BackgroundThe Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function.ResultsHere, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory.ConclusionWe conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.

Immune checkpoint blockade therapies have shown clinical promise in a variety of cancers, but how tumor-infiltrating T cells are activated remains unclear. In this study, we explore the functions of PD-L1 on dendritic cells (DCs), which highly express PD-L1. We observe that PD-L1 on DC plays a critical role in limiting T cell responses. Type 1 conventional DCs are essential for PD-L1 blockade and they upregulate PD-L1 upon antigen uptake. Upregulation of PD-L1 on DC is mediated by type II interferon. While DCs are the major antigen presenting cells for cross-presenting tumor antigens to T cells, subsequent PD-L1 upregulation protects them from killing by cytotoxic T lymphocytes, yet dampens the antitumor responses. Blocking PD-L1 in established tumors promotes re-activation of tumor-infiltrating T cells for tumor control. Our study identifies a critical and dynamic role of PD-L1 on DC, which needs to be harnessed for better invigoration of antitumor immune responses.

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Abstract2D transition metal dichalcogenide (2D‐TMD) materials and their van der Waals heterostructures (vdWHs) have inspired worldwide efforts in the fields of electronics and optoelectronics. However, photodetectors based on 2D/2D vdWHs suffer from performance limitations due to the weak optical absorption of their atomically thin nature. In this work, taking advantage of an excellent light absorption coefficient, low‐temperature solution‐processability, and long charge carrier diffusion length, all‐inorganic halides perovskite CsPbI3− xBrx quantum dots are integrated with monolayer MoS2 for high‐performance and low‐cost photodetectors. A favorable energy band alignment facilitating interfacial photocarrier separation and efficient carrier injection into the MoS2 layer inside the 0D–2D mixed‐dimensional vdWHs are confirmed by a series of optical characterizations. Owing to the synergistic effect of the photogating mechanism and the modulation of Schottky barriers, the corresponding phototransistor exhibits a high photoresponsivity of 7.7 × 104 A W−1, a specific detectivity of ≈5.6 × 1011 Jones, and an external quantum efficiency exceeding 107%. The demonstration of such 0D–2D mixed‐dimensional heterostructures proposed here would open up a wide realm of opportunities for designing low‐cost, flexible transparent, and high‐performance optoelectronics.

Supplementary data are available at Bioinformatics online.

Fundamental understanding of charge behavior inside heterostructures is of vital importance for advancing high-performance optoelectronic applications. However, the charge behavior of 0D-2D mixed-dimensional van der Waals heterostructures (MvdWHs) in the photoexcited state remains elusive. In this work, an energy band alignment protocol is adopted to realize effective energy band structure engineering inside 0D-2D MvdWHs of perovskite quantum dots and MoS 2 monolayer with precisely designed typical type I and type II heterostructures, respectively. A profile and in-depth understanding of interfacial photoinduced charge behavior is determined from two opposite perspectives based on MvdWHs. Sufficient comparison of a series of optical characterization results, including Raman shift, quenched photoluminescence, visualized suppressed fluorescence intensity, and shortened fluorescence lifetime imaging, clearly verifies that interfacial charge behavior can be tailored by varying the band alignment in 0D-2D MvdWHs. Furthermore, the photoresponse performance and the relatively stronger and weaker photogating effects of such MvdWH-based phototransistors also demonstrate modulation of interfacial charge behavior in 0D-2D MvdWHs via energy band structure engineering, which is still feasible for optoelectronic performance optimization. These results are expected to shed light on designing novel functional devices and advancing the development process of 0D-2D MvdWHs in the foreseeable future.proposed stacked van der Waals heterostructures (vdWHs) have inspired worldwide efforts with rapid development of 2D materials. Such layer-by-layer assembled vdWHs could benefit from the high carrier mobilities, large surface-to-volume ratios, and especially flexible and semitransparent properties of atomically thin 2D materials. [4] However, the enhanced interlayer Coulombic interactions and Auger scattering processes in these 2D/2D vdWHs [5] as well as the inability to easily tune the energy band alignment for of the two given 2D layered materials has a great influence on the interfacial charge behavior, which is crucial to the performance of heterostructure-based functional devices. More recently, another type of vdWH was developed by integrating sizetunable semiconducting OD quantum dots (QDs) with 2D layered materials. This type of 0D-2D mixed-dimensional van der Waals heterostructure (MvdWH) has been demonstrated to possess various advantages, such as reduced Coulombic interactions, [6] easy preparation, and less constrained interfacial states. In addition, the interface in MvdWHs is more complex than that in conventional heterostructures, inducing interfacial disorder, synergistic effects, proximity effects, abrupt transitions of state density, and many other intriguing phenomena or properties. [4b,7] Hence, by combining the various remarkable optical properties of 0D-QDs with the unusual physical properties of 2D layered materials, 0D-2D MvdWHs may generate a fascinating interfacial charge behavior and exciting device performanc...

Atomic engineering is envisioned to involve selectively inducing the desired dynamics of single atoms and combining these steps for larger-scale assemblies. Here, we focus on the first part by surveying the single-step dynamics of graphene dopants, primarily phosphorus, caused by electron irradiation both in experiment and simulation, and develop a theory for describing the probabilities of competing configurational outcomes depending on the postcollision momentum vector of the primary knock-on atom. The predicted branching ratio of configurational transformations agrees well with our atomically resolved experiments. This suggests a way for biasing the dynamics toward desired outcomes, paving the road for designing and further upscaling atomic engineering using electron irradiation.

Electroluminescence efficiencies and stabilities of quasi-two-dimensional halide perovskites are restricted by the formation of multiple-quantum-well structures with broad and uncontrollable phase distributions. Here, we report a ligand design strategy to substantially suppress diffusion-limited phase disproportionation, thereby enabling better phase control. We demonstrate that extending the π-conjugation length and increasing the cross-sectional area of the ligand enables perovskite thin films with dramatically suppressed ion transport, narrowed phase distributions, reduced defect densities, and enhanced radiative recombination efficiencies. Consequently, we achieved efficient and stable deep-red light-emitting diodes with a peak external quantum efficiency of 26.3% (average 22.9% among 70 devices and cross-checked) and a half-life of ~220 and 2.8 h under a constant current density of 0.1 and 12 mA/cm2, respectively. Our devices also exhibit wide wavelength tunability and improved spectral and phase stability compared with existing perovskite light-emitting diodes. These discoveries provide critical insights into the molecular design and crystallization kinetics of low-dimensional perovskite semiconductors for light-emitting devices.