...we evaluated omicron nAbT in four patients with a history of breakthrough delta infection after two vaccine doses. The exact correlates of immune protection against VOC remain undefined; however, ...multiple studies have shown that higher nAbT correlate with reduced risk of symptomatic infection.10,11 Finally, we did not evaluate vaccine-induced cellular responses to omicron as we had for other VOCs.2 We note that emerging reports suggest T-cell responses against omicron remain comparable to ancestral variants in the general population without cancer.12,13 In conclusion, we show that most of the patients with cancer in the CAPTURE cohort lacked detectable nAbT against omicron following two vaccine doses, independent of the vaccine type. CS is funded by CRUK (TRACERx, PEACE and CRUK Cancer Immunotherapy Catalyst Network), the CRUK Lung Cancer Centre of Excellence (C11496/A30025), the Rosetrees Trust, Butterfield and Stoneygate Trusts, the Novo Nordisk Foundation (ID16584), a Royal Society Professorship Enhancement award (RP/EA/180007), the National Institute of Health Research (NIHR) Biomedical Research Centre at University College London Hospitals, the CRUK University College London Centre, the Experimental Cancer Medicine Centre and the Breast Cancer Research Foundation (BCRF 20-157). ST is funded by Cancer Research UK (A29911); the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC10988), the UK Medical Research Council (FC10988), and the Wellcome Trust (FC10988); the NIHR Biomedical Research Centre at the Royal Marsden Hospital and Institute of Cancer Research (grant reference number A109), the Royal Marsden Cancer Charity, The Rosetrees Trust (A2204), Ventana Medical Systems (grant reference numbers 10467 and 10530), the National Institute of Health (U01 CA247439) and Melanoma Research Alliance (686061).
We present precise photospheric parameters of 282 M dwarfs determined from fitting the most recent version of PHOENIX models to high-resolution CARMENES spectra in the visible (0.52–0.96
μ
m) and NIR ...wavelength range (0.96–1.71
μ
m). With its aim to search for habitable planets around M dwarfs, several planets of different masses have been detected. The characterization of the target sample is important for the ability to derive and constrain the physical properties of any planetary systems that are detected. As a continuation of previous work in this context, we derived the fundamental stellar parameters effective temperature, surface gravity, and metallicity of the CARMENES M-dwarf targets from PHOENIX model fits using a
χ
2
method. We calculated updated PHOENIX stellar atmosphere models that include a new equation of state to especially account for spectral features of low-temperature stellar atmospheres as well as new atomic and molecular line lists. We show the importance of selecting magnetically insensitive lines for fitting to avoid effects of stellar activity in the line profiles. For the first time, we directly compare stellar parameters derived from multiwavelength range spectra, simultaneously observed for the same star. In comparison with literature values we show that fundamental parameters derived from visible spectra and visible and NIR spectra combined are in better agreement than those derived from the same spectra in the NIR alone.
The most appropriate definition of perioperative myocardial infarction (pMI) after coronary artery bypass grafting (CABG) and its impact on clinically relevant long-term events is controversial. We ...aimed to (i) analyse the incidence of pMI depending on various current definitions in a 'real-life' setting of CABG surgery and (ii) determine the long-term prognosis of patients with pMI depending on current definitions.
A consecutive cohort of 2829 coronary artery disease patients undergoing CABG from two tertiary university centres with the presence of serial perioperative cardiac biomarker measurements (cardiac troponin and creatine kinase-myocardial band) were retrospectively analysed. The incidence and prognostic impact of pMI were assessed according to (i) the 4th Universal Definition of Myocardial Infarction (4UD), (ii) the definition of the Society for Cardiovascular Angiography and Interventions (SCAI), and (iii) the Academic Research Consortium (ARC). The primary endpoint of this study was a composite of myocardial infarction, all-cause death, and repeat revascularization; secondary endpoints were mortality at 30 days and during 5-year follow-up. There was a significant difference in the occurrence of pMI (49.5% SCAI vs. 2.9% 4UD vs. 2.6% ARC). The 4th Universal Definition of Myocardial Infarction and ARC criteria remained strong independent predictors of all-cause mortality at 30 days 4UD: odds ratio (OR) 12.18; 95% confidence interval (CI) 5.00-29.67; P < 0.001; ARC: OR 13.16; 95% CI 5.41-32.00; P < 0.001 and 5 years 4UD: hazard ratio (HR) 2.13; 95% CI 1.19-3.81; P = 0.011; ARC: HR 2.23; 95% CI 1.21-4.09; P = 0.010. Moreover, the occurrence of new perioperative electrocardiographic changes was prognostic of both primary and secondary endpoints.
Incidence and prognosis of pMI differ markedly depending on the underlying definition of myocardial infarction for patients undergoing CABG. Isolated biomarker release-based definitions (such as troponin) were not associated with pMI relevant to prognosis. Additional signs of ischaemia detected by new electrocardiographic abnormalities, regional wall motion abnormalities, or coronary angiography should result in rapid action in everyday clinical practice.
We aimed to (i) analyse the incidence of perioperative myocardial infarction (pMI) depending on different current definitions in a 'real-life' setting of coronary artery bypass graft surgery and (ii) determine the long-term prognosis of patients with pMI according to current definitions.
There was a significant difference in the occurrence of pMI. The 4th Universal Definition of Myocardial Infarction and Academic Research Consortium criteria remained strong independent predictors for all-cause mortality at 30 days and during 5-year follow-up.
Isolated biomarker release-based definitions were not associated with pMI relevant to prognosis. Additional signs of ischaemia detected by new electrocardiogram abnormalities, regional wall motion abnormalities, or coronary angiography should result in rapid action in clinical practice.
Context.
For years, the standard procedure to measure radial velocities (RVs) of spectral observations consisted in cross-correlating the spectra with a binary mask, that is, a simple stellar ...template that contains information on the position and strength of stellar absorption lines. The cross-correlation function (CCF) profiles also provide several indicators of stellar activity.
Aims.
We present a methodology to first build weighted binary masks and, second, to compute the CCF of spectral observations with these masks from which we derive radial velocities and activity indicators. These methods are implemented in a python code that is publicly available.
Methods.
To build the masks, we selected a large number of sharp absorption lines based on the profile of the minima present in high signal-to-noise ratio (S/N) spectrum templates built from observations of reference stars. We computed the CCFs of observed spectra and derived RVs and the following three standard activity indicators: full-width-at-half-maximum as well as contrast and bisector inverse slope.
Results.
We applied our methodology to CARMENES high-resolution spectra and obtain RV and activity indicator time series of more than 300 M dwarf stars observed for the main CARMENES survey. Compared with the standard CARMENES template matching pipeline, in general we obtain more precise RVs in the cases where the template used in the standard pipeline did not have enough S/N. We also show the behaviour of the three activity indicators for the active star YZ CMi and estimate the absolute RV of the M dwarfs analysed using the CCF RVs.
Vascular endothelial growth factor (VEGF) is associated with tumor angiogenesis and poor prognosis in human colorectal cancer (CRC). VEGF receptor-1 (VEGFR-1 or Flt-1) is a high-affinity receptor for ...VEGF and is typically considered specific to endothelial cells. Here we report the expression and function of VEGFR-1 in CRC cell lines. VEGFR-1 was expressed in all CRC cell lines studied as determined by RT-PCR, Western blot analysis, FACS, and ELISA. Treatment of the human CRC cell lines HT-29 and SW480 with VEGF-A (a ligand for both VEGFR-1 and -2) or VEGF-B (a ligand specific for VEGFR-1) led to activation of Erk-1/2, SAPK/JNK, and translocation of the p65 subunit of nuclear factor-kappaB into the nucleus. Both VEGF-A and -B led to significant induction of cell motility and invasiveness of CRC cells. Stimulation of cells with VEGF-A or -B also led to larger and more numerous colonies in soft agar. However, activation of VEGFR-1 did not increase CRC cell proliferation. In contrast to the previous paradigm that VEGFRs are not present on tumor cells of epithelial origin, we found that VEGFR-1 is present and functional on CRC cells, and activation by VEGF family ligands can activate processes involved in tumor progression and metastasis.
CD20 is an important target for the treatment of B-cell malignancies, including non-Hodgkin lymphoma as well as autoimmune disorders. B-cell depletion therapy using monoclonal antibodies against ...CD20, such as rituximab, has revolutionized the treatment of these disorders, greatly improving overall survival in patients. Here, we report the development of GA101 as the first Fc-engineered, type II humanized IgG1 antibody against CD20. Relative to rituximab, GA101 has increased direct and immune effector cell-mediated cytotoxicity and exhibits superior activity in cellular assays and whole blood B-cell depletion assays. In human lymphoma xenograft models, GA101 exhibits superior antitumor activity, resulting in the induction of complete tumor remission and increased overall survival. In nonhuman primates, GA101 demonstrates superior B cell–depleting activity in lymphoid tissue, including in lymph nodes and spleen. Taken together, these results provide compelling evidence for the development of GA101 as a promising new therapy for the treatment of B-cell disorders.
Chiral magnets are promising materials for the realisation of high-density and low-power spintronic memory devices. For these future applications, a key requirement is the synthesis of appropriate ...materials in the form of thin films ordering well above room temperature. Driven by the Dzyaloshinskii-Moriya interaction, the cubic compound FeGe exhibits helimagnetism with a relatively high transition temperature of 278 K in bulk crystals. We demonstrate that this temperature can be enhanced significantly in thin films. Using x-ray scattering and ferromagnetic resonance techniques, we provide unambiguous experimental evidence for long-wavelength helimagnetic order at room temperature and magnetic properties similar to the bulk material. We obtain α
= 0.0036 ± 0.0003 at 310 K for the intrinsic damping parameter. We probe the dynamics of the system by means of muon-spin rotation, indicating that the ground state is reached via a freezing out of slow dynamics. Our work paves the way towards the fabrication of thin films of chiral magnets that host certain spin whirls, so-called skyrmions, at room temperature and potentially offer integrability into modern electronics.
Context.
The nearby ultra-compact multiplanetary system YZ Ceti consists of at least three planets, and a fourth tentative signal. The orbital period of each planet is the subject of discussion in ...the literature due to strong aliasing in the radial velocity data. The stellar activity of this M dwarf also hampers significantly the derivation of the planetary parameters.
Aims.
With an additional 229 radial velocity measurements obtained since the discovery publication, we reanalyze the YZ Ceti system and resolve the alias issues.
Methods.
We use model comparison in the framework of Bayesian statistics and periodogram simulations based on a method by Dawson and Fabrycky to resolve the aliases. We discuss additional signals in the RV data, and derive the planetary parameters by simultaneously modeling the stellar activity with a Gaussian process regression model. To constrain the planetary parameters further we apply a stability analysis on our ensemble of Keplerian fits.
Results.
We find no evidence for a fourth possible companion. We resolve the aliases: the three planets orbit the star with periods of 2.02 d, 3.06 d, and 4.66 d. We also investigate an effect of the stellar rotational signal on the derivation of the planetary parameters, in particular the eccentricity of the innermost planet. Using photometry we determine the stellar rotational period to be close to 68 d and we also detect this signal in the residuals of a three-planet fit to the RV data and the spectral activity indicators. From our stability analysis we derive a lower limit on the inclination of the system with the assumption of coplanar orbits which is
i
min
= 0.9 deg. From the absence of a transit event with TESS, we derive an upper limit of the inclination of
i
max
= 87.43 deg.
Conclusions.
YZ Ceti is a prime example of a system where strong aliasing hindered the determination of the orbital periods of exoplanets. Additionally, stellar activity influences the derivation of planetary parameters and modeling them correctly is important for the reliable estimation of the orbital parameters in this specific compact system. Stability considerations then allow additional constraints to be placed on the planetary parameters.
Many of the next generation of global climate models will include aerosol schemes which explicitly simulate the microphysical processes that determine the particle size distribution. These models ...enable aerosol optical properties and cloud condensation nuclei (CCN) concentrations to be determined by fundamental aerosol processes, which should lead to a more physically based simulation of aerosol direct and indirect radiative forcings. This study examines the global variation in particle size distribution simulated by 12 global aerosol microphysics models to quantify model diversity and to identify any common biases against observations. Evaluation against size distribution measurements from a new European network of aerosol supersites shows that the mean model agrees quite well with the observations at many sites on the annual mean, but there are some seasonal biases common to many sites. In particular, at many of these European sites, the accumulation mode number concentration is biased low during winter and Aitken mode concentrations tend to be overestimated in winter and underestimated in summer. At high northern latitudes, the models strongly underpredict Aitken and accumulation particle concentrations compared to the measurements, consistent with previous studies that have highlighted the poor performance of global aerosol models in the Arctic. In the marine boundary layer, the models capture the observed meridional variation in the size distribution, which is dominated by the Aitken mode at high latitudes, with an increasing concentration of accumulation particles with decreasing latitude. Considering vertical profiles, the models reproduce the observed peak in total particle concentrations in the upper troposphere due to new particle formation, although modelled peak concentrations tend to be biased high over Europe. Overall, the multi-model-mean data set simulates the global variation of the particle size distribution with a good degree of skill, suggesting that most of the individual global aerosol microphysics models are performing well, although the large model diversity indicates that some models are in poor agreement with the observations. Further work is required to better constrain size-resolved primary and secondary particle number sources, and an improved understanding of nucleation and growth (e.g. the role of nitrate and secondary organics) will improve the fidelity of simulated particle size distributions.
Context.
A challenge with radial-velocity (RV) data is disentangling the origin of signals either due to a planetary companion or to stellar activity. In fact, the existence of a planetary companion ...has been proposed, as well as contested, around the relatively bright, nearby M3.0 V star AD Leo at the same period as the stellar rotation of 2.23 days.
Aims.
We further investigate the nature of this signal. We introduce new CARMENES optical and near-IR RV data and an analysis in combination with archival data taken by HIRES and HARPS, along with more recent data from HARPS-N, GIANO-B, and HPF. Additionally, we address the confusion concerning the binarity of AD Leo.
Methods.
We consider possible correlations between the RVs and various stellar activity indicators accessible with CARMENES. We additionally applied models within a Bayesian framework to determine whether a Keplerian model, a red-noise quasi-periodic model using a Gaussian process, or a mixed model would explain the observed data best. We also exclusively focus on spectral lines potentially associated with stellar activity.
Results.
The CARMENES RV data agree with the previously reported periodicity of 2.23 days, correlate with some activity indicators, and exhibit chromaticity. However, when considering the entire RV data set, we find that a mixed model composed of a stable and a variable component performs best. Moreover, when recomputing the RVs using only spectral lines insensitive to activity, there appears to be some residual power at the period of interest. We therefore conclude that it is not possible to determinedly prove that there is no planet orbiting in synchronization with the stellar rotation given our data, current tools, machinery, and knowledge of how stellar activity affects RVs. We do rule out planets more massive than 27
M
⊕
(=0.084
M
Jup
). Likewise, we exclude any binary companion around AD Leo with M sin
i
greater than 3–6
M
Jup
on orbital periods <14 yr.
PDF
