We present results from high-resolution, optical to near-IR imaging of host stars of Kepler Objects of Interest (KOIs), identified in the original Kepler field. Part of the data were obtained under ...the Kepler imaging follow-up observation program over six years (2009-2015). Almost 90% of stars that are hosts to planet candidates or confirmed planets were observed. We combine measurements of companions to KOI host stars from different bands to create a comprehensive catalog of projected separations, position angles, and magnitude differences for all detected companion stars (some of which may not be bound). Our compilation includes 2297 companions around 1903 primary stars. From high-resolution imaging, we find that ∼10% (∼30%) of the observed stars have at least one companion detected within 1″ (4″). The true fraction of systems with close ( 4″) companions is larger than the observed one due to the limited sensitivities of the imaging data. We derive correction factors for planet radii caused by the dilution of the transit depth: assuming that planets orbit the primary stars or the brightest companion stars, the average correction factors are 1.06 and 3.09, respectively. The true effect of transit dilution lies in between these two cases and varies with each system. Applying these factors to planet radii decreases the number of KOI planets with radii smaller than 2 by ∼2%-23% and thus affects planet occurrence rates. This effect will also be important for the yield of small planets from future transit missions such as TESS.
Small heat shock proteins (sHSPs) are a class of ATP-independent molecular chaperones that play vital roles in maintaining protein solubility and preventing aberrant protein aggregation. They form ...highly dynamic, polydisperse oligomeric ensembles and contain long intrinsically disordered regions. Experimental challenges posed by these properties have greatly impeded our understanding of sHSP structure and mechanism of action. Here we characterize interactions between the human sHSP HspB1 (Hsp27) and microtubule-associated protein tau, which is implicated in multiple dementias, including Alzheimer’s disease. We show that tau binds both to a well-known binding groove within the structured alpha-crystallin domain (ACD) and to sites within the enigmatic, disordered N-terminal region (NTR) of HspB1. However, only interactions involving the NTR lead to productive chaperone activity, whereas ACD binding is uncorrelated with chaperone function. The taubinding groove in the ACD also binds short hydrophobic regions within HspB1 itself, and HspB1 mutations that disrupt these intrinsic ACD–NTR interactions greatly enhance chaperone activity toward tau. This leads to a mechanism in which the release of the disordered NTR from a binding groove on the ACD enhances chaperone activity toward tau. The study advances understanding of the mechanisms by which sHSPs achieve their chaperone activity against amyloid-forming clients and how cells defend against pathological tau aggregation. Furthermore, the resulting mechanistic model points to ways in which sHSP chaperone activity may be increased, either by native factors within the cell or by therapeutic intervention.
For primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), higher pretreatment tumor-infiltrating lymphocytes (TILs) correlates with increased pathologic complete ...response (pCR) rates, and improved survival. We evaluated the added prognostic value of residual disease (RD) TILs to residual cancer burden (RCB) in predicting survival post-NAC.
We combined four TNBC NAC patient cohorts who did not achieve pCR. RD TILs were investigated for associations with recurrence-free survival (RFS), and overall survival (OS) using Cox models with stromal TILs as a continuous variable (per 10% increment). The likelihood ratio test was used to evaluate added prognostic value of RD TILs.
A total of 375 RD TNBC samples were evaluable for TILs and RCB. The median age was 50 years, with 62% receiving anthracycline/taxane chemotherapy. The RCB class after NAC was 11%, 50%, and 39% for I, II, and III, respectively. The median RD TIL level was 20% (IQR 10–40). There was a positive correlation between RD TIL levels and CD8+ T-cell density (ρ = 0.41). TIL levels were significantly lower with increasing post-NAC tumor (P = 0.005), nodal stage (P = 0.032), but did not differ by RCB class (P = 0.84). Higher RD TILs were significantly associated with improved RFS (HR: 0.86; 95% CI 0.79–0.92; P < 0.001), and improved OS (HR: 0.87; 95% CI 0.80–0.94; P < 0.001), and remained significant predictors in multivariate analysis (RFS P = 0.032; OS P = 0.038 for OS). RD TILs added significant prognostic value to multivariate models including RCB class (P < 0.001 for RFS; P = 0.021 for OS). The positive prognostic effect of RD TILs significantly differed by RCB class for RFS (PInt=0.003) and OS (PInt=0.008) with a greater magnitude of positive effect observed for RCB class II than class III.
TIL levels in TNBC RD are significantly associated with improved RFS and OS and add further prognostic information to RCB class, particularly in RCB class II.
Observations with the Interstellar Boundary Explorer (IBEX) have shown enhanced energetic neutral atom (ENA) emission from a narrow, circular ribbon likely centered on the direction of the local ...interstellar medium (LISM) magnetic field. Here, we show that recent determinations of the local interstellar velocity, based on interstellar atom measurements with IBEX, are consistent with the interstellar modulation of high-energy (tera–electron volts, TeV) cosmic rays and diffusive propagation from supernova sources revealed in global anisotropy maps of ground-based high-energy cosmic-ray observatories (Milagro, Asγ, and IceCube). Establishing a consistent local interstellar magnetic field direction using IBEX ENAs at hundreds to thousands of eV and galactic cosmic rays at tens of TeV has wide-ranging implications for the structure of our heliosphere and its interactions with the LISM, which is particularly important at the time when the Voyager spacecraft are leaving our heliosphere.
Belatacept, a T cell costimulation blocker, demonstrated superior renal function, lower cardiovascular risk, and improved graft and patient survival in renal transplant recipients. Despite the ...potential benefits, adoption of belatacept has been limited in part due to concerns regarding higher rates and grades of acute rejection in clinical trials. Since July 2011, we have utilized belatacept‐based immunosuppression regimens in clinical practice. In this retrospective analysis of 745 patients undergoing renal transplantation at our center, we compared patients treated with belatacept (n = 535) with a historical cohort receiving a tacrolimus‐based protocol (n = 205). Patient and graft survival were equivalent for all groups. An increased rate of acute rejection was observed in an initial cohort treated with a protocol similar to the low‐intensity regimen from the BENEFIT trial versus the historical tacrolimus group (50.5% vs. 20.5%). The addition of a transient course of tacrolimus reduced rejection rates to acceptable levels (16%). Treatment with belatacept was associated with superior estimated GFR (belatacept 63.8 mL/min vs. tacrolimus 46.2 mL/min at 4 years, p < 0.0001). There were no differences in serious infections including rates of cytomegalovirus or BK viremia. We describe the development of a costimulatory blockade‐based strategy that ultimately allows renal transplant recipients to achieve calcineurin inhibitor–free immunosuppression.
This retrospective clinical experience highlights the use of belatacept and transient tacrolimus therapy to control rejection, limit donor‐specific antibody production, and improve long‐term renal allograft function.
We present near-infrared light curves of supernova (SN) 2011fe in M101, including 34 epochs in H band starting 14 days before maximum brightness in the B band. The light curve data were obtained with ...the WIYN High-Resolution Infrared Camera. When the data are calibrated using templates of other Type Ia SNe, we derive an apparent H-band magnitude at the epoch of B-band maximum of 10.85 + or - 0.04. This implies a distance modulus for M101 that ranges from 28.86 to 29.17 mag, depending on which absolute calibration for Type Ia SNe is used.
Epoxy coatings are commonly used to protect the interior (and exterior) surfaces of water mains and storage tanks and can be used on the interior surfaces of water pipes in homes, hospitals, hotels, ...and other buildings. Common major components of epoxies include bisphenols, such as bisphenol A (BPA) or bisphenol F (BPF), and their reactive prepolymers, bisphenol A diglycidyl ether (BADGE) and bisphenol F diglycidyl ether (BFDGE), respectively. There currently are health concerns about the safety of BPA and BPF due to known estrogenic effects. Determination of key bisphenol leachates, development of a hydrolysis model, and identification of stable hydrolysis products will aid in assessment of human bisphenol exposure through ingestion of drinking water. Liquid chromatography/mass spectrometry (LC/MS/MS) was used for quantitation of key analytes, and a pseudo-first order kinetic approach was used for modeling. In fill-and-dump studies on epoxy-coated pipe specimens, BADGE and a BPA-like compound were identified as leachates. The BADGE hydrolysis model predicts BADGE half-lives at pH 7 and 15, 25, 35, and 40 °C to be 11, 4.6, 2.0, and 1.4 days respectively; the BFDGE half-life was 5 days at pH 7 and 25 °C. The two identified BADGE hydrolysis products are BADGE-H2O and BADGE 2H2O, with BADGE 2H2O being the final end product under the conditions studied.
•Bisphenol A diglycidyl ether (BADGE) can leach into drinking water and hydrolyze.•BADGE hydrolysis was modeled as a function of pH (2–12) and temperature (15–40 °C).•BADGE half-lives at pH 7 and 15, 25, 35, and 40 °C were 11, 4.6, 2.0, and 1.4 days.•At 25 °C and pH 2–12 bisphenol F diglycidyl ether hydrolyzed similarly to BADGE.•BADGE-2H2O was the final end product of BADGE hydrolysis; bisphenol A was stable.
The first
James Webb
Space Telescope (JWST) data on the massive colliding cluster
El Gordo
allow for 23 known families of multiply lensed images to be confirmed and for eight new members of these ...families to be identified. Based on these families, which have been confirmed spectroscopically by MUSE, we derived an initial lens model. This model guided the identification of 37 additional families of multiply lensed galaxies, among which 28 are entirely new systems, and nine were previously known. The initial lens model determined geometric redshifts for the 37 new systems. The geometric redshifts agree reasonably well with spectroscopic or photometric redshifts when those are available. The geometric redshifts enable two additional models that include all 60 families of multiply lensed galaxies spanning a redshift range 2 <
z
< 6. The derived dark-matter distribution confirms the double-peak configuration of mass found by earlier work with the southern and northern clumps having similar masses. We confirm that El Gordo is the most massive known cluster at
z
> 0.8 and has an estimated virial mass close the maximum mass allowed by standard cosmological models. The JWST images also reveal the presence of small-mass perturbers that produce small lensing distortions. The smallest of these is consistent with being a dwarf galaxy at
z
= 0.87 and has an estimated mass of 3.8 × 10
9
M
⊙
, making it the smallest substructure found at
z
> 0.5. The JWST images also show several candidate caustic-crossing events. One of them is detected at high significance at the expected position of the critical curve and is likely a red supergiant star at
z
= 2.1878. This would be the first red supergiant found at cosmological distances. The cluster lensing should magnify background objects at
z
> 6, making more of them visible than in blank fields of a similar size, but there appears to be a deficiency of such objects.
The bulk composition of an exoplanet is commonly inferred from its average density. For small planets, however, the average density is not unique within the range of compositions. Variations of a ...number of important planetary parameters-which are difficult or impossible to constrain from measurements alone-produce planets with the same average densities but widely varying bulk compositions. We find that adding a gas envelope equivalent to 0.1%-10% of the mass of a solid planet causes the radius to increase 5%-60% above its gas-free value. A planet with a given mass and radius might have substantial water ice content (a so-called ocean planet), or alternatively a large rocky iron core and some H and/or He. For example, a wide variety of compositions can explain the observed radius of GJ 436b, although all models require some H/He. We conclude that the identification of water worlds based on the mass-radius relationship alone is impossible unless a significant gas layer can be ruled out by other means.
Few studies have focused on caring professionals and their emotional exhaustion from working with traumatized clients, referred to as compassion fatigue (CF). The present study had 2 goals: (a) to ...assess the psychometric properties of a CF scale, and (b) to examine the scale's predictive validity in a multivariate model. The data came from a survey of social workers living in New York City following the September 11, 2001, terrorist attacks on the World Trade Center. Factor analyses indicated that the CF scale measured multiple dimensions. After overlapping items were eliminated, the scale measured 2 key underlying dimensions-secondary trauma and job burnout. In a multivariate model, these dimensions were related to psychological distress, even after other risk factors were controlled. The authors discuss the results in light of increasing the ability of professional caregivers to meet the emotional needs of their clients within a stressful environment without experiencing CF.
PDF
