gridded_fields.html. The gridded fields based on Argo data used to compute the steric sea level data are available at http://www.argo.ucsd.edu/Gridded_fields.html. The research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration. B. D. H., F. W. L., J. T. R., and P. R. T. acknowledge support from NASA grant 80NSSC17K0564 (NASA Sea Level Change Team). C. G. P. acknowledges support from NSF awards OCE‐1558966 and OCE‐1834739. K. Y. K. was partially supported for this research by the National Science Foundation of Korea under the grant NRF‐ 2017R1A2B4003930.2019-09-2