Abstract
Establishing and maintaining tolerance to self-antigens or innocuous foreign antigens is vital for the preservation of organismal health. Within the thymus, medullary thymic epithelial cells ...(mTECs) expressing autoimmune regulator (AIRE) have a critical role in self-tolerance through deletion of autoreactive T cells and promotion of thymic regulatory T (T
reg
) cell development
1–4
. Within weeks of birth, a separate wave of T
reg
cell differentiation occurs in the periphery upon exposure to antigens derived from the diet and commensal microbiota
5–8
, yet the cell types responsible for the generation of peripheral T
reg
(pT
reg
) cells have not been identified. Here we describe the identification of a class of RORγt
+
antigen-presenting cells called Thetis cells, with transcriptional features of both mTECs and dendritic cells, comprising four major sub-groups (TC I–TC IV). We uncover a developmental wave of Thetis cells within intestinal lymph nodes during a critical window in early life, coinciding with the wave of pT
reg
cell differentiation. Whereas TC I and TC III expressed the signature mTEC nuclear factor AIRE, TC IV lacked AIRE expression and was enriched for molecules required for pT
reg
generation, including the TGF-β-activating integrin αvβ8. Loss of either major histocompatibility complex class II (MHCII) or ITGB8 by Thetis cells led to a profound impairment in intestinal pT
reg
differentiation, with ensuing colitis. By contrast, MHCII expression by RORγt
+
group 3 innate lymphoid cells (ILC3) and classical dendritic cells was neither sufficient nor required for pT
reg
generation, further implicating TC IV as the tolerogenic RORγt
+
antigen-presenting cell with an essential function in early life. Our studies reveal parallel pathways for the establishment of tolerance to self and foreign antigens in the thymus and periphery, respectively, marked by the involvement of shared cellular and transcriptional programmes.
Abstract
We describe Keck-telescope spectrophotometry and imaging of the companion of the “black widow” pulsar PSR J0952−0607, the fastest known spinning neutron star (NS) in the disk of the Milky ...Way. The companion is very faint at minimum brightness, presenting observational challenges, but we have measured multicolor light curves and obtained radial velocities over the illuminated “day” half of the orbit. The model fits indicate system inclination
i
= 59.°8 ± 1.°9 and a pulsar mass
M
NS
= 2.35 ± 0.17
M
⊙
, the largest well-measured mass found to date. Modeling uncertainties are small, since the heating is not extreme; the companion lies well within its Roche lobe and a simple direct-heating model provides the best fit. If the NS started at a typical pulsar birth mass, nearly 1
M
⊙
has been accreted; this may be connected with the especially low intrinsic dipole surface field, estimated at 6 × 10
7
G. Joined with reanalysis of other black widow and redback pulsars, we find that the minimum value for the maximum NS mass is
M
max
>
2.19
M
⊙
(2.09
M
⊙
) at 1
σ
(3
σ
) confidence. This is ∼ 0.15
M
⊙
heavier than the lower limit on
M
max
implied by the white dwarf–pulsar binaries measured via radio Shapiro-delay techniques.
Abstract
Keck-telescope spectrophotometry of the companion of PSR J1810+1744 shows a flat, but asymmetric light-curve maximum and a deep, narrow minimum. The maximum indicates strong gravity ...darkening (GD) near the
L
1
point, along with a heated pole and surface winds. The minimum indicates a low underlying temperature and substantial limb darkening. The GD is a consequence of extreme pulsar heating and the near-filling of the Roche lobe. Light-curve modeling gives a binary inclination
i
= 65.°7 ± 0.°4. With the Keck-measured radial-velocity amplitude
K
c
= 462.3 ± 2.2 km s
−1
, this gives an accurate neutron star mass
M
NS
= 2.13 ± 0.04
M
⊙
, with important implications for the dense-matter equation of state. A classic direct-heating model, ignoring the
L
1
gravitational darkening, would predict an unphysical
M
NS
> 3
M
⊙
. A few other “spider” pulsar binaries have similar large heating and fill factor; thus, they should be checked for such effects.
We study the sudden optical and ultraviolet (UV) brightening of 1ES 1927+654, which until now was known as a narrow-line active galactic nucleus (AGN). 1ES 1927+654 was part of the small and peculiar ...class of "true Type-2" AGNs that lack broad emission lines and line-of-sight obscuration. Our high-cadence spectroscopic monitoring captures the appearance of a blue, featureless continuum, followed several weeks later by the appearance of broad Balmer emission lines. This timescale is generally consistent with the expected light travel time between the central engine and the broadline emission region in (persistent) broadline AGN. Hubble Space Telescope spectroscopy reveals no evidence for broad UV emission lines (e.g., C iv λ1549, C iii λ1909, Mg ii λ2798), probably owing to dust in the broadline emission region. To the best of our knowledge, this is the first case where the lag between the change in continuum and in broadline emission of a "changing look" AGN has been temporally resolved. The nature and timescales of the photometric and spectral evolution disfavor both a change in line-of-sight obscuration and a change of the overall rate of gas inflow as driving the drastic spectral transformations seen in this AGN. Although the peak luminosity and timescales are consistent with those of tidal disruption events seen in inactive galaxies, the spectral properties are not. The X-ray emission displays a markedly different behavior, with frequent flares on timescales of hours to days, and will be presented in a companion publication.
Abstract
We present three epochs of early-time ultraviolet (UV) and optical HST/STIS spectroscopy of the young, nearby Type IIP supernova (SN) 2021yja. We complement the HST data with two earlier ...epochs of Swift UVOT spectroscopy. The HST and Swift UVOT spectra are consistent with those of other well-studied Type IIP SNe. The UV spectra exhibit rapid cooling at early times, while less dramatic changes are seen in the optical. We also present Lick/KAIT optical photometry up to the late-time tail phase, showing a very long plateau and shallow decline compared with other SNe IIP. Our modeling of the UV spectrum with the
TARDIS
radiative transfer code produces a good fit for a high-velocity explosion, a low total extinction
E
(
B
−
V
) = 0.07 mag, and a subsolar metallicity. We do not find a significant contribution to the UV flux from an additional heating source, such as interaction with the circumstellar medium, consistent with the observed flat plateau. Furthermore, the velocity width of the Mg
ii
λ
2798 line is comparable to that of the hydrogen Balmer lines, suggesting that the UV emission is confined to a region close to the photosphere.
ABSTRACT
We present 637 low-redshift optical spectra collected by the Berkeley Supernova Ia Program (BSNIP) between 2009 and 2018, almost entirely with the Kast double spectrograph on the Shane 3 m ...telescope at Lick Observatory. We describe our automated spectral classification scheme and arrive at a final set of 626 spectra (of 242 objects) that are unambiguously classified as belonging to Type Ia supernovae (SNe Ia). Of these, 70 spectra of 30 objects are classified as spectroscopically peculiar (i.e. not matching the spectral signatures of ‘normal’ SNe Ia) and 79 SNe Ia (covered by 328 spectra) have complementary photometric coverage. The median SN in our final set has one epoch of spectroscopy, has a redshift of 0.0208 (with a low of 0.0007 and high of 0.1921), and is first observed spectroscopically 1.1 d after maximum light. The constituent spectra are of high quality, with a median signal-to-noise ratio of 31.8 pixel−1, and have broad wavelength coverage, with $\sim\! 95{{\ \rm per\ cent}}$ covering at least 3700–9800 Å. We analyse our data set, focusing on quantitative measurements (e.g. velocities, pseudo-equivalent widths) of the evolution of prominent spectral features in the available early-time and late-time spectra. The data are available to the community, and we encourage future studies to incorporate our spectra in their analyses.
We have identified a progenitor candidate in archival Hubble Space Telescope (HST) images for the Type Ic supernova (SN Ic) SN 2017ein in NGC 3938, pinpointing the candidate's location via HST Target ...of Opportunity imaging of the SN itself. This would be the first identification of a stellar-like object as a progenitor candidate for any SN Ic to date. We also present observations of SN 2017ein during the first ∼49 days since explosion. We find that SN 2017ein most resembles the well-studied SN Ic SN 2007gr. We infer that SN 2017ein experienced a total visual extinction of AV 1.0-1.9 mag, predominantly because of dust within the host galaxy. Although the distance is not well known, if this object is the progenitor, it was likely of high initial mass, ∼47-48 M if a single star, or ∼60-80 M if in a binary system. However, we also find that the progenitor candidate could be a very blue and young compact cluster, further implying a very massive (>65 M ) progenitor. Furthermore, the actual progenitor might not be associated with the candidate at all and could be far less massive. From the immediate stellar environment, we find possible evidence for three different populations; if the SN progenitor was a member of the youngest population, this would be consistent with an initial mass of ∼57 M . After it has faded, the SN should be reobserved at high spatial resolution and sensitivity, to determine whether the candidate is indeed the progenitor.
Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) -positive primary breast cancer triaged to chemotherapy when the protein encoded by the MKI67 gene (Ki67) ...level was > 10% after 2 to 4 weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objective was to examine risk of relapse using the Ki67-based Preoperative Endocrine Prognostic Index (PEPI). Methods The American College of Surgeons Oncology Group (ACOSOG) Z1031A trial enrolled postmenopausal women with stage II or III ER-positive (Allred score, 6 to 8) breast cancer whose treatment was randomly assigned to neoadjuvant AI therapy with anastrozole, exemestane, or letrozole. For the trial ACOSOG Z1031B, the protocol was amended to include a tumor Ki67 determination after 2 to 4 weeks of AI. If the Ki67 was > 10%, patients were switched to neoadjuvant chemotherapy. A pCR rate of > 20% was the predefined efficacy threshold. In patients who completed neoadjuvant AI, stratified Cox modeling was used to assess whether time to recurrence differed by PEPI = 0 score (T1 or T2, N0, Ki67 < 2.7%, ER Allred > 2) versus PEPI > 0 disease. Results Only two of the 35 patients in ACOSOG Z1031B who were switched to neoadjuvant chemotherapy experienced a pCR (5.7%; 95% CI, 0.7% to 19.1%). After 5.5 years of median follow-up, four (3.7%) of the 109 patients with a PEPI = 0 score relapsed versus 49 (14.4%) of 341 of patients with PEPI > 0 (recurrence hazard ratio PEPI = 0 v PEPI > 0, 0.27; P = .014; 95% CI, 0.092 to 0.764). Conclusion Chemotherapy efficacy was lower than expected in ER-positive tumors exhibiting AI-resistant proliferation. The optimal therapy for these patients should be further investigated. For patients with PEPI = 0 disease, the relapse risk over 5 years was only 3.6% without chemotherapy, supporting the study of adjuvant endocrine monotherapy in this group. These Ki67 and PEPI triage approaches are being definitively studied in the ALTERNATE trial (Alternate Approaches for Clinical Stage II or III Estrogen Receptor Positive Breast Cancer Neoadjuvant Treatment in Postmenopausal Women: A Phase III Study; clinical trial information: NCT01953588).
Abstract
We present six epochs of optical spectropolarimetry of the Type II supernova (SN) 2023ixf ranging from ∼2 to 15 days after the explosion. Polarimetry was obtained with the Kast double ...spectrograph on the Shane 3 m telescope at Lick Observatory, representing the earliest such observations ever captured for an SN. We observe a high continuum polarization
p
cont
≈ 1% on days +1.4 and +2.5 before dropping to 0.5% on day +3.5, persisting at that level up to day +14.5. Remarkably, this change coincides temporally with the disappearance of highly ionized “flash” features. The decrease of the continuum polarization is accompanied by a ∼70° rotation of the polarization position angle (PA) as seen across the continuum. The early evolution of the polarization may indicate different geometric configurations of the electron-scattering atmosphere as seen before and after the disappearance of the emission lines associated with highly ionized species (e.g., He
ii
, C
iv
, and N
iii
), which are likely produced by elevated mass loss shortly prior to the SN explosion. We interpret the rapid change of polarization and PA from days +2.5 to +4.5 as the time when the SN ejecta emerge from the dense asymmetric circumstellar material (CSM). The temporal evolution of the continuum polarization and the PA is consistent with an aspherical SN explosion that exhibits a distinct geometry compared to the CSM. The rapid follow-up spectropolarimetry of SN 2023ixf during the shock ionization phase reveals an exceptionally asymmetric mass-loss process leading up to the explosion.
We present extensive optical photometric and spectroscopic observations, from 4 to 482 days after explosion, of the Type II-plateau (II-P) supernova (SN) 2017eaw in NGC 6946. SN 2017eaw is a normal ...SN II-P intermediate in properties between, for example, SN 1999em and SN 2012aw and the more luminous SN 2004et, also in NGC 6946. We have determined that the extinction to SN 2017eaw is primarily due to the Galactic foreground and that the SN site metallicity is likely subsolar. We have also independently confirmed a tip-of-the-red-giant-branch (TRGB) distance to NGC 6946 of 7.73 0.78 Mpc. The distances to the SN that we have also estimated via both the standardized candle method and expanding photosphere method corroborate the TRGB distance. We confirm the SN progenitor identity in pre-explosion archival Hubble Space Telescope (HST) and Spitzer Space Telescope images, via imaging of the SN through our HST Target of Opportunity program. Detailed modeling of the progenitor's spectral energy distribution indicates that the star was a dusty, luminous red supergiant consistent with an initial mass of ∼15 M .
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