Fitting the Viking lander surface pressure cycle with a Mars General Circulation Model

We present a systematic attempt to fit the Viking lander surface pressure cycle using a Mars General Circulation Model, MarsWRF. Following the earlier study by Wood and Paige (1992) using a one-dimensional model, high-precision fitting was achieved by tuning five time-independent parameters: the albedo and emissivity of the seasonal caps of the two hemispheres and the total CO_2 inventory in the atmosphere frost system. We used a linear iterative method to derive the best fit parameters: albedo of the northern cap = 0.795, emissivity of the northern cap = 0.485, albedo of the southern cap = 0.461, emissivity of the southern cap = 0.785, and total CO_2 mass = 2.83 × 10^(16) kg. If these parameters are used in MarsWRF, the smoothed surface pressure residual at the VL1 site is always smaller than several Pascal through a year. As in other similar studies, the best fit parameters do not match well with the current estimation of the seasonal cap radiative properties, suggesting that important physics contributing to the energy balance not explicitly included in MarsWRF have been effectively aliased into the derived parameters. One such effect is likely the variation of thermal conductivity with depth in the regolith due to the presence of water ice. Including such a parameterization in the fitting process improves the reasonableness of the best fit cap properties, mostly improving the emissivities. The conductivities required in the north to provide the best fit are higher than those required in the south. A completely physically reasonable set of fit parameters could still not be attained. Like all prior published GCM simulations, none of the cases considered are capable of predicting a residual southern CO_2 cap

Probabilistic state estimation in regimes of nonlinear error growth

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Earth, Atmospheric, and Planetary Sciences, 2005.Includes bibliographical references (p. 273-286).State estimation, or data assimilation as it is often called, is a key component of numerical weather prediction (NWP). Nearly all implementable methods of state estimation suitable for NWP are forced to assume that errors remain in regimes of linear error growth and retain distributions of Gaussian uncertainty, yet nonlinear systems like the atmosphere can readily allow regimes of nonlinear error growth and, in turn, produce distributions of non- Gaussian uncertainty. State-of-the-art, ensemble-based methods of state estimation suitable for NWP are examined to gauge the consequences and relevance of violating the linear error growth assumption. For quite generic sources of non-Gaussian uncertainty, the methods are observed to fail, as they must, and the obtained analyses become probabilistically unreliable before becoming inaccurate. The mispositioning of coherent features is identified as a specific, geophysically relevant source of non-Gaussian uncertainty that can easily cause the state-of-the-art methods of state estimation to fail. However, an understanding of relevant phenomenology sometimes allows these same methods to remain successful owing to an available redefinition of the involved errors. The redefinition is phrased as an alternative error model. It is recognized and exploited that non-Gaussian additive Eulerian errors can come from Gaussian Lagrangian position errors. A two-step, augmented state vector approach is developed that is suitable for use with coherent features and that relies only on implementable methods of state estimation.(cont.) By combining the dual Eulerian and Lagrangian state information into one vector, an ensemble can approximate their covariance, thus allowing each component's uncertainty to be reduced. The first step of the two-step approach reduces the feature position errors in an effort to render the residual additive errors Gaussian, thereby allowing the second step of an implementable state estimation method to proceed successfully. Philosophically, the two-step approach uses physical knowledge of the problem (as phrased by the error model) to compensate for neglected important non-Gaussian uncertainty structure in the state estimation process. The proposed two-step approach successfully allows use of implementable methods of state estimation to obtain probabilistically reliable analyses in regimes of nonlinear error growth, something unavailable using current standards.by W. Gregory Lawson.Ph.D

Outer Membrane Vesicles of a Human Commensal Mediate Immune Regulation and Disease Protection

Commensal bacteria impact host health and immunity through various mechanisms, including the production of immunomodulatory molecules. Bacteroides fragilis produces a capsular polysaccharide (PSA), which induces regulatory T cells and mucosal tolerance. However, unlike pathogens, which employ secretion systems, the mechanisms by which commensal bacteria deliver molecules to the host remain unknown. We reveal that Bacteroides fragilis releases PSA in outer membrane vesicles (OMVs) that induce immunomodulatory effects and prevent experimental colitis. Dendritic cells (DCs) sense OMV-associated PSA through TLR2, resulting in enhanced regulatory T cells and anti-inflammatory cytokine production. OMV-induced signaling in DCs requires growth arrest and DNA-damage-inducible protein (Gadd45α). DCs treated with PSA-containing OMVs prevent experimental colitis, whereas Gadd45α^(−/−) DCs are unable to promote regulatory T cell responses or suppress proinflammatory cytokine production and host pathology. These findings demonstrate that OMV-mediated delivery of a commensal molecule prevents disease, uncovering a mechanism of interkingdom communication between the microbiota and mammals

Geometry of Deformations of Relativistic Membranes

A kinematical description of infinitesimal deformations of the worldsheet spanned in spacetime by a relativistic membrane is presented. This provides a framework for obtaining both the classical equations of motion and the equations describing infinitesimal deformations about solutions of these equations when the action describing the dynamics of this membrane is constructed using {\it any} local geometrical worldsheet scalars. As examples, we consider a Nambu membrane, and an action quadratic in the extrinsic curvature of the worldsheet.Comment: 20 pages, Plain Tex, sign errors corrected, many new references added. To appear in Physical Review

Surface magnetic fields on two accreting T Tauri stars: CV Cha and CR Cha

We have produced brightness and magnetic field maps of the surfaces of CV Cha and CR Cha: two actively accreting G and K-type T Tauri stars in the Chamaeleon I star-forming cloud with ages of 3-5 Myr. Our magnetic field maps show evidence for strong, complex multi-polar fields similar to those obtained for young rapidly rotating main sequence stars. Brightness maps indicate the presence of dark polar caps and low latitude spots -- these brightness maps are very similar to those obtained for other pre-main sequence and rapidly rotating main sequence stars. Only two other classical T Tauri stars have been studied using similar techniques so far: V2129 Oph and BP Tau. CV Cha and CR Cha show magnetic field patterns that are significantly more complex than those recovered for BP Tau, a fully convective T Tauri star. We discuss possible reasons for this difference and suggest that the complexity of the stellar magnetic field is related to the convection zone; with more complex fields being found in T Tauri stars with radiative cores (V2129 Oph, CV Cha and CR Cha). However, it is clearly necessary to conduct magnetic field studies of T Tauri star systems, exploring a wide range of stellar parameters in order to establish how they affect magnetic field generation, and thus how these magnetic fields are likely to affect the evolution of T Tauri star systems as they approach the main sequence.Comment: Accepted for publication by MNRAS: 15 pages, 11 figure

Gaining access to agency and structure in industrial marketing theory : a critical pluralist approach.

This article is concerned with gaining greater insight into the interplay between agency and structure in industrial marketing (IM) scholarship. The article’s intent is to embed Midgley’s notion of critical pluralism within this endeavour. The article commends the movement towards increased deployment of critical realism, but cautions against the dangers of creating further atomism in marketing theory by generating another paradigm of thought with strongly defended boundaries, impervious to outside influence. The article advances a case for critical pluralism within IM scholarship and offers a three-dimensional (theoretical, methodological and methodical) framework to aid this. The discussion demonstrates how critical pluralism can be deployed to gain insights into agency and structure using a number of ‘integrative’ theoretical perspectives

Radial Velocity Discovery of an Eccentric Jovian World Orbiting at 18 au

Based on two decades of radial velocity (RV) observations using Keck/High Resolution Echelle Spectrometer (HIRES) and McDonald/Tull, and more recent observations using the Automated Planet Finder, we found that the nearby star HR 5183 (HD 120066) hosts a 3 minimum mass planet with an orbital period of yr. The orbit is highly eccentric (e ≃ 0.84), shuttling the planet from within the orbit of Jupiter to beyond the orbit of Neptune. Our careful survey design enabled high cadence observations before, during, and after the planet\u27s periastron passage, yielding precise orbital parameter constraints. We searched for stellar or planetary companions that could have excited the planet\u27s eccentricity, but found no candidates, potentially implying that the perturber was ejected from the system. We did identify a bound stellar companion more than 15,000 au from the primary, but reasoned that it is currently too widely separated to have an appreciable effect on HR 5183 b. Because HR 5183 b\u27s wide orbit takes it more than 30 au (1\u27\u27) from its star, we also explored the potential of complimentary studies with direct imaging or stellar astrometry. We found that a Gaia detection is very likely, and that imaging at 10 μm is a promising avenue. This discovery highlights the value of long-baseline RV surveys for discovering and characterizing long-period, eccentric Jovian planets. This population may offer important insights into the dynamical evolution of planetary systems containing multiple massive planets

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.)

Genotyping of Human Lice Suggests Multiple Emergences of Body Lice from Local Head Louse Populations

While being phenotypically and physiologically different, human head and body lice are indistinguishable based on mitochondrial and nuclear genes. As protein-coding genes are too conserved to provide significant genetic diversity, we performed strain-typing of a large collection of human head and body lice using variable intergenic spacer sequences. Ninety-seven human lice were classified into ninety-six genotypes based on four intergenic spacer sequences. Genotypic and phylogenetic analyses using these sequences suggested that human head and body lice are still indistinguishable. We hypothesized that the phenotypic and physiological differences between human head and body lice are controlled by very limited mutations. Under conditions of poor hygiene, head lice can propagate very quickly. Some of them will colonize clothing, producing a body louse variant (genetic or phenetic), which can lead to an epidemic. Lice collected in Rwanda and Burundi, where outbreaks of louse-borne diseases have been recently reported, are grouped tightly into a cluster and those collected from homeless people in France were also grouped into a cluster with lice collected in French non-homeless people. Our strain-typing approach based on highly variable intergenic spacers may be helpful to elucidate louse evolution and to survey louse-borne diseases