Formation of Super-Earths

Super-Earths are the most abundant planets known to date and are characterized by having sizes between that of Earth and Neptune, typical orbital periods of less than 100 days and gaseous envelopes that are often massive enough to significantly contribute to the planet's overall radius. Furthermore, super-Earths regularly appear in tightly-packed multiple-planet systems, but resonant configurations in such systems are rare. This chapters summarizes current super-Earth formation theories. It starts from the formation of rocky cores and subsequent accretion of gaseous envelopes. We follow the thermal evolution of newly formed super-Earths and discuss their atmospheric mass loss due to disk dispersal, photoevaporation, core-cooling and collisions. We conclude with a comparison of observations and theoretical predictions, highlighting that even super-Earths that appear as barren rocky cores today likely formed with primordial hydrogen and helium envelopes and discuss some paths forward for the future.Comment: Invited review accepted for publication in the 'Handbook of Exoplanets,' Planet Formation section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Ed

Opportunities for improving pLDH-based malaria diagnostic tests

<p>Abstract</p> <p>Background</p> <p>Monoclonal antibodies to <it>Plasmodium </it>lactate dehydrogenase (pLDH) have been previously used to format immunochromatographic tests for the diagnosis of malaria. Using pLDH as an antigen has several advantages as a sensitive measure of the presence of parasites within patient blood samples. However, variable results in terms of specificity and sensitivity among different commercially available diagnostic kits have been reported and it has not been clear from these studies whether the performance of an individual test is due simply to how it is engineered or whether it is due to the biochemical nature of the pLDH-antibody reaction itself.</p> <p>Methods</p> <p>A series of systematic studies to determine how various pLDH monoclonal antibodies work in combination was undertaken. Different combinations of anti-pLDH monoclonal antibodies were used in a rapid-test immunochromatographic assay format to determine parameters of sensitivity and specificity with regard to individual <it>Plasmodium </it>species.</p> <p>Results</p> <p>Dramatic differences were found in both species specificity and overall sensitivity depending on which antibody is used on the immunochromatographic strip and which is used on the colorimetric colloidal-gold used for visual detection.</p> <p>Discussion</p> <p>The results demonstrate the feasibility of different test formats for the detection and speciation of malarial infections. In addition, the data will enable the development of a universal rapid test algorithm that may potentially provide a cost-effective strategy to diagnose and manage patients in a wide range of clinical settings.</p> <p>Conclusion</p> <p>These data emphasize that using different anti-pLDH antibody combinations offers a tractable way to optimize immunochromatographic pLDH tests.</p

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

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

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