Gravity Waves in the Sun

We present numerical simulations of penetrative convection and gravity wave excitation in the Sun. Gravity waves are self-consistently generated by a convective zone overlying a radiative interior. We produce power spectra for gravity waves in the radiative region as well as estimates for the energy flux of gravity waves below the convection zone. We calculate a peak energy flux in waves below the convection zone to be three orders of magnitude smaller than previous estimates for m=1. The simulations show that the linear dispersion relation is a good approximation only deep below the convective-radiative boundary. Both low frequency propagating gravity waves as well as higher frequency standing modes are generated; although we find that convection does not continually drive the standing g-mode frequencies.Comment: 22 pages, 14 figures, submitted to MNRA

Grain boundary pinning and glassy dynamics in stripe phases

We study numerically and analytically the coarsening of stripe phases in two spatial dimensions, and show that transient configurations do not achieve long ranged orientational order but rather evolve into glassy configurations with very slow dynamics. In the absence of thermal fluctuations, defects such as grain boundaries become pinned in an effective periodic potential that is induced by the underlying periodicity of the stripe pattern itself. Pinning arises without quenched disorder from the non-adiabatic coupling between the slowly varying envelope of the order parameter around a defect, and its fast variation over the stripe wavelength. The characteristic size of ordered domains asymptotes to a finite value $R_g \sim \lambda_0\ \epsilon^{-1/2}\exp(|a|/\sqrt{\epsilon})$, where$\epsilon\ll 1$is the dimensionless distance away from threshold,$\lambda_0$the stripe wavelength, and$a$ a constant of order unity. Random fluctuations allow defect motion to resume until a new characteristic scale is reached, function of the intensity of the fluctuations. We finally discuss the relationship between defect pinning and the coarsening laws obtained in the intermediate time regime.Comment: 17 pages, 8 figures. Corrected version with one new figur

DEVELOP EUROGOOS MARINE CLIMATE SERVICE WITH A SEAMLESS EARTH SYSTEM APPROACH

The ocean is an important pathway to a low-carbon and climate resilient society, e.g. in areas of blue carbon, green shipping, offshore renewable energy, aquaculture, fi shery and coastal adaptation. Currently, 26 EU member states have made their National Adaptation Strategy (NAS) and/or National Strategy Plan (NAP) which needs a strong climate information service. European Global Ocean Observing System (EuroGOOS) has a strategy to expand existing operational marine service to climate change in 2020-2030. As focal points of national marine, climate and/or weather services, ROOS (Regional Sea Operational Oceanographic System) members have extensive experiences in working with citizens, stakeholders and decision-makers at national, regional and municipality levels. This paper will review current marine climate service capacity in ROOS members, identify gaps in modelling, products and service, and propose a seamless earth system approach for developing EuroGOOS and ROOS marine climate service capacities.Versión del edito

Acquired Resistance to KRAS (G12C) Inhibition in Cancer

BACKGROUND: Clinical trials of the KRAS inhibitors adagrasib and sotorasib have shown promising activity in cancers harboring KRAS glycine-to-cysteine amino acid substitutions at codon 12 (KRAS(G12C)). The mechanisms of acquired resistance to these therapies are currently unknown. METHODS: Among patients with KRAS(G12C) -mutant cancers treated with adagrasib monotherapy, we performed genomic and histologic analyses that compared pretreatment samples with those obtained after the development of resistance. Cell-based experiments were conducted to study mutations that confer resistance to KRAS(G12C) inhibitors. RESULTS: A total of 38 patients were included in this study: 27 with non-small-cell lung cancer, 10 with colorectal cancer, and 1 with appendiceal cancer. Putative mechanisms of resistance to adagrasib were detected in 17 patients (45% of the cohort), of whom 7 (18% of the cohort) had multiple coincident mechanisms. Acquired KRAS alterations included G12D/R/V/W, G13D, Q61H, R68S, H95D/Q/R, Y96C, and high-level amplification of the KRAS(G12C) allele. Acquired bypass mechanisms of resistance included MET amplification; activating mutations in NRAS, BRAF, MAP2K1, and RET; oncogenic fusions involving ALK, RET, BRAF, RAF1, and FGFR3; and loss-of-function mutations in NF1 and PTEN. In two of nine patients with lung adenocarcinoma for whom paired tissue-biopsy samples were available, histologic transformation to squamous-cell carcinoma was observed without identification of any other resistance mechanisms. Using an in vitro deep mutational scanning screen, we systematically defined the landscape of KRAS mutations that confer resistance to KRAS(G12C) inhibitors. CONCLUSIONS: Diverse genomic and histologic mechanisms impart resistance to covalent KRAS(G12C) inhibitors, and new therapeutic strategies are required to delay and overcome this drug resistance in patients with cancer. (Funded by Mirati Therapeutics and others; ClinicalTrials.gov number, NCT03785249.)

Diversity of Cl− Channels

Cl− channels are widely found anion pores that are regulated by a variety of signals and that play various roles. On the basis of molecular biologic findings, ligand-gated Cl− channels in synapses, cystic fibrosis transmembrane conductors (CFTRs) and ClC channel types have been established, followed by bestrophin and possibly by tweety, which encode Ca2+-activated Cl− channels. The ClC family has been shown to possess a variety of functions, including stabilization of membrane potential, excitation, cellvolume regulation, fluid transport, protein degradation in endosomal vesicles and possibly cell growth. The molecular structure of Cl− channel types varies from 1 to 12 transmembrane segments. By means of computer-based prediction, functional Cl− channels have been synthesized artificially, revealing that many possible ion pores are hidden in channel, transporter or unidentified hydrophobic membrane proteins. Thus, novel Cl−-conducting pores may be occasionally discovered, and evidence from molecular biologic studies will clarify their physiologic and pathophysiologic roles