Abstract
SY Cha is a T Tauri star surrounded by a protoplanetary disk with a large cavity seen in the millimeter continuum but has the spectral energy distribution of a full disk. Here we report the ...first results from JWST/Mid-InfraRed Instrument (MIRI) Medium Resolution Spectrometer (MRS) observations taken as part of the MIRI mid-INfrared Disk Survey (MINDS) GTO Program. The much improved resolution and sensitivity of MIRI-MRS compared to Spitzer enables a robust analysis of the previously detected H
2
O, CO, HCN, and CO
2
emission as well as a marginal detection of C
2
H
2
. We also report the first robust detection of mid-infrared OH and rovibrational CO emission in this source. The derived molecular column densities reveal the inner disk of SY Cha to be rich in both oxygen- and carbon-bearing molecules. This is in contrast to PDS 70, another protoplanetary disk with a large cavity observed with JWST, which displays much weaker line emission. In the SY Cha disk, the continuum, and potentially the line, flux varies substantially between the new JWST observations and archival Spitzer observations, indicative of a highly dynamic inner disk.
We present JWST-MIRI Medium Resolution Spectrometer (MRS) spectra of the protoplanetary disk around the low-mass T Tauri star GW Lup from the MIRI mid-INfrared Disk Survey Guaranteed Time ...Observations program. Emission from 12CO2, 13CO2, H2O, HCN, C2H2, and OH is identified with 13CO2 being detected for the first time in a protoplanetary disk. We characterize the chemical and physical conditions in the inner few astronomical units of the GW Lup disk using these molecules as probes. The spectral resolution of JWST-MIRI MRS paired with high signal-to-noise data is essential to identify these species and determine their column densities and temperatures. The Q branches of these molecules, including those of hot bands, are particularly sensitive to temperature and column density. We find that the 12CO2 emission in the GW Lup disk is coming from optically thick emission at a temperature of ∼400 K. 13CO2 is optically thinner and based on a lower temperature of ∼325 K, and thus may be tracing deeper into the disk and/or a larger emitting radius than 12CO2. The derived NCO2/NH2O ratio is orders of magnitude higher than previously derived for GW Lup and other targets based on Spitzer-InfraRed-Spectrograph data. This high column density ratio may be due to an inner cavity with a radius in between the H2O and CO2 snowlines and/or an overall lower disk temperature. This paper demonstrates the unique ability of JWST to probe inner disk structures and chemistry through weak, previously unseen molecular features.
Streaming instability is hypothesized to be triggered at particular protoplanetary disk locations where the volume density of the solid particles is enriched comparable to that of the gas. A ring of ...planetesimals thus forms when this condition is fulfilled locally. These planetesimals collide with each other and accrete inward drifting pebbles from the outer disk to further increase masses. We investigate the growth of the planetesimals that form in a ring-belt at various disk radii. Their initial mass distributions are calculated based on the formula summarized from the streaming instability simulations. We simulate the subsequent dynamical evolution of the planetesimals with a protoplanetary disk model based either on the minimum mass solar nebula (MMSN) or on the Toomre stability criterion. For the MMSN model, both pebble accretion and planetesimal accretion are efficient at a close-in orbit of 0.3 AU, resulting in the emergence of several super-Earth mass planets after 1 Myr. For comparison, only the most massive planetesimals undergo substantial mass growth when they are born at
r
= 3 AU, while the planetesimals at
r
= 30 AU experience little or no growth. On the other hand, in the denser Toomre disk, the most massive forming planets can reach Earth mass at
t
= 1 Myr and reach a mass between that of Neptune and that of Saturn within 3 Myr at 30 AU and 100 AU. Both the pebble and planetesimal accretion rate decrease with disk radial distance. Nevertheless, planetesimal accretion is less pronounced than pebble accretion at more distant disk regions. Taken together, the planets acquire higher masses when the disk has a higher gas density, a higher pebble flux, and/or a lower Stokes number of pebbles.
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Background/aimsTo evaluate efficacy, safety, pharmacokinetics (PK) and immunogenicity of SB15 versus reference aflibercept (AFL), and switching from AFL to SB15 in neovascular age-related macular ...degeneration (nAMD).DesignProspective, double-masked, randomised, phase 3 trial.MethodsParticipants with nAMD were randomised 1:1 to receive SB15 (N=224 participants) or AFL (N=225). At week 32, participants either continued on SB15 (SB15/SB15, N=219) or AFL (AFL/AFL, N=108), or switched from AFL to SB15 (AFL/SB15, N=111). This manuscript reports 1-year and switching results of secondary efficacy endpoints such as changes from baseline to week 56 in best-corrected visual acuity (BCVA), central subfield thickness (CST, from internal limiting membrane (ILM) to retinal pigment epithelium), and total retinal thickness (TRT, from ILM to Bruch’s membrane). Additional endpoints included safety, PK and immunogenicity.ResultsEfficacy results were comparable between groups. The least squares mean (LSmean) change in BCVA from baseline to week 56 was 7.4 letters for SB15/SB15 and 7.0 letters for AFL/AFL (difference (95% CI)=0.4 (−2.5 to 3.2)). The LSmean changes from baseline to week 56 in CST and TRT were −119.2 µm and −132.4 µm for SB15/SB15 and −126.6 µm and −136.3 µm for AFL/AFL, respectively (CST: difference (95% CI)=7.4 µm (−6.11 to 20.96); TRT: difference (95% CI)=3.9 µm (−18.35 to 26.10)). Switched and non-switched participants showed similar LSmean changes in BCVA from baseline to week 56 (AFL/SB15, 7.9 letters vs AFL/AFL, 7.8 letters; difference (95% CI)=0.0 (−2.8 to 2.8)). Safety, PK and immunogenicity were comparable between groups.ConclusionsEfficacy, safety, PK and immunogenicity were comparable between SB15 and AFL and between switched and non-switched participants.
Context. Crystalline silicates are an important tracer of the evolution of dust, the main building block of planet formation. In an inner protoplanetary disk, amorphous silicates are annealed because ...of the high temperatures that prevail there. These crystalline silicates are radially and vertically distributed by a disk turbulence and/or radial transport. Mid-infrared spectrographs are sensitive to the presence and temperature of micron-sized silicates, and the dust temperature can be used to infer their spatial distribution. Aims. We aim to model the spatial distribution of crystalline silicate dust in protoplanetary disks taking into account thermal annealing of silicate dust and radial transport of dust in the midplane. Using the resulting spatial distribution of crystalline and amorphous silicates, we calculated mid-infrared spectra to study the effect on dust features and to compare these to observations. Methods. We modeled a Class II T-Tauri protoplanetary disk and defined the region where crystallization happens by thermal annealing process from the comparison between crystallization and residence timescales ($ cryst res $). Radial mixing and drift were also compared to find a vertically well mixed region ($ ver drift $). We used the DISKLAB code to model the radial transport in the midplane and obtained the spatial distribution of the crystalline silicates for different grain sizes. We used MCMax, a radiative transfer code, to model the mid-infrared spectrum. Results. In our modeled T-Tauri disk, different grain sizes get crystallized in different radial and vertical ranges within 0.2 au. Small dust gets vertically mixed up efficiently, so crystallized small dust in the disk surface is well mixed with the midplane. Inward of 0.075 au, all grains are fully crystalline irrespective of their size. We also find that the crystallized dust is distributed out to a few au by radial transport, smaller grains more so than larger ones. Our fiducial model shows different contributions of the inner and outer disks to the dust spectral features. The $10 forsterite feature has an $ 30 <!PCT!>$ contribution from the innermost disk (0.07-0.09 au) and $<1 <!PCT!>$ from the disk beyond 10 au while the $33 feature has an $ 10 <!PCT!>$ contribution from both innermost and outer disks. We also find that feature strengths change when varying the spatial distribution of crystalline dust. Our modeled spectra qualitatively agree with observations from the Spitzer Space Telescope, but the modeled 10 mu m feature is strongly dominated by crystalline dust, unlike observations. Models with reduced crystallinity and depletion of small crystalline dust within 0.2 au show a better match with observations. Conclusions. Mid-infrared observations of the disk surface represent the radial distribution of small dust grains in the midplane and provide us with abundances of crystalline and amorphous dust, size distribution, and chemical composition in the inner disk. The inner and outer disks contribute more to shorter and longer wavelength features, respectively. In addition to the crystallization and dynamical processes, amorphization, sublimation of silicates, and dust evolution have to be taken into account to match observations, especially at $ where the inner disk mostly contributes. This study could interpret spectra of protoplanetary disks taken with the Mid-Infrared Instrument (MIRI) on board the James Webb Space Telescope.
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Exoplanetary systems host giant planets on substantially noncircular, close-in orbits. We propose that these eccentricities arise in a phase of giant impacts, analogous to the final stage of solar ...system assembly that formed Earth's Moon. In this scenario, the planets scatter each other and collide, with corresponding mass growth as they merge. We numerically integrate an ensemble of systems with varying total planet mass, allowing for collisional growth, to show that (1) the high-eccentricity giants observed today may have formed preferentially in systems of higher initial total planet mass, and (2) the upper bound on the observed giant planet eccentricity distribution is consistent with planet-planet scattering. We predict that mergers will produce a population of high-mass giant planets between 1 and 8 au from their stars.
To describe, compare similarity of pharmacokinetic (PK), pharmacodynamic (PD) and efficacy of SB12 and reference eculizumab (ECU) and find clinically significant covariate relationships.
The PK, PD ...(terminal complement activity) and efficacy (LDH) data of SB12 and ECU were obtained from 289 subjects from phase I and phase III studies. One- and two-compartment PK models with first-order elimination were evaluated for SB12 and ECU. For PD and efficacy, both direct and indirect models were tested. The impact of covariates on PK, PD and efficacy parameters was assessed. Relationship between PK/PD and PD/efficacy was characterized. This modeling was performed using NONMEM version 7.4 (Icon Development Solutions, Ellicott City, MD, USA).
The two-compartment model adequately described the PK of SB12 and ECU, and the subject's weight was chosen as a clinically significant covariate affecting drugs' clearance and central volume of distribution. Treatment group was not a significant covariate affecting clearance. The direct response model using inhibitory sigmoid E
and sigmoid E
relationship well described the PK/PD relationship and PD/efficacy relationship of SB12 and ECU, respectively. Through this modeling, the relationships between PK, PD and efficacy were characterized. There were no differences in PK, PD and efficacy parameters between SB12 and ECU in pooled populations of healthy subjects and paroxysmal nocturnal haemoglobinuria (PNH) patients.
The population modeling showed PK, PD and efficacy similarities between SB12 and ECU in pooled population of healthy subjects and PNH patients, supporting the totality of evidence on biosimilarity for SB12.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background: SB12 has been developed as a biosimilar of the reference product (RP) eculizumab. Eculizumab is a humanized monoclonal antibody (IgG2/4 kappa immunoglobulin) that binds to the human C5 ...complement protein with high affinity. Binding to this protein blocks its cleavage into C5a and C5b, thereby inhibiting terminal complement-mediated intravascular haemolysis. It is currently indicated for the treatment of patients with paroxysmal nocturnal haemoglobinuria, atypical haemolytic uremic syndrome (aHUS), refractory generalized Myasthenia Gravis (gMG) and Neuromyelitis Optica Spectrum Disorder (NMOSD).
Objectives: To demonstrate pharmacokinetic (PK) equivalence and evaluate pharmacodynamic (PD), safety, tolerability, and immunogenicity profiles between SB12 and the RP eculizumab.
Methods: This was a double-blind, three-arm, parallel group, and single-dose study in healthy subjects, between 18-55 years of age, randomized in a ratio of 1:1:1 to receive a single 300 mg dose of either SB12, European Union (EU) sourced eculizumab, or United States of America (US) sourced eculizumab via intravenous (IV) infusion for 35 minutes. Blood samples for PK and PD analysis were collected over 64 days. The primary objective of this study was to demonstrate PK similarity between the investigational products (IPs), as assessed by area under the concentration-time curve from time zero to infinity (AUC inf). Secondary PK endpoints included area under the concentration-time curve from time zero to the last quantifiable concentration (AUC last) and maximum observed concentration (C max). Equivalence for the primary endpoint (AUC inf) was determined if 90% confidence intervals (CIs) for the ratio of geometric least squared means (LSMeans) of SB12 to EU sourced eculizumab, SB12 to US sourced eculizumab, and EU sourced eculizumab to US sourced eculizumab was within the equivalence margin of 80.00% to 125.00%, respectively. Other objectives for the study were to evaluate safety, tolerability, immunogenicity, and PD profiles for the IPs.
Results: A total of 240 subjects (80 in each treatment group) were enrolled. Back transformation provided the geometric LSMean ratio for the comparison of SB12/EU sourced eculizumab, SB12/US sourced eculizumab and EU sourced eculizumab/US sourced eculizumab for AUC inf were 99.1 % (95.41,102.85), 95.1 % (91.40, 99.04), and 96.0 % (92.16, 100.10), respectively. The corresponding 90% CI was within the pre-defined equivalence margin of 80.00-125.00%, indicating that the each of two treatments are bioequivalent.
The profiles of mean terminal complement activity and mean change from baseline of complement activity were superimposable following administration of SB12, EU sourced eculizumab, and US sourced eculizumab. There was a rapid decrease in the complement activity at the end of infusion and then a slow restoration. There was no non-responder in the aspect of the measured complement activity after treatment.
There were no deaths or discontinuation of IP due to treatment-emergent adverse events (TEAEs) during the study. Two serious adverse events (SAEs) (renal colic in the SB12 treatment group and back pain in the US eculizumab treatment group) were reported, in 2 subjects. Both events were considered not related to the IP. The proportion of subjects who experienced TEAEs were similar between the SB12, EU sourced eculizumab, and US sourced eculizumab treatment groups (70.0%, 65.0%, and 71.3% of subjects, respectively). The overall incidence of subjects with post-dose anti-drug antibodies (ADA) to eculizumab was 2 (2.5%), 1 (1.3%), and 0 (0.0%) subjects in the SB12, EU sourced eculizumab, and US sourced eculizumab treatment groups, respectively. There was no significant difference between treatment groups. None of the subjects with post-dose ADA to eculizumab had a positive result for neutralizing antibodies.
Conclusion: The Phase I study demonstrated PK bioequivalence and showed comparable PD, safety, immunogenicity between SB12 and the RP eculizumab.
Lee: Samsung Bioepis, Co., Ltd.: Current Employment. Jang: Samsung Bioepis, Co., Ltd.: Current Employment. Kim: Samsung Bioepis, Co., Ltd.: Current Employment. Jeong: Samsung Bioepis, Co., Ltd.: Current Employment. Lee: Samsung Bioepis, Co., Ltd.: Current Employment. Jung: Samsung Bioepis, Co., Ltd.: Current Employment. Demichelis: Novartis: Consultancy, Research Funding, Speakers Bureau; Bristol/Celgene: Consultancy, Speakers Bureau; AMGEN: Consultancy, Speakers Bureau; ASH: Research Funding; Jazz: Consultancy; Gilead: Consultancy; Astellas: Consultancy; Abbvie: Consultancy, Speakers Bureau.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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