Thousands of transiting exoplanets have been discovered, but spectral analysis of their atmospheres has so far been dominated by a small number of exoplanets and data spanning relatively narrow ...wavelength ranges (such as 1.1-1.7 micrometres). Recent studies show that some hot-Jupiter exoplanets have much weaker water absorption features in their near-infrared spectra than predicted. The low amplitude of water signatures could be explained by very low water abundances, which may be a sign that water was depleted in the protoplanetary disk at the planet's formation location, but it is unclear whether this level of depletion can actually occur. Alternatively, these weak signals could be the result of obscuration by clouds or hazes, as found in some optical spectra. Here we report results from a comparative study of ten hot Jupiters covering the wavelength range 0.3-5 micrometres, which allows us to resolve both the optical scattering and infrared molecular absorption spectroscopically. Our results reveal a diverse group of hot Jupiters that exhibit a continuum from clear to cloudy atmospheres. We find that the difference between the planetary radius measured at optical and infrared wavelengths is an effective metric for distinguishing different atmosphere types. The difference correlates with the spectral strength of water, so that strong water absorption lines are seen in clear-atmosphere planets and the weakest features are associated with clouds and hazes. This result strongly suggests that primordial water depletion during formation is unlikely and that clouds and hazes are the cause of weaker spectral signatures.
Most transiting planets orbit very close to their parent star, causing strong tidal forces between the two bodies. Tidal interaction can modify the dynamics of the system through orbital alignment, ...circularization, synchronization and orbital decay by exchange of angular moment. Evidence for tidal circularization in close–in giant planet is well known. Here, we review the evidence for excess rotation of the parent stars due to the pull of tidal forces towards spin–orbit synchronization. We find suggestive empirical evidence for such a process in the present sample of transiting planetary systems. The corresponding angular momentum exchange would imply that some planets have spiralled towards their star by substantial amounts since the dissipation of the protoplanetary disc. We suggest that this could quantitatively account for the observed mass–period relation of close–in gas giants. We discuss how this scenario can be further tested and point out some consequences for theoretical studies of tidal interactions and for the detection and confirmation of transiting planets from radial velocity and photometric surveys.
High-definition transcriptomic studies through single-cell RNA sequencing (scRNA-Seq) have revealed the heterogeneity and functionality of the various microenvironments across numerous solid tumors. ...Those pioneer studies have highlighted different cellular signatures correlated with clinical response to immune checkpoint inhibitors. scRNA-Seq offers also a unique opportunity to unravel the intimate heterogeneity of the ecosystems across different lymphoma entities. In this review, we will first cover the basics and future developments of the technology, and we will discuss its input in the field of translational lymphoma research, from determination of cell-of-origin and functional diversity, to monitoring of anti-cancer targeted drugs response and toxicities, and how new improvements in both data collection and interpretation will further foster precision medicine in the upcoming years.
Hot Jupiters, due to the proximity to their parent stars, are subjected to a strong irradiating flux that governs their radiative and dynamical properties. We compute a suite of three-dimensional ...circulation models with dual-band radiative transfer, exploring a relevant range of irradiation temperatures, both with and without temperature inversions. Our simulations indicate that the efficiency of redistribution is primarily governed by the ratio of advective to radiative timescales. Models with temperature inversions display a higher day-night contrast due to the deposition of starlight at higher altitudes, but we find this opacity-driven effect to be secondary compared to the effects of irradiation. The total dissipated Ohmic power increases steeply with the strength of the irradiating flux and the dissipation depth recedes into the atmosphere, favoring radius inflation in the most irradiated objects. A survey of the existing data, as well as the inferences made from them, reveals that our results are broadly consistent with the observational trends.
Abstract
The momentum of scRNA-seq datasets prompts for simple and powerful tools exploring their meaningful signatures. Here we present Single-Cell_Signature_Explorer ...(https://sites.google.com/site/fredsoftwares/products/single-cell-signature-explorer), the first method for qualitative and high-throughput scoring of any gene set-based signature at the single cell level and its visualization using t-SNE or UMAP. By scanning datasets for single or combined signatures, it rapidly maps any multi-gene feature, exemplified here with signatures of cell lineages, biological hallmarks and metabolic pathways in large scRNAseq datasets of human PBMC, melanoma, lung cancer and adult testis.
Ibrutinib, an irreversible Bruton Tyrosine Kinase (BTK) inhibitor, has revolutionized Chronic Lymphocytic Leukemia (CLL) treatment, but resistances to ibrutinib have emerged, whether related or not ...to BTK mutations. Patterns of CLL evolution under ibrutinib therapy are well characterized for the leukemic cells but not for their microenvironment.
Here, we addressed this question at the single cell level of both transcriptome and immune-phenotype. The PBMCs from a CLL patient were monitored during ibrutinib treatment using Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-Seq) technology.
This unveiled that the short clinical relapse of this patient driven by BTK mutation is associated with intraclonal heterogeneity in B leukemic cells and up-regulation of common signaling pathways induced by ibrutinib in both B leukemic cells and immune cells. This approach also pinpointed a subset of leukemic cells present before treatment and highly enriched during progression under ibrutinib. These latter exhibit an original gene signature including up-regulated BCR, MYC-activated, and other targetable pathways. Meanwhile, although ibrutinib differentially affected the exhaustion of T lymphocytes, this treatment enhanced the T cell cytotoxicity even during disease progression.
These results could open new alternative of therapeutic strategies for ibrutinib-refractory CLL patients, based on immunotherapy or targeting B leukemic cells themselves.
Preeclampsia (PE) is a multifactorial pregnancy disease, characterized by new-onset gestational hypertension with (or without) proteinuria or end-organ failure, exclusively observed in humans. It is ...a leading cause of maternal morbidity affecting 3–7% of pregnant women worldwide. PE pathophysiology could result from abnormal placentation due to a defective trophoblastic invasion and an impaired remodeling of uterine spiral arteries, leading to a poor adaptation of utero-placental circulation. This would be associated with hypoxia/reoxygenation phenomena, oxygen gradient fluctuations, altered antioxidant capacity, oxidative stress, and reduced nitric oxide (NO) bioavailability. This results in part from the reaction of NO with the radical anion superoxide (O2•−), which produces peroxynitrite ONOO-, a powerful pro-oxidant and inflammatory agent. Another mechanism is the progressive inhibition of the placental endothelial nitric oxide synthase (eNOS) by oxidative stress, which results in eNOS uncoupling via several events such as a depletion of the eNOS substrate L-arginine due to increased arginase activity, an oxidation of the eNOS cofactor tetrahydrobiopterin (BH4), or eNOS post-translational modifications (for instance by S-glutathionylation). The uncoupling of eNOS triggers a switch of its activity from a NO-producing enzyme to a NADPH oxidase-like system generating O2•−, thereby potentiating ROS production and oxidative stress. Moreover, in PE placentas, eNOS could be post-translationally modified by lipid peroxidation-derived aldehydes such as 4-oxononenal (ONE) a highly bioreactive agent, able to inhibit eNOS activity and NO production. This review summarizes the dysfunction of placental eNOS evoked by oxidative stress and lipid peroxidation products, and the potential consequences on PE pathogenesis.
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•Physiological ROS production is enhanced during pregnancy.•eNOS is one of the main target of oxidative stress in PE placenta.•eNOS is S-glutathionylated in PE placentas.•eNOS is modified by lipid oxidation products in PE placentas.
Since the discovery of short-period exoplanets a decade ago, photometric surveys have been recognized as a feasible method to detect transiting hot Jupiters. Many transit surveys are now underway, ...with instruments ranging from 10-cm cameras to the Hubble Space Telescope. However, the results of these surveys have been much below the expected capacity, estimated in the dozens of detections per year. One of the reasons is the presence of systematics (‘red noise’) in photometric time-series. In general, yield predictions assume uncorrelated noise (‘white noise’). In this paper, we show that the effect of red noise on the detection threshold and the expected yields cannot be neglected in typical ground-based surveys. We develop a simple method to determine the effect of red noise on photometric planetary transit detections. This method can be applied to determine detection thresholds for transit surveys. We show that the detection threshold in the presence of systematics can be much higher than that with the assumption of white noise, and obeys a different dependence on magnitude, orbital period and the parameters of the survey. Our method can also be used to estimate the significance level of a planetary transit candidate (to select promising candidates for spectroscopic follow-up). We apply our method to the OGLE planetary transit search, and show that it provides a reliable description of the actual detection threshold with real correlated noise. We point out in what way the presence of red noise could be at least partly responsible for the dearth of transiting planet detections from existing surveys, and examine some possible adaptations in survey planning and strategy. Finally, we estimate the photometric stability necessary to the detection of transiting ‘hot Neptunes’.
This phase 1 trial was aimed to determine the safety, pharmacokinetics, and preliminary clinical activity of CYL-02, a nonviral gene therapy product that sensitizes pancreatic cancer cells to ...chemotherapy. CYL-02 was administrated using endoscopic ultrasound in 22 patients with pancreatic cancer that concomitantly received chemotherapy (gemcitabine). The maximum-tolerated dose (MTD) exceeded the maximal feasible dose of CYL-02 and was not identified. Treatment-related toxicities were mild, without serious adverse events. Pharmacokinetic analysis revealed a dose-dependent increase in CYL-02 DNA exposure in blood and tumors, while therapeutic RNAs were detected in tumors. No objective response was observed, but nine patients showed stable disease up to 6 months following treatment and two of these patients experienced long-term survival. Panels of plasmatic microRNAs and proteins were identified as predictive of gene therapy efficacy. We demonstrate that CYL-02 nonviral gene therapy has a favorable safety profile and is well tolerated in patients. We characterize CYL-02 biodistribution and demonstrate therapeutic gene expression in tumors. Treated patients experienced stability of disease and predictive biomarkers of response to treatment were identified. These promising results warrant further evaluation in phase 2 clinical trial.
CoRoT-7 is an 11 th magnitude K-star whose light curve shows transits with a depth of 0.3 mmag and a period of 0.854 d, superimposed on variability at the 1 per cent level, due to the modulation of ...evolving active regions with the star's 23-d rotation period. In this paper, we revisit the published HARPS radial-velocity (RV) measurements of the object, which were previously used to estimate the companion mass, but have been the subject of ongoing debate.
We build a realistic model of the star's activity during the HARPS observations, by fitting simultaneously the linewidth (as measured by the width of the cross-correlation function) and the line bisector, and use it to evaluate the contribution of activity to the RV variations. The data show clear evidence of errors above the level of the formal uncertainties, which are accounted for neither by activity nor by any plausible planet model and which increase rapidly with a decreasing signal-to-noise ratio (S/N) of the spectra. We cite evidence of similar systematics in mid-S/N spectra of other targets obtained with HARPS and other high-precision RV spectrographs, and discuss possible sources. Allowing for these, we re-evaluate the semi-amplitude of the CoRoT-7b signal, finding Kb
= 1.6 ± 1.3 m s−1, a tentative detection with a much reduced significance (1.2σ) compared to previous estimates. We also argue that the combined presence of activity and additional errors precludes a meaningful search for additional low-mass companions, despite previous claims to the contrary.
Taken at face value, our analysis points to a lower density for CoRoT-7b, the 1σ mass range spanning 1-4 M ⊕ and allowing for a wide range of bulk compositions. In particular, an ice-rich composition is compatible with the RV constraints. More generally, this study highlights the importance of a realistic treatment of both activity and uncertainties, particularly in the medium S/N regime, which applies to most small planet candidates from CoRoT and Kepler.
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