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3,161 result(s) for "Liu, Liming"
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Pharmacokinetics of monoclonal antibodies and Fc-fusion proteins
There are many factors that can influence the pharmacokinetics (PK) of a mAb or Fc-fusion molecule with the primary determinant being FcRn-mediated recycling. Through Fab or Fc engineering, IgG-FcRn interaction can be used to generate a variety of therapeutic antibodies with significantly enhanced half-life or ability to remove unwanted antigen from circulation. Glycosylation of a mAb or Fc-fusion protein can have a significant impact on the PK of these molecules. mAb charge can be important and variants with pI values of 1-2 unit difference are likely to impact PK with lower pI values being favorable for a longer half-life. Most mAbs display target mediated drug disposition (TMDD), which can have significant consequences on the study designs of preclinical and clinical studies. The PK of mAb can also be influenced by anti-drug antibody (ADA) response and off-target binding, which require careful consideration during the discovery stage. mAbs are primarily absorbed through the lymphatics via convection and can be conveniently administered by the subcutaneous (sc) route in large doses/volumes with co-formulation of hyaluronidase. The human PK of a mAb can be reasonably estimated using cynomolgus monkey data and allometric scaling methods.
Plasmonic coupling at a metal/semiconductor interface
Integrating plasmonic nanoparticles with semiconductor substrates introduces strong optical resonances that extend and enhance the spectrum of photocatalytic and photovoltaic activity. The effect of plasmonic resonances has been variously attributed to the field nanoconfinement, plasmon–exciton coupling, hot electron transfer, and so on, based on action spectra of enhanced photoactivity. It remains unclear, however, whether energized carriers in the substrate are generated by the transfer of plasmonically generated hot electrons from the metal, as broadly believed, or directly by dephasing of the plasmonic field at the interface. Here, we demonstrate the importance of the direct plasmonic coupling across the chemical interface for hot electron generation at a prototypical Ag nanocluster/TiO 2 heterojunction by direct probing of the coherence and hot electron dynamics with two-photon photoemission spectroscopy. Energy, time and material distributions of excitations in the Ag nanocluster/TiO 2 heterojunction indicate that dielectric coupling with the substrate renormalizes the plasmon resonance of the Ag nanoparticle, and its dephasing directly generates hot electrons in TiO 2 on a <10 fs timescale. The role of direct plasmonic coupling in hot-electron generation at Ag/TiO 2 interfaces is clarified by two-photon photoemission spectroscopy.
Engineering redox balance through cofactor systems
•Redox balance is achieved through three cofactor systems.•Synthetic balance reshapes the whole-cell response to redox balance.•Future research on redox balance will enable advancements in cofactor engineering. Redox balance plays an important role in the production of enzymes, pharmaceuticals, and chemicals. To meet the demands of industrial production, it is desirable that microbes maintain a maximal carbon flux towards target metabolites with no fluctuations in redox. This requires functional cofactor systems that support dynamic homeostasis between different redox states or functional stability in a given redox state. Redox balance can be achieved by improving the self-balance of a cofactor system, regulating the substrate balance of a cofactor system, and engineering the synthetic balance of a cofactor system. This review summarizes how cofactor systems can be manipulated to improve redox balance in microbes.
Pathway dissection, regulation, engineering and application: lessons learned from biobutanol production by solventogenic clostridia
The global energy crisis and limited supply of petroleum fuels have rekindled the interest in utilizing a sustainable biomass to produce biofuel. Butanol, an advanced biofuel, is a superior renewable resource as it has a high energy content and is less hygroscopic than other candidates. At present, the biobutanol route, employing acetone–butanol–ethanol (ABE) fermentation in Clostridium species, is not economically competitive due to the high cost of feedstocks, low butanol titer, and product inhibition. Based on an analysis of the physiological characteristics of solventogenic clostridia, current advances that enhance ABE fermentation from strain improvement to product separation were systematically reviewed, focusing on: (1) elucidating the metabolic pathway and regulation mechanism of butanol synthesis; (2) enhancing cellular performance and robustness through metabolic engineering, and (3) optimizing the process of ABE fermentation. Finally, perspectives on engineering and exploiting clostridia as cell factories to efficiently produce various chemicals and materials are also discussed.
The Construction of Ecological Security Pattern under Rapid Urbanization in the Loess Plateau: A Case Study of Taiyuan City
Taiyuan City in the eastern Loess Plateau has experienced severe ecological problems caused by urban expansion. For cities undergoing rapid urbanization, building an ecological security pattern (ESP) is an effective means to improve urban resilience. Here, geographic information systems (GIS) were used to analyze, manipulate, and visualize urban ecological multi-source information and remote sensing (RS) for the history of land use/land-cover (LULC) changes and the structure of the urban ecological system. Four important ecosystem service functions were estimated: soil conservation, habitat quality, water yield, and carbon storage. The minimum cumulative resistance (MCR) model was combined with the circuit theory method to determine the ecological corridors, pinch points, and barrier points. Our results showed that: (1) from 1980 to 2020, Taiyuan’s built-up area showed increased construction land and enhanced landscape fragmentation. The decline in cultivated land was mainly attributed to construction land. During the period from 2000 to 2010, a greater amount of land was changed in Taiyuan than in other periods; (2) The ecosystem service evaluation based on the LULC in 2020 revealed that the central urban area was lower than the other areas; (3) 38 ecological source sites were identified, accounting for 16% of the total study area. An area of 106 km2 was allocated to construct 79 ecological corridors. We identified 31 ecological pinch points and 6 ecological barrier points; (4) an ESP optimization governance model of “two rings, four zones, and nine corridors” was proposed. Our study provides theoretical guidance for sustainable development and ecological design in Taiyuan City and other regions.
HFNet-SLAM: An Accurate and Real-Time Monocular SLAM System with Deep Features
Image tracking and retrieval strategies are of vital importance in visual Simultaneous Localization and Mapping (SLAM) systems. For most state-of-the-art systems, hand-crafted features and bag-of-words (BoW) algorithms are the common solutions. Recent research reports the vulnerability of these traditional algorithms in complex environments. To replace these methods, this work proposes HFNet-SLAM, an accurate and real-time monocular SLAM system built on the ORB-SLAM3 framework incorporated with deep convolutional neural networks (CNNs). This work provides a pipeline of feature extraction, keypoint matching, and loop detection fully based on features from CNNs. The performance of this system has been validated on public datasets against other state-of-the-art algorithms. The results reveal that the HFNet-SLAM achieves the lowest errors among systems available in the literature. Notably, the HFNet-SLAM obtains an average accuracy of 2.8 cm in EuRoC dataset in pure visual configuration. Besides, it doubles the accuracy in medium and large environments in TUM-VI dataset compared with ORB-SLAM3. Furthermore, with the optimisation of TensorRT technology, the entire system can run in real-time at 50 FPS.
Light-powered Escherichia coli cell division for chemical production
Cell division can perturb the metabolic performance of industrial microbes. The C period of cell division starts from the initiation to the termination of DNA replication, whereas the D period is the bacterial division process. Here, we first shorten the C and D periods of E. coli by controlling the expression of the ribonucleotide reductase NrdAB and division proteins FtsZA through blue light and near-infrared light activation, respectively. It increases the specific surface area to 3.7 μm −1 and acetoin titer to 67.2 g·L −1 . Next, we prolong the C and D periods of E. coli by regulating the expression of the ribonucleotide reductase NrdA and division protein inhibitor SulA through blue light activation-repression and near-infrared (NIR) light activation, respectively. It improves the cell volume to 52.6 μm 3 and poly(lactate-co-3-hydroxybutyrate) titer to 14.31 g·L −1 . Thus, the optogenetic-based cell division regulation strategy can improve the efficiency of microbial cell factories. Manipulation of genes controlling microbial shapes can affect bio-production. Here, the authors employ an optogenetic method to realize dynamic morphological engineering of E. coli replication and division and show the increased production of acetoin and poly(lactate-co-3-hydroxybutyrate).
MXene-supported Ni–Co bimetallic MOF 2D lamellar membrane for enhanced electrochemical oxygen reactions and Li–O2 battery
Challenges associated with the cathode material of Lithium–oxygen (Li–O 2 ) battery, particularly the sluggish kinetics of oxygen reduction reaction (ORR) and oxygen evolution reaction, as well as the accumulation of discharge product Li 2 O 2 , have hindered its further advancement. Here, an in-situ synthesis strategy was adopted to load a bimetallic Ni–Co metal–organic framework (Ni/Co-MOF) onto MXene (Ti 3 C 2 ) layers. Subsequently, a free-standing and flexible Ni/Co-MOF@Ti 3 C 2 hybrid membrane is prepared via a layer-by-layer self-assembly method, specifically designed for efficient ORR and as a cathode for Li–O 2 batteries. The Ni/Co-MOF@Ti 3 C 2 hybrid membrane integrates the high conductivity, unique two-dimensional layered structure, and excellent mechanical properties of Ti 3 C 2 with the bimetallic active sites of Ni/Co-MOF, exhibiting remarkable ORR catalytic activity in an O 2 -saturated 1 M LiTFSI electrolyte. The structural characteristics of the hybrid membrane provide smoother expansion pathways for Li + and O 2 , effectively promoting the deposition and decomposition of Li 2 O 2 . This not only enhances the electrochemical performance of the Li–O 2 battery but also overcomes the inherent limitations of traditional slurry-based cathode preparation methods. Experimental results demonstrate that Li–O 2 batteries utilizing the Ni/Co-MOF@Ti 3 C 2 hybrid membrane as the cathode achieve an ultra-high capacity of 36,125 mAh/g at a current density of 1000 mA/g, while exhibiting excellent cycle stability (271 cycles with a limited capacity of 1000 mAh/g at 1000 mA/g) and outstanding rate performance. The hybrid membrane’s capacity and cycle performance can be further optimized by controlling its thickness. These promising results offer novel insights into the innovative design of air cathodes for metal–air batteries, and the proposed method provides a new route for the manufacture of high-performance battery cathodes.
Data-driven quantification and visualization of resilience metrics of power distribution systems
This paper presents a data-driven approach for quantifying the resilience of distribution power grids to extreme weather events using two key metrics: (a) the number of outages and (b) restoration time. The method leverages historical outage records maintained by power utilities and weather measurements collected by the National Oceanic and Atmospheric Administration (NOAA) to evaluate resilience across a utility’s service territory. The proposed framework consists of three stages. First, outage events are systematically extracted from the outage records by temporally and spatially aggregating coincident component outages. In the second stage, weather zones across the service territory are delineated using a Voronoi polygon approach, based on the locations of NOAA weather sensors. Finally, data-driven models for outage fragility and restoration time are developed for each weather zone. These models enable the quantification and visualization of resilience metrics under varying intensities of extreme weather events. The proposed method is demonstrated using real-world data from a Midwestern US distribution utility, focused on wind- and precipitation-related events. The dataset spans two decades and includes over 160,000 outage records. The data-driven models accurately capture the nonlinear relationship between weather intensity, outage accumulation, and restoration time, and the resulting zone-specific resilience maps provide utilities with actionable insights for prioritizing hardening and operational planning.
Study on arc behavior and droplet transfer in twin-electrode TIG-MIG indirect arc welding
A twin-electrode TIG-MIG (T-TIG-MIG) indirect arc welding method was proposed in this paper. The arc behavior and droplet transfer process were preliminarily investigated; moreover, the process stability was assessed, and bead-on-plate welding was conducted. Results showed T-TIG-MIG indirect arc burnt between a wire and two tungsten electrodes and was essentially formed by the coupling of two single-electrode TIG-MIG indirect arcs. The wire feeding speed (WFS) determined the equilibrium position of the wire end, and the vicinity of the tungsten tips was an ideal position for arc shape and droplet detachment, where the arc was more concentrated with a higher coupling degree. With the increase of the welding current, the arc length and stiffness increased gradually; so did the process stability and the spreadability of the weld bead. When the current exceeded the critical current, the droplet transfer mode changed into streaming spray transfer, since the electromagnetic force and the arc pressure increased considerably. Compared to conventional cold-wire T-TIG welding under the same current, the wire deposition rate of T-TIG-MIG indirect arc welding increased by about 186%, while the range of the heat-affected zone reduced by about 41%.