Combinations of chemotherapy with immunotherapy have seen recent clinical success, including two approvals of anti-PD-1/L1 agents in combination with taxane-based chemotherapy in non-small cell lung ...cancer and triple-negative breast cancer. Here, we present a study on the combination activity and mechanistic rationale of a novel EphA2-targeted liposomal taxane (EphA2-ILs-DTXp) and anti-PD-1. This combination was highly active in mouse syngeneic tumor models, with complete responses observed in 3 of 5 models. In the EMT-6 tumor model, combination of EphA2-ILs-DTXp with anti-PD-1 resulted in a 60% complete response rate, with durable responses that were resistant to rechallenge. These responses were not observed in the absence of CD8
T cells. Characterization of the immune infiltrates in EMT-6 tumors reveals increased CD8
T cells, increased CD8
IFNγ
CTLs, and an increased CD8/regulatory T-cell (Treg) ratio. These immunomodulatory effects were not observed in mice treated with a combination of docetaxel and anti-PD-1. Pharmacokinetic analysis revealed that the AUC of docetaxel was increased 15 times, from 52.1 to 785 ng/mL/hour, when delivered by EphA2-ILs-DTXp. A dose reduction study of EphA2-ILs-DTXp showed a dose-response relationship for both tumor growth inhibition and the CD8/Treg ratio. Our data indicate that synergism between docetaxel and anti-PD-1 is achievable with nanoliposomal delivery.
To evaluate a semiautomated image analysis software package, Retinal Image multiScale Analysis (RISA), for the diagnosis of plus disease in preterm infants with retinopathy of prematurity (ROP).
...Digital images of the posterior pole showing both disc and macula in preterm infants with ROP were analyzed with an enhanced version of RISA. Venules (N = 106) and arterioles (N = 44) were identified, and integrated curvature, diameter, and tortuosity of the vessels were calculated. After the RISA calculations were completed, the origins of the vessels were determined to be 32 eyes in 16 infants (12 eyes with plus disease, 20 with no plus disease, as diagnosed by ophthalmic examination). Vessels were sorted into two groups-plus disease and no plus disease-and each RISA parameter was compared using the Mann-Whitney test. For each parameter, sensitivity and specificity were plotted as a function of cutoff criterion, receiver operating characteristic (ROC) curves were constructed, and the areas under the curve (AUC) were calculated.
For both arterioles and venules, each of the three parameters was significantly larger for the plus disease group. For instance, the median estimated arteriolar and venular diameters were approximately 12 mum greater in plus disease. Sensitivity and specificity plots indicated good accuracy of each parameter for the diagnosis of plus disease. The AUC showed that curvature had the highest diagnostic accuracy (0.911 for arterioles, 0.824 for venules).
The strong performance of RISA parameters in this sample suggests that RISA may be useful for diagnosing plus disease in preterm infants with ROP.
ABSTRACT
We report detection of quasi-periodic (1.5-d) dimming of HD 240779, the solar-mass primary in a 5 arcsec visual binary (also TIC 284730577), by the Transiting Exoplanet Survey Satellite. ...This dimming, as has been shown for other ‘dipper’ stars, is likely due to occultation by circumstellar dust. The barycentric space motion, lithium abundance, rotation, and chromospheric emission of the stars in this system point to an age of ≈125 Myr, and possible membership in the AB Doradus moving group. As such it occupies an important but poorly explored intermediate regime of stars with transient dimming between young stellar objects in star-forming regions and main-sequence stars, and between UX Orionis-type Ae/Be stars and M-type ‘dippers’. HD 240779, but not its companion BD+10 714B, has Wide-field Infrared Survey Explorer (WISE)-detected excess infrared emission at 12 and 22 μm indicative of circumstellar dust. We propose that infrared emission is produced by collisions of planetesimals during clearing of a residual disc at the end of rocky planet formation, and that quasi-periodic dimming is produced by the rapid disintegration of a ≳100 km planetesimal near the silicate evaporation radius. Further studies of this and similar systems will illuminate a poorly understood final phase of rocky planet formation like that which produced the inner Solar system.
We present a search for eclipses of ~1700 white dwarfs (WDs) in the Pan-STARRS1 medium-deep fields. Candidate eclipse events are selected by identifying low outliers in over 4.3 million light curve ...measurements. We find no short-duration eclipses consistent with being caused by a planetary size companion. This large data set enables us to place strong constraints on the close-in planet occurrence rates around WDs for planets as small as 2 R sub(+ in circle). Our results indicate that gas giant planets orbiting just outside the Roche limit are rare, occurring around less than 0.5% of WDs. Habitable-zone super-Earths and hot super-Earths are less abundant than similar classes of planets around main-sequence stars. These constraints provide important insight into the ultimate fate of the large population of exoplanets orbiting main-sequence stars.
Abstract
The transiting planet HD 80606 b undergoes a 1000 fold increase in insolation during its 111 days orbit due to it being highly eccentric (
e
= 0.93). The planet’s effective temperature ...increases from 400 to over 1400 K in a few hours as it makes a rapid passage to within 0.03 au of its host star during periapsis. Spectroscopic observations during the eclipse (which is conveniently oriented a few hours before periapsis) of HD 80606 b with the James Webb Space Telescope (JWST) are poised to exploit this highly variable environment to study a wide variety of atmospheric properties, including composition, chemical and dynamical timescales, and large scale atmospheric motions. Critical to planning and interpreting these observations is an accurate knowledge of the planet’s orbit. We report on observations of two full-transit events: 2020 February 7 as observed by the TESS spacecraft and 2021 December 7–8 as observed with a worldwide network of small telescopes. We also report new radial velocity observations which, when analyzed with a coupled model to the transits, greatly improves the planet’s orbital ephemeris. Our new orbit solution reduces the uncertainty in the transit and eclipse timing of the JWST era from tens of minutes to a few minutes. When combined with the planned JWST observations, this new precision may be adequate to look for non-Keplerian effects in the orbit of HD 80606 b.
We present the discovery and characterization of a transiting sub-Neptune that orbits the nearby (28 pc) and bright (
V
= 8.37) K0V star HD 207897 (TOI-1611) with a 16.20-day period. This discovery ...is based on photometric measurements from the Transiting Exoplanet Survey Satellite mission and radial velocity (RV) observations from the SOPHIE, Automated Planet Finder, and HIRES high-precision spectrographs. We used EXOFASTv2 to model the parameters of the planet and its host star simultaneously, combining photometric and RV data to determine the planetary system parameters. We show that the planet has a radius of 2.50 ± 0.08
R
E
and a mass of either 14.4 ± 1.6
M
E
or 15.9 ± 1.6
M
E
with nearly equal probability. The two solutions correspond to two possibilities for the stellar activity period. The density accordingly is either 5.1 ± 0.7 g cm
−3
or 5.5
−0.7
+0.8
g cm
−3
, making it one of the relatively rare dense sub-Neptunes. The existence of this dense planet at only 0.12 AU from its host star is unusual in the currently observed sub-Neptune (2 <
R
E
< 4) population. The most likely scenario is that this planet has migrated to its current position.
ABSTRACT We report the discovery of EPIC 201702477b, a transiting brown dwarf in a long period (40.73691 0.00037 day) and eccentric (e = 0.2281 0.0026) orbit. This system was initially reported as a ...planetary candidate based on two transit events seen in K2 Campaign 1 photometry and later validated as an exoplanet candidate. We confirm the transit and refine the ephemeris with two subsequent ground-based detections of the transit using the Las Cumbres Observatory Global Telescope 1 m telescope network. We rule out any transit timing variations above the level of ∼30 s. Using high precision radial velocity measurements from HARPS and SOPHIE we identify the transiting companion as a brown dwarf with a mass, radius, and bulk density of 66.9 1.7 MJ, 0.757 0.065 RJ, and 191 51 g cm−3 respectively. EPIC 201702477b is the smallest radius brown dwarf yet discovered, with a mass just below the H-burning limit. It has the highest density of any planet, substellar mass object, or main-sequence star discovered so far. We find evidence in the set of known transiting brown dwarfs for two populations of objects-high mass brown dwarfs and low mass brown dwarfs. The higher-mass population have radii in very close agreement to theoretical models, and show a lower-mass limit around 60 MJ. This may be the signature of mass-dependent ejection of systems during the formation process.
Imprime PGG (Imprime) is in late-stage clinical development as a combinatorial agent with several therapeutic modalities. Here we present pre-clinical mechanistic data supportive of Imprime, a ...soluble yeast β-1,3/1,6-glucan pathogen-associated molecular pattern able to prime innate immune cells in a Dectin-1dependent manner. In tumor-free mice, Imprime evoked broad innate immune responses (type I interferon signature, mobilization of myeloid cells, dendritic cell and monocyte/macrophage expression of co-stimulatory ligands like CD86, and activation of natural killer cells). Imprime-mediated activation of myeloid cells also resulted in functional priming of antigen-specific CD8 T cell response. In tumor-bearing mice, Imprime monotherapy further resulted in activation of systemic and tumor infiltrating macrophages and enhanced cytotoxic CD8 T cell trafficking. Imprime enhanced the anti-tumor activity of several combinatorial agents in mouse cancer models; anti-tyrosinase-related protein 1 antibody in B16F10 melanoma experimental lung metastasis model, anti-vascular endothelial growth factor receptor 2 antibody in H1299 and H441 lung cancer, and anti-programmed cell death protein 1 antibody in MC38 colon cancer models. Mechanistically, combining Imprime with these combinatorial therapeutic agents elicited enhanced innate immune activation, supporting immunological synergy. Finally, Imprime treatment induced similar
phenotypic and functional activation of human innate immune cells. Collectively, these data demonstrate Imprime's potential to orchestrate a broad, yet coordinated, anti-cancer immune response and complement existing cancer immunotherapies.
Abstract
We report the discovery by the HATNet survey of HAT-TR-318-007, a
period detached double-lined M dwarf binary with total secondary eclipses. We combine radial velocity (RV) measurements from ...TRES/FLWO 1.5 m and time-series photometry from HATNet, FLWO 1.2 m, BOS 0.8 m, and NASA
K2
Campaign 5, to determine the masses and radii of the component stars:
,
,
, and
. We obtained a FIRE/Magellan near-infrared spectrum of the primary star during a total secondary eclipse, and we use this to obtain disentangled spectra of both components. We determine spectral types of
and
and effective temperatures of
and
for the primary and secondary star, respectively. We also measure a metallicity of Fe/H
for the system. We find that the system has a small, but significant, nonzero eccentricity of
. The
K2
light curve shows a coherent variation at a period of
days, which is slightly longer than the orbital period, and which we demonstrate comes from the primary star. We interpret this as the rotation period of the primary. We perform a quantitative comparison between the Dartmouth stellar evolution models and the seven systems, including HAT-TR-318-007, that contain M dwarfs with
, have metallicity measurements, and have masses and radii determined to better than 5% precision. Discrepancies between the predicted and observed masses and radii are found for three of the systems.
We find transient transit-like dimming events within the K2 time series photometry of the young star RIK-210 in the Upper Scorpius OB association. These dimming events are variable in depth, ...duration, and morphology. High spatial resolution imaging revealed that the star is single and radial velocity monitoring indicated that the dimming events cannot be due to an eclipsing stellar or brown dwarf companion. Archival and follow-up photometry suggest the dimming events are transient in nature. The variable morphology of the dimming events suggests they are not due to a single spherical body. The ingress of each dimming event is always shallower than egress, as one would expect for an orbiting body with a leading tail. The dimming events are periodic and synchronous with the stellar rotation. However, we argue it is unlikely the dimming events could be attributed to anything on the stellar surface based on the observed depths and durations. Variable obscuration by a protoplanetary disk is unlikely on the basis that the star is not actively accreting and lacks the infrared excess associated with an inner disk. Rather, we explore the possibilities that the dimming events are due to magnetospheric clouds, a transiting protoplanet surrounded by circumplanetary dust and debris, eccentric orbiting bodies undergoing periodic tidal disruption, or an extended field of dust or debris near the corotation radius.
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