Context . Understanding the physical conditions of circumstellar material around young stars is crucial to star and planet formation studies. In particular, very low-mass stars ( M ★ < 0.2 M ⊙ ) are ...interesting sources to characterize as they are known to host a diverse population of rocky planets. Molecular and atomic hydrogen lines can probe the properties of the circumstellar gas. Aims . This work aims to measure the mass accretion rate, the accretion luminosity, and more generally the physical conditions of the warm emitting gas in the inner disk of the very low-mass star 2MASS-J16053215-1933159. We investigate the source mid-infrared spectrum for atomic and molecular hydrogen line emission. Methods . We present the full James Webb Space Telescope (JWST) Mid-InfraRed Instrument (MIRI) Medium Resolution Spectrometer (MRS) spectrum of the protoplanetary disk around the very low-mass star 2MASS-J16053215-1933159 from the MINDS GTO program, previously shown to be abundant in hydrocarbon molecules. We analyzed the atomic and molecular hydrogen lines in this source by fitting one or multiple Gaussian profiles. We then built a rotational diagram for the H 2 lines to constrain the rotational temperature and column density of the gas. Finally, we compared the observed atomic line fluxes to predictions from two standard emission models. Results . We identify five molecular hydrogen pure rotational lines and 16 atomic hydrogen recombination lines in the 5–20 µm spectral range. The spectrum indicates optically thin emission for both species. We use the molecular hydrogen lines to constrain the mass and temperature of the warm emitting gas. We derive a total gas mass of only 2.3 × 10 −5 M Jup and a temperature of 635 K for the warm H 2 gas component located in the very inner disk ( r < 0.033 au), which only accounts for a small fraction of the upper limit for the disk mass from continuum observations (0.2 M Jup ). The HI (7−6) recombination line is used to measure the mass accretion rate (4.0 × 10 −10 M ⊙ yr −1 ) and luminosity (3.1 × 10 −3 L ⊙ ) onto the central source. This line falls close to the HI (11−8) line, however at the spectral resolution of JWST MIRI we managed to measure both separately. Previous studies based on Spitzer have measured the combined flux of both lines to measure accretion rates. HI recombination lines can also be used to derive the physical properties of the gas using atomic recombination models. The model predictions of the atomic line relative intensities constrain the atomic hydrogen density to about 10 9 −10 10 cm −3 and temperatures up to 5000 K. Conclusions . The JWST-MIRI MRS observations for the very low-mass star 2MASS-J16053215-1933159 reveal a large number of emission lines, many originating from atomic and molecular hydrogen because we are able to look into the disk warm molecular layer. Their analysis constrains the physical properties of the emitting gas and showcases the potential of JWST to deepen our understanding of the physical and chemical structure of protoplanetary disks.
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FMFMET, NUK, UL, UM, UPUK
Abstract
Background: SB3 (trastuzumab-dttb) is a biosimilar approved globally based on its similarity with reference trastuzumab (TRZ) demonstrated by thorough comparability exercises in analytical, ...biological, and clinical studies. In a randomized, double-blind, multicenter Phase 3 study of 875 patients with HER2-positive early or locally advanced breast cancer in the neoadjuvant setting, equivalent efficacy, similar safety, pharmacokinetics, and immunogenicity between SB3 and TRZ were shown. However, when quality attributes of TRZ were examined, downward drifts in antibody-dependent cell-mediated cytotoxicity activities (ADCC) were observed in the TRZ lots with expiry dates ranging from Aug 2018 to Dec 2019. Some of these lots of the reference product were found to be used in the Phase 3 study. After completing the Phase 3 study, patients from select countries were included in a follow-up observational study to monitor cardiac safety and survival. Here, we report the final survival results, including post-hoc subgroup analysis based on ADCC status, at a median follow-up of 68 months. Methods: During the follow-up observational study, the protocol was amended to include additional patients who originally were enrolled in the Phase 3 study but had not been followed in the observational study, in order to collect a larger sample of survival data. For these additional patients, medical records from the last assessment in the Phase 3 study through the date of enrollment in the follow-up study were collected retrospectively. As post-hoc analysis, patients in the TRZ arm were stratified into two subgroups: patients who received during neoadjuvant treatment at least one vial of TRZ with downward drift in ADCC as “Drifted TRZ”, and the others as “Non-drifted TRZ”. Event-free survival (EFS) and overall survival (OS) were assessed. Results: Of 875 patients randomized in the Phase 3 study, 538 patients (SB3, N=267; TRZ, N=271) were enrolled in the follow-up observational study: 367 patients were initially enrolled in the follow-up study, and 171 patients were additionally enrolled following the protocol amendment. The median follow-up duration was 68 months from randomization in the Phase 3 study. 54 events (20.2%) in the SB3 arm, and 67 events (24.7%) in the TRZ arm were reported (HR 0.84 0.58, 1.20, p=0.335). 22 deaths (8.2%) and 38 deaths (14%) were reported in SB3 and TRZ arms, respectively (HR 0.61 0.36, 1.05, p=0.073). In post-hoc analysis, of 271 patients in TRZ arm, 107 patients were grouped as “Non-drifted TRZ”, and 164 patients as “Drifted TRZ”. 19 events (17.8%) in the Non-drifted TRZ group and 48 (29.3%) events in the Drifted TRZ group occurred (HR 2.57 1.28, 5.14, p=0.008). 9 deaths (8.4%) in the Non-drifted TRZ group and 29 deaths (17.7%) in the Drifted TRZ group were reported (HR 3.87 1.37, 10.93, p=0.011). No difference was observed between SB3 arm and Non-drifted TRZ group in terms of EFS (HR 1.28 0.73, 2.22, p=0.391) and OS (HR 0.99 0.42, 2.31, p=0.975). Conclusions: Comparable long-term efficacy results in EFS and OS were shown at 68 months of follow-up, further supporting biosimilarity of SB3 to the reference product. Currently, these follow-up results represent the longest monitoring data of patients treated with a trastuzumab biosimilar for HER2-positive early or locally advanced breast cancer.
Citation Format: Xavier Pivot, Mark D Pegram, Javier Cortes, Diana Lüftner, Gary H Lyman, Giuseppe Curigliano, Igor M Bondarenko, Mikhail Dvorkin, Jin Hee Ahn, Seock-Ah Im, Maria Litwiniuk, Yaroslav V Shparyk, Gwo Fuang Ho, Nikolay V Kislov, Marek Wojtukiewicz, Tomasz Sarosiek, Yee Soo Chae, Jin Seok Ahn, Hyerin Jang, Sujung Kim, Jiwon Lee, Soo Young Lee, Ye Chan Yoon. Final survival analysis of a phase 3 study comparing SB3 (trastuzumab biosimilar) and reference trastuzumab in HER2-positive early or locally advanced breast cancer abstract. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-04.
The understanding of planet formation has changed recently, embracing the new idea of pebble accretion. This means that the influx of pebbles from the outer regions of planet-forming disks to their ...inner zones could determine the composition of planets and their atmospheres. The solid and molecular components delivered to the planet-forming region can be best characterized by mid-infrared spectroscopy. With Spitzer low-resolution (
R
= 100, 600) spectroscopy, this approach was limited to the detection of abundant molecules, such as H
2
O, C
2
H
2
, HCN and CO
2
. This contribution will present the first results of the MINDS (MIRI mid-INfrared Disk Survey, PI:Th Henning) project. Due do the sensitivity and spectral resolution provided by the James Webb Space Telescope (JWST), we now have a unique tool to obtain the full inventory of chemistry in the inner disks of solar-type stars and brown dwarfs, including also less-abundant hydrocarbons and isotopologues. The Integral Field Unit (IFU) capabilities will enable at the same time spatial studies of the continuum and line emission in extended sources such as debris disks, the flying saucer and also the search for mid-IR signatures of forming planets in systems such as PDS 70. These JWST observations are complementary to ALMA and NOEMA observations of outer-disk chemistry; together these datasets will provide an integral view of the processes occurring during the planet-formation phase.
The Mid-InfraRed Instrument/Medium-Resolution Spectrometer (MIRI/MRS) on board the James Webb Space Telescope reveals the rich and diverse chemistry in the planet forming regions around Sun-like and low-mass stars.
MINDS: The JWST MIRI Mid-INfrared Disk Survey Henning, Thomas; Kamp, Inga; Samland, Matthias ...
Publications of the Astronomical Society of the Pacific,
05/2024, Volume:
136, Issue:
5
Journal Article
Peer reviewed
Open access
Abstract The study of protoplanetary disks has become increasingly important with the Kepler satellite finding that exoplanets are ubiquitous around stars in our galaxy and the discovery of enormous ...diversity in planetary system architectures and planet properties. High-resolution near-IR and ALMA images show strong evidence for ongoing planet formation in young disks. The JWST MIRI mid-INfrared Disk Survey (MINDS) aims to (1) investigate the chemical inventory in the terrestrial planet-forming zone across stellar spectral type, (2) follow the gas evolution into the disk dispersal stage, and (3) study the structure of protoplanetary and debris disks in the thermal mid-IR. The MINDS survey will thus build a bridge between the chemical inventory of disks and the properties of exoplanets. The survey comprises 52 targets (Herbig Ae stars, T Tauri stars, very low-mass stars and young debris disks). We primarily obtain MIRI/MRS spectra with high signal-to-noise ratio (∼100–500) covering the complete wavelength range from 4.9 to 27.9 μ m. For a handful of selected targets we also obtain NIRSpec IFU high resolution spectroscopy (2.87–5.27 μ m). We will search for signposts of planet formation in thermal emission of micron-sized dust—information complementary to near-IR scattered light emission from small dust grains and emission from large dust in the submillimeter wavelength domain. We will also study the spatial structure of disks in three key systems that have shown signposts for planet formation, TW Hya and HD 169142 using the MIRI coronagraph at 15.5 μ m and 10.65 μ m respectively and PDS 70 using NIRCam imaging in the 1.87 μ m narrow and the 4.8 μ m medium band filter. We provide here an overview of the MINDS survey and showcase the power of the new JWST mid-IR molecular spectroscopy with the TW Hya disk spectrum where we report the detection of the molecular ion CH 3 + and the robust confirmation of HCO + earlier detected with Spitzer.
Abstract
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
12
CO
2
,
13
CO
2
, H
2
O, HCN, C
2
H
2
, and OH is identified with
13
CO
2
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
12
CO
2
emission in the GW Lup disk is coming from optically thick emission at a temperature of ∼400 K.
13
CO
2
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
12
CO
2
. The derived
N
CO
2
/
N
H
2
O
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 H
2
O and CO
2
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.
Trastuzumab has been the standard of care for the treatment of patients with ERBB2-positive breast cancer; however, cardiac events have been reported. This long-term follow-up study provides clinical ...evidence supporting the similarity of a trastuzumab biosimilar (SB3) to reference trastuzumab (TRZ).
To compare cardiac safety and efficacy between SB3 and TRZ for patients with ERBB2-positive early or locally advanced breast cancer after up to 6 years of follow-up.
This prespecified secondary analysis of a randomized clinical trial, conducted from April 2016 to January 2021, included patients with ERBB2-positive early or locally advanced breast cancer from a multicenter double-blind, parallel-group, equivalence phase 3 randomized clinical trial of SB3 vs TRZ with concomitant neoadjuvant chemotherapy who completed neoadjuvant and adjuvant treatment.
In the original trial, patients were randomized to either SB3 or TRZ with concomitant neoadjuvant chemotherapy for 8 cycles (4 cycles of docetaxel followed by 4 cycles of fluorouracil, epirubicin, and cyclophosphamide). After surgery, patients continued SB3 or TRZ monotherapy for 10 cycles of adjuvant treatment per previous treatment allocation. Following neoadjuvant and adjuvant treatment, patients were monitored for up to 5 years.
The primary outcomes were the incidence of symptomatic congestive heart failure and asymptomatic, significant decrease in left ventricular ejection fraction (LVEF). The secondary outcomes were event-free survival (EFS) and overall survival (OS).
A total of 538 female patients were included (median age, 51 years range, 22-65 years). Baseline characteristics were comparable between the SB3 and TRZ groups. Cardiac safety was monitored for 367 patients (SB3, n = 186; TRZ, n = 181). Median follow-up was 68 months (range, 8.5-78.1 months). Asymptomatic, clinically significant LVEF decreases were rarely reported (SB3, 1 patient 0.4%; TRZ, 2 0.7%). No patient experienced symptomatic cardiac failure or death due to a cardiovascular event. Survival was evaluated for the 367 patients in the cardiac safety cohort and an additional 171 patients enrolled after a protocol amendment (538 patients SB3, n = 267; TRZ, n = 271). No difference was observed in EFS or OS between treatment groups (EFS: hazard ratio HR, 0.84; 95% CI, 0.58-1.20; P = .34; OS: HR, 0.61; 95% CI, 0.36-1.05; P = .07). Five-year EFS rates were 79.8% (95% CI, 74.8%-84.9%) in the SB3 group and 75.0% (95% CI, 69.7%-80.3%) in the TRZ group, and OS rates were 92.5% (95% CI, 89.2%-95.7%) in the SB3 group and 85.4% (95% CI, 81.0%-89.7%) in the TRZ group.
In this secondary analysis of a randomized clinical trial, SB3 demonstrated cardiac safety and survival comparable to those of TRZ after up to 6 years of follow-up in patients with ERBB2-positive early or locally advanced breast cancer.
ClinicalTrials.gov Identifier: NCT02771795.
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.
Crystalline silicates are an important tracer to the dust evolution in protoplanetary disks. In the inner disk, amorphous silicates are annealed by the high temperatures. These crystalline silicates ...are radially and vertically distributed in the disk. We aim to model the spatial distribution of crystalline silicate in the disk and its mid-IR spectra to study the effect on dust spectral features and to compare these to observations. We modeled a T-Tauri protoplanetary disk and defined the crystallization region from the crystallization and residence timescales. Radial mixing and drift were compared to find a vertically mixed region. We used the DISKLAB code to obtain the spatial distribution of the crystalline silicates, and MCMax code to model the mid-infrared spectrum. In our modeled disk, different grain sizes get crystallized in different regions in the disk. Crystallized dust in the disk surface is well mixed with the midplane due to vertical mixing and gets distributed to the outer disk by radial transport. Our model shows different contributions of the disk zones to the dust spectral features. Feature strengths change when varying the spatial distribution of crystalline dust. Our modeled spectra qualitatively agree with observations, but the modeled 10 \(\mu\)m feature is strongly dominated by crystalline dust. Models with reduced crystallinity and depletion of small crystalline dust in the inner disk show a better match with observations. Mid-IR observations of the disk surface represent the radial distribution of small dust in the midplane and provide us with dust properties in the inner disk. The inner and outer disks contribute more to shorter and longer wavelength features, respectively. Amorphization, sublimation, and dust evolution have to be considered to match observations. This study could interpret the spectra of protoplanetary disks taken with the MIRI on board the JWST.
The MRS mode of the JWST-MIRI instrument gives insights into the chemical
richness and complexity of the inner regions of planet-forming disks. Here, we
analyse the H$_2$O-rich spectrum of the ...compact disk DR Tau. We probe the
excitation conditions of the H$_2$O transitions observed in different
wavelength regions across the entire spectrum using LTE slab models, probing
both the rovibrational and rotational transitions. These regions suggest a
radial temperature gradient, as the excitation temperature (emitting radius)
decreases (increases) with increasing wavelength. To explain the derived
emitting radii, we require a larger inclination for the inner disk (i~20-23
degrees) compared to the outer disk (i~5 degrees), agreeing with our previous
analysis on CO. We also analyse the pure rotational spectrum (<10 micron) using
a large, structured disk (CI Tau) as a template, confirming the presence of the
radial gradient, and by fitting multiple components to further characterise the
radial and vertical temperature gradients present in the spectrum. At least
three temperature components (T~180-800 K) are required to reproduce the
rotational spectrum of H$_2$O arising from the inner ~0.3-8 au. These
components describe a radial temperature gradient that scales roughly as
~R$^{-0.5}$ in the emitting layers. As the H$_2$O is mainly optically thick, we
derive a lower limit on the abundance ratio of H$_2$O/CO~0.17, suggesting a
potential depletion of H$_2$O. Similarly to previous work, we detect a cold
H$_2$O component (T~180 K) originating from near the snowline. We cannot
conclude if an enhancement of the H$_2$O reservoir is observed following radial
drift. A consistent analysis of a larger sample of compact disks is necessary
to study the importance of drift in enhancing the H$_2$O abundances.
Exoplanetary systems host giant planets on substantially non-circular, 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.
