Scientific ethics. Discovery of Pluto contender contested in planetary court.
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BACKGROUND AND PURPOSE: Clopidogrel is widely used in patients after recent ischemic stroke; however, its ability to yield additional antiplatelet protection on top of aspirin has never been explored in a controlled study. To determine whether clopidogrel with aspirin (C+ASA) will produce more potent platelet inhibition than aspirin alone (ASA) in patients after ischemic stroke, we conducted the Plavix Use for Treatment of Stroke trial. METHODS: Seventy patients after ischemic stroke were randomly assigned to C+ASA or ASA groups. Platelet studies included aggregometry; cartridge-based analyzers; expression of PECAM-1, P-selectin, GP IIb/IIIa (antigen and activity), vitronectin receptor, and formation of platelet-leukocyte microparticles by flow cytometry. Platelet tests were performed at baseline and after 30 days after randomization. RESULTS: There were no deaths, hospitalizations, or serious adverse events. There were no differences in the baseline platelet characteristics between C+ASA and ASA groups, or significant changes in platelet parameters in the ASA group, except diminished collagen-induced aggregation (P=0.001). In contrast, therapy with C+ASA resulted in a significant inhibition of platelet activity assessed by ADP- (P=0.00001) and collagen-induced (P=0.02) aggregation; closure time prolongation (P=0.03), and reduction of platelet activation units with Ultegra (P=0.00001); expression of PECAM-1 (P=0.01), and GP IIb/IIIa activity with PAC-1 (P=0.02) when compared with ASA group. Therapy with C+ASA also resulted in the reduced formation of platelet-leukocyte microparticles (P=0.02). CONCLUSIONS: Treatment with C+ASA for 1 month provides significantly greater inhibition of platelet activity than ASA alone in patients after recent ischemic stroke in the frame of the small randomized trial.
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Dramatic changes occur in expression of the type I collagenase gene during the process of immortalization in simian virus 40 large T antigen-transformed human fibroblasts (S. Imai and T. Takano, Biochem. Biophys. Res. Commun. 189:148-153, 1992). From transient transfection assays, it was determined that these changes involved the functions of two immortalization-susceptible cis-acting elements, ISE1 and ISE2, located in a 100-bp region about 1.7 kb upstream. The profiles of binding of an activator, Proserpine, to the enhancer ISE1 were similar in the extracts of young, senescent preimmortalized and immortalized cells. ISE2 contained both negative and positive regulatory elements located adjacent to each other. The positive regulatory element consisted of a tandem array of putative Ets family- and AP-1-binding sites. An activator, Pluto, interacted with this positive regulatory element and had an AP-1-related component as a complex. The binding activity of Pluto was predominantly detected only in the extract from senescent preimmortalized cells. In contrast, a repressor, Orpheus, which bound to the ATG-rich negative regulatory element of ISE2, was prominently detected in extracts from both young preimmortalized and immortalized cells and appeared to suppress transcription in an orientation-dependent manner. Thus, the interplay of Pluto and Orpheus was suggested to be crucial for regulation of the collagenase gene accompanying in vitro aging and immortalization. Proserpine seemed to interact with Pluto to mediate strong expression of the collagenase gene in cellular senescence. On the basis of these results, we propose a model for regulation of the collagenase gene during in vitro aging and immortalization.
Detailed models of the internal structures of Pluto and Charon, assuming rock and water ice as the only constituents, indicate that the mean silicate mass fraction of this two-body system is on the order of 0.7; thus the Pluto/Charon system is significantly "rockier" than the satellites of the giant planets (silicate mass fraction approximately 0.55). This compositional contrast reflects different formation mechanisms: it is likely that Pluto and Charon formed directly from the solar nebula, while the circumplanetary nebulae that produced the giant planet satellites were derived from envelopes that surrounded the forming giant planets (envelopes in which icy planetesimals dissolved more readily than rocky planetesimals). Simple cosmic abundance calculations, and the assumption that the Pluto/Charon system formed directly from solar nebula condensates, strongly suggest that the majority of the carbon in the outer solar nebula was in the form of carbon monoxide; these results are consistent with (1) inheritance from the dense molecular clouds in the interstellar medium (where CH4/CO < 10(-2) in the gas phase) and/or (2) of the Lewis and Prinn kinetic inhibition model of solar nebula chemistry. Theoretical predictions of the C/H enhancements in the atmospheres of the giant planets, when compared to the actual observed enhancements, suggest that 10%, or slightly more, of the carbon in the outer solar nebula was in the form of condensed materials (although the amount of condensed C may have dropped slightly with increasing heliocentric distance). Strict compositional limits computed for the Pluto/Charon system using the densities of CH4 and CO ices indicate that these pure ices are at best minor components in the interiors of these bodies, and imply that CH4 and CO ices were not the dominant C-bearing solids in the outer nebula. Clathrate-hydrates could not have appropriated enough CH4 or CO to be the major form of condensed carbon, although such clathrates may be necessary to explain the presence of methane on Pluto after its formation from a CO-rich nebula. Laboratory studies of carbonaceous chondrites, and spacecraft observations of Comet Halley, strongly suggest that of the remaining possibilities, organic material, rather than elemental carbon, is the most likely candidate for the dominant C-bearing solid in the outer solar nebula. We conclude that the majority of the carbon in the outer solar nebula was in gaseous CO; 10% to a few tens of percent of the C was in condensed organic materials; and at least a trace amount of carbon was in methane gas.
Pluto and its satellite, Charon (discovered in 1978; ref. 1), appear to form a double planet, rather than a hierarchical planet/satellite couple. Charon is about half Pluto's size and about one-eighth its mass. The precise radii of Pluto and Charon have remained uncertain, leading to large uncertainties on their densities. Although stellar occultations by Charon are in principle a powerful way of measuring its size, they are rare, as the satellite subtends less than 0.3 microradians (0.06 arcsec) on the sky. One occultation (in 1980) yielded a lower limit of 600 km for the satellite's radius, which was later refined to 601.5 km (ref. 4). Here we report observations from a multi-station stellar occultation by Charon, which we use to derive a radius, R(C) = 603.6 +/- 1.4 km (1sigma), and a density of rho = 1.71 +/- 0.08 g cm(-3). This occultation also provides upper limits of 110 and 15 (3sigma) nanobar for an atmosphere around Charon, assuming respectively a pure nitrogen or pure methane atmosphere.
OBJECTIVE: This study examined the polymerization stress of different established composite resins (Tetric Ceram, Vivadent; EsthetX, Surefil, Dentsply/DeTrey; Clearfil AP-X, Clearfil Photo Posterior, Kuraray; Prodigy Condensable, sds Kerr; Filtek P 60, 3M ESPE; Solitaire 2, Heraeus-Kulzer) by means of a photo-elastic investigation and investigated six new, experimental composite resins, which have been claimed to exhibit less polymerization shrinkage (InTen-S, Vivadent; K 112, K 051, Dentsply/DeTrey; Compox, Pluto, Hermes 3M ESPE). METHODS: Cylindrical cavities (phi 5 mm) in Araldit B epoxide resin plates (40 x 40 x 3 mm3) were pretreated with the Rocatec system to ensure bonding of the composite resin. Ten composite resin specimens of each material, embedded in the Araldit plates, were exposed for 60 s (Elipar TriLight, Standard-mode, 800 mW/cm2). Polymerization contraction stress data (MPa) were calculated at 4 min and 24 h after exposure, based on the diameter of the isochromatic curves of first order obtained from the Araldit-plates. The statistical analysis was carried out with the Wilcoxon test (5% level). RESULTS: After 24 h, the calculated mean polymerization stress values were 4.4+/-0.1 MPa for Tetric Ceram, 4.6+/-0.1 MPa for EsthetX, 3.7+/-0.1 MPa for Z 250, 4.6+/-0.1 MPa for Clearfil AP-X, 4.1+/-0.1 MPa for Prodigy Condensable, 4.0+/-0.1 MPa for Filtek P 60, 4.5+/-0.1 MPa for Surefil, 4,5+/-0.1 MPa for Clearfil Photo Posterior, 5.4+/-0.04 MPa for Solitaire 2, 3.2+/-0.1 MPa for In Ten-S, 3.9+/-0.1 MPa for K 112, 3.1+/-0.04 MPa for K 051, 3.2+/-0.1 MPa for Compox, and 2.0+/-0.1 MPa for Hermes. CONCLUSIONS: The new and experimental composite resins In Ten-S, K 051, Compox, and Hermes showed significantly less polymerization shrinkage stress than the controls (p < 0.0005, Bonferroni correction). For the experimental material Pluto, no determination of isochromatic rings was possible.
The physical characteristics of Pluto and its moon, Charon, provide insight into the evolution of the outer Solar System. Although previous measurements have constrained the masses of these bodies, their radii and densities have remained uncertain. The observation of a stellar occultation by Charon in 1980 established a lower limit on its radius of 600 km (ref. 3) (later refined to 601.5 km; ref. 4) and suggested a possible atmosphere. Subsequent, mutual event modelling yielded a range of 600-650 km (ref. 5), corresponding to a density of 1.56 +/- 0.22 g cm(-3) (refs 2, 5). Here we report multiple-station observations of a stellar occultation by Charon. From these data, we find a mean radius of 606 +/- 8 km, a bulk density of 1.72 +/- 0.15 g cm(-3), and rock-mass fraction 0.63 +/- 0.05. We do not detect a significant atmosphere and place 3sigma upper limits on atmospheric number densities for candidate gases. These results seem to be consistent with collisional formation for the Pluto-Charon system in which the precursor objects may have been differentiated, and they leave open the possibility of atmospheric retention by the largest objects in the outer Solar System.
Triton is Neptune's principal satellite and is by far the largest retrograde satellite in the Solar System (its mass is approximately 40 per cent greater than that of Pluto). Its inclined and circular orbit lies between a group of small inner prograde satellites and a number of exterior irregular satellites with both prograde and retrograde orbits. This unusual configuration has led to the belief that Triton originally orbited the Sun before being captured in orbit around Neptune. Existing models for its capture, however, all have significant bottlenecks that make their effectiveness doubtful. Here we report that a three-body gravitational encounter between a binary system (of approximately 10(3)-kilometre-sized bodies) and Neptune is a far more likely explanation for Triton's capture. Our model predicts that Triton was once a member of a binary with a range of plausible characteristics, including ones similar to the Pluto-Charon pair.
Like all low- and moderate-mass stars, the Sun will burn as a red giant during its later evolution, generating of solar luminosities for some tens of millions of years. During this post-main sequence phase, the habitable (i.e., liquid water) thermal zone of our Solar System will lie in the region where Triton, Pluto-Charon, and Kuiper Belt objects orbit. Compared with the 1 AU habitable zone where Earth resides, this "delayed gratification habitable zone" (DGHZ) will enjoy a far less biologically hazardous environment - with lower harmful radiation levels from the Sun, and a far less destructive collisional environment. Objects like Triton, Pluto-Charon, and Kuiper Belt objects, which are known to be rich in both water and organics, will then become possible sites for biochemical and perhaps even biological evolution. The Kuiper Belt, with >10(5) objects > or =50 km in radius and more than three times the combined surface area of the four terrestrial planets, provides numerous sites for possible evolution once the Sun's DGHZ reaches it. The Sun's DGHZ might be thought to only be of academic interest owing to its great separation from us in time. However, approximately 10(9) Milky Way stars burn as luminous red giants today. Thus, if icy-organic objects are common in the 20-50 AU zones of these stars, as they are in our Solar System (and as inferred in numerous main sequence stellar disk systems), then DGHZs may form a niche type of habitable zone that is likely to be numerically common in the Galaxy.
OBJECTIVES: Proton pump inhibitors reduce ulcer recurrence in non-steroidal anti-inflammatory drug (NSAID) users, but their impact in at-risk ulcer-free patients using the current spectrum of prescribed agents has not been clearly defined. We assessed esomeprazole for ulcer prevention in at-risk patients (> or = 60 yr and/or ulcer history) taking NSAIDs, including COX-2 inhibitors. Such studies are particularly relevant, given that concerns regarding adverse cardiovascular outcomes among COX-2 inhibitor users may prompt re-evaluation of their use. METHODS: We conducted two similar double-blind, placebo-controlled, randomized, multicenter studies; VENUS (United States) and PLUTO (multinational). A total of 844 and 585 patients requiring daily NSAIDs, including COX-2 inhibitors were randomized to receive esomeprazole (20 or 40 mg) or placebo, daily for 6 months. RESULTS: In the VENUS study, the life table estimated proportion of patients who developed ulcers over 6 months (primary variable, intent-to-treat population) was 20.4% on placebo, 5.3% on esomeprazole 20 mg (p < 0.001), and 4.7% on esomeprazole 40 mg (p < 0.0001). In the PLUTO study, the values were 12.3% on placebo, 5.2% with esomeprazole 20 mg (p = 0.018), and 4.4% with esomeprazole 40 mg (p = 0.007). Significant reductions were observed for users of both non-selective NSAIDs and COX-2 inhibitors. Pooled ulcer rates for patients using COX-2 inhibitors (n = 400) were 16.5% on placebo, 0.9% on esomeprazole 20 mg (p < 0.001) and 4.1% on esomeprazole 40 mg (p= 0.002). Esomeprazole was well tolerated and associated with better symptom control than placebo. CONCLUSIONS: For at-risk patients, esomeprazole was effective in preventing ulcers in long-term users of NSAIDs, including COX-2 inhibitors.
The competition between impact erosion and impact supply of volatiles to planetary atmospheres can determine whether a planet or satellite accumulates an atmosphere. In the absence of other processes (e.g., outgassing), we find either that a planetary atmosphere should be thick, or that there should be no atmosphere at all. The boundary between the two extreme cases is set by the mass and velocity distributions and intrinsic volatile content of the impactors. We apply our model specifically to Titan, Callisto, and Ganymede. The impacting population is identified with comets, either in the form of stray Uranus-Neptune planetesimals or as dislodged Kuiper belt comets. Systematically lower impact velocities on Titan allow it to retain a thick atmosphere, while Callisto and Ganymede get nothing. Titan's atmosphere may therefore be an expression of a late-accreting, volatile-rich veneer. An impact origin for Titan's atmosphere naturally accounts for the high D/H ratio it shares with Earth, the carbonaceous meteorites, and Halley. It also accounts for the general similarity of Titan's atmosphere to those of Triton and Pluto, which is otherwise puzzling in view of the radically different histories and bulk compositions of these objects.
In the context of prebiotic chemistry in space, some of the outer planetary objects display H, C, N and O rich chemistry similar to the one in the biosphere of Earth. Of particular interest are Saturn's moon, Titan; Neptune's moon, Triton; and Pluto where extreme cold conditions prevail. Identifications of chemical species on these objects (surfaces and atmospheres) is essential to a better understanding of the radiation induced chemical reactions occurring thereon. There have been several ground based observations of these planetary objects in the infrared windows from 1 to 2.5 micrometers. Voyager also provided spectra in the thermal infrared (6 to 50 micrometers) region. Interpretation of these data require laboratory infrared spectra of relevant species under the temperature conditions appropriate to these objects. The results of some of these studies carried out in our laboratory and elsewhere and their impact on the analyses of the observed data will be summarized.
We present laboratory measurements of the radiation yields of complex organic solids produced from N2/CH4 gas mixtures containing 10 or 0.1% CH4. These tholins are thought to resemble organic aerosols produced in the atmospheres of Titan, Pluto, and Triton. The tholin yields are large compared to the total yield of gaseous products: nominally, 13 (C + N)/100 eV for Titan tholin and 2.1 (C + N)/100 eV for Triton tholin. High-energy magnetospheric electrons responsible for tholin production represent a class distinct from the plasma electrons considered in models of Titan's airglow. Electrons with E > 20 keV provide an energy flux approximately 1 x 10(-2) erg cm-2 sec-1, implying from our measured tholin yields a mass flux of 0.5 to 4.0 x 10(-14) g cm-2 sec-1 of tholin. (The corresponding thickness of the tholin sedimentary column accumulated over 4 Gyr on Titan's surface is 4 to 30 m.) This figure is in agreement with required mass fluxes computed from recent radiative transfer and sedimentation models. If, however, these results, derived from experiments at approximately 2 mb, are applied to lower pressure levels toward peak auroral electron energy deposition and scaled with pressure as the gas-phase organic yields, the derived tholin mass flux is at least an order of magnitude less. We attribute this difference to the fact that tholin synthesis occurs well below the level of maximum electron energy deposition and to possible contributions to tholins from UV-derived C2-hydrocarbons. We conclude that Titan tholin, produced by magnetospheric electrons, is alone sufficient to supply at least a significant fraction of Titan's haze--a result consistent with the fact that the optical properties of Titan tholin, among all proposed materials, are best at reproducing Titan's geometric albedo spectrum from near UV to mid-IR in light-scattering models.