Search

Pulse tube refrigerators are a critical enabling technology for many disciplines that require low temperatures. These refrigerators dominate the total power consumption of most modern cryostats, including those that reach millikelvin temperatures using additional cooling stages. In state-of-the-art commercial pulse tube refrigerators, the acoustic coupling between the driving compressor and the refrigerator is fixed and optimized for operation at base temperature. We show that this optimization is incorrect during the cooldown process, which results in wasted power consumption by the compressor and slow cooldown speed. After developing analytic expressions that demonstrate the need for acoustic tuning as a function of temperature, we dynamically optimize the acoustics of a commercial pulse tube refrigerator and show that the cooldown speed can be increased to 1.7 to 3.5 times the original value. Acoustic power measurements show that loss mechanism(s)-and not the capacity of the compressor-limit the maximum cooling available at high temperatures, suggesting that even faster cooldown speeds can be achieved in the future. This work has implications for the accessibility of cryogenic temperatures and the cadence of research in many disciplines such as quantum computing., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The success of the CD8 T cell-mediated immune response against infections and tumors depends on the formation of a long-lived memory pool, and the protection of effector cells from exhaustion. The advent of checkpoint blockade therapy has significantly improved anti-tumor therapeutic outcomes by reversing CD8 T cell exhaustion, but fails to generate effector cells with memory potential. Here, using in vivo mouse models, we show that let-7 miRNAs determine CD8 T cell fate, where maintenance of let-7 expression during early cell activation results in memory CD8 T cell formation and tumor clearance. Conversely, let-7-deficiency promotes the generation of a terminal effector population that becomes vulnerable to exhaustion and cell death in immunosuppressive environments and fails to reject tumors. Mechanistically, let-7 restrains metabolic changes that occur during T cell activation through the inhibition of the PI3K/AKT/mTOR signaling pathway and production of reactive oxygen species, potent drivers of terminal differentiation and exhaustion. Thus, our results reveal a role for let-7 in the time-sensitive support of memory formation and the protection of effector cells from exhaustion. Overall, our data suggest a strategy in developing next-generation immunotherapies by preserving the multipotency of effector cells rather than enhancing the efficacy of differentiation., (© 2023. Springer Nature Limited.)