The Guanylate Cyclase C-cGMP Signaling Axis Opposes Intestinal Epithelial Injury and Neoplasia.

Guanylate cyclase C (GUCY2C) is a transmembrane receptor expressed on the luminal aspect of the intestinal epithelium. Its ligands include bacterial heat-stable enterotoxins responsible for traveler\u27s diarrhea, the endogenous peptide hormones uroguanylin and guanylin, and the synthetic agents, linaclotide, plecanatide, and dolcanatide. Ligand-activated GUCY2C catalyzes the synthesis of intracellular cyclic GMP (cGMP), initiating signaling cascades underlying homeostasis of the intestinal epithelium. Mouse models of GUCY2C ablation, and recently, human populations harboring GUCY2C mutations, have revealed the diverse contributions of this signaling axis to epithelial health, including regulating fluid secretion, microbiome composition, intestinal barrier integrity, epithelial renewal, cell cycle progression, responses to DNA damage, epithelial-mesenchymal cross-talk, cell migration, and cellular metabolic status. Because of these wide-ranging roles, dysregulation of the GUCY2C-cGMP signaling axis has been implicated in the pathogenesis of bowel transit disorders, inflammatory bowel disease, and colorectal cancer. This review explores the current understanding of cGMP signaling in the intestinal epithelium and mechanisms by which it opposes intestinal injury. Particular focus will be applied to its emerging role in tumor suppression. In colorectal tumors, endogenous GUCY2C ligand expression is lost by a yet undefined mechanism conserved in mice and humans. Further, reconstitution of GUCY2C signaling through genetic or oral ligand replacement opposes tumorigenesis in mice. Taken together, these findings suggest an intriguing hypothesis that colorectal cancer arises in a microenvironment of functional GUCY2C inactivation, which can be repaired by oral ligand replacement. Hence, the GUCY2C signaling axis represents a novel therapeutic target for preventing colorectal cancer

Formation of Short-Period Binary Pulsars in Globular Clusters

We present a new dynamical scenario for the formation of short-period binary millisecond pulsars in globular clusters. Our work is motivated by the recent observations of 20 radio pulsars in 47 Tuc. In a dense cluster such as 47 Tuc, most neutron stars acquire binary companions through exchange interactions with primordial binaries. The resulting systems have semimajor axes in the range \~0.1-1 AU and neutron star companion masses ~1-3 Msun. For many of these systems we find that, when the companion evolves off the main sequence and fills its Roche lobe, the subsequent mass transfer is dynamically unstable. This leads to a common envelope phase and the formation of short-period neutron star - white dwarf binaries. For a significant fraction of these binaries, the decay of the orbit due to gravitational radiation will be followed by a period of stable mass transfer driven by a combination of gravitational radiation and tidal heating of the companion. The properties of the resulting short-period binaries match well those of observed binary pulsars in 47 Tuc.Comment: To appear in ApJ Letters, slightly abbreviated version with only minor change

Fire extinguishment in oxygen enriched atmospheres

Current state-of-the-art of fire suppression and extinguishment techniques in oxygen enriched atmosphere is reviewed. Four classes of extinguishment action are considered: cooling, separation of reactants, dilution or removal of fuel, and use of chemically reactive agents. Current practice seems to show preference for very fast acting water spray applications to all interior surfaces of earth-based chambers. In space, reliance has been placed on fire prevention methods through the removal of ignition sources and use of nonflammable materials. Recommendations are made for further work related to fire suppression and extinguishment in oxygen enriched atmospheres, and an extensive bibliography is appended

Tidally-driven Roche-Lobe Overflow of Hot Jupiters with MESA

Many exoplanets have now been detected in orbits with ultra-short periods, very close to the Roche limit. Building upon our previous work, we study the possibility that mass loss through Roche lobe overflow (RLO) may affect the evolution of these planets, and could possibly transform a hot Jupiter into a lower-mass planet (hot Neptune or super-Earth). We focus here on systems in which the mass loss occurs slowly ("stable mass transfer" in the language of binary star evolution) and we compute their evolution in detail with the binary evolution code MESA. We include the effects of tides, RLO, irradiation and photo-evaporation of the planet, as well as the stellar wind and magnetic braking. Our calculations all start with a hot Jupiter close to its Roche limit, in orbit around a sun-like star. The initial orbital decay and onset of RLO are driven by tidal dissipation in the star. We confirm that such a system can indeed evolve to produce lower-mass planets in orbits of a few days. The RLO phase eventually ends and, depending on the details of the mass transfer and on the planetary core mass, the orbital period can remain around a few days for several Gyr. The remnant planets have a rocky core and some amount of envelope material, which is slowly removed via photo-evaporation at nearly constant orbital period; these have properties resembling many of the observed super-Earths and sub-Neptunes. For these remnant planets we also predict an anti-correlation between mass and orbital period; very low-mass planets ($M_{\rm pl}\,\lesssim\,5\,M_{\oplus}$) in ultra-short periods ($P_{\rm orb}$<1d) cannot be produced through this type of evolution.Comment: 14 pages, 7 figures, 2 tables. Accepted by ApJ. The manuscript has been revised significantly to address the referee's comments. A link to MESA inlist files is now provided on page

On the Possibility of Tidal Formation of Binary Planets Around Ordinary Stars

The planet formation process and subsequent planet migration may lead to configurations resulting in strong dynamical interactions among the various planets. Well-studied possible outcomes include collisions between planets, scattering events that eject one or more of the planets, and a collision of one or more of the planets with the parent star. In this work we consider one other possibility that has seemingly been overlooked in the various scattering calculations presented in the literature: the tidal capture of two planets which leads to the formation of a binary planet (or binary brown dwarf) in orbit about the parent star. We carry out extensive numerical simulations of such dynamical and tidal interactions to explore the parameter space for the formation of such binary planets. We show that tidal formation of binary planets is possible for typical planet masses and distances from the host star. The detection (or lack thereof) of planet-planet binaries can thus be used to constrain the properties of planetary systems, including their mutual spacing during formation, and the fraction of close planets in very eccentric orbits which are believed to form by a closely related process.Comment: 11 pages, 10 Figures, submitted to Ap