Significance Regression: Robust Regression for Collinear Data

This paper examines robust linear multivariable regression from collinear data. A brief review of M-estimators discusses the strengths of this approach for tolerating outliers and/or perturbations in the error distributions. The review reveals that M-estimation may be unreliable if the data exhibit collinearity. Next, significance regression (SR) is discussed. SR is a successful method for treating collinearity but is not robust. A new significance regression algorithm for the weighted-least-squares error criterion (SR-WLS) is developed. Using the weights computed via M-estimation with the SR-WLS algorithm yields an effective method that robustly mollifies collinearity problems. Numerical examples illustrate the main points

Significance Regression: A Statistical Approach to Biased Linear Regression and Partial Least Squares

This paper first examines the properties of biased regressors that proceed by restricting the search for the optimal regressor to a subspace. These properties suggest features such biased regression methods should incorporate. Motivated by these observations, this work proposes a new formulation for biased regression derived from the principle of statistical significance. This new formulation, significance regression (SR), leads to partial least squares (PLS) under certain model assumptions and to more general methods under various other model kumptions. For models with multiple outputs, SR will be shown to have certain advantages over PLS. Using the new formulation a significance test is advanced for determining the number of directions to be used; for PLS, cross-validation has been the primary method for determining this quantity. The prediction and estimation properties of SR are discussed. A brief numerical example illustrates the relationship between SR and PLS

Significance Regression: Improved Estimation from Collinear Data for the Measurement Error Model

This paper examines improved regression methods for the linear multivariable measurement error model (MEM) when the data suffers from "collinearity." The difficulty collinearity presents for reliable estinlation is discussed and a systematic procedure, significance regression (SR-MEM), is developed to address collinearity. In addition to mitigating collinearity difficulties SR-MEM produces asymptotically unbiased estimates. The use of ordinary least squares (OLS) for the MEM is examined. For collinear data OLS can improve the mean squared error of estimation over the maximum likelihood (ML) unbiased estimator in a manner analogous to ridge regression (RR). The significance regression method developed for the classical model (SR-classical) can also be used for data with measurement errors. SR-classical is similar SR-MEM and can yield better estimation than the ML estimator for collinear data. Numerical examples illustrate several points

Modulation of Syndecan-1 Shedding after Hemorrhagic Shock and Resuscitation

The early use of fresh frozen plasma as a resuscitative agent after hemorrhagic shock has been associated with improved survival, but the mechanism of protection is unknown. Hemorrhagic shock causes endothelial cell dysfunction and we hypothesized that fresh frozen plasma would restore endothelial integrity and reduce syndecan-1 shedding after hemorrhagic shock. A prospective, observational study in severely injured patients in hemorrhagic shock demonstrated significantly elevated levels of syndecan-1 (554±93 ng/ml) after injury, which decreased with resuscitation (187±36 ng/ml) but was elevated compared to normal donors (27±1 ng/ml). Three pro-inflammatory cytokines, interferon-γ, fractalkine, and interleukin-1β, negatively correlated while one anti-inflammatory cytokine, IL-10, positively correlated with shed syndecan-1. These cytokines all play an important role in maintaining endothelial integrity. An in vitro model of endothelial injury then specifically examined endothelial permeability after treatment with fresh frozen plasma orlactated Ringers. Shock or endothelial injury disrupted junctional integrity and increased permeability, which was improved with fresh frozen plasma, but not lactated Ringers. Changes in endothelial cell permeability correlated with syndecan-1 shedding. These data suggest that plasma based resuscitation preserved endothelial syndecan-1 and maintained endothelial integrity, and may help to explain the protective effects of fresh frozen plasma after hemorrhagic shock

The TESS-Keck Survey. XV. Precise Properties of 108 TESS Planets and Their Host Stars

We present the stellar and planetary properties for 85 TESS Objects of Interest (TOIs) hosting 108 planet candidates which comprise the TESS-Keck Survey (TKS) sample. We combine photometry, high-resolution spectroscopy, and Gaia parallaxes to measure precise and accurate stellar properties. We then use these parameters as inputs to a lightcurve processing pipeline to recover planetary signals and homogeneously fit their transit properties. Among these transit fits, we detect significant transit-timing variations among at least three multi-planet systems (TOI-1136, TOI-1246, TOI-1339) and at least one single-planet system (TOI-1279). We also reduce the uncertainties on planet-to-star radius ratios $R_p/R_\star$ across our sample, from a median fractional uncertainty of 8.8$\%$ among the original TOI Catalog values to 3.0$\%$ among our updated results. With this improvement, we are able to recover the Radius Gap among small TKS planets and find that the topology of the Radius Gap among our sample is broadly consistent with that measured among Kepler planets. The stellar and planetary properties presented here will facilitate follow-up investigations of both individual TOIs and broader trends in planet properties, system dynamics, and the evolution of planetary systems.Comment: Accepted at The Astronomical Journal; 21 pages, 9 figure

The TESS-Keck Survey. XVI. Mass Measurements for 12 Planets in Eight Systems

With JWST's successful deployment and unexpectedly high fuel reserves, measuring the masses of sub-Neptunes transiting bright, nearby stars will soon become the bottleneck for characterizing the atmospheres of small exoplanets via transmission spectroscopy. Using a carefully curated target list and more than two years' worth of APF-Levy and Keck-HIRES Doppler monitoring, the TESS-Keck Survey is working toward alleviating this pressure. Here we present mass measurements for 11 transiting planets in eight systems that are particularly suited to atmospheric follow-up with JWST. We also report the discovery and confirmation of a temperate super-Jovian-mass planet on a moderately eccentric orbit. The sample of eight host stars, which includes one subgiant, spans early-K to late-F spectral types ($T_\mathrm{eff} =$ 5200--6200 K). We homogeneously derive planet parameters using a joint photometry and radial velocity modeling framework, discuss the planets' possible bulk compositions, and comment on their prospects for atmospheric characterization.Comment: Accepted for publication in The Astronomical Journal on 2023-Jun-22. 60 pages, 17 Tables, 28 Figure

The TESS-Keck Survey. XII. A Dense 1.8 R ⊕ Ultra-short-period Planet Possibly Clinging to a High-mean-molecular-weight Atmosphere after the First Gigayear

The extreme environments of ultra-short-period planets (USPs) make excellent laboratories to study how exoplanets obtain, lose, retain, and/or regain gaseous atmospheres. We present the confirmation and characterization of the USP TOI-1347 b, a 1.8±0.1 R⊕ planet on a 0.85 day orbit that was detected with photometry from the TESS mission. We measured radial velocities of the TOI-1347 system using Keck/HIRES and HARPS-N and found the USP to be unusually massive at 11.1±1.2 M⊕. The measured mass and radius of TOI-1347 b imply an Earth-like bulk composition. A thin H/He envelope (>0.01% by mass) can be ruled out at high confidence. The system is between 1 and 1.8 Gyr old; therefore, intensive photoevaporation should have concluded. We detected a tentative phase curve variation (3σ) and a secondary eclipse (2σ) in TESS photometry, which if confirmed could indicate the presence of a high-mean-molecular-weight atmosphere. We recommend additional optical and infrared observations to confirm the presence of an atmosphere and investigate its composition

The TESS-Keck Survey. XI. Mass Measurements for Four Transiting sub-Neptunes orbiting K dwarf TOI-1246

Multi-planet systems are valuable arenas for investigating exoplanet architectures and comparing planetary siblings. TOI-1246 is one such system, with a moderately bright K dwarf (V=11.6, K=9.9) and four transiting sub-Neptunes identified by TESS with orbital periods of 4.31 d, 5.90 d, 18.66 d, and 37.92 d. We collected 130 radial velocity observations with Keck/HIRES and TNG/HARPS-N to measure planet masses. We refit the 14 sectors of TESS photometry to refine planet radii (2.97±0.06 R⊕,2.47±0.08 R⊕,3.46±0.09 R⊕, 3.72±0.16 R⊕), and confirm the four planets. We find that TOI-1246 e is substantially more massive than the three inner planets (8.1±1.1M⊕, 8.8±1.2M⊕, 5.3±1.7M⊕, 14.8±2.3M⊕). The two outer planets, TOI-1246 d and TOI-1246 e, lie near to the 2:1 resonance (Pe/Pd=2.03) and exhibit transit timing variations. TOI-1246 is one of the brightest four-planet systems, making it amenable for continued observations. It is one of only six systems with measured masses and radii for all four transiting planets. The planet densities range from 0.70±0.24 to 3.21±0.44g/cm3, implying a range of bulk and atmospheric compositions. We also report a fifth planet candidate found in the RV data with a minimum mass of 25.6 ± 3.6 M⊕. This planet candidate is exterior to TOI-1246 e with a candidate period of 93.8 d, and we discuss the implications if it is confirmed to be planetary in nature

The TESS-Keck Survey. XI. Mass Measurements for Four Transiting Sub-Neptunes Orbiting K Dwarf TOI-1246

Multiplanet systems are valuable arenas for investigating exoplanet architectures and comparing planetary siblings. TOI-1246 is one such system, with a moderately bright K dwarf (V = 11.6, K = 9.9) and four transiting sub-Neptunes identified by TESS with orbital periods of 4.31, 5.90, 18.66, and 37.92 days. We collected 130 radial velocity observations with Keck/HIRES and TNG/HARPS-N to measure planet masses. We refit the 14 sectors of TESS photometry to refine planet radii (2.97 +/- 0.06 R (circle plus), 2.47 +/- 0.08 R (circle plus), 3.46 +/- 0.09 R (circle plus), and 3.72 +/- 0.16 R (circle plus)) and confirm the four planets. We find that TOI-1246 e is substantially more massive than the three inner planets (8.1 +/- 1.1 M (circle plus), 8.8 +/- 1.2 M (circle plus), 5.3 +/- 1.7 M (circle plus), and 14.8 +/- 2.3 M (circle plus)). The two outer planets, TOI-1246 d and TOI-1246 e, lie near to the 2:1 resonance (P (e)/P ( d ) = 2.03) and exhibit transit-timing variations. TOI-1246 is one of the brightest four-planet systems, making it amenable for continued observations. It is one of only five systems with measured masses and radii for all four transiting planets. The planet densities range from 0.70 +/- 0.24 to 3.21 +/- 0.44 g cm(-3), implying a range of bulk and atmospheric compositions. We also report a fifth planet candidate found in the RV data with a minimum mass of 25.6 +/- 3.6 M (circle plus). This planet candidate is exterior to TOI-1246 e, with a candidate period of 93.8 days, and we discuss the implications if it is confirmed to be planetary in nature

Bone Marrow Derived Mesenchymal Stem Cells Inhibit Inflammation and Preserve Vascular Endothelial Integrity in the Lungs after Hemorrhagic Shock

Hemorrhagic shock (HS) and trauma is currently the leading cause of death in young adults worldwide. Morbidity and mortality after HS and trauma is often the result of multi-organ failure such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), conditions with few therapeutic options. Bone marrow derived mesenchymal stem cells (MSCs) are a multipotent stem cell population that has shown therapeutic promise in numerous pre-clinical and clinical models of disease. In this paper, in vitro studies with pulmonary endothelial cells (PECs) reveal that conditioned media (CM) from MSCs and MSC-PEC co-cultures inhibits PEC permeability by preserving adherens junctions (VE-cadherin and β-catenin). Leukocyte adhesion and adhesion molecule expression (VCAM-1 and ICAM-1) are inhibited in PECs treated with CM from MSC-PEC co-cultures. Further support for the modulatory effects of MSCs on pulmonary endothelial function and inflammation is demonstrated in our in vivo studies on HS in the rat. In a rat “fixed volume” model of mild HS, we show that MSCs administered IV potently inhibit systemic levels of inflammatory cytokines and chemokines in the serum of treated animals. In vivo MSCs also inhibit pulmonary endothelial permeability and lung edema with concurrent preservation of the vascular endothelial barrier proteins: VE-cadherin, Claudin-1, and Occludin-1. Leukocyte infiltrates (CD68 and MPO positive cells) are also decreased in lungs with MSC treatment. Taken together, these data suggest that MSCs, acting directly and through soluble factors, are potent stabilizers of the vascular endothelium and inflammation. These data are the first to demonstrate the therapeutic potential of MSCs in HS and have implications for the potential use of MSCs as a cellular therapy in HS-induced lung injury