Minor planet 1566 Icarus: Asteroid or comet?

By employing a cometary nongravitational force model, based on the outgassing of a water ice nucleus, the orbital fits to the optical and radar astrometric data are improved for both Apollo and Icarus. A reliable value for the magnitude of these nongravitational effects can be determined for Icarus, but not Apollo. Because Icarus is less than a kilometer in extent, the small amount of outgassing required to explain its anomalous orbital behavior would probably not be sufficient to create an easily visible coma. While these results do not prove that 1566 Icarus is an active comet masquerading as an asteroid, this object certainly deserves future scrutiny to determine its true identity. A near-Earth asteroid showing cometary activity must represent only the tip of a much larger cometary iceburg. For such an object whose aphelion is well inside Jupiter's orbit, the time scale for losing its volatiles is much shorter than the time scale for evolving out of the inner solar system. Thus, for each active member of the near-Earth asteroid population, there must be many more that are temporarily or permanently inactive

Comet and asteroid dynamics

In order to provide the ground-based observing community and NASA flight projects with accurate comet and asteroids ephemerides, improvements are being made to the existing dynamic models and new data type are being investigated. For active comets, non-gravitational forces must be taken into account; these forces are assumed due to the rocket-like thrusting of outgassing cometary ices

Comet and asteroid dynamics

In order to provide observers with accurate ephemerides of comets and asteroids, up-to-date astrometric positions must be used to improve the existing orbits. For active comets, nongravitational forces must be taken into account; these forces are assumed due to the rocket-like effect of outgassing cometary ices and are used to characterize the volatility and rotation properties of icy cometary nuclei. In an effort to improve ephemeris accuracies, the benefits of a new nongravitational force model for comets as well as new radar data types are being investigated. The first successful attempts to improve the orbits of close Earth approaching asteroids using radar data have been completed for asteroids 1982XB and 1986JK. The radar Doppler measurements of 1982XB, made on Dec. 5-6, 1987, were represented to less than 0.1 Hz while the Doppler observations of 1986Jk, made on May 28 - June 1, 1986, were represented to within a few Hz for each of the 11 measurements. Last minute orbit updates for asteroid 324 Bamberga allowed a successful stellar occultation prediction to be made on Dec. 8, 1987. A new paradigm for the cometary nongravitational force model has been successfully tested on a few comets. This new model allows the water vaporization curve to peak on either side of perihelion, thus introducing a nongravitational force via an asymmetric radial force, rather than through a symmetric transverse effect that the old model requires

Surveys, Astrometric Follow-up & Population Statistics

Asteroid surveys are the backbone of asteroid science, and with this in mind we begin with a broad review of the impact of asteroid surveys on our field. We then provide a brief history of asteroid discoveries so as to place contemporary and future surveys in perspective. Surveys in the United States have discovered the vast majority of the asteroids and this dominance has been consolidated since the publication of Asteroids III. Our descriptions of the asteroid surveys that have been operational since that time are focussed upon those that have contributed the vast majority of asteroid observations and discoveries. We also provide some insight into upcoming next-generation surveys that are sure to alter our understanding of the small bodies in the inner solar system and provide evidence to untangle their complicated dynamical and physical histories. The Minor Planet Center, the nerve center of the asteroid discovery effort, has improved its operations significantly in the past decade so that it can manage the increasing discovery rate, and ensure that it is well-placed to handle the data rates expected in the next decade. We also consider the difficulties associated with astrometric follow-up of newly identified objects. It seems clear that both of these efforts must operate in new modes in order to keep pace with expected discovery rates of next-generation ground- and space-based surveys.Comment: Chapter to appear in the book ASTEROIDS IV, (University of Arizona Press) Space Science Series, edited by P. Michel, F. DeMeo and W. Bottk

Intrathecal Administration of AYX2 DNA Decoy Produces a Long-Term Pain Treatment in Rat Models of Chronic Pain by Inhibiting the KLF6, KLF9, and KLF15 Transcription Factors

Background: Nociception is maintained by genome-wide regulation of transcription in the dorsal root ganglia—spinal cord network. Hence, transcription factors constitute a promising class of targets for breakthrough pharmacological interventions to treat chronic pain. DNA decoys are oligonucleotides and specific inhibitors of transcription factor activities. A methodological series of in vivo–in vitro screening cycles was performed with decoy/transcription factor couples to identify targets capable of producing a robust and long-lasting inhibition of established chronic pain. Decoys were injected intrathecally and their efficacy was tested in the spared nerve injury and chronic constriction injury models of chronic pain in rats using repetitive von Frey testing. Results: Results demonstrated that a one-time administration of decoys binding to the Kruppel-like transcription factors (KLFs) 6, 9, and 15 produces a significant and weeks–month long reduction in mechanical hypersensitivity compared to controls. In the spared nerve injury model, decoy efficacy was correlated to its capacity to bind KLF15 and KLF9 at a specific ratio, while in the chronic constriction injury model, efficacy was correlated to the combined binding capacity to KLF6 and KLF9. AYX2, an 18-bp DNA decoy binding KLF6, KLF9, and KLF15, was optimized for clinical development, and it demonstrated significant efficacy in these models. Conclusions: These data highlight KLF6, KLF9, and KLF15 as transcription factors required for the maintenance of chronic pain and illustrate the potential therapeutic benefits of AYX2 for the treatment of chronic pain

Pharmacology, Pharmacokinetics, and Metabolism of the DNA-Decoy AYX1 for the Prevention of Acute and Chronic Post-Surgical Pain

Background: AYX1 is an unmodified DNA-decoy designed to reduce acute post-surgical pain and its chronification with a single intrathecal dose at the time of surgery. AYX1 inhibits the transcription factor early growth response protein 1, which is transiently induced at the time of injury and triggers gene regulation in the dorsal root ganglia and spinal cord that leads to long-term sensitization and pain. This work characterizes the AYX1 dose-response profile in rats and the link to AYX1 pharmacokinetics and metabolism in the cerebrospinal fluid, dorsal root ganglia, and spinal cord. Results: The effects of ascending dose-levels of AYX1 on mechanical hypersensitivity were measured in the spared nerve injury model of chronic pain and in a plantar incision model of acute post-surgical pain. AYX1 dose-response profile shows that efficacy rapidly increases from a minimum effective dose of ∼ 0.5 mg to a peak maximum effective dose of ∼ 1 mg. With further dose escalation, the efficacy paradoxically appears to decrease by ∼ 30% and then returns to full efficacy at the maximum feasible dose of ∼ 4 mg. The reduction of efficacy is associated to doses triggering a near-saturation of AYX1 metabolism by nucleases in the cerebrospinal fluid and a paradoxical reduction of AYX1 exposure during the period of early growth response protein 1 induction. This effect is overcome at higher doses that compensate for the effect of metabolism. Discussion: AYX1 is a competitive antagonist of early growth response protein 1, which is consistent with the overall increased efficacy observed as dose-levels initially escalate. Chemically, AYX1 is unprotected against degradation by nucleases. The sensitivity to nucleases is reflected in a paradoxical reduction of efficacy in the dose-response curve. Conclusions: These findings point to the importance of the nuclease environment of the cerebrospinal fluid to the research and development of AYX1 and other intrathecal nucleotide-based therapeutics

Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs

Background: Misoprostol is effective for ulcers associated with the use of nonsteroidal antiinflammatory drugs (NSAIDs) but is often poorly tolerated because of diarrhea and abdominal pain. We compared the efficacy of omeprazole and misoprostol in healing and preventing ulcers associated with NSAIDs. Methods: in a double-blind study, we randomly assigned 935 patients who required continuous NSAID therapy and who had ulcers or more than 10 erosions in the stomach or duodenum (or both) to receive 20 mg or 40 mg of omeprazole orally in the morning or 200 microg of misoprostol orally four times daily. Patients were treated for four weeks or, in the absence of healing, eight weeks. Treatment success was defined as the absence of ulcers and the presence of fewer than five erosions at each site and not more than mild dyspepsia. We then randomly reassigned 732 patients in whom treatment was successful to maintenance therapy with 20 mg of omeprazole daily, 200 microg of misoprostol twice daily, or placebo for six months. Results: at eight weeks, treatment was successful in 76 percent of the patients given 20 mg of omeprazole (233 of 308), 75 percent of those given 40 mg of omeprazole (237 of 315), and 71 percent of those given misoprostol (212 of 298). The rates of gastric-ulcer healing were significantly higher with 20 mg of omeprazole (but not 40 mg of omeprazole) than with misoprostol. Healing rates among patients with duodenal ulcers were higher with either dose of omeprazole than with misoprostol, whereas healing rates among patients with erosions alone were higher with misoprostol. More patients remained in remission during maintenance treatment with omeprazole (61 percent) than with misoprostol (48 percent, P=0.001) and with either drug than with placebo (27 percent, P<0.001). There were more adverse events during the healing phase in the misoprostol group than in the groups given 20 mg and 40 mg of omeprazole (59 percent, 48 percent, and 46 percent, respectively). Conclusions: the overall rates of successful treatment of ulcers, erosions, and symptoms associated with NSAIDs were similar for the two doses of omeprazole and misoprostol. Maintenance therapy with omeprazole was associated with a lower rate of relapse than misoprostol. Omeprazole was better tolerated than misoprostol