Substrate entering and product leaving trajectories predict an engulfing dynamic for the major conformational change of the β-lactam acylase

It is still a major challenge to acquire insight into the conformational changes between the ground state and the transition state of an enzyme, although conformational fluctuation within interconverting conformers has been widely investigated (1-4). Here, we utilize different enzymatic reactions in b-lactam acylase to figure out the substrate/product trajectories in the enzyme, thereby probing the overall conformational changes in transition state. First, an auto-proteolytic intermediate of cephalosporin acylase (EC 3.5.1.11) with partial spacer segment was identified. As a final proteolytic step, the deletion of this spacer segment was revealed to be a first-order reaction, suggesting an intramolecular Ntn mechanism for the auto-proteolysis. Accordingly, the different proteolytic sites in the acylase precursor indicate a substrate entering pathway along the spacer peptide. Second, bromoacyl-7ACA can interact with penicillin G acylase (EC 3.5.1.11) in two distinguish aspects, to be hydrolyzed as a substrate analogue and to affinity alkylate the conserved Trpb4 as a product analogue. The kinetic correlation between these two reactions suggests a channel opening from Serb1 to Trpb4, responsible for the main product leaving. These two reaction trajectories relaying at the active centre, together with the crystal structures (5-10), predict an engulfing dynamic involving pocket constriction and channel opening

Phonemic Adversarial Attack against Audio Recognition in Real World

Recently, adversarial attacks for audio recognition have attracted much attention. However, most of the existing studies mainly rely on the coarse-grain audio features at the instance level to generate adversarial noises, which leads to expensive generation time costs and weak universal attacking ability. Motivated by the observations that all audio speech consists of fundamental phonemes, this paper proposes a phonemic adversarial tack (PAT) paradigm, which attacks the fine-grain audio features at the phoneme level commonly shared across audio instances, to generate phonemic adversarial noises, enjoying the more general attacking ability with fast generation speed. Specifically, for accelerating the generation, a phoneme density balanced sampling strategy is introduced to sample quantity less but phonemic features abundant audio instances as the training data via estimating the phoneme density, which substantially alleviates the heavy dependency on the large training dataset. Moreover, for promoting universal attacking ability, the phonemic noise is optimized in an asynchronous way with a sliding window, which enhances the phoneme diversity and thus well captures the critical fundamental phonemic patterns. By conducting extensive experiments, we comprehensively investigate the proposed PAT framework and demonstrate that it outperforms the SOTA baselines by large margins (i.e., at least 11X speed up and 78% attacking ability improvement)

On the morphology and pressure-filtration characteristics of filter cake formation: insight from coupled CFD–DEM simulations

The slurry filtration process at a tunnel face plays an important role in supporting pressure transmission, which is crucial to the stability of a tunnel face during shield tunneling. In this paper, a series of coupled computational fluid dynamics (CFD)–discrete element method (DEM) numerical simulations were carried out to model the slurry filtration column test. A simplified JKR (Johnson-Kendall-Roberts) model was used to simulate the cohesion between slurry particles. Four types of filter cake formation were identified under different combinations of size ratios between slurry and sand particles, and cohesion between slurry particles according to morphology and pore pressure distribution characteristics. These types were external filter cake, external & internal filter cake, internal filter cake & deep penetration and external & internal filter cake & deep penetration. The contact-based analysis of the constriction (void throat) sizes reveals that the dynamic evolution of the pore structure is closely related to the slurry infiltration process, i.e., the infiltration of slurry particles tends to seal the infiltration channel, which prevents infiltration of any more particles. The variation of Dc50 (the median constriction size) is closely related to the infiltration state of the slurry particles. The pressure drop within the filter cake becomes significant, i.e., the filter cake will become effective, only when the ratio of Dc50 to the size of slurry particles is below a threshold value. The current study provides new insight into the fundamental mechanism underlying the slurry filtration process during shield tunneling

The Influence of Mullite Shape and Amount on the Tribological Properties of Non-Asbestos Brake Friction Composites

For investigating the effect of mullite as a reinforced fiber of the non-asbestos brake friction material on the performance of brake pads, mullite reinforced composites with different contents (5% and 10%) and shapes (powder-based and fiber-based) were developed, and the physical and mechanical properties of the composites were analyzed. The tribological properties of the composites were tested by a Chase tester followed by the IS-2742 standard, and the worn surface was investigated by three-dimensional surface topography and SEM. The results show that the brake friction material with 5% powdered mullite performs best, having the highest stable friction performance (0.86), the lowest wear rate (3%), the lowest friction variation performance (0.263), and the best fade-recovery performance. With the increase of mullite content, the friction variation, wear resistance, and friction stability of the composites become worse. Meanwhile, the performance of powder-based mullite composites is better than that of fiber-based. The worn surface analysis shows that the fiber-based mullite composite has a higher surface roughness, fewer contact platforms, more wear debris, and peeling pits. In contrast, the powder-based mullite composites have a better surface performance. It provides a practical basis for mullite-reinforced non-asbestos brake friction materials

A Coupled CFD–DEM Simulation of Slurry Infiltration and Filter Cake Formation during Slurry Shield Tunneling

Tunneling in highly permeable ground using a slurry shield machine can be challenging because it is difficult to form the so-called filter cake on the tunnel face to transport the support pressure. Consequently, destructive accidents might happen, such as face instability and water inrush. How to form an efficient filter cake in time is crucial during engineering practice, especially in ground with high permeability. Various theoretical and experimental analyses regarding the formation of filter cakes have been conducted. However, due to the complexity of this problem, which has to incorporate the mechanical and hydraulic behaviors of the fluid–solid mixture system, few numerical simulations are found in the literature. In this paper, with the aid of a newly developed numerical tool, a coupled CFD (computational fluid dynamics)–DEM (discrete element method) simulation is established to study the slurry infiltration and filter cake formation during slurry shield tunneling. The slurry infiltration process is simulated by modelling the scheme of the infiltration column test, in which sedimentation behaviors of slurry particles are captured and compared with experimental results. The results show that the sedimentation behaviors of the slurry particles and filter cake formation phenomenon are well captured by simulations and in accordance with the experiments, which indicates the robustness of the coupled CFD–DEM simulation used in present work

Impact Load Behavior between Different Charge and Lifter in a Laboratory-Scale Mill

The impact behavior between the charge and lifter has significant effect to address the mill processing, and is affected by various factors including mill speed, mill filling, lifter height and media shape. To investigate the multi-body impact load behavior, a series of experiments and Discrete Element Method (DEM) simulations were performed on a laboratory-scale mill, in order to improve the grinding efficiency and prolong the life of the lifter. DEM simulation hitherto has been extensively applied as a leading tool to describe diverse issues in granular processes. The research results shown as follows: The semi-empirical power draw of Bond model in this paper does not apply very satisfactorily for the ball mills, while the power draw determined by DEM simulation show a good approximation for the measured power draw. Besides, the impact force on the lifter was affected by mill speed, grinding media filling, lifter height and iron ore particle. The maximum percent of the impact force between 600 and 1400 N is at 70–80% of critical speed. The impact force can be only above 1400 N at the grinding media filling of 20%, and the maximum percent of impact force between 200 and 1400 N is obtained at the grinding media filling of 20%. The percent of impact force ranging from 0 to 200 N decreases with the increase of lifter height. However, this perfect will increase above 200 N. The impact force will decrease when the iron ore particles are added. Additionally, for the 80% of critical speed, the measured power draw has a maximum value. Increasing the grinding media filling increases the power draw and increasing the lifter height does not lead to any variation in power draw