Transit Timing and Duration Variations for the Discovery and Characterization of Exoplanets

Transiting exoplanets in multi-planet systems have non-Keplerian orbits which can cause the times and durations of transits to vary. The theory and observations of transit timing variations (TTV) and transit duration variations (TDV) are reviewed. Since the last review, the Kepler spacecraft has detected several hundred perturbed planets. In a few cases, these data have been used to discover additional planets, similar to the historical discovery of Neptune in our own Solar System. However, the more impactful aspect of TTV and TDV studies has been characterization of planetary systems in which multiple planets transit. After addressing the equations of motion and parameter scalings, the main dynamical mechanisms for TTV and TDV are described, with citations to the observational literature for real examples. We describe parameter constraints, particularly the origin of the mass/eccentricity degeneracy and how it is overcome by the high-frequency component of the signal. On the observational side, derivation of timing precision and introduction to the timing diagram are given. Science results are reviewed, with an emphasis on mass measurements of transiting sub-Neptunes and super-Earths, from which bulk compositions may be inferred.Comment: Revised version. Invited review submitted to 'Handbook of Exoplanets,' Exoplanet Discovery Methods section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Eds. TeX and figures may be found at https://github.com/ericagol/TTV_revie

Dynamical Evolution of Planetary Systems

Planetary systems can evolve dynamically even after the full growth of the planets themselves. There is actually circumstantial evidence that most planetary systems become unstable after the disappearance of gas from the protoplanetary disk. These instabilities can be due to the original system being too crowded and too closely packed or to external perturbations such as tides, planetesimal scattering, or torques from distant stellar companions. The Solar System was not exceptional in this sense. In its inner part, a crowded system of planetary embryos became unstable, leading to a series of mutual impacts that built the terrestrial planets on a timescale of ~100 My. In its outer part, the giant planets became temporarily unstable and their orbital configuration expanded under the effect of mutual encounters. A planet might have been ejected in this phase. Thus, the orbital distributions of planetary systems that we observe today, both solar and extrasolar ones, can be different from the those emerging from the formation process and it is important to consider possible long-term evolutionary effects to connect the two.Comment: Review to appear as a chapter in the "Handbook of Exoplanets", ed. H. Deeg & J.A. Belmont

Mass constraints of the WASP-47 planetary system from radial velocities

We report precise radial velocity (RV) measurements of WASP-47, a G star that hosts three transiting planets in close proximity (a hot Jupiter, a super-Earth, and a Neptune-sized planet) and a non-transiting planet at 1.4 au. Through a joint analysis of previously published RVs and our own Keck-HIRES RVs, we significantly improve the planet mass and bulk density measurements. For the super-Earth WASP-47e (P = 0.79 days), we measure a mass of 9.11 ± 1.17 Ṁ, and a bulk density of 7.63 ± 1.90 g cm-3, consistent with a rocky composition. For the hot Jupiter WASP-47b (P = 4.2 days), we measure a mass of 356 ± 12Ṁ(1.12 ± 0.04 MJup) and constrain its eccentricity to at 3σ confidence. For the Neptune-size planet WASP-47d (P = 9.0 days), we measure a mass of 12.75 ± 50.0 and a bulk density of g cm-3, suggesting that it has a thick H/He envelope. For the outer non-transiting planet, we measure a minimum mass of 411 ±18Ṁ(1.29 ± 0.06 MJup), an orbital period of days, and an orbital eccentricity of . Our new measurements are consistent with but two to four times more precise than previous mass measurements

A Chemical Analog of Curcumin as an Improved Inhibitor of Amyloid Abeta Oligomerization

Amyloid-like plaques are characteristic lesions defining the neuropathology of Alzheimer's disease (AD). The size and density of these plaques are closely associated with cognitive decline. To combat this disease, the few therapies that are available rely on drugs that increase neurotransmission; however, this approach has had limited success as it has simply slowed an imminent decline and failed to target the root cause of AD. Amyloid-like deposits result from aggregation of the Aβ peptide, and thus, reducing amyloid burden by preventing Aβ aggregation represents an attractive approach to improve the therapeutic arsenal for AD. Recent studies have shown that the natural product curcumin is capable of crossing the blood-brain barrier in the CNS in sufficient quantities so as to reduce amyloid plaque burden. Based upon this bioactivity, we hypothesized that curcumin presents molecular features that make it an excellent lead compound for the development of more effective inhibitors of Aβ aggregation. To explore this hypothesis, we screened a library of curcumin analogs and identified structural features that contribute to the anti-oligomerization activity of curcumin and its analogs. First, at least one enone group in the spacer between aryl rings is necessary for measureable anti-Aβ aggregation activity. Second, an unsaturated carbon spacer between aryl rings is essential for inhibitory activity, as none of the saturated carbon spacers showed any margin of improvement over that of native curcumin. Third, methoxyl and hydroxyl substitutions in the meta- and para-positions on the aryl rings appear necessary for some measure of improved inhibitory activity. The best lead inhibitors have either their meta- and para-substituted methoxyl and hydroxyl groups reversed from that of curcumin or methoxyl or hydroxyl groups placed in both positions. The simple substitution of the para-hydroxy group on curcumin with a methoxy substitution improved inhibitor function by 6-7-fold over that measured for curcumin

Aconitase Regulation of Erythropoiesis Correlates with a Novel Licensing Function in Erythropoietin-Induced ERK Signaling

Erythroid development requires the action of erythropoietin (EPO) on committed progenitors to match red cell output to demand. In this process, iron acts as a critical cofactor, with iron deficiency blunting EPO-responsiveness of erythroid progenitors. Aconitase enzymes have recently been identified as possible signal integration elements that couple erythropoiesis with iron availability. In the current study, a regulatory role for aconitase during erythropoiesis was ascertained using a direct inhibitory strategy.In C57BL/6 mice, infusion of an aconitase active-site inhibitor caused a hypoplastic anemia and suppressed responsiveness to hemolytic challenge. In a murine model of polycythemia vera, aconitase inhibition rapidly normalized red cell counts, but did not perturb other lineages. In primary erythroid progenitor cultures, aconitase inhibition impaired proliferation and maturation but had no effect on viability or ATP levels. This inhibition correlated with a blockade in EPO signal transmission specifically via ERK, with preservation of JAK2-STAT5 and Akt activation. Correspondingly, a physical interaction between ERK and mitochondrial aconitase was identified and found to be sensitive to aconitase inhibition.Direct aconitase inhibition interferes with erythropoiesis in vivo and in vitro, confirming a lineage-selective regulatory role involving its enzymatic activity. This inhibition spares metabolic function but impedes EPO-induced ERK signaling and disturbs a newly identified ERK-aconitase physical interaction. We propose a model in which aconitase functions as a licensing factor in ERK-dependent proliferation and differentiation, thereby providing a regulatory input for iron in EPO-dependent erythropoiesis. Directly targeting aconitase may provide an alternative to phlebotomy in the treatment of polycythemia vera

Acyl-Protein Thioesterase 2 Catalizes the Deacylation of Peripheral Membrane-Associated GAP-43

An acylation/deacylation cycle is necessary to maintain the steady-state subcellular distribution and biological activity of S-acylated peripheral proteins. Despite the progress that has been made in identifying and characterizing palmitoyltransferases (PATs), much less is known about the thioesterases involved in protein deacylation. In this work, we investigated the deacylation of growth-associated protein-43 (GAP-43), a dually acylated protein at cysteine residues 3 and 4. Using fluorescent fusion constructs, we measured in vivo the rate of deacylation of GAP-43 and its single acylated mutants in Chinese hamster ovary (CHO)-K1 and human HeLa cells. Biochemical and live cell imaging experiments demonstrated that single acylated mutants were completely deacylated with similar kinetic in both cell types. By RT-PCR we observed that acyl-protein thioesterase 1 (APT-1), the only bona fide thioesterase shown to mediate deacylation in vivo, is expressed in HeLa cells, but not in CHO-K1 cells. However, APT-1 overexpression neither increased the deacylation rate of single acylated GAP-43 nor affected the steady-state subcellular distribution of dually acylated GAP-43 both in CHO-K1 and HeLa cells, indicating that GAP-43 deacylation is not mediated by APT-1. Accordingly, we performed a bioinformatic search to identify putative candidates with acyl-protein thioesterase activity. Among several candidates, we found that APT-2 is expressed both in CHO-K1 and HeLa cells and its overexpression increased the deacylation rate of single acylated GAP-43 and affected the steady-state localization of diacylated GAP-43 and H-Ras. Thus, the results demonstrate that APT-2 is the protein thioesterase involved in the acylation/deacylation cycle operating in GAP-43 subcellular distribution

New Insights on Planet Formation in WASP-47 from a Simultaneous Analysis of Radial Velocities and Transit Timing Variations

Measuring precise planet masses, densities, and orbital dynamics in individual planetary systems is an important pathway toward understanding planet formation. The WASP-47 system has an unusual architecture that motivates a complex formation theory. The system includes a hot Jupiter ("b") neighbored by interior ("e") and exterior ("d") sub-Neptunes, and a long-period eccentric giant planet ("c"). We simultaneously modeled transit times from the Kepler K2 mission and 118 radial velocities to determine the precise masses, densities, and Keplerian orbital elements of the WASP-47 planets. Combining RVs and TTVs provides a better estimate of the mass of planet d () than that obtained with only RVs () or TTVs (). Planets e and d have high densities for their size, consistent with a history of photoevaporation and/or formation in a volatile-poor environment. Through our RV and TTV analysis, we find that the planetary orbits have eccentricities similar to the solar system planets. The WASP-47 system has three similarities to our own solar system: (1) the planetary orbits are nearly circular and coplanar, (2) the planets are not trapped in mean motion resonances, and (3) the planets have diverse compositions. None of the current single-process exoplanet formation theories adequately reproduce these three characteristics of the WASP-47 system (or our solar system). We propose that WASP-47, like the solar system, formed in two stages: first, the giant planets formed in a gas-rich disk and migrated to their present locations, and second, the high-density sub-Neptunes formed in situ in a gas-poor environment

TWO TRANSITING LOW DENSITY SUB-SATURNS FROM K2

We report the discovery and confirmation of K2-24 b and c, two sub-Saturn planets orbiting a bright (V = 11.3), metal-rich ([Fe/H] = 0.42 ± 0.04 dex) G3 dwarf in the K2 Campaign 2 field. The planets are 5.68 ± 0.56 R⊕ and 7.82 ± 0.72 R⊕ and have orbital periods of 20.8851 ± 0.0003 days and 42.3633 ± 0.0006 days, near the 2:1 mean-motion resonance. We obtained 32 radial velocities with Keck/HIRES and detected the reflex motion due to K2-24 b and c. These planets have masses of 21.0 ± 5.4 M⊕ and 27.0 ± 6.9 M⊕, respectively. With low densities of 0.63 ± 0.25 g cm-3 and 0.31 ± 0.12 g cm-3, respectively, the planets require thick envelopes of H/He to explain their large sizes and low masses. Interior structure models predict that the planets have fairly massive cores of 17.6 ± 4.3 M⊕ and 16.1, ± 4.2 M⊕, respectively. They may have formed exterior to their present locations, accreted their H/He envelopes at large orbital distances, and migrated in as a resonant pair. The proximity to resonance, large transit depths, and host star brightness offers rich opportunities for TTV follow-up. Finally, the low surface gravities of the K2-24 planets make them favorable targets for transmission spectroscopy by Hubble Space Telescope, Spitzer, and James Webb Space Telescope