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Artificial-intelligence-assisted decision-making is appearing increasingly more frequently in our daily lives; however, it has been shown that biased data can cause unfairness in decision-making. In light of this, computational techniques are needed to limit the inequities in algorithmic decision-making. In this letter, we present a framework to join fair feature selection and fair meta-learning to do few-shot classification, which contains three parts: (1) a pre-processing component acts as an intermediate bridge between fair genetic algorithm (FairGA) and fair few-shot (FairFS) to generate the feature pool; (2) the FairGA module considers the presence or absence of words as gene expression, and filters out key features by a fairness clustering genetic algorithm; (3) the FairFS part carries out the task of representation and fairness constraint classification. Meanwhile, we propose a combinatorial loss function to cope with fairness constraints and hard samples. Experiments show that the proposed method achieves strong competitive performance on three public benchmarks.

Cephalosporins play an indispensable role against bacterial infections. Deacetyloxycephalosporin C synthase (DAOCS), also called expandase, is a key enzyme in cephalosporin biosynthesis that epoxides penicillin to form the hexavalent thiazide ring of cephalosporin. DAOCS in fungus Acremonium chrysogenum was identified as a bifunctional enzyme with both ring expansion and hydroxylation, whereas two separate enzymes in bacteria catalyze these two reactions. In this review, we briefly summarize its source and function, improvement of the conversion rate of penicillin to deacetyloxycephalosporin C through enzyme modification, crystallography features, the prediction of the active site, and application perspective.

The task of extracting entities and relations has evolved from distributed extraction to joint extraction. The joint model overcomes the disadvantages of distributed extraction method and strengthens the information interaction between entities and relations. However, the existing methods of the joint model rarely pay attention to the semantic information between words, which have limitations in solving the problem of overlapping relations. In this paper, we propose an RMAN model for joint extraction of entities and relations, which includes multi-feature fusion encoder sentence representation and decoder sequence annotation. We first add a multi-head attention layer after Bi-LSTM to obtain sentence representations, and leverage the attention mechanism to capture relation-based sentence representations. Then, we perform sequence annotation on the sentence representation to obtain entity pairs. Experiments on NYT-single, NYT-multi and WebNLG datasets demonstrate that our model can efficiently extract overlapping triples, which outperforms other baselines.

The global regulator LaeA and its orthologs govern the morphogenetic development and secondary metabolism of several filamentous ascomycetes. In Aspergillus niger, it has been shown that an LaeA ortholog (AnLaeA) regulates the production of citric acid and secondary metabolites. In this work, we constructed AnlaeA disruption and overexpression strains to investigate the roles of AnLaeA in morphological development and ochratoxin A (OTA) biosynthesis in A. niger. Phenotypic observation, chemical analysis, and gene expression analysis indicated that AnLaeA acts as a negative regulator of conidial morphogenesis and positively regulates gene expression of the OTA cluster in A. niger grown in CYA medium. However, it was observed that the upregulation of gene expression of the OTA cluster does not necessarily increase OTA production. Our results contribute to a better understanding of the AnlaeA regulatory mechanism and suggest the AnlaeA gene as a potential target for developing control strategies for A. niger infection and OTA biosynthesis.

Manchu is a low-resource language that is rarely involved in text recognition technology. Because of the combination of typefaces, ordinary text recognition practice requires segmentation before recognition, which affects the recognition accuracy. In this paper, we propose a Manchu text recognition system divided into two parts: text recognition and text retrieval. First, a deep CNN model is used for text recognition, using a sliding window instead of manual segmentation. Second, text retrieval finds similarities within the image and locates the position of the recognized text in the database; this process is described in detail. We conducted comparative experiments on the FAST-NU dataset using different quantities of sample data, as well as comparisons with the latest model. The experiments revealed that the optimal results of the proposed deep CNN model reached 98.84%.

This paper addresses the trajectory tracking control issue of a quadrotor with environmental disturbances, which particularly focuses on attitude correction during flight and response speed improvement. In this paper, the proposed control method uses the differential equation to transform the desired trajectory for improving the robustness of a quadrotor during high-speed flight. Meanwhile, a nonlinear controller based on the rotation matrix is designed to avoid singularities of Euler angles. The controller can also stabilize the position error to zero without reducing the control thrust when the attitude error is large. Finally, we conduct simulations on a tethered quadrotor to achieve high-speed flight in limited space. The simulation results show that the control method can stabilize a quadrotor at high-speed trajectory flight and keep a quadrotor stable when it is disturbed by aerodynamic drag and mass change.

Event extraction is a challenging task in text mining. Current research on event extraction is often based on the sentence level, while the research based on the document level is less investigated. In this paper, we propose a deep learning model, termed BLMA, which combines Bi-LSTM and Multi-head weighted Attention to detect multiple event types. Unlike traditional methods, BLMA can directly detect events in texts without trigger words. We regard the event detection task of the chapter as a multi-label classification problem and apply the BLMA onto the application of detecting events in movie scripts. Experiment results show that BLMA performs well on an automatically tagged screenplay dataset containing 11 event types. F1 score of event detection using BLMA reaches 91.6% for a chapter with a single event, and 93.9% with multiple events, which outperforms other models. Therefore, our deep learning approach can effectively extract events from a chapter, which can be used for event detection on movie scripts. In addition, we explore the contribution of each component of the BLMA to the results, and find that multi-head attention has a significant impact on the performance. Keywords: Event Detection, Bi-LSTM, Attention.

In this paper, we investigate two sub-tasks of aspect-based sentiment analysis (ABSA) through the pre-trained language model BERT, namely opinion target extraction (OTE) and target-oriented opinion words extraction (TOWE). Specifically, we build a novel framework for the joint extraction model of opinion target and target-oriented opinion words feedback, which aims to extract the opinion target and corresponding opinion words. In order to accomplish the TOWE task more effectively, we proposed an IO-LSTM+Transformer structure, termed IOT, which has excellent performance in domain-specific datasets when combined with the BERT pre-training model. To validate the effectiveness of our model, we develop a pipeline model for comparison. Experiment results show that our model can extract the pair of opinion target and opinion words from the sentence more effectively than the pipeline model. Therefore, our joint model has the potential to facilitate other tasks of ABSA.

Background Aspergillus niger is a filamentous fungus used for the majority of global citric acid production. Recent developments in genome editing now enable biotechnologists to engineer and optimize A. niger. Currently, however, genetic-leads for maximizing citric acid titers in industrial A. niger isolates is limited. Results In this study, we try to engineer two citric acid A. niger production isolates, WT-D and D353, to serve as platform strains for future high-throughput genome engineering. Consequently, we used genome editing to simultaneously disrupt genes encoding the orotidine-5′-decarboxylase (pyrG) and non-homologous end-joining component (kusA) to enable use of the pyrG selection/counter selection system, and to elevate homologous recombination rates, respectively. During routine screening of these pyrG mutant strains, we unexpectedly observed a 2.17-fold increase in citric acid production when compared to the progenitor controls, indicating that inhibition of uridine/pyrimidine synthesis may increase citric acid titers. In order to further test this hypothesis, the pyrG gene was placed under the control of a tetracycline titratable cassette, which confirmed that reduced expression of this gene elevated citric acid titers in both shake flask and bioreactor fermentation. Subsequently, we conducted intracellular metabolomics analysis, which demonstrated that pyrG disruption enhanced the glycolysis flux and significantly improved abundance of citrate and its precursors. Conclusions In this study, we deliver two citric acid producing isolates which are amenable to high throughput genetic manipulation due to pyrG/kusA deletion. Strikingly, we demonstrate for the first time that A. niger pyrG is a promising genetic lead for generating citric acid hyper-producing strains. Our data support the hypothesis that uridine/pyrimidine biosynthetic pathway offer future avenues for strain engineering efforts.

Additional file 1: Figure S1. Phenotypic comparison of pyrG and kusA mutants derived by A. niger D and D353. Figure S2. Insertion inactivation of the albA gene in A. niger D10 and D353.8. Figure S3. Titratable expression of pyrG mutagenesis constructed in A. niger. Figure S4. Extracellular organic acids of pyrG titratable expression mutant in 5 L bioreactor. Table S1. Protospacers used in this study, Table S2. Primers used in this study. Table S3. DNA sequences of sgRNA constructs used in this study. Table S4. DNA sequences of donor DNAs used in this study.

The veA gene is a key regulator governing morphogenetic development and secondary metabolism in many fungi. Here, we characterized and disrupted a veA orthologue in an ochratoxigenic Aspergillus niger strain. Morphological development, ochratoxin A (OTA) biosynthesis, and oxidative stress tolerance in the wild-type and veA disruption strains were further analyzed. Accordingly, the link between the veA gene and development of specific gene brlA, OTA biosynthesis key gene pks, and oxidative-stress-tolerance-related gene cat was explored. Results demonstrated that the veA gene acts as a positive regulator of conidia production, OTA biosynthesis, and oxidative stress tolerance in A. niger, regardless of light conditions. Darkness promoted conidial production and OTA biosynthesis in the A. niger wild-type strain. Our results contribute to a better understanding of the veA regulatory mechanism and suggest the veA gene as a potential target for developing control strategies for A. niger infection and OTA biosynthesis.

In this work, we constructed the aox1 disruption strains 3-4 and 4-10, as well as the aox1 overexpression strains 72 and 102 in Aspergillus niger. The energy metabolism, EMP, TCA pathways, and flux were investigated for the citric acid (CA) overproduction via the aox1 overexpression among them. As expected, the overexpression of the aox1 gene enabled a higher growth rate than that of the rate of its parent strain in medium with respiratory chain inhibitors. In liquefied corn starch medium supplemented with 0.2 μg/mL antimycin A, the CA production of the overexpression strain 102 reached up to 169.1 g/L, whereas the highest value of the parent strain was 158.9 g/L. For the perspective of the aox1 disruption strain 4-10, the yield of CA dropped to 125.6 g/L, and the loose mycelial pellets forming in the medium also revealed that the fundamentally important role of AOX in A. niger lies in the resistance to oxidative stress under fully aerobic conditions. Based on real-time qPCR gene expression analysis and measurement of intracellular ATP and NADH levels, we came to a conclusion that the higher NADH oxidation rate resulting from the overexpression of the aox1 gene mainly contributed to rate-limited step's acceleration and strengthened metabolic flow via mycelia and led to the CA yield in these strains increased by 13.5 and 10.8%, respectively. Subsequently, it was found that overexpression strains had higher AOX relative content and more oxygen consumption at different fermentation stages, which fully confirmed the close relationship between aox1 gene and energy metabolism, and comprehensively revealed aox1 gene function through the combination with the above conclusions.

Glutamate decarboxylase (GAD) is the sole enzyme that synthesizes γ-aminobutyric acid through the irreversible decarboxylation of l-glutamate. In this study, the purification and characterization of an unreported GAD from a novel strain of Enterococcus raffinosus TCCC11660 were investigated. The native GAD from E. raffinosus TCCC11660 was purified 32.3-fold with a recovery rate of 8.3%, using ultrafiltration and ammonium sulfate precipitation, followed by ion-exchange and size-exclusion chromatography. The apparent molecular weight of purified GAD, as determined by SDS-PAGE and size-exclusion chromatography was 55 and 110 kDa, respectively, suggesting that GAD exists as a dimer of identical subunits in solution. In the best sodium citrate buffer, metal ions of Mo6+ and Mg2+ had positive effects, while Cu2+, Fe2+, Zn2+ and Co2+ showed significant adverse effects on enzyme activity. The optimum pH and temperature of GAD were determined to be 4.6 and 45 °C, while the K m and V max values for the sole l-glutamate substrate were 5.26 and 3.45 μmol L−1 min−1, respectively.

The polyketide synthase gene An15g07920 was known in Aspergillus niger CBS 513.88 as putatively involved in the production of ochratoxin A (OTA). Genome resequencing analysis revealed that the gene An15g07920 is also present in the ochratoxin-producing A. niger strain 1062. Disruption of An15g07920 in A. niger 1062 removed its capacity to biosynthesize ochratoxin β (OTβ), ochratoxin α (OTα), and OTA. These results indicate that the polyketide synthase encoded by An15g07920 is a crucial player in the biosynthesis of OTA, in the pathway prior to the phenylalanine ligation step. The gene An15g07920 reached its maximum transcription level before OTA accumulation reached its highest level, confirming that gene transcription precedes OTA production. These findings will not only help explain the mechanism of OTA production in A. niger but also provide necessary information for the development of effective diagnostic, preventive, and control strategies to reduce the risk of OTA contamination in foods.

Citric acid is produced by an industrial-scale process of fermentation using Aspergillus niger as a microbial cell factory. However, citric acid production was hindered by the non-fermentable isomaltose and insufficient saccharification ability in A. niger when liquefied corn starch was used as a raw material. In this study, A. niger TNA 101ΔagdA was constructed by deletion of the α-glucosidase-encoding agdA gene in A. niger CGMCC 10142 genome using Agrobacterium tumefaciens-mediated transformation. The transformants A. niger OG 1, OG 17, and OG 31 then underwent overexpression of glucoamylase in A. niger TNA 101ΔagdA. The results showed that the α-glucosidase activity of TNA 101ΔagdA was decreased by 62.5 % compared with CGMCC 10142, and isomaltose was almost undetectable in the fermentation broth. The glucoamylase activity of the transformants OG 1 and OG 17 increased by 34.5 and 16.89 % compared with that of TNA 101ΔagdA, respectively. In addition, for the recombinants TNA 101ΔagdA, OG 1 and OG 17, there were no apparent defects in the growth development. Consequently, in comparison with CGMCC 10142, TNA 101ΔagdA and OG 1 decreased the residual reducing sugar by 52.95 and 88.24 %, respectively, and correspondingly increased citric acid production at the end of fermentation by 8.68 and 16.87 %. Citric acid production was further improved by decreasing the non-fermentable residual sugar and increasing utilization rate of corn starch material in A. niger. Besides, the successive saccharification and citric acid fermentation processes were successfully integrated into one step.

Lactobacillus brevis TCCC 13007 was used to produce γ-aminobutyric acid. The fermentation broth was degermed, decolorized and deionized before the green-style spray drying, and the process parameters were optimized. Single-factor experiments were carried out to optimize 7 factors to investigate their effects on spray drying. Maltodextrin was found to be a good drying aid that significantly improves the drying process. Response surface methodology was used to assess the combined effects of air inlet temperature, spray pressure and amount of maltodextrin, to optimize the spray drying process parameters of the γ-aminobutyric acid-containing eluent. The optimized variables were applied for the following evaluation of the powder collection rate and comprehensive product score evaluation. Using the optimum parameters of spray drying, the powder collection rate reached 62.74 %, the comprehensive score was 85, and the γ-aminobutyric acid content was 67.5 %, and the recovery rate of GABA was 60.71 %. These results lay the foundation of further industrial scale-up of γ-aminobutyric acid production from fermentation broth.

Pyruvate decarboxylase (PDC), a key enzyme in alcoholic fermentation in Saccharomyces cerevisiae, can degrade pyruvic acid to further convert acetaldehyde into ethanol. The main structural genes encoding PDC are PDC1 and PDC5. In this study, metabolic engineering principles were used to block the further metabolism of pyruvic acid; Saccharomyces cerevisiae Y2-1 with PDC1 disruption and Y2-15 with both PDC1 and PDC5 disruption were obtained using the LiAc/SS carrier DNA/PEG method. The specific PDC activity of mutant S. cerevisiae Y2-1 decreased by 31 % compared to that of the parent strain Y2, while specific PDC activity was barely detectable in mutant S. cerevisiae Y2-15. Moreover, the mutant Y2-1 with PDC1 disruption displayed no obvious effect on the rate of growth in the yeast nitrogen base with glucose (YNBG) medium, but the growth rate of S. cerevisiae Y2-15 was significantly lower than that of the parent strain Y2. Finally, through optimization of the fermentation medium, the accumulation of pyruvic acid by Y2-15 increased to 24.65 g/L over a period of 96 h, 16.86-fold higher than with the parental strain Y2 by shake flask cultivation.

Histamine (HIS) producers in fermented wines are generally believed to be lactic acid bacteria (LAB), and other microorganisms have received little or no attention. In this work, HIS-producing bacteria were isolated from Qu fermentation starter for Chinese rice wine brewing by decarboxylase medium, and their identity was confirmed by RP-HPLC and PCR. Surprisingly, the histidine decarboxylase gene (hdc) was present in only 2 out of 26 isolates. All 26 isolates were genotyped using the randomly amplified polymorphic DNA (RAPD)-PCR assay, which revealed the presence of 21 biotypes. Single type isolates were identified via 16S rRNA sequence analysis, in some cases coupled with partial sequencing of the rpoB or dnaJ gene. All isolates belonged to the Enterobacteriaceae, and included Enterobacter asburiae, Enterobacter cloacae, Enterobacter hormaechei, Citrobacter amalonaticus and Cronobacter sakazakii. All these strains were capable of producing >3.5 mg/L of HIS in TS medium without ethanol, but did not grow in TS medium with 8% ethanol. Small-scale Chinese rice wine fermentation revealed that HIS contents exhibited the same trend as the LAB and ethanol no matter what kinds of Qu were used. However, in the early stages of fermentation (from day 2 to day 4), the HIS contents had a stronger correlation with Enterobacteriaceae (0.943) than with LAB (0.369) when the Qu fermented samples are analyzed as a whole. Moreover, the lowest HIS content was measured in Xiao Qu (Q) fermented sample at the end of fermentation, which suggests that the formation of HIS in the early stages of fermentation has a decisive effect on HIS content in the final product. Our results demonstrate that Enterobacteriaceae from Qu are an important cause for HIS formation in Chinese rice wine. Consequently, selecting Qu with a low content of Enterobacteriaceae contaminants and inhibiting the growth of Enterobacteriaceae in the early stages of fermentation are useful approaches for preventing excessive amounts of HIS formation in Chinese rice wine brewing.

The detection and separation of circulating tumor cells (CTCs) are crucial in early cancer diagnosis and cancer prognosis. Filtration through a thin film is one of the size and deformability based separation methods, which can isolate rare CTCs from the peripheral blood of cancer patients regardless of their heterogeneity. In this paper, volume of fluid (VOF) multiphase flow models are employed to clarify the cells’ filtering processes. The cells may deform significantly when they enter a channel constriction, which will induce cell membrane stress and damage if the area strain is larger than the critical value. Therefore, the cellular damage criterion characterized by membrane area strain is presented in our model, i.e., the lysis limit of the lipid bilayer is taken as the critical area strain. Under this criterion, we discover that the microfilters with slit-shaped pores do less damage to cells than those with circular pores. The influence of contact angle between the microfilters and blood cells on cellular injury is also discussed. Moreover, the optimal film thickness and flux in our simulations are obtained as 0.5 μm and 0.375 mm/s, respectively. These findings will provide constructive guidance for the improvement of next generation microfilters with higher throughput and less cellular damage.

On the basis of the similar fluorescence of ethyl carbamate (EC) and urea derivatives, a high-performance liquid chromatography method coupled with fluorescence detection was developed for the simultaneous determination of EC and urea in alcoholic beverages. The chromatographic separation and derivatization conditions of EC and urea were optimized. Under the established conditions, the detection limit, relative standard deviation, linear range, and recovery were 4.8 μg/L, 1.0-4.2%, 10-500 μg/L, and 93.8-104.6%, respectively, for EC; the corresponding values were 0.003 mg/L, 1.2-4.8%, 0.01-100 mg/L, and 90.7-104.8%, respectively, for urea. The method showed satisfactory values for precision, recovery, and sensitivity for both analytes and is well-suited for routine analysis and kinetic studies of the formation of EC from urea alcoholysis in alcoholic beverages.

It was found that S-adenosylmethionine (SAM) could effectively improve avermectin titer with 30–60 μg/mL addition to FH medium. To clearly elucidate the mechanism of SAM on intracellular metabolites of Streptomyces avermitilis, a GC–MS-based comparative metabolomics approach was carried out. First, 230 intracellular metabolites were identified and 14 of them remarkably influenced avermectin biosynthesis were discriminative biomarkers between non-SAM groups and SAM-treated groups by principal components analysis (PCA) and partial least squares (PLS). Based on further key metabolic pathway analyses, these biomarkers, such as glucose, oxaloacetic acid, fatty acids (in soybean oil), threonine, valine, and leucine, were identified as potentially beneficial precursors and added in medium. Compared with single-precursor feeding, the combined feeding of the precursors and SAM markedly increased the avermectin titer. The co-feeding approach not only directly verified our hypothesis on the mechanism of SAM by comparative metabolomics, but also provided a novel strategy to increase avermectin production.

In this study, we reported the effects of temperature, malic acid loading concentration, and resin dose on malic acid adsorption by IRA-67 in batch experiments. The kinetic data well fitted the pseudo-second-order kinetic model. Both the equilibrium and ultimate adsorption slightly decreased with increased temperature from 303 to 323 K at 74.7 g/L malic acid loading concentration. The malic acid adsorption was revealed as a homogeneous adsorbent process by the Langmuir model and film diffusion process at loading concentrations of 18.2–94.5 g/L malic acid by the Boyd plot. The values of effective diffusion coefficient D i also increased with the temperature. Based on Eq. (15) , the negative values of Δ G ° and Δ H ° revealed that the adsorption process was spontaneous and exothermic. The negative value of Δ S ° also indicated the decrease in the solid–liquid interface randomness at this interface when malic acid is adsorbed by IRA-67.

A statistically based method was used to optimize the fermentation medium for enhancing citric acid production by Aspergillus niger TCCC 41661. The optimization of single-factor experiments (soy peptone, (NH4)2SO4, dextrin) and an orthogonal experiment were applied to determine the optimal concentration of each significant variable. The optimum values for the critical components were obtained as follows: 0.25 g/L soy peptone, 12.0 g/L dextrin, 2.0 g/L KH2PO4, 2.0 g/L (NH4)SO4, 0.1 % Tween 80. Under this condition, the citric acid production of 16.11 g/L was obtained.