Clouds, Gravity, and Metallicity in Blue L Dwarfs: The Case of 2MASS J11263991–5003550

Optical and near-infrared spectroscopy of the newly discovered peculiar L dwarf 2MASS J11263991–5003550 are presented. Folkes et al. classified this source as a high proper motion L9±1 dwarf based on its strong H2O absorption at 1.4 μ m . We find that the optical spectrum of 2MASS J1126–5003 is in fact consistent with that of a normal L4.5 dwarf with notably enhanced FeH absorption at 9896 Å. However, its near-infrared spectrum is unusually blue, with strong H2O and weak CO bands similar in character to several recently identified "blue L dwarfs." Using 2MASS J1126–5003 as a case study, and guided by trends in the condensate cloud models of Burrows et al. and Marley et al., we find that the observed spectral peculiarities of these sources can be adequately explained by the presence of thin and/or large-grained condensate clouds as compared to normal field L dwarfs. Atypical surface gravities or metallicities alone cannot reproduce the observed peculiarities, although they may be partly responsible for the unusual condensate properties. We also rule out unresolved multiplicity as a cause for the spectral peculiarities of 2MASS J1126–5003. Our analysis is supported by examination of Spitzer mid-infrared spectral data from Cushing et al. which show that bluer L dwarfs tend to have weaker 10 μ m absorption, a feature tentatively associated with silicate oxide grains. With their unique spectral properties, blue L dwarfs like 2MASS J1126–5003 should prove useful in studying the formation and properties of condensates and condensate clouds in low-temperature atmospheres

Investigation of probe substrates to assess hepatic transport function

The objective of this research project was to identify and characterize probe substrates for specific hepatic transport proteins. Identification of specific probe substrates for basolateral and canalicular transport proteins is necessary to elucidate mechanisms of hepatobiliary drug transport, phenotype for interindividual differences in transport protein function, and identify potential drug-drug interactions at the hepatic transport level. Three probe substrates were selected for investigation: fexofenadine, 99mTechnetium mebrofenin (99mTc-MEB), and 99mTechnetium sestamibi (99mTc-MIBI). Although fexofenadine has been touted as a P-gp specific probe substrate, pharmacokinetic modeling/siumulation of clinical data, sandwich-cultured human hepatocyte experiments and perfused liver studies in rats and mice demonstrated that fexofenadine is not a suitable probe for a specific transport protein due to compensatory efflux pathways. The hepatic uptake and excretion of 99mTc-MEB and 99mTc-MIBI have not been investigated fully despite their use as non-invasive probes to assess transport function. Therefore, suspended and sandwich-cultured rat and human hepatocytes were used to fully characterize the mechanisms of hepatic transport of 99mTc-MEB and 99mTc-MIBI. Then to validate the use of 99mTc-MEB and/or 99mTc-MIBI as probe substrates to predict the hepatic clearance of the anticancer agent, sorafenib studies were conducted to confirm similar mechanisms of hepatic uptake. Lastly, the pharmacokinetics and hepatic exposure of 99mTc-MIBI and 99mTc-MEB were compared in a patient with hepatocellular carcinoma and Child's Pugh B cirrhosis vs. healthy human volunteers. Pharmacokinetic models were constructed to describe the distribution and elimination of 99mTc-MEB and 99mTc-MIBI, to compare alterations in key rate constants representing hepatic uptake and efflux mechanisms secondary to disease. In conclusion, 99mTc-MEB and 99mTc-MIBI may be very useful phenotypic probes that are sensitive to changes in hepatic function associated with liver disease. The hepatic exposure to 99mTc-MIBI was decreased in the patient with hepatocellular carcinoma and cirrhosis compared to healthy volunteers, whereas the hepatic exposure of 99mTc-MEB was similar but the hepatic exposure profile was notably different with a lower maximum but more prolonged exposure. Collectively, the results of this research negate the use of fexofenadine as a probe for hepatic transport, but support the use of 99mTc-MEB and 99mTc-MIBI as probe substrates, which add the unique ability to quantify liver concentrations

Discovery of an M9.5 Candidate Brown Dwarf in the TW Hydrae Association - DENIS J124514.1-442907

We report the discovery of a fifth candidate substellar system in the ~5-10 Myr TW Hydrae Association - DENIS J124514.1-442907. This object has a NIR spectrum remarkably similar to that of 2MASS J1139511-315921, a known TW Hydrae brown dwarf, with low surface gravity features such as a triangular-shaped H-band, deep H2O absorption, weak alkali lines, and weak hydride bands. We find an optical spectral type of M9.5 and estimate a mass of <24 M_Jup, assuming an age of ~5-10 Myr. While the measured proper motion for DENIS J124514.1-442907 is inconclusive as a test for membership, its position in the sky is coincident with the TW Hydrae Association. A more accurate proper motion measurement, higher resolution spectroscopy for radial velocity, and a parallax measurement are needed to derive the true space motion and to confirm its membership.Comment: 8 pages - emulateapj style, 2 figures, 3 tables. Accepted to ApJL. Fixed typos, added reference, added footnot

Influence of Seeding Density and Extracellular Matrix on Bile Acid Transport and Mrp4 Expression in Sandwich-Cultured Mouse Hepatocytes

This study was undertaken to examine the influence of seeding density, extracellular matrix and days in culture on bile acid transport proteins and hepatobiliary disposition of the model bile acid taurocholate. Mouse hepatocytes were cultured in a sandwich configuration on six-well Biocoat™ plates with an overlay of Matigel™ (BC/MG) or gelled-collagen (BC/GC) for 3 or 4 days at seeding densities of 1.0, 1.25 or 1.5 × 106 cells/well. The lower seeding densities of 1.0 and 1.25 × 106 cells/well resulted in good hepatocyte morphology and bile canalicular network formation, as visualized by 5- (and 6)-carboxy-2′,7′dichlorofluorescein accumulation. In general, taurocholate cellular accumulation tended to increase as a function of seeding density in BC/GC; cellular accumulation was significantly increased in hepatocytes cultured in BC/MG compared to BC/GC at the same seeding density on both days 3 and 4 of culture. In general, in vitro intrinsic biliary clearance of taurocholate was increased at higher seeding densities. Levels of bile acid transport proteins on days 3 and 4 were not markedly influenced by seeding density or extracellular matrix except for multidrug resistance protein 4 (Mrp4), which was inversely related to seeding density. Mrp4 levels decreased ~2- to 3-fold between seeding densities of 1.0 × 106 and 1.25 × 106 cells/well regardless of extracellular matrix; an additional ~3- to 5-fold decrease in Mrp4 protein was noted in BC/GC between seeding densities of 1.25 × 106 and 1.5 × 106 cells/well. Results suggest that seeding density, extracellular matrix and days in culture profoundly influence Mrp4 expression in sandwich-cultured mouse hepatocytes. Primary mouse hepatocytes seeded in a BC/MG configuration at densities of 1.25 × 106 cells/well or below, and cultured for 3 days, yielded optimal transport based on the probes studied. This work demonstrates the applicability of the sandwich-cultured model to mouse hepatocytes

Evaluation of 99mTechnetium-Mebrofenin and 99mTechnetium-Sestamibi as Specific Probes for Hepatic Transport Protein Function in Rat and Human Hepatocytes

This study characterized 99mTc-Mebrofenin (MEB) and 99mTc-Sestamibi (MIBI) hepatic transport and preferential efflux routes (canalicular vs. basolateral) in rat and human sandwich-cultured hepatocytes (SCH)

Integration of Preclinical and Clinical Data with Pharmacokinetic Modeling and Simulation to Evaluate Fexofenadine as a Probe for Hepatobiliary Transport Function

The suitability of fexofenadine as a probe substrate to assess hepatobiliary transport function in humans was evaluated by pharmacokinetic modeling/simulation and in vitro/in situ studies using chemical modulators

Sandwich-cultured hepatocytes: an in vitro model to evaluate hepatobiliary transporter-based drug interactions and hepatotoxicity

Sandwich-cultured hepatocytes (SCH) are a powerful in vitro tool that can be utilized to study hepatobiliary drug transport, species differences in drug transport, transport protein regulation, drug-drug interactions, and hepatotoxicity. This review provides an up-to-date summary of the SCH model, including a brief history of, and introduction to, the use of SCH, as well as methodology to evaluate hepatobiliary drug disposition. A summary of the literature that has utilized this model to examine the interplay between drug metabolizing enzymes and transport proteins, drug-drug interactions at the transport level, and hepatotoxicity as a result of altered hepatic transport also is provided

Ultracool Subdwarfs: The Halo Population Down to the Substellar Limit

Ultracool subdwarfs are low luminosity, late-type M and L dwarfs that exhibit spectroscopic indications of subsolar metallicity and halo kinematics. Their recent discovery and ongoing investigation have led to new insights into the role of metallicity in the opacity structure, chemistry (e.g. dust formation) and evolution of low-temperature atmospheres; the long-term evolution of magnetic activity and angular momentum amongst the lowest-mass stars; the form of the halo luminosity and mass functions down to the hydrogen-burning mass limit; and even fundamental issues such as spectral classification and absolute brightness scales. This Splinter Session was devoted to bringing advances in observational and theoretical ultracool subdwarf research to the attention of the low-mass stellar and brown dwarf communities, as well as to share results among ultracool subdwarf enthusiasts.Comment: 8 pages, 5 figures, Splinter Session contribution for Cool Stars 15 (AIP formatting