Synthetic biology: advancing biological frontiers by building synthetic systems

Advances in synthetic biology are contributing to diverse research areas, from basic biology to biomanufacturing and disease therapy. We discuss the theoretical foundation, applications, and potential of this emerging field

TGF-β-responsive CAR-T cells promote anti-tumor immune function.

A chimeric antigen receptor (CAR) that responds to transforming growth factor beta (TGF-β) enables the engineering of T cells that convert this immunosuppressive cytokine into a potent T-cell stimulant. However, clinical translation of TGF-β CAR-T cells for cancer therapy requires the ability to productively combine TGF-β responsiveness with tumor-targeting specificity. Furthermore, the potential concern that contaminating, TGF-β?producing regulatory T (Treg) cells may preferentially expand during TGF-β CAR-T cell manufacturing and suppress effector T (Teff) cells demands careful evaluation. Here, we demonstrate that TGF-β CAR-T cells significantly improve the anti-tumor efficacy of neighboring cytotoxic T cells. Furthermore, the introduction of TGF-β CARs into mixed T-cell populations does not result in the preferential expansion of Treg cells, nor do TGF-β CAR-Treg cells cause CAR-mediated suppression of Teff cells. These results support the utility of incorporating TGF-β CARs in the development of adoptive T-cell therapy for cancer

Hybrid multi-fluid-particle simulations of the cosmic neutrino background

Simulation of the cosmic clustering of massive neutrinos is a daunting task, due both to their large velocity dispersion and to their weak clustering power becoming swamped by Poisson shot noise. We present a new approach, the multi-fluid hybrid-neutrino simulation, which partitions the neutrino population into multiple flows, each of which is characterised by its initial momentum and treated as a separate fluid. These fluid flows respond initially linearly to nonlinear perturbations in the cold matter, but slowest flows are later converted to a particle realisation should their clustering power exceed some threshold. After outlining the multi-fluid description of neutrinos, we study the conversion of the individual flows into particles, in order to quantify transient errors, as well as to determine a set of criteria for particle conversion. Assembling our results into a total neutrino power spectrum, we demonstrate that our multi-fluid hybrid-neutrino simulation is convergent to $<3\%$ if conversion happens at $z=19$ and agrees with more expensive simulations in the literature for neutrino fractions as high as $\Omega_\nu h^2 = 0.005$. Moreover, our hybrid-neutrino approach retains fine-grained information about the neutrinos' momentum distribution. However, the momentum resolution is currently limited by free-streaming transients excited by missing information in the neutrino particle initialisation procedure, which restricts the particle conversion to z $\gtrsim 19$ if percent-level resolution is desired.Comment: 43 pages, 19 figures; v2: 45 pages, added references, extended discussion on timing, matches version accepted by JCA

Practical Guide for Building Superconducting Quantum Devices

Quantum computing offers a powerful new paradigm of information processing that has the potential to transform a wide range of industries. In the pursuit of the tantalizing promises of a universal quantum computer, a multitude of new knowledge and expertise has been developed, enabling the construction of novel quantum algorithms as well as increasingly robust quantum hardware. In particular, we have witnessed rapid progress in the circuit quantum electrodynamics (cQED) technology, which has emerged as one of the most promising physical systems that is capable of addressing the key challenges in realizing full-stack quantum computing on a large scale. In this Tutorial, we present some of the most crucial building blocks developed by the cQED community in recent years and a précis of the latest achievements towards robust universal quantum computation. More importantly, we aim to provide a synoptic outline of the core techniques that underlie most cQED experiments and offer a practical guide for a novice experimentalist to design, construct, and characterize their first quantum device