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Large-scale GPU clusters are widely used to speed up both latency-critical (online) and best-effort (offline) deep learning (DL) workloads. However, similar to the common practice, the DL clusters at ByteDance dedicate each GPU to one workload or share workloads in time dimension, leading to very low GPU resource utilization. Existing techniques like NVIDIA MPS provide an opportunity to share multiple workloads in space on widely-deployed NVIDIA GPUs, but it cannot guarantee the performance of online workloads. We present MuxFlow, the first production system that can scale over massive GPUs to support highly efficient space-sharing for DL workloads. MuxFlow introduces a two-level protection mechanism for both memory and computation to guarantee the performance of online workloads. MuxFlow leverages dynamic streaming multiprocessor (SM) allocation to improve the efficiency of offline workloads. Based on our practical error analysis, we design a mixed error-handling mechanism to improve system reliability. MuxFlow has been deployed at ByteDance on more than 18000 GPUs. The deployment results indicate that MuxFlow substantially improves the GPU utilization from 26% to 76%, SM activity from 16% to 33%, and GPU memory usage from 42% to 48%. [ABSTRACT FROM AUTHOR]

Tetracycline repressor (TetR) family regulators (TFRs) are the largest group of DNA-binding transcription factors and are widely distributed in bacteria and archaea. TFRs play vital roles in controlling the expression of various genes and regulating diverse physiological processes. Recently, a TFR protein Pseudomonas virulence regulator A (PvrA), was identified from Pseudomonas aeruginosa as the transcriptional activator of genes involved in fatty acid utilization and bacterial virulence. Here, we show that PvrA can simultaneously bind to multiple pseudo-palindromic sites and upregulate the expression levels of target genes. Cryo-electron microscopy (cryo-EM) analysis indicates the simultaneous DNA recognition mechanism of PvrA and suggests that the bound DNA fragments consist of a distorted B-DNA double helix. The crystal structure and functional analysis of PvrA reveal a hinge region that secures the correct domain motion for recognition of the promiscuous promoter. Additionally, our results showed that mutations disrupting the regulatory hinge region have differential effects on biofilm formation and pyocyanin biosynthesis, resulting in attenuated bacterial virulence. Collectively, these findings will improve the understanding of the relationship between the structure and function of the TetR family and provide new insights into the mechanism of regulation of P. aeruginosa virulence. [ABSTRACT FROM AUTHOR]

Non-ribosomal peptide synthetases are mega-enzyme assembly lines that synthesize many clinically useful compounds. As a gatekeeper, they have an adenylation (A)-domain that controls substrate specificity and plays an important role in product structural diversity. This review summarizes the natural distribution, catalytic mechanism, substrate prediction methods, and in vitro biochemical analysis of the A-domain. Taking genome mining of polyamino acid synthetases as an example, we introduce research on mining non-ribosomal peptides based on A-domains. We discuss how non-ribosomal peptide synthetases can be engineered based on the A-domain to obtain novel non-ribosomal peptides. This work provides guidance for screening non-ribosomal peptide-producing strains, offers a method to discover and identify A-domain functions, and will accelerate the engineering and genome mining of non-ribosomal peptide synthetases. Key points: • Introducing adenylation domain structure, substrate prediction, and biochemical analysis methods • Advances in mining homo polyamino acids based on adenylation domain analysis • Creating new non-ribosomal peptides by engineering adenylation domains [ABSTRACT FROM AUTHOR]

Objectives: To investigate the outcome and short-term follow-up of autogenous tooth shell (TS) grafting for bone augmentation in the esthetic zone, as well as stability and esthetics of implant-supported restoration. Materials and methods: A total of 8 patients with 11 implants in 11 sites were enrolled in this study. All the horizontal and/or vertical bone defects in the esthetic zone were augmented by tooth shells, which were fixed laterally to the residual bone with osteosynthesis screws. The gap between the shell and residual bone was filled with Bio-Oss® granules. Four months after bone augmentation, dimensionally sufficient dental implants were inserted and implants-supported prostheses were made 3 months later. The esthetic outcome was evaluated by pink esthetic score (PES) and white esthetic score (WES) one year after prosthetic restoration. Horizontal ridge width (HRW) was assessed before and immediately after bone augmentation, as well as 4 and 19 months post-augmentation by radiography. The stability and absorption of TS grafts were evaluated at the 4th and 19th months post-augmentation. Results: Though wound dehiscences occurred in 3 cases, secondary healings were obtained after TS modification and irrigation. The other 5 cases went through uneventful healing during the whole observation period. Radiographic examination showed that HRW was 8.01 ± 0.93 mm (median: 7.80, 95% CI 7.38, 8.64) 4 months after TS augmentation, which was statistically different compared to HRW (2.72 ± 1.73 mm) at the baseline. Mean HRW gain was 5.29 ± 2.03 mm (median: 4.60, 95% CI 3.92, 6.66). Three-dimensional bone volume in all the augmented sites was sufficient for dental implants insertion and prosthetic restoration. Follow-up of one year showed stable marginal bone around dental implants. The implant survival rate was 100%. HRW losses were 0.65 ± 0.43 mm (the 4th month) and 1.05 ± 0.54 mm (the 19th month) compared to HRW immediately after augmentation. The PES and WES of final prosthetic restorations were 8.09 ± 0.70 and 8.91 ± 0.54, respectively. Conclusions: Autogenous tooth shell grafting is a reliable approach for bone augmentation in the esthetic zone for dental implant treatment, allowing for favorable stability and esthetic outcome of implant-supported prosthesis within the one-year follow-up period. [ABSTRACT FROM AUTHOR]

MucA and MucB are critical negative modulators of sigma factor AlgU and regulate the mucoid conversion of Pseudomonas aeruginosa. Previous studies have revealed that lipid signals antagonize MucA-MucB binding. Here we report the crystal structure of MucB in complex with the periplasmic domain of MucA and polyethylene glycol (PEG), which unveiled an intermediate state preceding the MucA-MucB dissociation. Based on the biochemical experiments, the aliphatic side chain with a polar group was found to be of primary importance for inducing MucA cleavage. These results provide evidence that the hydrophobic cavity of MucB is a primary site for sensing lipid molecules and illustrates the detailed control of conformational switching within MucA-MucB in response to lipophilic effectors. Tao Li et al. report crystal structure of MucA-MucB complex and identify a cavity region of MucB that binds PEG molecule. They further show that this hydrophobic cavity of MucB is a primary site for sensing lipid molecules and that lipid A stimulates MucB to release MucA for AlgW cleavage, helping to understand the regulation mechanism of alginate biosynthesis. [ABSTRACT FROM AUTHOR]

Immediately after the demonstration of the high-quality electronic properties in various two dimensional (2D) van der Waals (vdW) crystals fabricated with mechanical exfoliation, many methods have been reported to explore and control large scale fabrications. Comparing with recent advancements in fabricating 2D atomic layered crystals, large scale production of one dimensional (1D) nanowires with thickness approaching molecular or atomic level still remains stagnant. Here, we demonstrate the high yield production of a 1D vdW material, semiconducting Ta2Pd3Se8 nanowires, by means of liquid-phase exfoliation. The thinnest nanowire we have readily achieved is around 1 nm, corresponding to a bundle of one or two molecular ribbons. Transmission electron microscopy (TEM) and transport measurements reveal the as-fabricated Ta2Pd3Se8 nanowires exhibit unexpected high crystallinity and chemical stability. Our low-frequency Raman spectroscopy reveals clear evidence of the existing of weak inter-ribbon bindings. The fabricated nanowire transistors exhibit high switching performance and promising applications for photodetectors. [ABSTRACT FROM AUTHOR]

Mechanisms of glutathione (GSH) over-accumulation in mutant Saccharomyces cerevisiae Y518 screened by ultraviolet and nitrosoguanidine-induced random mutagenesis were studied. Y518 accumulated higher levels of GSH and l-cysteine than its wild-type strain. RNA-Seq and pathway enrichment analysis indicated a difference in the expression of key genes involved in cysteine production, the GSH biosynthesis pathway, and antioxidation processes. GSH1, MET17, CYS4, GPX2, CTT1, TRX2, and SOD1 and the transcriptional activators SKN7 and YAP1 were up-regulated in the mutant. Moreover, Y518 showed a dysfunctional respiratory chain resulting from dramatically weakened activity of complex III and significant elevation of intracellular reactive oxygen species (ROS) levels. The supplementation of antimycin A in the culture of the parent strain showed equivalent changes of ROS and GSH level. This study indicates that defective complex III prompts abundant endogenic ROS generation, which triggers an oxidative stress response and upregulation of gene expression associated with GSH biosynthesis. This finding may be helpful for developing new strategies for GSH fermentation process optimization or metabolic engineering. [ABSTRACT FROM AUTHOR]

Objectives: The Tyr52 residue of d-lactate dehydrogenase ( d-LDH) from Lactobacillus pentosus was replaced with small hydrophobic residues and overexpressed in E. coli BL21 (DE3) to enhance 3-phenyllactic acid (PLA) synthesis by whole-cell catalyst. Results: Escherichia coli pET-28a- d- ldh produced 12.2 g PLA l in 3 h, with a molar conversion rate of 61 %, while E. coli pET-28a- d- ldh produced 15.6 g PLA l, with a molar conversion rate of 77 %. This study demonstrates the feasibility of using engineered E. coli for PLA production from phenylpyruvate (PPA) and showed that site-directed mutagenesis of d- ldh markedly improved PLA yield and substrate conversion rate. Conclusion: This biocatalytic system is a promising platform for PLA production from PPA. [ABSTRACT FROM AUTHOR]

The influences of fractal pore structure in coal reservoir on coalbed methane (CBM) migration were analyzed in detail by coupling theoretical models and numerical methods. Different types of fractals were generated based on the construction thought of the standard Menger Sponge to model the 3D nonlinear coal pore structures. Then a correlation model between the permeability of fractal porous medium and its pore-size-distribution characteristics was derived using the parallel and serial modes and verified by Lattice Boltzmann Method (LBM). Based on the coupled method, porosity ( φ), fractal dimension of pore structure ( D), pore size range ( r, r) and other parameters were systematically analyzed for their influences on the permeability ( κ) of fractal porous medium. The results indicate that: ① the channels connected by pores with the maximum size ( r) dominate the permeability κ, approximating in the quadratic law; ② the greater the ratio of r and r is, the higher κ is; ③ the relationship between D and κ follows a negative power law model, and breaks into two segments at the position where D≌2.5. Based on the results above, a predicting model of fractal porous medium permeability was proposed, formulated as κ= Cfr, where C and n (approximately equal to 2) are constants and f is an expression only containing parameters of fractal pore structure. In addition, the equivalence of the new proposed model for porous medium and the Kozeny-Carman model κ= Cr was verified at D=2.0. [ABSTRACT FROM AUTHOR]

In the present study, we investigated the mode of cell response induced by D-limonene in Saccharomyces cerevisiae. D-limonene treatment was found to be accompanied by intracellular accumulation of reactive oxygen species (ROS). Since ROS impair cell membranes, an engineered strain with enhanced membrane biosynthesis exhibited a higher tolerance to D-limonene. Subsequent addition of an ROS scavenger significantly reduced the ROS level and alleviated cell growth inhibition. Thus, D-limonene-induced ROS accumulation plays an important role in cell death in S. cerevisiae. In D-limonene-treated S. cerevisiae strains, higher levels of antioxidants, antioxidant enzymes, and nicotinamide adenine dinucleotide phosphate (NADPH) were synthesized. Quantitative real-time PCR results also verified that D-limonene treatment triggered upregulation of genes involved in the antioxidant system and the regeneration of NADPH at the transcription level in S. cerevisiae. These data indicate that D-limonene treatment results in intracellular ROS accumulation, an important factor in cell death, and several antioxidant mechanisms in S. cerevisiae were enhanced in response to D-limonene treatment. [ABSTRACT FROM AUTHOR]

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