Superforms in six-dimensional superspace

Indexación: Web of ScienceWe investigate the complex of differential forms in curved, six-dimensional, N = (1, 0) superspace. The superconformal group acts on this complex by super-Weyl transformations. An ambi-twistor-like representation of a second conformal group arises on a pure spinor subspace of the cotangent space. The p-forms are defined by super-Weylcovariant tensor fields on this pure spinor subspace. The on-shell dynamics of such fields is superconformal. We construct the superspace de Rham complex by successively obstructing the closure of forms. We then extend the analysis to composite forms obtained by wedging together forms of lower degree. Finally, we comment on applications to integration in curved superspace and propose a superspace formulation of the abelian limit of the non-abelian tensor hierarchy of N = (1, 0) superconformal models.http://link.springer.com/article/10.1007%2FJHEP05%282016%29016#aboutarticl

Oncogenic BRAF, unrestrained by TGFβ-receptor signalling, drives right-sided colonic tumorigenesis.

Right-sided (proximal) colorectal cancer (CRC) has a poor prognosis and a distinct mutational profile, characterized by oncogenic BRAF mutations and aberrations in mismatch repair and TGFβ signalling. Here, we describe a mouse model of right-sided colon cancer driven by oncogenic BRAF and loss of epithelial TGFβ-receptor signalling. The proximal colonic tumours that develop in this model exhibit a foetal-like progenitor phenotype (Ly6a/Sca1+) and, importantly, lack expression of Lgr5 and its associated intestinal stem cell signature. These features are recapitulated in human BRAF-mutant, right-sided CRCs and represent fundamental differences between left- and right-sided disease. Microbial-driven inflammation supports the initiation and progression of these tumours with foetal-like characteristics, consistent with their predilection for the microbe-rich right colon and their antibiotic sensitivity. While MAPK-pathway activating mutations drive this foetal-like signature via ERK-dependent activation of the transcriptional coactivator YAP, the same foetal-like transcriptional programs are also initiated by inflammation in a MAPK-independent manner. Importantly, in both contexts, epithelial TGFβ-receptor signalling is instrumental in suppressing the tumorigenic potential of these foetal-like progenitor cells

NOTUM from Apc-mutant cells biases clonal competition to initiate cancer

The tumour suppressor APC is the most commonly mutated gene in colorectal cancer. Loss of Apc in intestinal stem cells drives the formation of adenomas in mice via increased WNT signalling1, but reduced secretion of WNT ligands increases the ability of Apc-mutant intestinal stem cells to colonize a crypt (known as fixation)2. Here we investigated how Apc-mutant cells gain a clonal advantage over wild-type counterparts to achieve fixation. We found that Apc-mutant cells are enriched for transcripts that encode several secreted WNT antagonists, with Notum being the most highly expressed. Conditioned medium from Apc-mutant cells suppressed the growth of wild-type organoids in a NOTUM-dependent manner. Furthermore, NOTUM-secreting Apc-mutant clones actively inhibited the proliferation of surrounding wild-type crypt cells and drove their differentiation, thereby outcompeting crypt cells from the niche. Genetic or pharmacological inhibition of NOTUM abrogated the ability of Apc-mutant cells to expand and form intestinal adenomas. We identify NOTUM as a key mediator during the early stages of mutation fixation that can be targeted to restore wild-type cell competitiveness and provide preventative strategies for people at a high risk of developing colorectal cancer

Optimization of the Observing Cadence for the Rubin Observatory Legacy Survey of Space and Time: A Pioneering Process of Community-focused Experimental Design

Vera C. Rubin Observatory is a ground-based astronomical facility under construction, a joint project of the National Science Foundation and the U.S. Department of Energy, designed to conduct a multipurpose 10 yr optical survey of the Southern Hemisphere sky: the Legacy Survey of Space and Time. Significant flexibility in survey strategy remains within the constraints imposed by the core science goals of probing dark energy and dark matter, cataloging the solar system, exploring the transient optical sky, and mapping the Milky Way. The survey's massive data throughput will be transformational for many other astrophysics domains and Rubin's data access policy sets the stage for a huge community of potential users. To ensure that the survey science potential is maximized while serving as broad a community as possible, Rubin Observatory has involved the scientific community at large in the process of setting and refining the details of the observing strategy. The motivation, history, and decision-making process of this strategy optimization are detailed in this paper, giving context to the science-driven proposals and recommendations for the survey strategy included in this Focus Issue

The maize root stem cell niche: a partnership between two sister cell populations

Using transcript profile analysis, we explored the nature of the stem cell niche in roots of maize (Zea mays). Toward assessing a role for specific genes in the establishment and maintenance of the niche, we perturbed the niche and simultaneously monitored the spatial expression patterns of genes hypothesized as essential. Our results allow us to quantify and localize gene activities to specific portions of the niche: to the quiescent center (QC) or the proximal meristem (PM), or to both. The data point to molecular, biochemical and physiological processes associated with the specification and maintenance of the niche, and include reduced expression of metabolism-, redox- and certain cell cycle-associated transcripts in the QC, enrichment of auxin-associated transcripts within the entire niche, controls for the state of differentiation of QC cells, a role for cytokinins specifically in the PM portion of the niche, processes (repair machinery) for maintaining DNA integrity and a role for gene silencing in niche stabilization. To provide additional support for the hypothesized roles of the above-mentioned and other transcripts in niche specification, we overexpressed, in Arabidopsis, homologs of representative genes (eight) identified as highly enriched or reduced in the maize root QC. We conclude that the coordinated changes in expression of auxin-, redox-, cell cycle- and metabolism-associated genes suggest the linkage of gene networks at the level of transcription, thereby providing additional insights into events likely associated with root stem cell niche establishment and maintenance

A dusty veil shading Betelgeuse during its Great Dimming

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this record.Data availability: Raw data were generated at the ESO under programs 0102.D-0240(A), 0102.D-0240(D), 104.20UZ and 104.20V6.004. Derived data that support the findings of this study are available at the Centre de Données Astronomiques de Strasbourg (CDS) via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/other/Nat (for the VLT/SPHERE–ZIMPOL images) and at the Optical Interferometry Database (OiDB; for the VLTI/GRAVITY and VLT/SPHERE–IRDIS SAM observations). Source data are provided with this paper.The SPHERE and GRAVITY pipelines are available on the ESO website: http://www.eso.org/sci/software/ pipelines/index.html. The RADMC3D code is publicly available online: https://github.com/dullemond/ radmc3d-2.0Code availability: The SPHERE and GRAVITY pipelines are available on the ESO website (http://www.eso.org/sci/software/pipelines/index.html). The PyRAF implementation of the Richardson–Lucy deconvolution algorithm is publicly available at https://astroconda.readthedocs.io/en/latest/. The RADMC3D code is publicly available at https://github.com/dullemond/radmc3d-2.0.Red supergiants represent the most common final stage of the evolution of stars with initial masses between 8 and 30-35 times the mass of the Sun. During this phase of lifetime lasting ≈ 105 yrs, they experience substantial mass loss of unknown mechanism. This mass loss can affect their evolutionary path, collapse, future supernova light curve, and ultimate fate as a neutron star or a black hole. From November 2019 to March 2020, the second closest red supergiant (RSG, 222+48 −34 pc) Betelgeuse experienced a historic dimming of its visible brightness, witnessed worldwide. Usually between 0.1 and 1.0 mag, it went down to 1.614±0.008 mag around 7-13 February 2020. Here we report high angular resolution observations showing that the southern hemisphere of the star was ten times darker than usual in the visible. Observations and modeling support the scenario of a dust clump recently formed in the vicinity of the star due to a local temperature decrease in a cool patch appearing on the photosphere. The directly imaged brightness variations of Betelgeuse evolved on a timescale of weeks. This event suggests that an inhomogeneous component of red supergiant mass loss is linked to a very contrasted and rapidly changing photosphere.European Research Council (ERC)European Union Horizon 2020Foundation FlandersKU LeuvenNAS

The Kerr-Schild double copy in curved spacetime

We thank Tim Adamo, Ricardo Monteiro and Donal O’Connell for discussions and / or comments on the manuscript. CDW and NBA are supported by the U.K. Science and Technology Facilities Council (STFC). AL is funded by a Conacyt studentship, and thanks Queen Mary University of London for hospitalit

Diffusion, Crowding & Protein Stability in a Dynamic Molecular Model of the Bacterial Cytoplasm

A longstanding question in molecular biology is the extent to which the behavior of macromolecules observed in vitro accurately reflects their behavior in vivo. A number of sophisticated experimental techniques now allow the behavior of individual types of macromolecule to be studied directly in vivo; none, however, allow a wide range of molecule types to be observed simultaneously. In order to tackle this issue we have adopted a computational perspective, and, having selected the model prokaryote Escherichia coli as a test system, have assembled an atomically detailed model of its cytoplasmic environment that includes 50 of the most abundant types of macromolecules at experimentally measured concentrations. Brownian dynamics (BD) simulations of the cytoplasm model have been calibrated to reproduce the translational diffusion coefficients of Green Fluorescent Protein (GFP) observed in vivo, and “snapshots” of the simulation trajectories have been used to compute the cytoplasm's effects on the thermodynamics of protein folding, association and aggregation events. The simulation model successfully describes the relative thermodynamic stabilities of proteins measured in E. coli, and shows that effects additional to the commonly cited “crowding” effect must be included in attempts to understand macromolecular behavior in vivo

A Program for At-Risk High School Students Informed by Evolutionary Science

Improving the academic performance of at-risk high school students has proven difficult, often calling for an extended day, extended school year, and other expensive measures. Here we report the results of a program for at-risk 9th and 10th graders in Binghamton, New York, called the Regents Academy that takes place during the normal school day and year. The design of the program is informed by the evolutionary dynamics of cooperation and learning, in general and for our species as a unique product of biocultural evolution. Not only did the Regents Academy students outperform their comparison group in a randomized control design, but they performed on a par with the average high school student in Binghamton on state-mandated exams. All students can benefit from the social environment provided for at-risk students at the Regents Academy, which is within the reach of most public school districts

Evidence-based Kernels: Fundamental Units of Behavioral Influence

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior