Dynamically constraining the length of the Milky Way bar

We present a novel method for constraining the length of the Galactic bar using 6D phase space information to directly integrate orbits. We define a pseudo-length for the Galactic bar, named $R_{Freq}$, based on the maximal extent of trapped bar orbits. We find the $R_{Freq}$ measured from orbits is consistent with the $R_{Freq}$ of the assumed potential only when the length of the bar and pattern speed of said potential is similar to the model from which the initial phase-space coordinates of the orbits are derived. Therefore, one can measure the model's or the Milky Way's bar length from 6D phase-space coordinates by determining which assumed potential leads to a self-consistent measured $R_{Freq}$. When we apply this method to $\approx$210,000 stars in APOGEE DR17 and $Gaia$ eDR3 data, we find a consistent result only for potential models with a dynamical bar length of $\approx$3.5 kpc. We find the Milky Way's trapped bar orbits extend out to only $\approx$3.5 kpc, but there is also an overdensity of stars at the end of the bar out to 4.8 kpc which could be related to an attached spiral arm. We also find that the measured orbital structure of the bar is strongly dependent on the properties of the assumed potential.Comment: 15 pages, 8 figures, 2 tables, accepted to MNRAS, comments welcom

Respecting Autonomy and Enabling Diversity: The Effect of Eligibility and Enrollment on Research Data Demographics

Many promising advances in precision health and other Big Data research rely on large data sets to analyze correlations among genetic variants, behavior, environment, and outcomes to improve population health. But these data sets are generally populated with demographically homogeneous cohorts. We conducted a retrospective cohort study of patients at a major academic medical center during 2012–19 to explore how recruitment and enrollment approaches affected the demographic diversity of participants in its research biospecimen and data bank. We found that compared with the overall clinical population, patients who consented to enroll in the research data bank were significantly less diverse in terms of age, sex, race, ethnicity, and socioeconomic status. Compared with patients who were recruited for the data bank, patients who enrolled were younger and less likely to be Black or African American, Asian, or Hispanic. The overall demographic diversity of the data bank was affected as much (and in some cases more) by which patients were considered eligible for recruitment as by which patients consented to enroll. Our work underscores the need for systemic commitment to diversify data banks so that different communities can benefit from research

Chemical Cartography of the Sagittarius Stream with Gaia

The stellar stream connected to the Sagittarius (Sgr) dwarf galaxy is the most massive tidal stream that has been mapped in the Galaxy, and is the dominant contributor to the outer stellar halo of the Milky Way. We present metallicity maps of the Sgr stream, using 34,240 red giant branch stars with inferred metallicities from Gaia BP/RP spectra. This sample is larger than previous samples of Sgr stream members with chemical abundances by an order of magnitude. We measure metallicity gradients with respect to Sgr stream coordinates $(\Lambda, B)$, and highlight the gradient in metallicity with respect to stream latitude coordinate $B$, which has not been observed before. We find $\nabla \mathrm{[M/H]} = -2.48 \pm 0.08 \times 10^{-2}$ dex/deg above the stream track ($B>B_0$ where $B_0=1.5$ deg is the latitude of the Sgr remnant) and $\nabla \mathrm{[M/H]} =- 2.02 \pm 0.08 \times 10^{-2}$ dex/deg below the stream track ($B<B_0$). By painting metallicity gradients onto a tailored N-body simulation of the Sgr stream, we find that the observed metallicities in the stream are consistent with an initial radial metallicity gradient in the Sgr dwarf galaxy of $\sim -0.1$ to $-0.2$ dex/kpc, well within the range of observed metallicity gradients in Local Group dwarf galaxies. Our results provide novel observational constraints for the internal structure of the dwarf galaxy progenitor of the Sgr stream. Leveraging new large datasets in conjunction with tailored simulations, we can connect the present day properties of disrupted dwarfs in the Milky Way to their initial conditions.Comment: 20 pages, 12 figures. Submitted to ApJ; comments welcome

Orbital Torus Imaging: Acceleration, density, and dark matter in the Galactic disk measured with element abundance gradients

Under the assumption of a simple and time-invariant gravitational potential, many Galactic dynamics techniques infer the Milky Way's mass and dark matter distribution from stellar kinematic observations. These methods typically rely on parameterized potential models of the Galaxy and must take into account non-trivial survey selection effects, because they make use of the density of stars in phase space. Large-scale spectroscopic surveys now supply information beyond kinematics in the form of precise stellar label measurements (especially element abundances). These element abundances are known to correlate with orbital actions or other dynamical invariants. Here, we use the Orbital Torus Imaging (OTI) framework that uses abundance gradients in phase space to map orbits. In many cases these gradients can be measured without detailed knowledge of the selection function. We use stellar surface abundances from the APOGEE survey combined with kinematic data from the Gaia mission. Our method reveals the vertical ($z$-direction) orbit structure in the Galaxy and enables empirical measurements of the vertical acceleration field and orbital frequencies in the disk. From these measurements, we infer the total surface mass density, $\Sigma$, and midplane volume density, $\rho_0$, as a function of Galactocentric radius and height. Around the Sun, we find $\Sigma_{\odot}(z=1.1$ kpc)$=72^{+6}_{-9}$M$_{\odot}$pc$^{-2}$ and $\rho_{\odot}(z=0)=0.081^{+0.015}_{-0.009}$ M$_{\odot}$pc$^{-3}$ using the most constraining abundance ratio, [Mg/Fe]. This corresponds to a dark matter contribution in surface density of $\Sigma_{\odot,\mathrm{DM}}(z=1.1$ kpc)$=24\pm4$ M$_{\odot}$pc$^{-2}$, and in total volume mass density of $\rho_{\odot,\mathrm{DM}}(z=0)=0.011\pm0.002$ M$_{\odot}$pc$^{-3}$. Moreover, using these mass density values we estimate the scale length of the low-$\alpha$ disc to be $h_R=2.24\pm0.06$kpc.Comment: Accepted for publication in ApJ. 19 pages, 11 figures, 3 Table

Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8+ T cell responses

Vaccinia virus immunization provides lifelong protection against smallpox, but the mechanisms of this exquisite protection are unknown. We used polychromatic flow cytometry to characterize the functional and phenotypic profile of CD8+ T cells induced by vaccinia virus immunization in a comparative vaccine trial of modified vaccinia virus Ankara (MVA) versus Dryvax immunization in which protection was assessed against subsequent Dryvax challenge. Vaccinia virus–specific CD8+ T cells induced by both MVA and Dryvax were highly polyfunctional; they degranulated and produced interferon γ, interleukin 2, macrophage inflammatory protein 1β, and tumor necrosis factor α after antigenic stimulation. Responding CD8+ T cells exhibited an unusual phenotype (CD45RO−CD27intermediate). The unique phenotype and high degree of polyfunctionality induced by vaccinia virus also extended to inserted HIV gene products of recombinant NYVAC. This quality of the CD8+ T cell response may be at least partially responsible for the profound efficacy of these vaccines in protection against smallpox and serves as a benchmark against which other vaccines can be evaluated

Colitis and Colon Cancer in WASP-Deficient Mice Require Helicobacter Species

Background: Wiskott–Aldrich syndrome protein–deficient patients and mice are immunodeficient and can develop inflammatory bowel disease. The intestinal microbiome is critical to the development of colitis in most animal models, in which Helicobacter spp. have been implicated in disease pathogenesis. We sought to determine the role of Helicobacter spp. in colitis development in Wiskott–Aldrich syndrome protein–deficient (WKO) mice. Methods: Feces from WKO mice raised under specific pathogen-free conditions were evaluated for the presence of Helicobacter spp., after which a subset of mice were rederived in Helicobacter spp.–free conditions. Helicobacter spp.–free WKO animals were subsequently infected with Helicobacter bilis. Results: Helicobacter spp. were detected in feces from WKO mice. After rederivation in Helicobacter spp.–free conditions, WKO mice did not develop spontaneous colitis but were susceptible to radiation-induced colitis. Moreover, a T-cell transfer model of colitis dependent on Wiskott–Aldrich syndrome protein–deficient innate immune cells also required Helicobacter spp. colonization. Helicobacter bilis infection of rederived WKO mice led to typhlitis and colitis. Most notably, several H. bilis–infected animals developed dysplasia with 10% demonstrating colon carcinoma, which was not observed in uninfected controls. Conclusions: Spontaneous and T-cell transfer, but not radiation-induced, colitis in WKO mice is dependent on the presence of Helicobacter spp. Furthermore, H. bilis infection is sufficient to induce typhlocolitis and colon cancer in Helicobacter spp.–free WKO mice. This animal model of a human immunodeficiency with chronic colitis and increased risk of colon cancer parallels what is seen in human colitis and implicates specific microbial constituents in promoting immune dysregulation in the intestinal mucosa.National Institutes of Health (U.S.) (R01OD011141)National Institutes of Health (U.S.) (R01CA067529)National Institutes of Health (U.S.) (P01CA026731)National Institutes of Health (U.S.) (P30ES02109

Brain structural and functional recovery following initiation of combination antiretroviral therapy

NeuroAIDS persists in the era of combination antiretroviral therapies. We describe here the recovery of brain structure and function following 6 months of therapy in a treatment-naive patient presenting with HIV-associated dementia. The patient’s neuropsychological test performance improved and his total brain volume increased by more than 5 %. Neuronal functional connectivity measured by magnetoencephalography changed from a pattern identical to that observed in other HIV-infected individuals to one that was indistinguishable from that of uninfected control subjects. These data suggest that at least some of the effects of HIV on the brain can be fully reversed with treatment

Genome-wide association study identifies 30 loci associated with bipolar disorder.

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P &lt; 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P &lt; 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder

Misfolded SOD1 Associated with Motor Neuron Mitochondria Alters Mitochondrial Shape and Distribution Prior to Clinical Onset

Mutations in superoxide dismutase (SOD1) are causative for inherited amyotrophic lateral sclerosis. A proportion of SOD1 mutant protein is misfolded onto the cytoplasmic face of mitochondria in one or more spinal cord cell types. By construction of mice in which mitochondrially targeted enhanced green fluorescent protein is selectively expressed in motor neurons, we demonstrate that axonal mitochondria of motor neurons are primary in vivo targets for misfolded SOD1. Mutant SOD1 alters axonal mitochondrial morphology and distribution, with dismutase active SOD1 causing mitochondrial clustering at the proximal side of Schmidt-Lanterman incisures within motor axons and dismutase inactive SOD1 producing aberrantly elongated axonal mitochondria beginning pre-symptomatically and increasing in severity as disease progresses. Somal mitochondria are altered by mutant SOD1, with loss of the characteristic cylindrical, networked morphology and its replacement by a less elongated, more spherical shape. These data indicate that mutant SOD1 binding to mitochondria disrupts normal mitochondrial distribution and size homeostasis as early pathogenic features of SOD1 mutant-mediated ALS

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie