Enceladus’s long-lived plume of ice grains and water vapor makes accessing oceanic material readily achievable from orbit (around Saturn or Enceladus) and from the moon’s surface. In preparation for ...the National Academies of Sciences, Engineering and Medicine 2023–2032 Planetary Science and Astrobiology Decadal Survey, we investigated four architectures capable of collecting and analyzing plume material from orbit and/or on the surface to address the most pressing questions at Enceladus: Is the subsurface ocean inhabited? Why, or why not? Trades specific to these four architectures were studied to allow an evaluation of the science return with respect to investment. The team found that Orbilander, a mission concept that would first orbit and then land on Enceladus, represented the best balance. Orbilander was thus studied at a higher fidelity, including a more detailed science operations plan during both orbital and landed phases, landing site characterization and selection analyses, and landing procedures. The Orbilander mission concept demonstrates that scientifically compelling but resource-conscious Flagship-class missions can be executed in the next decade to search for life at Enceladus.
Heterostructures of van der Waals bonded layered materials offer unique means to tailor dielectric screening with atomic-layer precision, opening a fertile field of fundamental research. The optical ...analyses used so far have relied on interband spectroscopy. Here we demonstrate how a capping layer of hexagonal boron nitride (hBN) renormalizes the internal structure of excitons in a WSe2 monolayer using intraband transitions. Ultrabroadband terahertz probes sensitively map out the full complex-valued mid-infrared conductivity of the heterostructure after optical injection of 1s A excitons. This approach allows us to trace the energies and line widths of the atom-like 1s–2p transition of optically bright and dark excitons as well as the densities of these quasiparticles. The excitonic resonance red shifts and narrows in the WSe2/hBN heterostructure compared to the bare monolayer. Furthermore, the ultrafast temporal evolution of the mid-infrared response function evidences the formation of optically dark excitons from an initial bright population. Our results provide key insight into the effect of nonlocal screening on electron–hole correlations and open new possibilities of dielectric engineering of van der Waals heterostructures.
•Climate change impacts on leaf rust of wheat are forecasted with a dynamic model.•Sub-models of microclimate and epidemic surfaces manage host-pathogen interaction.•Disease dynamics is simulated on ...3 French sites under 2.6, 4.5, 8.5 RCP scenarios.•Simulated crop-pathogen synchronism promotes disease at the end of the century.•Simulated microclimate at early wheat stages favors future disease development.
Leaf rust is responsible for significant wheat yield losses. Its occurrence and severity have increased in recent years, partly because of warmer climate. It is therefore critical to understand and anticipate the effects of climate change on leaf rust. Direct climate effects and indirect effects via host plants that provide a biophysical environment for disease development were both considered. The coupled STICS-MILA model simulates both crop and pathogen dynamics in a mechanistic way and their interaction is managed by two sub-models: one calculating the microclimate within the canopy and the other converting numbers of spores and lesions to affected surfaces. In this study, STICS-MILA was first calibrated and evaluated using leaf rust severity observed at various sites in France for multiple years. STICS-MILA was then run on three contrasting French sites under 2.6, 4.5 and 8.5 RCP future climate scenarios. Results focused firstly on changes in disease earliness and intensity, secondly on disease dynamics, particularly the synchronism between plant and disease developments, and finally on elementary epidemic processes.
The calibration and evaluation of STICS-MILA revealed a high sensitivity to the initial amount of primary inoculum (a forcing variable in STICS-MILA) and thus the need to properly simulate the summering and overwintering pathogen survival. The simulations in the context of future climate showed a significant change in host-pathogen synchronism: in the far future, according to RCP 4.5 and 8.5 scenarios, disease onset is expected to occur not only with an advance of around one month but also at an earlier developmental stage of wheat crops. This positive effect results from rising temperatures, nevertheless partly counter-balanced during spring by lower wetness frequency. The crop growth accelerates during juvenile stages, providing a greater support for disease development. The resulting microclimate shortens latency periods and increases infection and sporulation efficiencies, thus causing more infectious cycles. An increase of final disease severity is thus forecasted with climate change.
Abstract
LTT 1445 is a hierarchical triple M-dwarf star system located at a distance of 6.86 pc. The primary star LTT 1445A (0.257
M
⊙
) is known to host the transiting planet LTT 1445Ab with an ...orbital period of 5.36 days, making it the second-closest known transiting exoplanet system, and the closest one for which the host is an M dwarf. Using Transiting Exoplanet Survey Satellite data, we present the discovery of a second planet in the LTT 1445 system, with an orbital period of 3.12 days. We combine radial-velocity measurements obtained from the five spectrographs, Echelle Spectrograph for Rocky Exoplanets and Stable Spectroscopic Observations, High Accuracy Radial Velocity Planet Searcher, High-Resolution Echelle Spectrometer, MAROON-X, and Planet Finder Spectrograph to establish that the new world also orbits LTT 1445A. We determine the mass and radius of LTT 1445Ab to be 2.87 ± 0.25
M
⊕
and
1.304
−
0.060
+
0.067
R
⊕
, consistent with an Earth-like composition. For the newly discovered LTT 1445Ac, we measure a mass of
1.54
−
0.19
+
0.20
M
⊕
and a minimum radius of 1.15
R
⊕
, but we cannot determine the radius directly as the signal-to-noise ratio of our light curve permits both grazing and nongrazing configurations. Using MEarth photometry and ground-based spectroscopy, we establish that star C (0.161
M
⊙
) is likely the source of the 1.4 day rotation period, and star B (0.215
M
⊙
) has a likely rotation period of 6.7 days. We estimate a probable rotation period of 85 days for LTT 1445A. Thus, this triple M-dwarf system appears to be in a special evolutionary stage where the most massive M dwarf has spun down, the intermediate mass M dwarf is in the process of spinning down, while the least massive stellar component has not yet begun to spin down.
Hypoxia is a hallmark of cancer that is strongly associated with invasion, metastasis, resistance to therapy and poor clinical outcome. Tumour hypoxia affects immune responses and promotes the ...accumulation of macrophages in the tumour microenvironment. However, the signals linking tumour hypoxia to tumour-associated macrophage recruitment and tumour promotion are incompletely understood. Here we show that the damage-associated molecular pattern High-Mobility Group Box 1 protein (HMGB1) is released by melanoma tumour cells as a consequence of hypoxia and promotes M2-like tumour-associated macrophage accumulation and an IL-10 rich milieu within the tumour. Furthermore, we demonstrate that HMGB1 drives IL-10 production in M2-like macrophages by selectively signalling through the Receptor for Advanced Glycation End products (RAGE). Finally, we show that HMGB1 has an important role in murine B16 melanoma growth and metastasis, whereas in humans its serum concentration is significantly increased in metastatic melanoma. Collectively, our findings identify a mechanism by which hypoxia affects tumour growth and metastasis in melanoma and depict HMGB1 as a potential therapeutic target.
Implementation science methods and a theory-driven approach can enhance the understanding of whether, how, and why integrated care for frail older adults is successful in practice. In this study, we ...aimed to perform a contextual analysis, develop a logic model, and select preliminary implementation strategies for an integrated care model in newly created information and advice centers for older adults in Canton Basel-Landschaft, Switzerland.
We conducted a contextual analysis to determine factors which may influence the integrated care model and implementation strategies needed. A logic model depicting the overall program theory, including inputs, core components, outputs and outcomes, was designed using a deductive approach, and included stakeholders' feedback and preliminary implementation strategies.
Contextual factors were identified (e.g., lack of integrated care regulations, existing community services, and a care pathway needed). Core components of the care model include screening, referral, assessment, care plan creation and coordination, and follow-up. Outcomes included person-centred coordinated care experiences, hospitalization rate and symptom burden, among others. Implementation strategies (e.g., nurse training and co-developing educational materials) were proposed to facilitate care model adoption.
Contextual understanding and a clear logic model should enhance the potential for successful implementation of the integrated care model.
Shotgun metagenomics using next generation sequencing (NGS) is a promising technique to analyze both DNA and RNA microbial material from patient samples. Mostly used in a research setting, it is now ...increasingly being used in the clinical realm as well, notably to support diagnosis of viral infections, thereby calling for quality control and the implementation of ring trials (RT) to benchmark pipelines and ensure comparable results. The Swiss NGS clinical virology community therefore decided to conduct a RT in 2018, in order to benchmark current metagenomic workflows used at Swiss clinical virology laboratories, and thereby contribute to the definition of common best practices. The RT consisted of two parts (increments), in order to disentangle the variability arising from the experimental compared to the bioinformatics parts of the laboratory pipeline. In addition, the RT was also designed to assess the impact of databases compared to bioinformatics algorithms on the final results, by asking participants to perform the bioinformatics analysis with a common database, in addition to using their own in-house database. Five laboratories participated in the RT (seven pipelines were tested). We observed that the algorithms had a stronger impact on the overall performance than the choice of the reference database. Our results also suggest that differences in sample preparation can lead to significant differences in the performance, and that laboratories should aim for at least 5-10 Mio reads per sample and use depth of coverage in addition to other interpretation metrics such as the percent of coverage. Performance was generally lower when increasing the number of viruses per sample. The lessons learned from this pilot study will be useful for the development of larger-scale RTs to serve as regular quality control tests for laboratories performing NGS analyses of viruses in a clinical setting.
With the observation of high-energy astrophysical neutrinos by the IceCube Neutrino Observatory, interest has risen in models of PeV-mass decaying dark matter particles to explain the observed flux. ...We present two dedicated experimental analyses to test this hypothesis. One analysis uses 6 years of IceCube data focusing on muon neutrino ‘track’ events from the Northern Hemisphere, while the second analysis uses 2 years of ‘cascade’ events from the full sky. Known background components and the hypothetical flux from unstable dark matter are fitted to the experimental data. Since no significant excess is observed in either analysis, lower limits on the lifetime of dark matter particles are derived: we obtain the strongest constraint to date, excluding lifetimes shorter than
10
28
s
at 90% CL for dark matter masses above
10
TeV
.
In spring 2021, an increasing number of infections was observed caused by the hitherto rarely described SARS-CoV-2 variant A.27 in south-west Germany. From December 2020 to June 2021 this lineage has ...been detected in 31 countries. Phylogeographic analyses of A.27 sequences obtained from national and international databases reveal a global spread of this lineage through multiple introductions from its inferred origin in Western Africa. Variant A.27 is characterized by a mutational pattern in the spike gene that includes the L18F, L452R and N501Y spike amino acid substitutions found in various variants of concern but lacks the globally dominant D614G. Neutralization assays demonstrate an escape of A.27 from convalescent and vaccine-elicited antibody-mediated immunity. Moreover, the therapeutic monoclonal antibody Bamlanivimab and partially the REGN-COV2 cocktail fail to block infection by A.27. Our data emphasize the need for continued global monitoring of novel lineages because of the independent evolution of new escape mutations.
ABSTRACT We report the discovery of Kepler-432b, a giant planet ( , ) transiting an evolved star ( ) with an orbital period of days. Radial velocities (RVs) reveal that Kepler-432b orbits its parent ...star with an eccentricity of , which we also measure independently with asterodensity profiling (AP; ), thereby confirming the validity of AP on this particular evolved star. The well-determined planetary properties and unusually large mass also make this planet an important benchmark for theoretical models of super-Jupiter formation. Long-term RV monitoring detected the presence of a non-transiting outer planet (Kepler-432c; , days), and adaptive optics imaging revealed a nearby ( ), faint companion (Kepler-432B) that is a physically bound M dwarf. The host star exhibits high signal-to-noise ratio asteroseismic oscillations, which enable precise measurements of the stellar mass, radius, and age. Analysis of the rotational splitting of the oscillation modes additionally reveals the stellar spin axis to be nearly edge-on, which suggests that the stellar spin is likely well aligned with the orbit of the transiting planet. Despite its long period, the obliquity of the 52.5 day orbit may have been shaped by star-planet interaction in a manner similar to hot Jupiter systems, and we present observational and theoretical evidence to support this scenario. Finally, as a short-period outlier among giant planets orbiting giant stars, study of Kepler-432b may help explain the distribution of massive planets orbiting giant stars interior to 1 AU.