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  1. Abstract

    Safely expanding indications for cellular therapies has been challenging given a lack of highly cancer-specific surface markers. Here we explore the hypothesis that tumor cells express cancer-specific surface protein conformations that are invisible to standard target discovery pipelines evaluating gene or protein expression, and these conformations can be identified and immunotherapeutically targeted. We term this strategy integrating cross-linking mass spectrometry with glycoprotein surface capture ‘structural surfaceomics’. As a proof of principle, we apply this technology to acute myeloid leukemia (AML), a hematologic malignancy with dismal outcomes and no known optimal immunotherapy target. We identify the activated conformation of integrin β2as a structurally defined, widely expressed AML-specific target. We develop and characterize recombinant antibodies to this protein conformation and show that chimeric antigen receptor T cells eliminate AML cells and patient-derived xenografts without notable toxicity toward normal hematopoietic cells. Our findings validate an AML conformation-specific target antigen and demonstrate a tool kit for applying these strategies more broadly.

     
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  2. Quantum spin liquids, exotic phases of matter with topological order, have been a major focus in physics for the past several decades. Such phases feature long-range quantum entanglement that can potentially be exploited to realize robust quantum computation. We used a 219-atom programmable quantum simulator to probe quantum spin liquid states. In our approach, arrays of atoms were placed on the links of a kagome lattice, and evolution under Rydberg blockade created frustrated quantum states with no local order. The onset of a quantum spin liquid phase of the paradigmatic toric code type was detected by using topological string operators that provide direct signatures of topological order and quantum correlations. Our observations enable the controlled experimental exploration of topological matter and protected quantum information processing. 
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  3. Realizing quantum speedup for practically relevant, computationally hard problems is a central challenge in quantum information science. Using Rydberg atom arrays with up to 289 qubits in two spatial dimensions, we experimentally investigate quantum algorithms for solving the Maximum Independent Set problem. We use a hardware-efficient encoding associated with Rydberg blockade, realize closed-loop optimization to test several variational algorithms, and subsequently apply them to systematically explore a class of graphs with programmable connectivity. We find the problem hardness is controlled by the solution degeneracy and number of local minima, and experimentally benchmark the quantum algorithm’s performance against classical simulated annealing. On the hardest graphs, we observe a superlinear quantum speedup in finding exact solutions in the deep circuit regime and analyze its origins. 
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  5. Abstract

    We present Fermi Gamma-ray Burst Monitor (Fermi-GBM) and Swift Burst Alert Telescope (Swift-BAT) searches for gamma-ray/X-ray counterparts to gravitational-wave (GW) candidate events identified during the third observing run of the Advanced LIGO and Advanced Virgo detectors. Using Fermi-GBM onboard triggers and subthreshold gamma-ray burst (GRB) candidates found in the Fermi-GBM ground analyses, the Targeted Search and the Untargeted Search, we investigate whether there are any coincident GRBs associated with the GWs. We also search the Swift-BAT rate data around the GW times to determine whether a GRB counterpart is present. No counterparts are found. Using both the Fermi-GBM Targeted Search and the Swift-BAT search, we calculate flux upper limits and present joint upper limits on the gamma-ray luminosity of each GW. Given these limits, we constrain theoretical models for the emission of gamma rays from binary black hole mergers.

     
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  6. Free, publicly-accessible full text available January 1, 2025
  7. Free, publicly-accessible full text available December 1, 2024
  8. Abstract

    We search for gravitational-wave (GW) transients associated with fast radio bursts (FRBs) detected by the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst Project, during the first part of the third observing run of Advanced LIGO and Advanced Virgo (2019 April 1 15:00 UTC–2019 October 1 15:00 UTC). Triggers from 22 FRBs were analyzed with a search that targets both binary neutron star (BNS) and neutron star–black hole (NSBH) mergers. A targeted search for generic GW transients was conducted on 40 FRBs. We find no significant evidence for a GW association in either search. Given the large uncertainties in the distances of our FRB sample, we are unable to exclude the possibility of a GW association. Assessing the volumetric event rates of both FRB and binary mergers, an association is limited to 15% of the FRB population for BNS mergers or 1% for NSBH mergers. We report 90% confidence lower bounds on the distance to each FRB for a range of GW progenitor models and set upper limits on the energy emitted through GWs for a range of emission scenarios. We find values of order 1051–1057erg for models with central GW frequencies in the range 70–3560 Hz. At the sensitivity of this search, we find these limits to be above the predicted GW emissions for the models considered. We also find no significant coincident detection of GWs with the repeater, FRB 20200120E, which is the closest known extragalactic FRB.

     
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    Free, publicly-accessible full text available September 28, 2024