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  1. Manipulating gene expression in the host genome with high precision is crucial for controlling cellular function and behavior. Here, we present a precise, non-invasive, and tunable strategy for controlling the expression of multiple endogenous genes both in vitro and in vivo, utilizing ultrasound as the stimulus. By engineering a hyper-efficient dCas12a and effector under a heat shock promoter, we demonstrate a system that can be inducibly activated through thermal energy produced by ultrasound absorption. This system allows versatile thermal induction of gene activation or base editing across cell types, including primary T cells, and enables multiplexed gene activation using a single guide RNA array. In mouse models, localized temperature elevation guided by high-intensity focused ultrasound effectively triggers reporter gene expression in implanted cells. Our work underscores the potential of ultrasound as a clinically viable approach to enhance cell and gene-based therapies via precision genome and epigenome engineering.

     
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    Free, publicly-accessible full text available December 1, 2024
  2. Abstract

    Entanglement has been known to boost target detection, despite it being destroyed by lossy-noisy propagation. Recently, Zhuang and Shapiro (2022Phys. Rev. Lett.128010501) proposed a quantum pulse-compression radar to extend entanglement’s benefit to target range estimation. In a radar application, many other aspects of the target are of interest, including angle, velocity and cross section. In this study, we propose a dual-receiver radar scheme that employs a high time-bandwidth product microwave pulse entangled with a pre-shared reference signal available at the receiver, to investigate the direction of a distant object and show that the direction-resolving capability is significantly improved by entanglement, compared to its classical counterpart under the same parameter settings. We identify the applicable scenario of this quantum radar to be short-range and high-frequency, which enables entanglement’s benefit in a reasonable integration time.

     
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  3. The NUMA architecture accommodates the hardware trend of an increasing number of CPU cores. It requires the coop- eration of memory allocators to achieve good performance for multithreaded applications. Unfortunately, existing allo- cators do not support NUMA architecture well. This paper presents a novel memory allocator – NUMAlloc , that is de- signed for the NUMA architecture. NUMAlloc is centered on a binding-based memory management. On top of it, NUMAl- loc proposes an “origin-aware memory management” to ensure the locality of memory allocations and deallocations, as well as a method called “incremental sharing” to balance the performance benefits and memory overhead of using transparent huge pages. According to our extensive evalua- tion, NUMAlloc hasthebestperformanceamongallevaluated allocators, running 15.7% faster than the second-best allo- cator (mimalloc), and 20.9% faster than the default Linux allocator with reasonable memory overhead. NUMAlloc is also scalable to 128 threads and is ready for deployment. 
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    Free, publicly-accessible full text available June 18, 2024
  4. Free, publicly-accessible full text available June 12, 2024
  5. Abstract Sweet orange originated from the introgressive hybridizations of pummelo and mandarin resulting in a highly heterozygous genome. How alleles from the two species cooperate in shaping sweet orange phenotypes under distinct circumstances is unknown. Here, we assembled a chromosome-level phased diploid Valencia sweet orange (DVS) genome with over 99.999% base accuracy and 99.2% gene annotation BUSCO completeness. DVS enables allele-level studies for sweet orange and other hybrids between pummelo and mandarin. We first configured an allele-aware transcriptomic profiling pipeline and applied it to 740 sweet orange transcriptomes. On average, 32.5% of genes have a significantly biased allelic expression in the transcriptomes. Different cultivars, transgenic lineages, tissues, development stages, and disease status all impacted allelic expressions and resulted in diversified allelic expression patterns in sweet orange, but particularly citrus Huanglongbing (HLB) shifted the allelic expression of hundreds of genes in leaves and calyx abscission zones. In addition, we detected allelic structural mutations in an HLB-tolerant mutant (T19) and a more sensitive mutant (T78) through long-read sequencing. The irradiation-induced structural mutations mostly involved double-strand breaks, while most spontaneous structural mutations were transposon insertions. In the mutants, most genes with significant allelic expression ratio alterations (≥1.5-fold) were directly affected by those structural mutations. In T19, alleles located at a translocated segment terminal were upregulated, including CsDnaJ, CsHSP17.4B, and CsCEBPZ. Their upregulation is inferred to keep phloem protein homeostasis under the stress from HLB and enable subsequent stress responses observed in T19. DVS will advance allelic level studies in citrus. 
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  6. Abstract Quantum repeater is an essential ingredient for quantum networks that link distant quantum modules such as quantum computers and sensors. Motivated by distributed quantum computing and communication, quantum repeaters that relay discrete-variable quantum information have been extensively studied; while continuous-variable (CV) quantum information underpins a variety of quantum sensing and communication application, a quantum-repeater architecture for genuine CV quantum information remains largely unexplored. This paper reports a CV quantum-repeater architecture based on CV quantum teleportation assisted by the Gottesman–Kitaev–Preskill code to significantly suppress the physical noise. The designed CV quantum-repeater architecture is shown to significantly improve the performance of entanglement-assisted communication, target detection based on quantum illumination and CV quantum key distribution, as three representative use cases for quantum communication and sensing. 
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  7. null (Ed.)
    Subgraph matching is a fundamental task in many applications which identifies all the embeddings of a query pattern in an input graph. Compilation-based subgraph matching systems generate specialized implementations for the provided patterns and often substantially outperform other systems. However, the generated code causes significant computation redundancy and the compilation process incurs too much overhead to be used online, both due to the inherent symmetry in the structure of the query pattern. In this paper, we propose an optimizing query compiler, named GraphZero, to completely address these limitations through symmetry breaking based on group theory. GraphZero implements three novel techniques. First, its schedule explorer efficiently prunes the schedule space without missing any high-performance schedule. Second, it automatically generates and enforces a set of restrictions to eliminate computation redundancy. Third, it generalizes orientation, a surprisingly effective optimization that was only used for clique patterns, to apply to arbitrary patterns. Evaluation on multiple query patterns shows that GraphZero outperforms two state-of-the-art compilation and non-compilation based systems by up to 40X and 2654X, respectively. 
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