Precision measurements of the stars in short-period orbits around the supermassive black hole at the Galactic Center are now being used to constrain general relativistic effects, such as the ...gravitational redshift and periapse precession. One of the largest systematic uncertainties in the measured orbits has been errors in the astrometric reference frame, which is derived from seven infrared-bright stars associated with SiO masers that have extremely accurate radio positions, measured in the Sgr A*-rest frame. We have improved the astrometric reference frame within 14″ of the Galactic Center by a factor of 2.5 in position and a factor of 5 in proper motion. In the new reference frame, Sgr A* is localized to within a position of 0.645 mas and proper motion of 0.03 mas yr−1. We have removed a substantial rotation (2 25 per decade), that was present in the previous less-accurate reference frame used to measure stellar orbits in the field. With our improved methods and continued monitoring of the masers, we predict that orbital precession predicted by general relativity will become detectable in the next ∼5 yr.
Abstract
Microlensing events have historically been discovered throughout the Galactic bulge and plane by surveys designed solely for that purpose. We conduct the first multiyear search for ...microlensing events on the Zwicky Transient Facility (ZTF), an all-sky optical synoptic survey that observes the entire visible northern sky every few nights. We discover 60 high-quality microlensing events in the 3 yr of ZTF-I using the bulk lightcurves in the ZTF Public Data Release 5.19 of our events are found outside of the Galactic plane (∣
b
∣ ≥ 10°), nearly doubling the number of previously discovered events in the stellar halo from surveys pointed toward the Magellanic Clouds and the Andromeda galaxy. We also record 1558 ongoing candidate events as potential microlensing that can continue to be observed by ZTF-II for identification. The scalable and computationally efficient methods developed in this work can be applied to future synoptic surveys, such as the Vera C. Rubin Observatory’s Legacy Survey of Space and Time and the Nancy Grace Roman Space Telescope, as they attempt to find microlensing events in even larger and deeper data sets.
Abstract
We measure the 3D kinematic structures of the young stars within the central 0.5 pc of our Galactic Center using the 10 m telescopes of the W. M. Keck Observatory over a time span of 25 yr. ...Using high-precision measurements of positions on the sky and proper motions and radial velocities from new observations and the literature, we constrain the orbital parameters for each young star. Our results show two statistically significant substructures: a clockwise stellar disk with 18 candidate stars, as has been proposed before, but with an improved disk membership; and a second, almost edge-on plane of 10 candidate stars oriented east–west on the sky that includes at least one IRS 13 star. We estimate the eccentricity distribution of each substructure and find that the clockwise disk has 〈
e
〉 = 0.39 and the edge-on plane has 〈
e
〉 = 0.68. We also perform simulations of each disk/plane with incompleteness and spatially variable extinction to search for asymmetry. Our results show that the clockwise stellar disk is consistent with a uniform azimuthal distribution within the disk. The edge-on plane has an asymmetry that cannot be explained by variable extinction or incompleteness in the field. The orientation, asymmetric stellar distribution, and high eccentricity of the edge-on plane members suggest that this structure may be a stream associated with the IRS 13 group. The complex dynamical structure of the young nuclear cluster indicates that the star formation process involved complex gas structures and dynamics and is inconsistent with a single massive gaseous disk.
We report new precision measurements of the properties of our Galaxy's supermassive black hole. Based on astrometric (1995-2007) and radial velocity (RV; 2000-2007) measurements from the W. M. Keck ...10 m telescopes, a fully unconstrained Keplerian orbit for the short-period star S0-2 provides values for the distance of image kpc, the enclosed mass of image, and the black hole's RV, which is consistent with zero with 30 km s super(-1) uncertainty. If the black hole is assumed to be at rest with respect to the Galaxy (e.g., has no massive companion to induce motion), we can further constrain the fit, obtaining image kpc and image. More complex models constrain the extended dark mass distribution to be less than 3-image within 0.01 pc, image100 times higher than predictions from stellar and stellar remnant models. For all models, we identify transient astrometric shifts from source confusion (up to 5 times the astrometric error) and the assumptions regarding the black hole's radial motion as previously unrecognized limitations on orbital accuracy and the usefulness of fainter stars. Future astrometric and RV observations will remedy these effects. Our estimates of image and the Galaxy's local rotation speed, which it is derived from combining image with the apparent proper motion of Sgr A*, (image km s super(-1)), are compatible with measurements made using other methods. The increased black hole mass found in this study, compared to that determined using projected mass estimators, implies a longer period for the innermost stable orbit, longer resonant relaxation timescales for stars in the vicinity of the black hole and a better agreement with the image -image relation.
We present significantly improved proper motion measurements of the Milky Way's central stellar cluster. These improvements are made possible by refining our astrometric reference frame with a new ...geometric optical distortion model for the W. M. Keck II 10 m telescope's adaptive optics camera (NIRC2) in its narrow field mode. For the first time, this distortion model is constructed from on-sky measurements and is made available to the public in the form of FITS files. When applied to widely dithered images, it produces residuals in the separations of stars that are a factor of ~3 smaller compared with the outcome using previous models. By applying this new model, along with corrections for differential atmospheric refraction, to widely dithered images of SiO masers at the Galactic center (GC), we improve our ability to tie into the precisely measured radio Sgr A*-rest frame. The resulting infrared reference frame is ~2-3 times more accurate and stable than earlier published efforts. In this reference frame, Sgr A* is localized to within a position of 0.6 mas and a velocity of 0.09 mas yr--1, or ~3.4 km s--1 at 8 kpc (1 Delta *s). Also, proper motions for members of the central stellar cluster are more accurate, although less precise, due to the limited number of these wide field measurements. These proper motion measurements show that, with respect to Sgr A*, the central stellar cluster has no rotation in the plane of the sky to within 0.3 mas yr--1 arcsec--1, has no net translational motion with respect to Sgr A* to within 0.1 mas yr--1, and has net rotation perpendicular to the plane of the sky along the Galactic plane, as has previously been observed. While earlier proper motion studies defined a reference frame by assuming no net motion of the stellar cluster, this approach is fundamentally limited by the cluster's intrinsic dispersion and therefore will not improve with time. We define a reference frame with SiO masers and this reference frame's stability should improve steadily with future measurements of the SiO masers in this region (t --3/2). This is essential for achieving the necessary reference frame stability required to detect the effects of general relativity and extended mass on short-period stars at the GC.
Objective
A hallmark of rheumatoid arthritis (RA) is the production of autoantibodies, including anti–citrullinated protein antibodies (ACPAs). Nevertheless, the specific targets of these ...autoantibodies remain incompletely defined. During an immune response, B cells specific for the inciting antigen(s) are activated and differentiate into plasmablasts, which are released into the blood. We undertook this study to sequence the plasmablast antibody repertoire to define the targets of the active immune response in RA.
Methods
We developed a novel DNA barcoding method to sequence the cognate heavy‐ and light‐chain pairs of antibodies expressed by individual blood plasmablasts in RA. The method uses a universal 5′ adapter that enables full‐length sequencing of the antibodies' variable regions and recombinant expression of the paired antibody chains. The sequence data sets were bioinformatically analyzed to generate phylogenetic trees that identify clonal families of antibodies sharing heavy‐ and light‐chain VJ sequences. Representative antibodies were expressed, and their binding properties were characterized using anti–cyclic citrullinated peptide 2 (anti–CCP‐2) enzyme‐linked immunosorbent assay (ELISA) and antigen microarrays.
Results
We used our sequencing method to generate phylogenetic trees representing the antibody repertoires of peripheral blood plasmablasts from 4 individuals with anti‐CCP+ RA, and recombinantly expressed 14 antibodies that were either “singleton” antibodies or representative of clonal antibody families. Anti–CCP‐2 ELISA identified 4 ACPAs, and antigen microarray analysis identified ACPAs that differentially targeted epitopes on α‐enolase, citrullinated fibrinogen, and citrullinated histone H2B.
Conclusion
Our data provide evidence that autoantibodies targeting α‐enolase, citrullinated fibrinogen, and citrullinated histone H2B are produced by the ongoing activated B cell response in, and thus may contribute to the pathogenesis of, RA.
We present improved relative astrometry for stars within the central half parsec of our Galactic Center (GC) based on data obtained with the 10 m W. M. Keck Observatory from 1995 to 2017. The new ...methods used to improve the astrometric precision and accuracy include correcting for local astrometric distortions, applying a magnitude-dependent additive error, and more carefully removing instances of stellar confusion. Additionally, we adopt jackknife methods to calculate velocity and acceleration uncertainties. The resulting median proper motion uncertainty is 0.05 mas yr−1 for our complete sample of 1184 stars in the central 10″ (0.4 pc). We have detected 24 accelerating sources, 2.6 times more than the number of previously published accelerating sources, which extend out to 4″ (0.16 pc) from the black hole. Based on S0-2's orbit, our new astrometric analysis has reduced the systematic error of the supermassive black hole (SMBH) by a factor of 2. The linear drift in our astrometric reference frame is also reduced in the north-south direction by a factor of 4. We also find the first potential astrometric binary candidate S0-27 in the GC. These astrometric improvements provide a foundation for future studies of the origin and dynamics of the young stars around the SMBH, the structure and dynamics of the old nuclear star cluster, the SMBH's properties derived from orbits, and tests of general relativity in a strong gravitational field.
Summary
Background
Bilirubin is a yellow breakdown product of heme catabolism. Increased serum levels of unconjugated bilirubin are conditions commonly seen in premature neonates and adults with ...acute hemolysis including thrombotic microangiopathy. Previous studies have shown that unconjugated bilirubin lowers plasma ADAMTS13 activity, but the mechanism is not fully understood.
Objectives
The study is to determine whether unconjugated bilirubin directly inhibits the cleavage of von Willebrand factor (VWF) and its analogs by ADAMTS13.
Methods
Fluorogenic, surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometric assay, and Western blotting analyses were used to address this question.
Results
Unconjugated bilirubin inhibits the cleavage of F485‐rVWF73‐H, D633‐rVWF73‐H, and GST‐rVWF71‐11K by ADAMTS13 in a concentration‐dependent manner with a half‐maximal inhibitory concentration of ~13, ~70, and ~17 μmol L–1, respectively. Unconjugated bilirubin also dose‐dependently inhibits the cleavage of multimeric VWF by ADAMTS13 under denaturing conditions. The inhibitory activity of bilirubin on the cleavage of D633‐rVWF73‐H and multimeric VWF, but not F485‐rVWF73‐H, was eliminated after incubation with bilirubin oxidase that converts bilirubin to biliverdin. Furthermore, plasma ADAMTS13 activity in patients with hyperbilirubinemia increased after treatment with bilirubin oxidase.
Conclusions
Unconjugated bilirubin directly inhibits ADAMTS13's ability to cleave both peptidyl and native VWF substrates in addition to its interference with certain fluorogenic assays. Our findings may help proper interpretation of ADAMTS13 results under pathological conditions. Whether elevated serum unconjugated bilirubin has prothrombotic effect in vivo remains to be determined in our future study.
Objective
To compare brain‐derived neurotrophic factor (BDNF) levels between offspring of individuals with bipolar disorders (BD) and healthy controls (HCs) and investigate the effects of BDNF levels ...and body mass index (BMI) on brain structures.
Method
Sixty‐seven bipolar offspring and 45 HCs were included (ages 8‐28). Structural images were acquired using 3.0 Tesla magnetic resonance imaging. Serum BDNF levels were measured using enzyme‐linked immunosorbent assay. Multivariate and univariate analyses of covariance were conducted.
Results
Significantly higher BDNF levels were observed among bipolar offspring, relative to HCs (P > 0.025). Offspring status moderated the association between BDNF and BMI (F1=4.636, P = 0.034). After adjustment for relevant covariates, there was a trend for a significant interaction of group and BDNF on neuroimaging parameters (Wilks’λ F56,94=1.463, P = 0.052), with significant effects on cerebellar white matter and superior and middle frontal regions. Brain volume and BDNF were positively correlated among HCs and negatively correlated among bipolar offspring. Interactions between BDNF and BMI on brain volumes were non‐significant among HCs (Wilks’λ F28,2=2.229, P = 0.357), but significant among bipolar offspring (Wilks’λ F28,12=2.899, P = 0.028).
Conclusion
Offspring status and BMI moderate the association between BDNF levels and brain structures among bipolar offspring, underscoring BDNF regulation and overweight/obesity as key moderators of BD pathogenesis.
Objective
Anti–citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA). While epitope spreading of the serum ACPA response is believed to contribute to RA pathogenesis, ...little is understood regarding how this phenomenon occurs. This study was undertaken to analyze the antibody repertoires of individuals with RA to gain insight into the mechanisms leading to epitope spreading of the serum ACPA response in RA.
Methods
Plasmablasts from the blood of 6 RA patients were stained with citrullinated peptide tetramers to identify ACPA‐producing B cells by flow cytometry. Plasmablasts were single‐cell sorted and sequenced to obtain antibody repertoires. Sixty‐nine antibodies were recombinantly expressed, and their anticitrulline reactivities were characterized using a cyclic citrullinated peptide enzyme‐linked immuosorbent assay and synovial antigen arrays. Thirty‐six mutated antibodies designed either to represent ancestral antibodies or to test paratope residues critical for binding, as determined from molecular modeling studies, were also tested for anticitrulline reactivities.
Results
Clonally related monoclonal ACPAs and their shared ancestral antibodies each exhibited differential reactivity against citrullinated antigens. Molecular modeling identified residues within the complementarity‐determining region loops and framework regions predicted to be important for citrullinated antigen binding. Affinity maturation resulted in mutations of these key residues, which conferred binding to different citrullinated epitopes and/or increased polyreactivity to citrullinated epitopes.
Conclusion
These results demonstrate that the different somatic hypermutations accumulated by clonally related B cells during affinity maturation alter the antibody paratope to mediate epitope spreading and polyreactivity of the ACPA response in RA, suggesting that these may be key properties that likely contribute to the pathogenicity of ACPAs.
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