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"Larson, Rebecca"
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Compass south
After escaping the Black Hook Gang in 1860 New York City, twelve-year-old twins Alexander and Cleopatra flee to New Orleans, become separated, and try to find each other in San Francisco, while being followed by pirates who think they hold the key to treasure.
Book
CAR-T cells secreting BiTEs circumvent antigen escape without detectable toxicity
Chimeric antigen receptor (CAR)-T-cell therapy for solid tumors is limited due to heterogeneous target antigen expression and outgrowth of tumors lacking the antigen targeted by CAR-T cells directed against single antigens. Here, we developed a bicistronic construct to drive expression of a CAR specific for EGFRvIII, a glioblastoma-specific tumor antigen, and a bispecific T-cell engager (BiTE) against EGFR, an antigen frequently overexpressed in glioblastoma but also expressed in normal tissues. CART.BiTE cells secreted EGFR-specific BiTEs that redirect CAR-T cells and recruit untransduced bystander T cells against wild-type EGFR. EGFRvIII-specific CAR-T cells were unable to completely treat tumors with heterogenous EGFRvIII expression, leading to outgrowth of EGFRvIII-negative, EGFR-positive glioblastoma. However, CART.BiTE cells eliminated heterogenous tumors in mouse models of glioblastoma. BiTE-EGFR was locally effective but was not detected systemically after intracranial delivery of CART.BiTE cells. Unlike EGFR-specific CAR-T cells, CART.BiTE cells did not result in toxicity against human skin grafts in vivo.
BiTE-secreting CAR-T cells overcome antigen escape from EGFRvIII-targeted therapy for glioblastoma.
Journal Article
On the Stellar Populations of Galaxies at z = 9–11: The Growth of Metals and Stellar Mass at Early Times
We present a detailed stellar population analysis of 11 bright (H < 26.6) galaxies at z = 9–11 (three spectroscopically confirmed) to constrain the chemical enrichment and growth of stellar mass of early galaxies. We use the flexible Bayesian spectral energy distribution (SED) fitting code Prospector with a range of star formation histories (SFHs), a flexible dust attenuation law, and a self-consistent model of emission lines. This approach allows us to assess how different priors affect our results and how well we can break degeneracies between dust attenuation, stellar ages, metallicity, and emission lines using data that probe only the rest-frame ultraviolet (UV) to optical wavelengths. We measure a median observed UV spectral slope β=−1.87−0.43+0.35 for relatively massive star-forming galaxies ( 9 10.
Journal Article
The best horror of the year. Volume ten
A group of mountain climbers, caught in the dark, fights to survive their descent; An American band finds more than they bargained for in Mexico while scouting remote locations for a photo shoot; A young student's exploration into the origins of a mysterious song leads him on a winding, dangerous path through the US's deep south; A group of kids scaring each other with ghost stories discovers alarming consequences. The Best Horror of the Year showcases the previous year's best offerings in horror short fiction. This edition includes award-winning and critically acclaimed authors Mark Morris, Kaaron Warren, John Langan, Carole Johnstone, Brian Hodge, and others. For more than three decades, award-winning editor and anthologist Ellen Datlow has had her finger on the pulse of the latest and most terrifying in horror writing. Night Shade Books is proud to present the tenth volume in this annual series, a new collection of stories to keep you up at night.
BOOK
Spectral Templates Optimal for Selecting Galaxies at z > 8 with the JWST
The selection of high-redshift galaxies often involves spectral energy distribution (SED) fitting to photometric data, an expectation for contamination levels, and measurement of sample completeness—all vetted through comparison to spectroscopic redshift measurements of a sub-sample. The first JWST data are now being taken over several extragalactic fields to different depths and across various areas, which will be ideal for the discovery and classification of galaxies out to distances previously uncharted. As spectroscopic redshift measurements for sources in this epoch will not be initially available to compare with the first photometric measurements of z > 8 galaxies, robust photometric redshifts are of the utmost importance. Galaxies at z > 8 are expected to have bluer rest-frame ultraviolet (UV) colors than typically used model SED templates, which could lead to catastrophic photometric redshift failures. We use a combination of BPASS and Cloudy models to create a supporting set of templates that match the predicted rest-UV colors of z > 8 simulated galaxies. We test these new templates by fitting simulated galaxies in a mock catalog, Yung et al., which mimic expected field depths and areas of the JWST Cosmic Evolution Early Release Science Survey (m 5σ ∼ 28.6 over ∼100 arcmin2). We use EAZY to highlight the improvements in redshift recovery with the inclusion of our new template set and suggest criteria for selecting galaxies at 8 < z < 10 with the JWST, providing an important test case for observers venturing into this new era of astronomy.
Journal Article
The new voices of science fiction
\"Your Future Is Bright! After all, your mother is a robot, your father has joined the alien hive mind, and your dinner will be counterfeit 3D-printed steak. Even though your worker bots have staged a mutiny, and your tour guide speaks only in memes, you can always sell your native language if you need some extra cash.\" -- From publisher's description.
Book
Searching for Islands of Reionization: A Potential Ionized Bubble Powered by a Spectroscopic Overdensity at z = 8.7
We present the results from a spectroscopic survey using the MOSFIRE near-infrared spectrograph on the 10 m Keck telescope to search for Lyα emission from candidate galaxies at z ∼ 9–10 in four of the CANDELS fields (GOODS-N, EGS, UDS, and COSMOS). We observed 11 target galaxies, detecting Lyα from one object in ∼8.1 hr of integration, at z = 8.665 ± 0.001 with an integrated signal-to-noise ratio > 7. This galaxy is in the CANDELS Extended Groth Strip (EGS) field and lies physically close (3.5 physical Mpc [pMpc]) to another confirmed galaxy in this field with Lyα detected at z = 8.683. The detection of Lyα suggests the existence of large (∼1 pMpc) ionized bubbles fairly early in the reionization process. We explore the ionizing output needed to create bubbles of this size at this epoch and find that such a bubble requires more than the ionizing power provided by the full expected population of galaxies (by integrating the UV luminosity function down to M UV = −13). The Lyα we detect would be able to escape the predominantly neutral intergalactic medium at this epoch if our detected galaxy is inhabiting an overdensity, which would be consistent with the photometric overdensity previously identified in this region by Finkelstein et al. This implies that the CANDELS EGS field is hosting an overdensity at z = 8.7 that is powering one or more ionized bubbles, a hypothesis that will be imminently testable with forthcoming James Webb Space Telescope observations in this field.
Journal Article
Silencing the Giant: Evidence of Active Galactic Nucleus Feedback and Quenching in a Little Red Dot at z = 4.13
The James Webb Space Telescope (JWST) has uncovered a ubiquitous population of dust-obscured compact sources at z ≳ 4. Many of these objects exhibit signs of active galactic nucleus (AGN) activity, making their study crucial for understanding the formation of supermassive black holes (SMBHs) and their growth with host galaxies. In this work, we examine low and medium-resolution JWST/NIRSpec spectra from the JADES GTO public data release in the GOODS-N field of a red, luminous (M B ∼ −22.2 mag) and compact (<500 pc) source at z = 4.13. The rest-optical (λ rest > 4000 Å) continuum of this source is strongly dominated by a massive (log10[M */M ⊙] ∼ 10.6), quenched (log10[sSFR/yr−1] < −11) galaxy, as indicated by the clear presence of a Balmer break and stellar absorption lines. Star formation history modeling reveals a starburst episode followed by rapid quenching about 200 Myr ago. The spectrum shows extremely broad (FWHM ∼2500 km s−1) Hα emission and elevated optical line ratios, indicating an actively accreting SMBH. Moreover, our work has potentially revealed clear AGN signatures in the rest-UV in little red dots for the first time via the detection of a strong Lyα emission and a broad Mg ii doublet. The derived black hole mass of log10(M BH/M ⊙) ∼ 7.3 results in M BH/M * ∼ 0.04%, consistent with the local relations, unlike the elevated ratios in other high-z reddened AGN. Finally, we use JWST data from AGN at z = 4–10 to explore an evolutionary link between high-z reddened AGN, early quiescent galaxies, and local ellipticals.
Journal Article
CRISPR activation screen identifies BCL-2 proteins and B3GNT2 as drivers of cancer resistance to T cell-mediated cytotoxicity
The cellular processes that govern tumor resistance to immunotherapy remain poorly understood. To gain insight into these processes, here we perform a genome-scale CRISPR activation screen for genes that enable human melanoma cells to evade cytotoxic T cell killing. Overexpression of four top candidate genes (
CD274
(PD-L1),
MCL1
,
JUNB
, and
B3GNT2
) conferred resistance in diverse cancer cell types and mouse xenografts. By investigating the resistance mechanisms, we find that MCL1 and JUNB modulate the mitochondrial apoptosis pathway.
JUNB
encodes a transcription factor that downregulates FasL and TRAIL receptors, upregulates the MCL1 relative BCL2A1, and activates the NF-κB pathway.
B3GNT2
encodes a poly-N-acetyllactosamine synthase that targets >10 ligands and receptors to disrupt interactions between tumor and T cells and reduce T cell activation. Inhibition of candidate genes sensitized tumor models to T cell cytotoxicity. Our results demonstrate that systematic gain-of-function screening can elucidate resistance pathways and identify potential targets for cancer immunotherapy.
Loss-of-function CRISPR-based screens have identified several genes associated with cancer resistance to T cell-induced cytotoxicity. Here the authors perform a genome-scale, gain-of-function CRISPR screen and identify candidate genes, including the poly-N-acetyllactosamine synthase B3GNT2, whose overexpression confers tumor cell resistance to T cell cytotoxicity
Journal Article