Coronal X-ray emission from an intermediate-age brown dwarf

We report the X-ray detection of the brown dwarf (BD) companion TWA 5B in a $\simeq 12$ Myr old pre-main sequence binary system. We clearly resolve the faint companion (35 photons) separated from the X-ray luminous primary by 2 arcsec in a {\it Chandra} ACIS image. TWA 5B shows a soft X-ray spectrum with a low plasma temperature of only 0.3 keV and a constant flux during the 3 hour observation, of which the characteristics are commonly seen in the solar corona. The X-ray luminosity is 4$\times10^{27}$ erg s$^{-1}$ (0.1--10 keV band) or $\log L_X/L_{bol} = -3.4$. Comparing these properties to both younger and older BDs, we discuss the evolution of the X-ray emission in BDs. During their first few Myr, they exhibit high levels of X-ray activity as seen in higher mass pre-main sequence stars. The level in TWA 5B is still high at $t \simeq 12$ Myr in $\log L_X/L_{bol}$ while $kT$ has already substantially cooled

Cancer Biology Data Curation at the Mouse Tumor Biology Database (MTB)

Many advances in the field of cancer biology have been made using mouse models of human cancer. The Mouse Tumor Biology (MTB, "http://tumor.informatics.jax.org":http://tumor.informatics.jax.org) database provides web-based access to data on spontaneous and induced tumors from genetically defined mice (inbred, hybrid, mutant, and genetically engineered strains of mice). These data include standardized tumor names and classifications, pathology reports and images, mouse genetics, genomic and cytogenetic changes occurring in the tumor, strain names, tumor frequency and latency, and literature citations.

Although primary source for the data represented in MTB is peer-reviewed scientific literature an increasing amount of data is derived from disparate sources. MTB includes annotated histopathology images and cytogenetic assay images for mouse tumors where these data are available from The Jackson Laboratory’s mouse colonies and from outside contributors. MTB encourages direct submission of mouse tumor data and images from the cancer research community and provides investigators with a web-accessible tool for image submission and annotation. 

Integrated searches of the data in MTB are facilitated by the use of several controlled vocabularies and by adherence to standard nomenclature. MTB also provides links to other related online resources such as the Mouse Genome Database, Mouse Phenome Database, the Biology of the Mammary Gland Web Site, Festing's Listing of Inbred Strains of Mice, the JAX® Mice Web Site, and the Mouse Models of Human Cancers Consortium's Mouse Repository. 

MTB provides access to data on mouse models of cancer via the internet and has been designed to facilitate the selection of experimental models for cancer research, the evaluation of mouse genetic models of human cancer, the review of patterns of mutations in specific cancers, and the identification of genes that are commonly mutated across a spectrum of cancers.

MTB is supported by NCI grant CA089713

X-ray emitting young stars in the Orion Nebula

The Orion Nebula Cluster and the molecular cloud in its vicinity have been observed with the ACIS-I detector on board the Chandra X-ray Observatory with 23 hours exposure. We detect 1075 X-ray sources: 91% are spatially associated with known stellar members of the cluster, and 7% are newly identified deeply embedded cloud members. This provides the largest X-ray study of a pre-main sequence stellar population. We examine here the X-ray properties of Orion young stars as a function of mass. Results include: (a) the discovery of rapid variability in the O9.5 31 M_o star \theta^2A Ori, and several early B stars, inconsistent with the standard model of X-ray production in small wind shocks; (b) support for the hypothesis that intermediate-mass mid-B through A type stars do not themselves produce significant X-ray emission; (c) confirmation that low-mass G- through M-type T Tauri stars exhibit powerful flaring but typically at luminosities considerably below the `saturation' level; (d) confirmation that the presence or absence of a circumstellar disk has no discernable effect on X-ray emission; (e) evidence that T Tauri plasma temperatures are often very high with T >= 100 MK, even when luminosities are modest and flaring is not evident; and (f) detection of the largest sample of pre-main sequence very low mass objects showing high flaring levels and a decline in magnetic activity as they evolve into L- and T-type brown dwarfs.Comment: 82 pages, 16 figures, 6 tables. To appear in the Astrophysical Journal. For a version with high quality images and electronic tables, see ftp://ftp.astro.psu.edu/pub/edf/orion1

STRprofiler: efficient comparisons of short tandem repeat profiles for biomedical model authentication.

SUMMARY: Short tandem repeat (STR) profiling is commonly performed for authentication of biomedical models of human origin, yet no tools exist to easily compare sets of STR profiles to each other or an existing database in a high-throughput manner. Here, we present STRprofiler, a Python package, command line tool, and Shiny application providing methods for STR profile comparison and cross-contamination detection. STRprofiler can be run with custom databases or used to query against the Cellosaurus cell line database. AVAILABILITY AND IMPLEMENTATION: STRprofiler is freely available as a Python package with a rich CLI from PyPI https://pypi.org/project/strprofiler/ with source code available under the MIT license on GitHub https://github.com/j-andrews7/strprofiler and at https://zenodo.org/records/10989034. A web server hosting an example STRprofiler Shiny application backed by a database with data from the National Cancer Institute-funded PDXNet consortium and The Jackson Laboratory PDX program is available at https://sj-bakerlab.shinyapps.io/strprofiler/. Full documentation is available at https://strprofiler.readthedocs.io/en/latest/

PDX Finder: A portal for patient-derived tumor xenograft model discovery.

Patient-derived tumor xenograft (PDX) mouse models are a versatile oncology research platform for studying tumor biology and for testing chemotherapeutic approaches tailored to genomic characteristics of individual patients\u27 tumors. PDX models are generated and distributed by a diverse group of academic labs, multi-institution consortia and contract research organizations. The distributed nature of PDX repositories and the use of different metadata standards for describing model characteristics presents a significant challenge to identifying PDX models relevant to specific cancer research questions. The Jackson Laboratory and EMBL-EBI are addressing these challenges by co-developing PDX Finder, a comprehensive open global catalog of PDX models and their associated datasets. Within PDX Finder, model attributes are harmonized and integrated using a previously developed community minimal information standard to support consistent searching across the originating resources. Links to repositories are provided from the PDX Finder search results to facilitate model acquisition and/or collaboration. The PDX Finder resource currently contains information for 1985 PDX models of diverse cancers including those from large resources such as the Patient-Derived Models Repository, PDXNet and EurOPDX. Individuals or organizations that generate and distribute PDXs are invited to increase the \u27findability\u27 of their models by participating in the PDX Finder initiative at www.pdxfinder.org

PDCM Finder: an open global research platform for patient-derived cancer models.

PDCM Finder (www.cancermodels.org) is a cancer research platform that aggregates clinical, genomic and functional data from patient-derived xenografts, organoids and cell lines. It was launched in April 2022 as a successor of the PDX Finder portal, which focused solely on patient-derived xenograft models. Currently the portal has over 6200 models across 13 cancer types, including rare paediatric models (17%) and models from minority ethnic backgrounds (33%), making it the largest free to consumer and open access resource of this kind. The PDCM Finder standardises, harmonises and integrates the complex and diverse data associated with PDCMs for the cancer community and displays over 90 million data points across a variety of data types (clinical metadata, molecular and treatment-based). PDCM data is FAIR and underpins the generation and testing of new hypotheses in cancer mechanisms and personalised medicine development

Chandra X-ray observations of Young Clusters II. Orion Flanking Fields Data

We present results of Chandra observations of two flanking fields (FF) in Orion, outside the Orion Nebula Cluster (ONC). The observations were taken with the ACIS-I camera with an exposure time of about 48 ks each field. We present a catalog of 417 sources, which includes X-ray luminosity, optical and infrared photometry and X-ray variability information. We have found 91 variable sources, 33 of which have a flare-like light curve, and 11 of which have a pattern of a steady increase or decrease over a 10 hour period. The optical and infrared photometry for the stars identified as X-ray sources are consistent with most of these objects being pre-main sequence stars with ages younger than 10 Myr. We present evidence for an age difference among the X-ray selected samples of NGC 2264, Orion FF, and ONC, with NGC 2264 being the oldest, and ONC being the youngest.Comment: AJ in press, 32 pages, 13 figures in total, 5 figures available at http://spider.ipac.caltech.edu/staff/solange/ramirez07_figs.p

The CD123 antibody-drug conjugate pivekimab sunirine exerts profound activity in preclinical models of pediatric acute lymphoblastic leukemia.

Antibody–drug conjugates (ADCs) combining monoclonal antibodies with cytotoxic payloads are a rapidly emerging class of immune‐based therapeutics with the potential to improve the treatment of cancer, including children with relapse/refractory acute lymphoblastic leukemia (ALL). CD123, the α subunit of the interleukin‐3 receptor, is overexpressed in ALL and is a potential therapeutic target. Here, we show that pivekimab sunirine (PVEK), a recently developed ADC comprising the CD123‐targeting antibody, G4723A, and the cytotoxic payload, DGN549, was highly effective in vivo against a large panel of pediatric ALL patient‐derived xenograft (PDX) models (n = 39). PVEK administered once weekly for 3 weeks resulted in a median event‐free survival (EFS) of 57.2 days across all PDXs. CD123 mRNA and protein expression was significantly higher in B‐lineage (n = 65) compared with T‐lineage (n = 25) ALL PDXs (p \u3c 0.0001), and mice engrafted with B‐lineage PDXs achieved significantly longer EFS than those engrafted with T‐lineage PDXs (p \u3c 0.0001). PVEK treatment also resulted in significant clearance of human leukemia cells in hematolymphoid organs in mice engrafted with B‐ALL PDXs. Notably, our results showed no direct correlation between CD123 expression and mouse EFS, indicating that CD123 is necessary but not sufficient for in vivo PVEK activity. Importantly, a PDX with very high CD123 cell surface expression but resistant to in vivo PVEK treatment, failed to internalize the G4723A antibody while remaining sensitive to the PVEK payload, DGN549, suggesting a novel mechanism of resistance. In conclusion, PVEK was highly effective against a large panel of B‐ALL PDXs supporting its clinical translation for B‐lineage pediatric ALL

Magnetic flaring in the pre-main sequence Sun and implications for the early solar system

To address the role of energetic processes in the solar nebula, we provide a detailed characterization of magnetic flaring in stellar analogs of the pre-main sequence Sun based on 23 hours observations of 43 analogs of the young Sun in the Orion Nebula Cluster obtained with the Chandra X-ray Observatory. We find the X-ray luminosities are strongly elevated over main sequence levels with average = 30.3 erg/s and = -3.9 (0.5-8 keV), and dozens of flares are present. Analogs of the <= 1 My old pre-main sequence Sun exhibit X-ray flares 10^{1.5} times more powerful and 10^{2.5} times more frequent than the most powerful flares seen on the contemporary Sun. Extrapolating the solar relationship between X-ray luminosity and proton fluence, we infer that the young Sun exhibited a 10^5-fold enhancement in energetic protons compared to contemporary levels. Unless the flare geometries are unfavorable, this inferred proton flux on the disk is sufficient to produce the observed meteoritic abundances of several important short-lived radioactive isotopes. Our study thus strengthens the astronomical foundation for local proton spallation models of isotopic anomalies in carbonaceous chondritic meteorites. The radiation, particles and shocks produced by the magnetic reconnection flares seen with Chandra may also have flash melted meteoritic chondrules and produced excess 21-Ne seen in meteoritic grains.Comment: 36 pages, 3 figures. Accepted for publication in the Astrophysical Journa