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This paper considers the initial stage of radiatively driven convection, when the perturbations from a quiescent but time-dependent background state are small. Radiation intensity is assumed to decay exponentially away from the surface, and we consider parameter regimes in which the depth of the water is greater than the decay scale of$e$of the radiation intensity. Both time-independent and time-periodic radiation are considered. In both cases, the background temperature profile of the water column is time-dependent. A linear analysis of the system is performed based on these time-dependent profiles. We find that the perturbations grow in time according to$\exp [(\sigma (t) t)]$, where$\sigma (t)$is a time-dependent growth rate. An appropriately defined Reynolds number is the primary dimensionless number characterising the system, determining the wavelength, vertical structure and growth rate of the perturbations. Simulations using a Boussinesq model (the Stratified Ocean Model with Adaptive Refinement) confirm the linear analysis.

 

Multi-version concurrency control (MVCC) is a widely used, sophisticated approach for handling concurrent transactions. vMVCC is the first MVCC-based transaction library that comes with a machine-checked proof of correctness, providing clients with a guarantee that it will correctly handle all transactions despite a complicated design and implementation that might otherwise be error-prone. vMVCC is implemented in Go, stores data in memory, and uses several optimizations, such as RDTSC-based timestamps, to achieve high performance (25–96% the throughput of Silo, a state-of-the-art in-memory database, for YCSB and TPC-C workloads). Formally specifying and verifying vMVCC required adopting advanced proof techniques, such as logical atomicity and prophecy variables, owing to the fact that MVCC transactions can linearize at timestamp generation prior to transaction execution. 

Adoptive chimeric antigen receptor (CAR)-engineered natural killer (NK) cells have shown promise in treating various cancers. However, limited immunological memory and access to sufficient numbers of allogenic donor cells have hindered their broader preclinical and clinical applications. Here, we first assess eight different CAR constructs that use an anti-PD-L1 nanobody and/or universal anti-fluorescein (FITC) single-chain variable fragment (scFv) to enhance antigen-specific proliferation and anti-tumor cytotoxicity of NK-92 cells against heterogenous solid tumors. We next genetically engineer human pluripotent stem cells (hPSCs) with optimized CARs and differentiate them into functional dual CAR-NK cells. The tumor microenvironment responsive anti-PD-L1 CAR effectively promoted hPSC-NK cell proliferation and cytotoxicity through antigen-dependent activation of phosphorylated STAT3 (pSTAT3) and pSTAT5 signaling pathways via an intracellular truncated IL-2 receptor β-chain (ΔIL-2Rβ) and STAT3-binding tyrosine-X-X-glutamine (YXXQ) motif. Anti-tumor activities of PD-L1-induced memory-like hPSC-NK cells were further boosted by administering a FITC-folate bi-specific adapter that bridges between a programmable anti-FITC CAR and folate receptor alpha-expressing breast tumor cells. Collectively, our hPSC CAR-NK engineering platform is modular and could constitute a realistic strategy to manufacture off-the-shelf CAR-NK cells with immunological memory-like phenotype for targeted immunotherapy. 

Immunotherapy is a powerful technique where immune cells are modified to improve cytotoxicity against cancerous cells to treat cancers that do not respond to surgery, chemotherapy, or radiotherapy. Expressing chimeric antigen receptor (CAR) in immune cells, typically T lymphocytes, is a practical modification that drives an immune response against cancerous tissue. CAR-T efficacy is suboptimal in solid tumors due to the tumor microenvironment (TME) that limits T lymphocyte cytotoxicity. In this study, we demonstrate that neutrophils differentiated from human pluripotent stem cells modified with AAVS1-inserted CAR constructs showed a robust cytotoxic effect against prostate-specific membrane antigen (PSMA) expressing LNCaP cells as a model for prostate cancer in vitro. Our results suggest that engineered CAR can significantly enhance the neutrophil anti-tumor effect, providing a new avenue in treating prostate cancers. 

Heart diseases are leading cause of death around the world. Given their unique capacity to self-renew and differentiate into all types of somatic cells, human pluripotent stem cells (hPSCs) hold great promise for heart disease modeling and cardiotoxic drug screening. hPSC-derived cardiac organoids are emerging biomimetic models for studying heart development and cardiovascular diseases, but it remains challenging to make mature organoids with a native-like structure in vitro . In this study, temporal modulation of Wnt signaling pathway co-differentiated hPSCs into beating cardiomyocytes and cardiac endothelial-like cells in 3D organoids, resulting in cardiac endothelial-bounded chamber formation. These chambered cardiac organoids exhibited more mature membrane potential compared to cardiac organoids composed of only cardiomyocytes. Furthermore, a better response to toxic drugs was observed in chamber-contained cardiac organoids. In summary, spatiotemporal signaling pathway modulation may lead to more mature cardiac organoids for studying cardiovascular development and diseases.