Pre-Darcy flow is widely found in many naturally porous media, such as low-permeability clay. Nonflowing liquid boundary layers strongly influence fluid flow in low-permeability porous media. There ...is evidence in the literature that the porosity and permeability of low-permeability porous media change with variations in the effective stress, which is called stress sensitivity. In this paper, a new mathematical model for pre-Darcy flow in low-permeability porous media is developed and validated with experimental data from the literature. The nonflowing boundary layer thickness can be obtained from the proposed model instead of the empirical equation. First, an equation for calculating the pore radius with stress sensitivity is derived. Two parameters εp and εr are defined to calculate the nonflowing boundary layer thickness. Second, based on the capillary bundle model, the apparent flow velocity and apparent liquid permeability of the porous media are determined. Finally, the stress sensitivity and boundary-layer effects on the apparent flow velocity and apparent liquid permeability are analyzed. The research results show that the effect of stress sensitivity on apparent flow velocity increases with increasing pore compressibility. When the pore compressibility Cp>0 MPa−1, the apparent liquid permeability increases continuously with increasing pressure gradient. When the pore compressibility Cp=0 MPa−1, the apparent liquid permeability continues to increase with increasing pressure gradient. The apparent liquid permeability eventually tends to a constant value. The apparent flow velocity decreases with εp, and εr decreases at a given pressure gradient. The larger εp and εr are, the faster the rate of increase in the apparent liquid permeability with increasing pressure gradient. The proposed model can estimate the apparent flow velocity at different pressure gradients with a high accuracy. This work is important for understanding flow phenomena in low permeability porous media, such as landslides caused by seepage of water in clay.
•A low-velocity pre-Darcy flow model in low permeability porous media is developed.•The nonflowing boundary layer thickness was obtained from a new model.•The relationship between the boundary layer and the pressure gradient is established.•The effect of stress sensitivity on velocity and permeability is analyzed.•The effect of nonflowing boundary layer on velocity and permeability is analyzed.
The mechanism of fluorescence detection of diethyl chlorophosphate (DCP) based on 2-substituted benzothiazole (BZ-DAM) was studied by a theoretical calculation method. It should not be ignored that ...both the BZ-DAM and the detection product BZ-CHO have two excited-state intramolecular proton transfer (ESIPT) channels. Density functional theory (DFT) and time-dependent DFT (TDDFT) theory were used to study the photophysical mechanism of two compounds in two channels in (acetonitrile) ACN solvent, and the temperature dependence of the two channels was given. Channel 1 is more likely to exist at low temperatures and channel 2 is more likely to exist at high temperatures. By theoretical analysis of the constructed potential energy curve, the hydrogen bond energy and electron-hole analysis, we confirmed that both molecules undergo ESIPT and intramolecular charge transfer (ICT) processes in channel 1 and ESIPT and twisted intramolecular charge transfer (TICT) coupling processes in channel 2. The formation of product BZ-CHO molecules led to a significant fluorescence blue-shift phenomenon and inhibited the ICT process, which confirmed that BZ-DAM could be used as a fluorescence probe for fluorescence detection. We sincerely hope that this work will not only help to clarify the excited-state dynamics behavior of the BZ-DAM probe but also provide a new idea for designing and optimizing a new chemical dosimeter.
•The impact of freeze-thaw process on hyporheic zone permeability is significant.•Permeability evolution of hyporheic zone has great impact on evolution of baseflow.•Baseflow recession range caused ...by hyporheic zone permeability recession exceed 40%.•Baseflow recession time caused by hyporheic zone permeability recession exceed 60 d.•Attention should be paid to freeze-thaw effect on groundwater discharge to river.
Baseflow is the main groundwater discharge mode from mountainous areas to rivers and is an important component of river runoff. Temperature changes in the hyporheic zone in seasonal freeze–thaw areas cause changes in its permeability, which then affect the recession of baseflow. It is critical to study underground surface water transformation processes in cold regions to explore baseflow recession and hysteresis effects caused by permeability changes in the hyporheic zone under variable temperatures. In this study, we investigated the Hanyangtun Basin in the Changbai Mountain District to determine the functional relationship between permeability and temperature in the hyporheic zone using theoretical analysis combined with laboratory saturated permeability experiments using medium- and fine-grained sand at variable temperatures. We then calculated and analyzed the recession amplitude and hysteresis time of the baseflow caused by permeability changes in the hyporheic zone of this freeze–thaw mountainous area using water temperature and reference baseflow data. The results indicate that owing to large temperature changes in the study area, the permeability of the hyporheic zone changed substantially. Lower permeability leads to the blocking of groundwater discharging to surface water, i.e., the baseflow hysteresis effect. The recession amplitude of the baseflow caused by lower permeability increased with decreasing temperatures, reaching a maximum of 41.67%. The groundwater discharge hysteresis time increased with decreasing temperature. The hysteresis effect was most obvious during the stable melting period, with a maximum hysteresis time of 16 days, while the total annual hysteresis time was 60 days. This study provides a new perspective for qualitative and quantitative studies of the relationship between groundwater and surface water in the mountainous areas that experience seasonal freeze–thaw.
DFT and TD-DFT were used in this article to investigate the effects of different substitutions at multiple sites on the photophysical mechanism of bis-HBX in the gas phase. Four different ...substitution modes were selected, denoted as Asub.1 (X=Me, Y=S), Asub.2 (X=OMe, Y=S), Bsub.1 (X=Me, Y=NH), and Csub.1 (X=Me, Y=O). The geometric parameters proved that the IHBs enhanced after photoexcitation, which was conducive to promote the ESIPT process. Combining the analysis of the PECs, it was revealed that the bis-HBX molecule underwent the ESIPT process, and the ease of the ESIPT process was in the order of Asub.1 > Asub.2> Bsub.1 > Csub.1. In particular, the TICT process in Asub.1 and Bsub.1 promoted the occurrence of the ESIPT process. In addition, the IC process was identified, particularly in Csub.1. Meanwhile, the calculation of fluorescence lifetime and fluorescence rate further confirmed that Asub.1 was the most effective fluorescent probe molecule. This theoretical research provides an innovative theoretical reference for regulating ESIPT reactions and optimizing fluorescent probe molecules.
Dengue virus (DENV) has four serotypes that complicate vaccine development. Envelope protein domain III (EDIII) of DENV is a promising target for therapeutic antibody development. One EDIII-specific ...antibody, dubbed 1A1D-2, cross-reacts with DENV 1, 2, and 3 but not 4. To improve the affinity of 1A1D-2, in this study, we analyzed the previously solved structure of 1A1D-2-DENV2 EDIII complex. Mutations were designed, including A54E and Y105R in the heavy chain, with charges complementary to the epitope. Molecular dynamics simulation was then used to validate the formation of predicted salt bridges. Interestingly, a surface plasmon resonance experiment showed that both mutations increased affinities of 1A1D-2 toward EDIII of DENV1, 2, and 3 regardless of their sequence variation. Results also revealed that A54E improved affinities through both a faster association and slower dissociation, whereas Y105R improved affinities through a slower dissociation. Further simulation suggested that the same mutants interacted with different residues in different serotypes. Remarkably, combination of the two mutations additively improved 1A1D-2 affinity by 8, 36, and 13-fold toward DENV1, 2, and 3, respectively. In summary, this study demonstrated the utility of tweaking antibody-antigen charge complementarity for affinity maturation and emphasized the complexity of improving antibody affinity toward multiple antigens.
In the field of data transmission and storage, serialization formats play a crucial role by converting complex data structures into a byte stream that can be easily stored, transmitted, and ...reconstructed. Despite the myriad available serialization formats, ranging from JSON to Protobuf, each has limitations, particularly in balancing schema flexibility, performance, and data copying overhead. This paper introduces Lite2, a novel data serialization format that addresses these challenges by combining schemaless flexibility with the efficiency of zero-copy operations for flat or key–value pair data types. Unlike traditional formats that often require a predefined schema and involve significant data copying during serialization and deserialization, Lite2 offers a dynamic schemaless approach that eliminates unnecessary data copying, optimizing system performance and efficiency. Built upon a contiguously stored B-tree structure, Lite2 enables efficient data lookup and modification without deserialization, thereby achieving zero-copy operations.
Ensemble learning of swarm intelligence evolutionary algorithm of artificial neural network (ANN) is one of the core research directions in the field of artificial intelligence (AI). As a ...representative member of swarm intelligence evolutionary algorithm, shuffled frog leaping algorithm (SFLA) has the advantages of simple structure, easy implementation, short operation time, and strong global optimization ability. However, SFLA is susceptible to fall into local optimas in the face of complex and multi-dimensional symmetric function optimization, which leads to the decline of convergence accuracy. This paper proposes an improved shuffled frog leaping algorithm of threshold oscillation based on simulated annealing (SA-TO-SFLA). In this algorithm, the threshold oscillation strategy and simulated annealing strategy are introduced into the SFLA, which makes the local search behavior more diversified and the ability to escape from the local optimas stronger. By using multi-dimensional symmetric function such as drop-wave function, Schaffer function N.2, Rastrigin function, and Griewank function, two groups (i: SFLA, SA-SFLA, TO-SFLA, and SA-TO-SFLA; ii: SFLA, ISFLA, MSFLA, DSFLA, and SA-TO-SFLA) of comparative experiments are designed to analyze the convergence accuracy and convergence time. The results show that the threshold oscillation strategy has strong robustness. Moreover, compared with SFLA, the convergence accuracy of SA-TO-SFLA algorithm is significantly improved, and the median of convergence time is greatly reduced as a whole. The convergence accuracy of SFLA algorithm on these four test functions are 90%, 100%, 78%, and 92.5%, respectively, and the median of convergence time is 63.67 s, 59.71 s, 12.93 s, and 8.74 s, respectively; The convergence accuracy of SA-TO-SFLA algorithm on these four test functions is 99%, 100%, 100%, and 97.5%, respectively, and the median of convergence time is 48.64 s, 32.07 s, 24.06 s, and 3.04 s, respectively.
Autoimmune hepatitis (AIH) is mediated by a cascade of T cell-mediated events directed at liver cells and persistent inflammation within the liver can eventually result in liver cirrhosis. Targeting ...glutamine metabolism has an impact on T cell activation and differentiation. However, the effect of glutamine metabolism blocking upon AIH remains unknown. We use glutaminase antagonist 6-diazo-5-oxo-L-norleucine (DON) for
assays and its prodrug 2-(2-amino-4-methylpentanamido)-DON (JHU083) for
assays to investigate the potential therapeutic effect and molecular mechanism of glutamine metabolism blocking in an AIH murine model.
AIH mice were treated with JHU083 or vehicle before concanavalin A (ConA) administration, and disease severity was examined. Then activation and differentiation including Th1/Th17 cells and cytotoxic T lymphocytes (CTL) of T cells from Vehicle-WT, JHU083-AIH and Vehicle-AIH mice were tested. Furthermore,
T cell activation and differentiation were measured using separated splenocytes stimulated with ConA with or without DON. The activation and differentiation of T cells were tested using flow cytometry, qRT-PCR and ELISA. Phosphorylation level of mammalian target of rapamycin (mTOR) and 70 kDa ribosomal protein S6 kinase (P70S6K) were examined by western blotting.
JHU083 and DON significantly suppressed the activation of T cells and inhibited the differentiation of Th1/Th17 cells and CTL
and
. Besides, we demonstrated that glutamine metabolism blocking inhibited T cells activation and differentiation through decreasing the mRNA expression of amino acid transporter solute carrier family 7 member 5 (SLC7A5) and mitigating the activation of mTOR signaling.
We proved that targeting glutamine metabolism represents a potential new treatment strategy for patients with AIH and other T cell-mediated disease. Mechanistically, we demonstrated that glutamine metabolism blocking inhibits T cells activation and suppresses the differentiation of Th1/Th17 cells and CTL.
The low-voltage compact gyrotron is suitable for industrial applications. However, the beam-wave interaction efficiency is low in conventional low-voltage gyrotron. To improve the whole tube ...efficiency, a compact depressed collector is introduced in developing a 75 GHz low-voltage compact gyrotron. The compact depressed collector is directly connected to the output waveguide. It is grounded and isolated with the cavity by a ceramic ring which is easy to be connected with the application system. The design of the original tube electron beam voltage and electron beam current are 10 kV and 1.2 A. In the particle-in-cell (PIC) simulation, the operating mode is TE
0,1
and the generated power is 1.2 kW operated at the frequency of 75.5 GHz, which corresponds to an electron efficiency of 10%. When the depressed collector is performed and the electron reflux is under 5%, the efficiency of the whole tube can reach 30%, and when the reflux rate is controlled at about 15%, the efficiency of the whole tube can reach 50%. The dissipation power would be sufficiently reduced.
Due to global change, increasing nutrient input to ecosystems dramatically affects the nitrogen cycle, especially the nitrification process. Nitrifiers including ammonia-oxidizing archaea (AOAs), ...ammonia-oxidizing bacteria (AOBs), nitrite-oxidizing bacteria (NOBs), and recently discovered complete ammonia oxidizers (comammoxs) perform nitrification individually or in a community. However, much remains to be learned about their niche differentiation, coexistence, and interactions among those metabolically distinct nitrifiers. Here, we used synthetic microbial ecology approaches to construct synthetic nitrifying communities (SNCs) with different combinations of
Nitrospira inopinata
as comammox,
Nitrososphaera gargensis
as AOA,
Nitrosomonas communis
as AOB, and
Nitrospira moscoviensis
as NOB. Our results showed that niche differentiation and potential interactions among those metabolically distinct nitrifiers were determined by their kinetic characteristics. The dominant species shifted from
N. inopinata
to
N. communis
in the N4 community (with all four types of nitrifiers) as ammonium concentrations increased, which could be well explained by the kinetic difference in ammonia affinity, specific growth rate, and substrate tolerance of nitrifiers in the SNCs. In addition, a conceptual model was developed to infer niche differentiation and possible interactions among the four types of nitrifiers. This study advances our understanding of niche differentiation and provides new strategies to further study their interactions among the four types of nitrifiers.
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