Ewinglemming1969

Nonviral mRNA delivery is an attractive therapeutic gene delivery strategy, as it achieves efficient protein overexpression in vivo and has a desirable safety profile. However, mRNA's short cytoplasmic half-life limits its utility to therapeutic applications amenable to repeated dosing or short-term overexpression. Here, we describe a biomaterial that enables a durable in vivo response to a single mRNA dose via an "overexpress and sequester" mechanism, whereby mRNA-transfected cells locally overexpress a growth factor that is then sequestered within the biomaterial to sustain the biologic response over time. In a murine diabetic wound model, this strategy demonstrated improved wound healing compared to delivery of a single mRNA dose alone or recombinant protein. In addition, codelivery of anti-inflammatory proteins using this biomaterial eliminated the need for mRNA chemical modification for in vivo therapeutic efficacy. The results support an approach that may be broadly applicable for single-dose delivery of mRNA without chemical modification.Cell lines are commonly used as cancer models. The tissue of origin provides context for understanding biological mechanisms and predicting therapy response. We therefore systematically examined whether cancer cell lines exhibit features matching the presumed cancer type of origin. Gene expression and DNA methylation classifiers trained on ~9000 tumors identified 35 (of 614 examined) cell lines that better matched a different tissue or cell type than the one originally assigned. Mutational patterns further supported most reassignments. For instance, cell lines identified as originating from the skin often exhibited a UV mutational signature. We cataloged 366 "golden set" cell lines in which transcriptomic and epigenomic profiles strongly resemble the cancer type of origin, further proposing their assignments to subtypes. Accounting for the uncertain tissue of origin in cell line panels can change the interpretation of drug screening and genetic screening data, revealing previously unknown genomic determinants of sensitivity or resistance.Increased appreciation of 5-hydroxymethylcytosine (5hmC) as a stable epigenetic mark, which defines cell identity and disease progress, has engendered a need for cost-effective, but high-resolution, 5hmC mapping technology. Current enrichment-based technologies provide cheap but low-resolution and relative enrichment of 5hmC levels, while single-base resolution methods can be prohibitively expensive to scale up to large experiments. To address this problem, we developed a deep learning-based method, "DeepH&M," which integrates enrichment and restriction enzyme sequencing methods to simultaneously estimate absolute hydroxymethylation and methylation levels at single-CpG resolution. Using 7-week-old mouse cerebellum data for training the DeepH&M model, we demonstrated that the 5hmC and 5mC levels predicted by DeepH&M were in high concordance with whole-genome bisulfite-based approaches. The DeepH&M model can be applied to 7-week-old frontal cortex and 79-week-old cerebellum, revealing the robust generalizability of this method to other tissues from various biological time points.Recent advances in quantum technologies are rapidly stimulating the building of quantum networks. With the parallel development of multiple physical platforms and different types of encodings, a challenge for present and future networks is to uphold a heterogeneous structure for full functionality and therefore support modular systems that are not necessarily compatible with one another. Central to this endeavor is the capability to distribute and interconnect optical entangled states relying on different discrete and continuous quantum variables. Here, we report an entanglement swapping protocol connecting such entangled states. We generate single-photon entanglement and hybrid entanglement between particle- and wave-like optical qubits and then demonstrate the heralded creation of hybrid entanglement at a distance by using a specific Bell-state measurement. This ability opens up the prospect of connecting heterogeneous nodes of a network, with the promise of increased integration and novel functionalities.Conducting or semiconducting materials embedded in insulating polymeric substrates can be useful in biointerface applications; however, attainment of this composite configuration by direct chemical processes is challenging. Laser-assisted synthesis has evolved as a fast and inexpensive technique to prepare various materials, but its utility in the construction of biophysical tools or biomedical devices is less explored. Here, we use laser writing to convert portions of polydimethylsiloxane (PDMS) into nitrogen-doped cubic silicon carbide (3C-SiC). The dense 3C-SiC surface layer is connected to the PDMS matrix via a spongy graphite layer, facilitating electrochemical and photoelectrochemical activity. We demonstrate the fabrication of arbitrary two-dimensional (2D) SiC-based patterns in PDMS and freestanding 3D constructs. To establish the functionality of the laser-produced composite, we apply it as flexible electrodes for pacing isolated hearts and as photoelectrodes for local peroxide delivery to smooth muscle sheets.The code capacity threshold for error correction using biased-noise qubits is known to be higher than with qubits without such structured noise. However, realistic circuit-level noise severely restricts these improvements. This is because gate operations, such as a controlled-NOT (CX) gate, which do not commute with the dominant error, unbias the noise channel. Here, we overcome the challenge of implementing a bias-preserving CX gate using biased-noise stabilized cat qubits in driven nonlinear oscillators. This continuous-variable gate relies on nontrivial phase space topology of the cat states. Furthermore, by following a scheme for concatenated error correction, we show that the availability of bias-preserving CX gates with moderately sized cats improves a rigorous lower bound on the fault-tolerant threshold by a factor of two and decreases the overhead in logical Clifford operations by a factor of five. Mycophenolic price Our results open a path toward high-threshold, low-overhead, fault-tolerant codes tailored to biased-noise cat qubits.