146 research outputs found
A low accretion efficiency of planetesimals formed at planetary gap edges
Observations and models of giant planets indicate that such objects are enriched in heavy elements compared to solar abundances. The prevailing view is that giant planets accreted multiple Earth masses of heavy elements after the end of core formation. Such late solid enrichment is commonly explained by the accretion of planetesimals. Planetesimals are expected to form at the edges of planetary gaps, and here we address the question of whether these planetesimals can be accreted in large enough amounts to explain the inferred high heavy element contents of giant planets. We performed a series of N-body simulations of the dynamics of planetesimals and planets during the planetary growth phase, taking gas drag into account as well as the enhanced collision cross section caused by the extended envelopes. We considered the growth of Jupiter and Saturn via gas accretion after reaching the pebble isolation mass and we included their migration in an evolving disk. We find that the accretion efficiency of planetesimals formed at planetary gap edges is very low: less than 10% of the formed planetesimals are accreted even in the most favorable cases, which in our model corresponds to a few Earth masses. When planetesimals are assumed to form beyond the feeding zone of the planets, extending to a few Hill radii from a planet, accretion becomes negligible. Furthermore, we find that the accretion efficiency increases when the planetary migration distance is increased and that the efficiency does not increase when the planetesimal radii are decreased. Based on these results, we conclude that it is difficult to explain the large heavy element content of giant planets with planetesimal accretion during the gas accretion phase. Alternative processes most likely are required, such as accretion of vapor deposited by drifting pebbles
Radium-223 in combination with paclitaxel in cancer patients with bone metastases : safety results from an open-label, multicenter phase Ib study
Purpose Concomitant treatment with radium-223 and paclitaxel is a potential option for cancer patients with bone metastases; however, myelosuppression risk during coadministration is unknown. This phase Ib study in cancer patients with bone metastases evaluated the safety of radium-223 and paclitaxel. Methods Eligible patients had solid tumor malignancies with >= 2 bone metastases and were candidates for paclitaxel. Treatment included seven paclitaxel cycles (90 mg/m(2) per week intravenously per local standard of care; 3 weeks on/1 week off) plus six radium-223 cycles (55 kBq/kg intravenously; one injection every 4 weeks, starting at paclitaxel cycle 2). The primary end point was percentage of patients with grade 3/4 neutropenia or thrombocytopenia during coadministration of radium-223 and paclitaxel (cycles 2, 3) versus paclitaxel alone (cycle 1). Results Of 22 enrolled patients, 15 were treated (safety population), with 7 completing all six radium-223 cycles. Treated patients had primary cancers of breast (n = 7), prostate (n = 4), bladder (n = 1), non-small cell lung (n = 1), myxofibrosarcoma (n = 1), and neuroendocrine (n = 1). No patients discontinued treatment from toxicity of the combination. In the 13 patients who completed cycle 3, the rates of grade 3 neutropenia in cycles 2 and 3 were 31% and 8%, respectively, versus 23% in cycle 1; there were no cases of grade 4 neutropenia or grade 3/4 thrombocytopenia. Breast cancer subgroup safety results were similar to the overall safety population. Conclusion Radium-223 was tolerated when combined with weekly paclitaxel, with no clinically relevant additive toxicities. This combination should be explored further in patients with bone metastases.Peer reviewe
The Heavy Element Composition of Disk Instability Planets Can Range From Sub- to Super-Nebular
Transit surveys combined with Doppler data have revealed a class of gas giant
planets that are massive and highly enriched in heavy elements (e.g.,
HD149026b, GJ436b, and HAT-P-20b). It is tempting to consider these planets as
validation of core accretion plus gas capture because it is often assumed that
disk instability planets should be of nebular composition. We show in this
paper, to the contrary, that gas giants that form by disk instability can have
a variety of heavy element compositions, ranging from sub- to super-nebular
values. High levels of enrichment can be achieved through one or multiple
mechanisms, including enrichment at birth, planetesimal capture, and
differentiation plus tidal stripping. As a result, the metallicity of an
individual gas giant cannot be used to discriminate between gas giant formation
modes.Comment: Accepted by Ap
Chern-Simons Theory and the Quark-Gluon Plasma
The generating functional for hard thermal loops in QCD is important in
setting up a resummed perturbation theory, so that all terms of a given order
in the coupling constant can be consistently taken into account. It is also the
functional which leads to a gauge invariant description of Debye screening and
plasma waves in the quark-gluon plasma. We have recently shown that this
functional is closely related to the eikonal for a Chern-Simons gauge theory.
In this paper, this relationship is explored and explained in more detail,
along with some generalizations.Comment: 28 pages (4 Feynman diagrams not included, available upon request
First-in-human phase I/IIa trial to evaluate the safety and initial clinical activity of DuoBody®-PD-L1×4–1BB (GEN1046) in patients with advanced solid tumors
Agonistic 4-1BB monoclonal antibodies were preclinically validated as promising cancer immunotherapies, both
as monotherapy and as potentiators of the activity of PD-(L)
1–blocking agents. However, toxicity and a narrow therapeutic
window have hampered their clinical development. DuoBodyPD-L1×4-1BB, a first-in-class, bispecific, next-generation
checkpoint immunotherapy, was designed to overcome these
limitations by activating T cells through conditional 4-1BB costimulation, while simultaneously blocking the PD-L1 axis. We
present preliminary data from the ongoing, first-in-human,
open-label, phase I/IIa trial of DuoBody-PD-L1×4-1BB in
advanced solid tumors (NCT03917381)
An Artemisinin-Derived Dimer Has Highly Potent Anti-Cytomegalovirus (CMV) and Anti-Cancer Activities
We recently reported that two artemisinin-derived dimers (dimer primary alcohol 606 and dimer sulfone 4-carbamate 832-4) are significantly more potent in inhibiting human cytomegalovirus (CMV) replication than artemisinin-derived monomers. In our continued evaluation of the activities of artemisinins in CMV inhibition, twelve artemisinin-derived dimers and five artemisinin-derived monomers were used. Dimers as a group were found to be potent inhibitors of CMV replication. Comparison of CMV inhibition and the slope parameter of dimers and monomers suggest that dimers are distinct in their anti-CMV activities. A deoxy dimer (574), lacking the endoperoxide bridge, did not have any effect on CMV replication, suggesting a role for the endoperoxide bridge in CMV inhibition. Differences in anti-CMV activity were observed among three structural analogs of dimer sulfone 4-carbamate 832-4 indicating that the exact placement and oxidation state of the sulfur atom may contribute to its anti-CMV activity. Of all tested dimers, artemisinin-derived diphenyl phosphate dimer 838 proved to be the most potent inhibitor of CMV replication, with a selectivity index of approximately 1500, compared to our previously reported dimer sulfone 4-carbamate 832-4 with a selectivity index of about 900. Diphenyl phosphate dimer 838 was highly active against a Ganciclovir-resistant CMV strain and was also the most active dimer in inhibition of cancer cell growth. Thus, diphenyl phosphate dimer 838 may represent a lead for development of a highly potent and safe anti-CMV compound
A chemical survey of exoplanets with ARIEL
Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio
Discovery and characterisation of two Neptune-mass planets orbiting HD 212729 with TESS
We report the discovery of two exoplanets orbiting around HD 212729
(TOI\,1052, TIC 317060587), a K star with V=9.51 observed by
TESS in Sectors 1 and 13. One exoplanet, TOI-1052b, is Neptune-mass and
transits the star, and an additional planet TOI-1052c is observed in radial
velocities but not seen to transit. We confirm the planetary nature of
TOI-1052b using precise radial velocity observations from HARPS and determined
its parameters in a joint RV and photometry analysis. TOI-1052b has a radius of
R, a mass of M, and
an orbital period of 9.14 days. TOI-1052c does not show any transits in the
TESS data, and has a minimum mass of M and an
orbital period of 35.8 days, placing it just interior to the 4:1 mean motion
resonance. Both planets are best fit by relatively high but only marginally
significant eccentricities of for planet b and
for planet c. We perform a dynamical analysis and
internal structure model of the planets as well as deriving stellar parameters
and chemical abundances. The mean density of TOI-1052b is g
cm consistent with an internal structure similar to Neptune. A nearby
star is observed in Gaia DR3 with the same distance and proper motion as
TOI-1052, at a sky projected separation of ~1500AU, making this a potential
wide binary star system.Comment: Accepted to MNRAS. 11 page
Polymorphisms in Toll-like receptor genes influence antibody responses to cytomegalovirus glycoprotein B vaccine
<p>Abstract</p> <p>Background</p> <p>Congenital Cytomegalovirus (CMV) infection is an important medical problem that has yet no current solution. A clinical trial of CMV glycoprotein B (gB) vaccine in young women showed promising efficacy. Improved understanding of the basis for prevention of CMV infection is essential for developing improved vaccines.</p> <p>Results</p> <p>We genotyped 142 women previously vaccinated with three doses of CMV gB for single nucleotide polymorphisms (SNPs) in TLR 1-4, 6, 7, 9, and 10, and their associated intracellular signaling genes. SNPs in the platelet-derived growth factor receptor (PDGFRA) and integrins were also selected based on their role in binding gB. Specific SNPs in TLR7 and IKBKE (inhibitor of nuclear factor kappa-B kinase subunit epsilon) were associated with antibody responses to gB vaccine. Homozygous carriers of the minor allele at four SNPs in TLR7 showed higher vaccination-induced antibody responses to gB compared to heterozygotes or homozygotes for the common allele. SNP rs1953090 in IKBKE was associated with changes in antibody level from second to third dose of vaccine; homozygotes for the minor allele exhibited lower antibody responses while homozygotes for the major allele showed increased responses over time.</p> <p>Conclusions</p> <p>These data contribute to our understanding of the immunogenetic mechanisms underlying variations in the immune response to CMV vaccine.</p
Neurons Controlling Aplysia Feeding Inhibit Themselves by Continuous NO Production
Neural activity can be affected by nitric oxide (NO) produced by spiking neurons. Can neural activity also be affected by NO produced in neurons in the absence of spiking?Applying an NO scavenger to quiescent Aplysia buccal ganglia initiated fictive feeding, indicating that NO production at rest inhibits feeding. The inhibition is in part via effects on neurons B31/B32, neurons initiating food consumption. Applying NO scavengers or nitric oxide synthase (NOS) blockers to B31/B32 neurons cultured in isolation caused inactive neurons to depolarize and fire, indicating that B31/B32 produce NO tonically without action potentials, and tonic NO production contributes to the B31/B32 resting potentials. Guanylyl cyclase blockers also caused depolarization and firing, indicating that the cGMP second messenger cascade, presumably activated by the tonic presence of NO, contributes to the B31/B32 resting potential. Blocking NO while voltage-clamping revealed an inward leak current, indicating that NO prevents this current from depolarizing the neuron. Blocking nitrergic transmission had no effect on a number of other cultured, isolated neurons. However, treatment with NO blockers did excite cerebral ganglion neuron C-PR, a command-like neuron initiating food-finding behavior, both in situ, and when the neuron was cultured in isolation, indicating that this neuron also inhibits itself by producing NO at rest.Self-inhibitory, tonic NO production is a novel mechanism for the modulation of neural activity. Localization of this mechanism to critical neurons in different ganglia controlling different aspects of a behavior provides a mechanism by which a humeral signal affecting background NO production, such as the NO precursor L-arginine, could control multiple aspects of the behavior
- …