Nucleic acid (NA) computation has been widely developed in the past years to solve kinds of logic and mathematic issues in both information technologies and biomedical analysis. However, the ...difficulty to integrate non‐NA molecules limits its power as a universal platform for molecular computation. Here, we report a versatile prototype of hybridized computation integrated with both nucleic acids and non‐NA molecules. Employing the conformationally controlled ligand converters, we demonstrate that non‐NA molecules, including both small molecules and proteins, can be computed as nucleic acid strands to construct the circuitry with increased complexity and scalability, and can be even programmed to solve arithmetical calculations within the computational nucleic acid system. This study opens a new door for molecular computation in which all‐NA circuits can be expanded with integration of various ligands, and meanwhile, ligands can be precisely programmed by the nuclei acid computation.
With utilization of conformationally controlled ligand converters, different kinds of non‐nucleic acid molecules, including both small molecules and proteins, can be integrated into nucleic acid computation to construct circuitries with increased complexity and scalability and to even perform algorithmic calculations. This hybridized system establishes a universal platform for molecular computation.
It has been established that grit has a fundamental role in the learning and teaching process since gritty learners are more likely to take part in classroom activities and they are also motivated to ...deal with challenges in difficult circumstances. In addition, to guard against these hardships as well as self-control in responding to unpredicted circumstances, a similar construct arouses in positive psychology called resilience that describes perseverance and emphasizes people's abilities. Besides, language learners' engagement and performance in the foreign or second language classroom can be improved through self-regulated learning (SRL) which is viewed as one of the most inspected issues in learning and psychology. A present review has been conducted to scrutinize the relationship between language learners' SRL and learners' resilience and grit based on their positive theoretical relationship with educational success. Consequently, the issue of educator training and administrative training is illuminated through several aspects.
Chemical structure of small molecule acceptors determines their performance in organic solar cells. Multiscale simulations are necessary to avoid trial‐and‐error based design, ultimately to save time ...and resources. In current study, the effect of sp2‐hybridized nitrogen substitution at the inner or the outmost position of central core, side chain, and terminal group of small molecule acceptors is investigated using multiscale computational modelling. Quantum chemical analysis is used to study the electronic behavior. Nitrogen substitution at end‐capping has significantly decreased the electron‐reorganization energy. No big change is observed in transfer integral and excited state behavior. However, nitrogen substitution at terminal group position is good way to improve electron‐mobility. Power conversion efficiency (PCE) of newly designed acceptors is predicted using machine learning. Molecular dynamics simulations are also performed to explore the dynamics of acceptor and their blends with PBDB‐T polymer donor. Florgy‐Huggins parameter is calculated to study the mixing of designed small molecule acceptors with PBDB‐T. Radial distribution function has indicated that PBDB‐T has a closer packing with N3 and N4. From all analysis, it is found that nitrogen substitution at end‐capping group is a better strategy to design efficient small molecule acceptors.
Multidimensional modelling is performed to envision the structural changes at atomic and molecular level. sp2‐hybridized nitrogen is substituted at the inner or the outmost position of central core, side chain, and terminal group of ITIC for improving the device performance. It is found that nitrogen substitution at end‐capping group is a better strategy to design efficient small molecule acceptors.
Abstract
Hypoxia inducible factor-1α (HIF-1α) up-regulates the expression of programmed death ligand-1 (PD-L1) in some extracranial malignancies. However, whether it could increase PD-L1 expression ...in intracranial tumor is still unknown. Here, we explored the relationship between HIF-1α and PD-L1 expression in glioma, and investigated their clinical significance. In glioma patients, HIF-1α and PD-L1 were overexpressed in high grade glioma tissues and were significantly associated with poor survival. In glioma cells, PD-L1 expression was induced under hypoxia condition, and the enhanced PD-L1 expression was abrogated by either HIF-1α knock-down or HIF-1α inhibitor treatment. Furthermore, ChIP-qPCR analysis showed the direct binding of HIF-1α to PD-L1 proximal promoter region, providing evidence that HIF-1α up-regulates PD-L1 in glioma. In glioma murine model, the combination treatment with HIF-1α inhibitor and anti-PD-L1 antibody caused a more pronounced suppressive effect on tumor growth compared to either monotherapy. Immunologically, the combination treatment improved both dendritic cell (DC) and CD8
+
T cell activation. Overall, our results demonstrated that positive correlation between PD-L1 and HIF-1α in glioma, and provide an alternative strategy, inhibiting HIF-1α, as combination therapies with immunotherapies to advance glioma treatment.
Electrocatalytic performance can be enhanced by engineering a purposely designed nanoheterojunction and fine‐tuning the interface electronic structure. Herein a new approach of developing atomic ...epitaxial in‐growth in Co‐Ni3N nanowires array is devised, where a nanoconfinement effect is reinforced at the interface. The Co‐Ni3N heterostructure array is formed by thermal annealing NiCo2O4 precursor nanowires under an optimized condition, during which the nanowire morphology is retained. The epitaxial in‐growth structure of Co‐Ni3N at nanometer scale facilitates the electron transfer between the two different domains at the epitaxial interface, leading to a significant enhancement in catalytic activities for both hydrogen and oxygen evolution reactions (10 and 16 times higher in the respective turn‐over frequency compared to Ni3N‐alone nanorods). The interface transfer effect is verified by electronic binding energy shift and density functional theory (DFT) calculations. This nanoconfinement effect occurring during in situ atomic epitaxial in‐growth of the two compatible materials shows an effective pathway toward high‐performance electrocatalysis and energy storages.
Co‐Ni3N nanorod arrays with an atomic epitaxial interface are synthesized, which exhibit significant enhancement in catalytic activities for both hydrogen and oxygen evolution reactions. A nanoconfinement effect is proposed to facilitate the interface charge transfer.
The incorporation of dynamic voltage scaling technology into computation offloading offers more flexibilities for mobile edge computing. In this paper, we investigate partial computation offloading ...by jointly optimizing the computational speed of smart mobile device (SMD), transmit power of SMD, and offloading ratio with two system design objectives: energy consumption of SMD minimization (ECM) and latency of application execution minimization (LM). Considering the case that the SMD is served by a single cloud server, we formulate both the ECM problem and the LM problem as nonconvex problems. To tackle the ECM problem, we recast it as a convex one with the variable substitution technique and obtain its optimal solution. To address the nonconvex and nonsmooth LM problem, we propose a locally optimal algorithm with the univariate search technique. Furthermore, we extend the scenario to a multiple cloud servers system, where the SMD could offload its computation to a set of cloud servers. In this scenario, we obtain the optimal computation distribution among cloud servers in closed form for the ECM and LM problems. Finally, extensive simulations demonstrate that our proposed algorithms can significantly reduce the energy consumption and shorten the latency with respect to the existing offloading schemes.
Different stimuli can polarize macrophages into two basic types, M1 and M2. Tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) are composed of heterogeneous subpopulations, which ...include the M1 anti-tumor and M2 pro-tumor phenotypes. TAMs predominantly play a M2-like tumor-promoting role in the TME and regulate various malignant effects, such as angiogenesis, immune suppression, and tumor metastasis; hence, TAMs have emerged as a hot topic of research in cancer therapy. This review focuses on three main aspects of TAMs. First, we summarize macrophage polarization along with the effects on the TME. Second, recent advances and challenges in cancer treatment and the role of M2-like TAMs in immune checkpoint blockade and CAR-T cell therapy are emphasized. Finally, factors, such as signaling pathways, associated with TAM polarization and potential strategies for targeting TAM repolarization to the M1 pro-inflammatory phenotype for cancer therapy are discussed.
Recently, skeleton-based action recognition becomes popular owing to the development of cost-effective depth sensors and fast pose estimation algorithms. Traditional methods based on pose descriptors ...often fail on large-scale datasets due to the limited representation of engineered features. Recent recurrent neural networks (RNN) based approaches mostly focus on the temporal evolution of body joints and neglect the geometric relations. In this paper, we aim to leverage the geometric relations among joints for action recognition. We introduce three primitive geometries: joints, edges, and surfaces. Accordingly, a generic end-to-end RNN based network is designed to accommodate the three inputs. For action recognition, a novel viewpoint transformation layer and temporal dropout layers are utilized in the RNN based network to learn robust representations. And for action detection, we first perform frame-wise action classification, then exploit a novel multi-scale sliding window algorithm. Experiments on the large-scale 3D action recognition benchmark datasets show that joints, edges, and surfaces are effective and complementary for different actions. Our approaches dramatically outperform the existing state-of-the-art methods for both tasks of action recognition and action detection.
Engineering of genetic networks with artificial signaling pathways (ASPs) can reprogram cellular responses and phenotypes under different circumstances for a variety of diagnostic and therapeutic ...purposes. However, construction of ASPs between originally independent endogenous genes in mammalian cells is highly challenging. Here we report an amplifiable RNA circuit that can theoretically build regulatory connections between any endogenous genes in mammalian cells. We harness the system of catalytic hairpin assembly with combination of controllable CRISPR‐Cas9 function to transduce the signals from distinct messenger RNA expression of trigger genes into manipulation of target genes. Through introduction of these RNA‐based genetic circuits, mammalian cells are endowed with autonomous capabilities to sense the changes of RNA expression either induced by ligand stimuli or from various cell types and control the cellular responses and fates via apoptosis‐related ASPs. Our design provides a generalized platform for construction of ASPs inside the genetic networks of mammalian cells based on differentiated RNA expression.
This study describes an amplifiable RNA circuit based on the system of catalytic hairpin assembly with combination of controllable CRISPR‐Cas9 function, which can directly build regulatory connections between originally independent endogenous genes in mammalian cells. With this design, artificial signaling pathways can be introduced into mammalian cells to control cellular responses and phenotypes through differentiated RNA expression.
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