Genome-scale metabolic model (GEM) is a powerful tool for interpreting and predicting cellular phenotypes under various environmental and genetic perturbations. However, GEM only consid-ers stoichiometric constraints, and the simulated growth and product yield values will show a monotonic linear increase with increasing substrate uptake rate, which deviates from the experi-mentally measured values. Recently, the integration of enzymatic constraints into stoichiometry-based GEMs was proven to be effective in making novel discoveries and predicting new engineer-ing targets. Here we present the first genome-scale enzyme-constrained model (eciCW773) for Corynebacterium glutamicum reconstructed by integrating enzyme kinetic data from various sources using ECMpy workflow based on the high-quality GEM of C. glutamicum (obtained by modifying the iCW773 model). The enzyme-constrained model improved the prediction of pheno-types and simulated overflow metabolism, while also recapitulating the trade-off between biomass yield and enzyme usage efficiency. Finally, we used eciCW773 to identify several gene modifica-tion targets for L-lysine production, most of which agree with previously reported genes. This study shows that incorporating enzyme kinetic information into the GEM enhances the cellular phenotypes prediction of C. glutamicum, which can help identify key enzymes and thus provide reliable guidance for metabolic engineering.

Genome-scale metabolic models (GEMs) play an important role in the phenotype prediction of microorganisms, and their accuracy can be further improved by integrating other types of biological data such as enzyme concentrations and kinetic coefficients. Enzyme-constrained models (ecModels) have been constructed for several species and were successfully applied to increase the production of commodity chemicals. However, there was still no genome-scale ecModel for the important model organism Bacillus subtilis prior to this study. Here, we integrated enzyme kinetic and proteomic data to construct the first genome-scale ecModel of B. subtilis (ecBSU1) using the ECMpy workflow. We first used ecBSU1 to simulate overflow metabolism and explore the trade-off between biomass yield and enzyme usage efficiency. Then, we simulated the growth rate on eight previously published substrates and found that the simulation results of ecBSU1 were in good agreement with the literature. Finally, we identified target genes that enhance the yield of commodity chemicals using ecBSU1, most of which were consistent with the experimental data, and some of which may be potential novel targets for metabolic engineering. This work demonstrates that the integration of enzymatic constraints is an effective method to improve the performance of GEMs. The ecModel can predict overflow metabolism more precisely and can be used for the identification of target genes to guide the rational design of microbial cell factories.

The over use of pharmaceutical compounds, essentially antibiotics, led to an increase of their concentrations in aquatic ecosystems. In this study, the white-rot fungus Coriolopsis gallica (high-laccase-producing fungus) was investigated for the biodegradation of ampicillin (AMP) under different cultivation conditions. The biotransformation of the antibiotic was confirmed by means of high-performance liquid chromatography (HPLC), and the antibacterial activity was evaluated via the bacterial growth inhibition agar well diffusion method using Escherichia coli as an ampicillin-sensitive test strain. The results showed that AMP (50 mg L-1) was totally removed by C. gallica after 6 days of incubation in a liquid medium. The antibiotic removal rate was maximal with a fungal culture aged 9 days. Such a culture achieved the removal of a higher concentration of up to 500 mg L-1 of ampicillin in 3 days. This higher antibiotic removal rate was concomitant with the maximal laccase production in culture supernatant. In addition, four consecutive doses of 500 mg L-1 of ampicillin were transformed by the same fungal culture in 24 days. After that, the fungus was unable to remove the antibiotic. The measurement of ligninolytic enzyme activity showed that laccase of C. gallica might participate in the biotransformation of AMP.

The lithium-ion batteries are widely used as a power source for portable devices, including cell phones. The useful life is about 2 years or 500 cycles, contributing to the generation of waste from electrical and electronic equipment (WEEE). Mining of lithium and cobalt damages the environment and is onerous; therefore, sustainable alternatives, such as obtaining these elements from secondary sources as recycling of lithium-ion batteries, are essential to provide the inputs used in the sector. However, the metallurgical route which will used to recovering them must be considered, due to this work aims for a more environmentally favorable process using DL-malic acid 1.5 M and instead of compared with sulfuric acid 2 M, heat pretreatment of 1 h and 3 h, and for all conditions, experiments were carried out with and without adding the oxidizing agent hydrogen peroxide. The best yields occurred in presence of H2O2 10 % v/v, and heat pretreatment of 1 h: 33.49 % Co and 4.63 % Li, and 29.78 % Co e 3.44 % Li were recovered by sulfuric acid and DL-malic acid, respectively.

Epithelial–mesenchymal transition (EMT) is defined as a cellular process during which epithelial cells acquire mesenchymal phenotypes and behavior following the downregulation of epithelial features. EMT and its reversed process, the mesenchymal-epithelial transition (MET), and the special form of EMT, the endothelial-mesenchymal transition (EndMT), have been thought as a universal dogma controlling developmental and pathological processes. More than half a century of EMT study has made it a large research field and a mainstream concept. However, discrepancies and disputes over EMT and EMT research have also grown over time. Particularly, neither the epithelial and mesenchymal states/properties nor their regulatory networks nor specific markers have been defined, rendering the EMT, MET and EndMT concepts groundless. Moreover, EMT and MET effects should not be a cause, but rather a consequence of or an accompanying effect during developmental and pathological processes. EMT and MET represented by the change in cell shapes or adhesiveness or symbolized by EMT factors are biased interpretation of the overall change in cellular property and regulatory networks during development and cancer progression. The true meaning of EMT effects in some developmental and pathological processes, such as fibrosis, needs re-evaluation. But the core EMT factors are actually a few components of the regulatory networks of neural stemness, which determines tumorigenicity and pluripotency. The EMT effects in cancer progression and neural crest formation are wrong attribution of the role of neural stemness during cancer progression and the cell-intrinsic property of neural crest cells to the unknown mesenchymal state. It is time to reassess the significance of EMT and its related concepts in scientific research.

Thromboembolic conditions, such as stroke and myocardial infarction [MI], are the primary causes of mortality globally. High efficiency was demonstrated by fibrinolytic enzymes isolated from microbial sources in dissolving various blood clots. The study aimed to investigate and produce bacterial fibrinolytic enzymes from various Egyptian soil conditions using recombinant DNA technology. Fifty soil samples were examined to determine the production of fibrinolytic enzymes. The plasmin plate technique assessed the thrombolytic activities of the strong fibrinolytic enzyme-producing bacterial isolates. In addition to determining the molecular mass using a mass spectrometer and the western blot method, the activity and thermostability of the enzymes were characterized. An affinity chromatography approach was used to purify the fibrinolytic enzymes. However, bacterial recombinant DNA technology produced the pure bacterial fibrinolytic enzyme. Several dosage formulations for the formulation of fibrinolytic enzymes were tested. By using affinity chromatography and the SDS-PAGE test, the isolated bacterial fibrinolytic enzyme in this investigation was almost 83% pure. Bacillus cereus ATCC 4342 was identified as the predominant bacterial isolate secreting fibrinolytic enzymes. It was discovered that the fibrinolytic enzyme activity of fifty soil samples ranged from 0.167 U/ml to 1.853 U/ml. The extracellular enzyme extracted from Bacillus cereus culture supernatant demonstrated a relatively stable fibrinolytic activity over 18 hours at a pH range of 7.4–10, as well as stability with maximum productivity at 43℃ for over 60 minutes. In this investigation, the enzyme was referred to as Fibrin-proteinase[ FP]. The fibrin clots were directly thrombolyzed by the FP. The calculated values for the specific activity and molecular mass of the FP were approximately 40.71 units/mg of protein and approximately 30 KDa, respectively. It was observed that the presence of Fe+3 marginally boosted protease activity, but the presence of EDTA decreased it. On the other hand, adding monovalent cations like K+1 and Na+1 significantly increased the fibrinolytic activity of FP. The enzyme exhibited activity throughout the temperature range of 20 to 65℃, peaking at 55℃. The ideal range for the generation of protease was 35–43℃ and 8.0–10. The thermostable fibrinolytic enzyme FP, which was isolated from Bacillus cereus ATCC 4342 in various soil environments in Egypt during the current study, was a promising fibrinolytic enzyme because it demonstrated a more extensive and effective fibrinolytic activity and fewer side effects than the fibrinolytic enzymes that are currently available worldwide. It is advised that further research be done on optimizing the right formulation of bacterial fibrinolytic enzymes in the future to help dissolve different types of blood clots and, as a result, lower the high death rate that exists worldwide.

Genome-scale metabolic models (GEMs) have been widely used for phenotypic prediction of microorganisms. However, the lack of other constraints in the stoichiometric model often leads to a large metabolic solution space inaccessible. Inspired by previous studies that take allocation of macromolecule resources into account, we developed a simplified Python-based workflow for constructing enzymatic constrained metabolic network model (ECMpy) and constructed an enzyme-constrained model for Escherichia coli (eciML1515) by directly adding a total enzyme amount constraint in the latest version of GEM for E. coli (iML1515), considering the protein subunit composition in the reaction, and automated calibration of enzyme kinetic parameters. Using eciML1515, we predicted the overflow metabolism of E. coli and revealed that redox balance was the key reason for the difference between E. coli and Saccharomyces cerevisiae in overflow metabolism. The growth rate predictions on 24 single-carbon sources were improved significantly when compared with other enzyme-constrained models of E. coli. Finally, we revealed the tradeoff between enzyme usage efficiency and biomass yield by exploring the metabolic behaviors under different substrate consumption rates. Enzyme-constrained models can improve simulation accuracy and thus can predict cellular phenotypes under various genetic perturbations more precisely, providing reliable guidance for metabolic engineering.

Soil extracellular enzyme activity (EEAs) and enzymatic stoichiometry (ES) can provide a crucial indication of changes in soil ecosystem's nutrient availability and the microbial resource limitations. However, the changing characteristics of soil EEAs and ES at different stages of the native succession process and their key drivers are unclear. In order to investigate the soil EEAs, ES and driving factors of soil under vegetation at different succession stages, we adopted the "spatio-temporal substitution" method to collect the surface soil of bryophyte community, herbaceous community, shrub community and tree community in the new volcanic lava platform of Wudalianchi Volcanic Nature Reserve. We measured seven soil EEA, including carbon(C)-acquiring enzyme (β-1,4-glucosidase (BG)), N-acquiring enzymes (β-N-acetyl-glucosaminidase (NAG) and leucine aminopeptidase (LAP)) and phosphorus (P)-acquiring enzyme (acid phosphatase (AP)) activities. The length and angle of vectors defined by ratios of enzyme activities (BG/(NAG + LAP) vs. BG/AP) were used to indicate relative microbial investments in C- (length), and N- and P- (angle) acquiring enzymes. Our results showed that the contents of TC, TN, TP, MBC, DOC and NO3-N in shrub community soil were significantly higher than those in bryophyte, herb and tree communities, and increased by 441%, 246%, 137%, 5570%, 12% and 484%, respectively. The highest soil EEA of C-, N- and P-acquiring were found in shrub community, and the soil EEAs/MBC of C-, N- and P-acquiring were the highest in bryophyte community. Enzyme C:N, C:P and N:P ratios increased progressively in the order of bryophyte, herb and shrub community, but the enzyme C:N, C:P and N:P ratios of tree community were both far less than shrub community. Vector lengths increased progressively in the order of bryophyte (1.16), herb (1.27), tree (1.29) and shrub (1.40), and Vector angles decreased progressively in the order of bryophyte (49.15°), herb (45.65°), Tree (45.31°) and shurb (44.54°), suggested that as succession progresses, soil microbial nutrients transforms from P limitation (angle＞45°) to N limitation (angle＜45°). Redundancy analysis showed that TC, TN, EC and C:N were important drivers of variation in soil EEAs and ES in vegetation at different succession stages. Our findings highlight that the primary succession process cause nutrient limitation transformation. Soil ES might be a sensitive indicator mediated by soil microorganisms to the relative resource limitation at different stages of the primary succession process.

The carbohydrate antigen Sda is expressed on cells and secretions of the vast majority of Caucasians. The epitope is formed by a terminal GalNAc residue β4-linked to a α3-sialylated galactose. Different carbohydrate chains N- or O-linked to glycoproteins can be terminated by this epitope. The final step of Sda biosynthesis is catalyzed by the GalNAc transferase B4GALNT2. In this review, we will discuss the multifaceted aspects of B4GALNT2/Sda biology. In particular, we will see its implications in fertility and pregnancy, in susceptibility to infectious diseases, in chronic kidney diseases and in Duchene muscular dystrophy. In particular, we will show its regulation and prognostic implications in cancer.

Buckling defect will appear on the outer surface of the deformed ring during constrained ring rolling (CRR) of aluminum alloy thin wall conical ring with inner high ribs (AATWCRIHR), if the geometrical dimension of the ribs doesn't match the wall thickness. To avoid the buckling defect, a quantitative method for characterizing the degree of the buckling defect is proposed using the area of buckling profile. Then an orthogonal experimental scheme was designed taking the width of the middle rib, thickness of wall, and height of the middle rib as design variables and defining the area of buckling profile as optimization objective. Subsequently, a quadratic polynomial response surface model was established by combining the optimization algorithm with the finite element method (FEM), and the geometrical dimension of the middle ribs of the deformed AATWCRIHR is optimized. Also the optimal parameter combination to minimize the area of buckling profile is obtained and verified using FE simulation. Results show that the AATWCRIHR after optimization doesn’t generate the buckling defect during constrained ring rolling, and it is proved that the quantitative buckling defect representation method and the optimization design method based on the response surface model and the finite element simulation results are feasible for the constrained ring rolling process of the AATWCRIHR.

Prior studies have focused on the overall behavior of randomly moving particle swarms. However, the characteristics of the stochastic-constrained particles that form ubiquitously within these swarms remain oblivious. This study demonstrates a generalized diffusion equation for stochastic-constrained particles that considers the velocity and location aggregation effects observed from their parent particle swarm (i.e., a completely random particle swarm). This equation can be approximated as the form of Schr\"odinger equation in the microcosmic case (low relative density) and describe the dynamics of the total mass distribution in the macrocosmic case (high relative density). The predicted density distribution of the particle swarm in the stable aggregation state is consistent with the total mass distribution of massive, relaxed galaxy clusters (at least in the range of r < r_s), preventing cuspy problems in the empirical Navarro-Frenk-White (NFW) profile. This study opens a window to observe the dynamics of stochastic-constrained particles from a third perspective, from which the aggregation effect of particles without gravitation can be saw.

Simple Summary: The distribution of typical bacterial redox enzymes such as pyruvate-ferredoxin oxidoreductase (PFOR) in protozoa remains interestingly puzzling. Previous studies have demonstrated diverse cellular localizations of PFOR in some amitochondriate anaerobic protozoa. PFOR is of particular pharmacological importance because it catalyzes the reductive bio-activation of nitro-based prodrugs to cytotoxic radical metabolites. Metronidazole was developed primarily as an antiprotozoal agent against infections caused by Trichomonas vaginalis. However, its antimicrobial spectrum was subsequently expanded to cover anaerobic bacterial infections. It has been shown that mutations in the genes encoding PFOR result in inherent resistance of PFOR-possessing anaerobic protozoa and bacteria to nitro-based prodrugs. Deciphering the evolutionary history of PFOR is crucial in deepening our understanding of the evolution of anaerobic pathogens and unfold new approaches for drug discovery and targeting in pathogen chemotherapy. Abstract: The present frontrunners in the chemotherapy of infections caused by protozoa are nitro-based prodrugs that are selectively activated by PFOR-mediated redox reactions. This study seeks to analyze the distribution of PFOR in selected protozoa and bacteria by applying comparative bioinformatics approaches to test the hypothesis that PFOR was most likely acquired through horizontal gene transfer (HGT) from bacteria. Furthermore, to identify other genes that were putatively acquired using proteome-wide and gene expression analyses. A plausible explanation for the patchy occurrence of PFOR in protozoa is based on the hypothesis that bacteria are potential sources of genes that enhance optimal adaptation of protozoa in hostile environments. The exclusively expressed proteins obtained from Entamoeba histolytica and the putative gene donor, Desulfovibrio vulgaris, showed an over-expression of eleven genes involved in intermediary metabolism. If these results can be reproduced in other PFOR-possessing protozoa, it would provide a more validated evidence to support the horizontal transfer of pfor from bacteria.

As the embedded device and internet of things (IoTs) concept prevalent in today's world, there is an increasing demand for the security and performance requirements on deploying these devices to private and public sectors. The crucial part of it is to protect privacy, confidentiality and integrity, meanwhile, maintain an adequate level of performance during transmission, storage and access of critical information. While the conventional cryptography methods, such as the Advanced Encryption Standard (AES), SHA$-$2 hashing method and RSA and Diffie Hellman for message authentication and identification, work well on systems which have reasonable processing power and memory capabilities. These do not scale well into a world with embedded systems and sensor networks, in conjunction with their nature of smaller size and lower cost. Thus, in the context of resource constrained device, lightweight cryptography methods are proposed to overcome many of the problems of conventional cryptography possessed. This includes constraints related to physical size, processing requirement, memory limitation, energy drain and production cost. This paper provides a survey of the architectures that are defined as replacements for conventional ciphers within an IoTs space and discuss some trends in the design of future lightweight algorithms. The performance metrics are carefully chosen to reflect and assess the suitability for embedded devices. The aim of this research is to identify the various performance metrics applied on different types of symmetric block ciphers especially lightweight ciphers and compare the results on versatile platforms with stream ciphers and public key methods. The comparative analysis on efficient LW cipher will be tested against other similar block ciphers on both MacBook Pro with Intel core and resource constrained device Raspberry Pi with ARM processor.

Glycerol represents a useful functional component of heat-transfer fluids. Glycerol is known to be triboelectrically active. We report how the flow of glycerol, stopped in a cylindrical coiled pipe, influences horseradish peroxidase (HRP) enzyme. Namely, glycerol flow was pumped through the coil and then stopped. After that, we incubated the 0.1 µM solution of HRP near the side of the coil, and then adsorbed HRP onto mica. This operation markedly increased the HRP aggregation on mica in comparison with the control sample. We explain this phenomenon by the influence of triboelectrically induced electromagnetic fields. Our results can be useful in the development of flow-based systems for biosensors and bioreactors.

The Dph1•Dph2 heterodimer from yeast is a radical SAM (RS) enzyme that generates the 3-amino-3-carboxy-propyl (ACP) precursor for diphthamide, a clinically relevant modification on eukaryotic elongation factor 2 (eEF2). ACP formation requires SAM cleavage and atypical Cys-bound Fe-S clusters in each Dph1 and Dph2 subunit. Intriguingly, the first Cys residue in each motif locates next to another, ill-defined cysteine that we show in-here is conserved across eukaryotes. As judged from structural modeling, the orientation of these tandem cysteine motifs (TCM) suggests a candidate Fe-S cluster ligand role. Hence, we generated by site-directed DPH1 and DPH2 mutagenesis, Dph1•Dph2 variants with cysteines from each TCM replaced individually or in combination by serines. Assays diagnostic for diphthamide formation in vivo reveal that while single substitutions in the TCM of Dph2 cause mild defects, double mutations almost entirely inactivate the RS enzyme. Based on enhanced Dph1 and Dph2 subunit instability in response to cycloheximide chases, the variants with Cys substitutions in their cofactor motifs are particularly prone to protein degradation. In sum, we identify a fourth functionally cooperative Cys residue within the Fe-S motif of Dph2 and show that the Cys-based cofactor binding motifs in Dph1 and Dph2 are critical for the structural integrity of the dimeric RS enzyme in vivo.

Conventional fertilization practices can lead to many ecological problems, such as nutrient imbalance, soil acidity, and reduced soil fertility in natural rubber plantations. To address these challenges, a field investigation was strategically carried out to substitute inorganic fertilizer with organic fertilizers consisted of six treatments, i.e., no fertilization (CK), inorganic fertilizer (NPK), 25 % replacement of inorganic through organic (25%M), 50 % replacement of inorganic through organic (50%M), 75 % replacement of inorganic through organic (75%M), and 100% organic fertilizer (100%M). The soil physicochemical properties (SOC, TN, AN, C:N, pH, NH4+-N, and NO3--N) and carbon and nitrogen converting enzymes (BG, NAG, and LAP) were all determined. The partial substitution of inorganic fertilizers with organic fertilizers (i.e., 75%M at surface soil layer) showed higher SOC (14.52 g.kg-1), TN (1.06 g.kg-1), AN (20.07 mg.kg-1), C:N (14.63), NH4+-N (10.63 mgkg-1), and NO3--N(11.06 mg.kg-1) than NPK and CK. Such increase in physicochemical properties in partial replacement of inorganic with organic fertilizers plots resulted from higher carbon and nitrogen enzymes activities (BG (143.17 nmol.g-1.h-1), NAG (153.96 nmol.g-1.h-1), and LAP (153.48 nmol.g-1.h-1)) compared to NPK and CK, and further the person correlation and RDA analysis confirmed a significant positive correlation between SOC, AN, and soil enzymes. This study presents a new strategy for assessing the impact of partially replacing inorganic fertilizers with organic fertilizers in rubber plantations, mainly by modifying the soil nutrient composition in tropical regions.

In this work, we explore new constraints on phantom scalar field cosmologies with a scalar field employing early times catalogues related to CMB measurements, along with the local standard observables, like Supernovae Type Ia (SNIa), H(z) measurements (Cosmic Clocks), and Baryon Acoustic Oscillations (BAO) baselines. In particular, we studied a tracker phantom field with hyperbolic polar coordinates that have been proposed in the literature. The main goal is to obtain precise cosmological constraints for H0 and σ8, in comparison to other constructions that present tension in early cosmological parameters. Our results show that phantom scalar field cosmologies have a reduced statistical tension on H0 that it is less than 3σ using model-independent CMB catalogues as SPT-3G+WMAP9 and ACTPol DR-4+WMAP9 baselines. This suggests these models using a different phantom potential might address the Hubble constant problem and reduce the systematics involved.

Real-world optimization problems are often gov- erned by one or more constraints. Over the last few decades, extensive research has been performed in Constrained Opti- mization Problems (COPs) fueled by advances in computational power. In particular, Evolutionary Algorithms (EAs) are a preferred tool for practitioners for solving these COPs within practicable time limits. We propose a novel hybrid Evolutionary Algorithm based on the Differential Evolution algorithm and Adaptive Parameter Gaining Sharing Knowledge-based algo- rithm to solve global real-world constrained parameter space. The proposed CHAGSKODE algorithm leverages the power of multiple adaptation strategies concerning the control parameters, search mechanisms, as well as uses knowledge sharing between junior and senior phases. We test our method on the benchmark functions taken from the CEC2020 special session & competition on real-world constrained optimization. Experimental results indicate that CHAGSKODE is able to achieve state-of-the- art performance on real-world constrained global optimization when compared against other well-known real-world constrained optimizers.

The increase in ecosystem biodiversity can be perceived as one of the universal processes converting energy into information across a wide range of living systems. This study delves into the dynamics of living systems, highlighting the distinction between ex-post adaptation, typically associated with natural selection, and its proactive counterpart, ex-ante adaptability. Through coalescence experiments using synthetic ecosystems, we (i) quantified an ecosystem stability, (ii) identified correlations between species richness and the stability, (iii) proposed a mechanism for increasing biodiversity through moderate inter-ecosystem interactions, and (iv) inferred that the information carrier of ecosystems is species composition, or merged genomic information. Additionally, we observed that (v) changes in ecosystems are constrained to a low-dimensional state space, with three distinct alteration trajectories—fluctuations, rapid environmental responses, and long-term changes—converging into this state space in common. These findings suggest that daily fluctuations may predict broader ecosystem changes. Our experimental insights, coupled with an exploration of living systems' information dynamics from an ecosystem perspective, enhance our predictive capabilities for natural ecosystem behavior, providing a universal framework for understanding a broad spectrum of living systems.

Background: This study analyzes sex-based differences in renal structure and response to the Angiotensin-Converting Enzyme (ACE) inhibitor enalapril in a mouse model of atherosclerosis. Methods: ApoE-/- mice (8 weeks old) received enalapril (5 mg/kg/day, subcutaneous) or PBS as a control for an additional 14 weeks. Each group consisted of six males and six females. Results: Females exhibited elevated LDL-cholesterol levels, while males presented higher creatinine levels and proteinuria. Enalapril effectively reduced blood pressure in both groups, but proteinuria decreased significantly only in females. Plaque size analysis and assessment of kidney inflammation revealed no significant sex-based differences. However, males displayed more severe glomerular injury, with increased mesangial expansion, mesangiolysis, glomerular foam cells and activated parietal epithelial cells (PECs). Enalapril mitigated mesangial expansion, glomerular inflammation (particularly in females), and the hypertrophy of PECs in males. Conclusion: This study demonstrates sex-based differences in the response to enalapril in a mouse model of atherosclerosis. Males exhibited more severe glomerular injury, while enalapril provided renal protection, particularly in females. These findings suggest potential sex-specific considerations for ACE inhibitor therapy in chronic kidney disease and atherosclerosis cardiovascular disease. Further research is needed to elucidate the underlying mechanism behind these observations.

Currently, obesity is a critical global public health burden. Numerous studies have demonstrated the regulation of the pathogenesis of obesity and metabolic abnormalities by the gut microbiota and microbial factors; however, their involvement in the various degrees of obesity is not yet understood well. Previously, obesity has been shown to be associated with decreased levels of vitamin B12. Considering exclusive microbial production of vitamin B12, we hypothesised that a decrease in cobalamin levels in obese individuals may be at least partially caused by its depleted production in the intestinal tract by the commensal microbiota. In the present study, our aim was to estimate the abundance of enzymes and metabolic pathways for vitamin B12 synthesis in the gut microbiota of mouse models of alimentary and genetically determined obesity, to evaluate the contribution of the obesogenic microbiome to vitamin B12 synthesis in the gut. We have defined a significantly lower representation of enzymes and metabolic pathways for vitamin B12 biosynthesis in obese mice compared to non-obese mice, wherein enzyme depletion was more pronounced in lepr(-/-) (db/db) mice, which developed severe obesity. The representation of enzymes involved in cobalamin synthesis is strongly correlated with representation of several microbes in high-fat diet fed mice, whereas there were almost no correlations in db/db mice. Therefore, the degree of obesity and the composition of the correspondent microbiota are the main contributors to the representation of genes and pathways for cobalamin biosynthesis in the mouse gut.

Background: Metabolic flux analysis (MFA) is an indispensable tool in metabolic engineering. The simplest variant of MFA relies on an overdetermined stoichiometric model of the cell’s metabolism under the pseudo-steady state assumption, to evaluate the intracellular flux distribution. Despite its long history, the issue of model error in the overdetermined MFA, particularly misspecifications of the stoichiometric matrix, has not received much attention. Method: We evaluated the performance of statistical tests from linear least square regressions, namely Ramsey RESET test, F-test and Lagrange multiplier test, in detecting model misspecifications in the overdetermined MFA, particularly missing reactions. We further proposed an iterative procedure using the F-test to correct such an issue. Result: Using Chinese hamster ovary and random metabolic networks, we demonstrated that: (1) a statistically significant regression does not guarantee high accuracy of the flux estimates, (2) the removal of a reaction with a low flux magnitude can cause disproportionately large biases in the flux estimates, (3) the F-test could efficiently detect missing reactions, and (4) the proposed iterative procedure could robustly resolve the omission of reactions. Conclusion: Our work demonstrated that statistical analysis and tests could be used to systematically assess, detect and resolve model misspecifications in the overdetermined MFA.

In this work, we propose a variation of the cellular particle swarm optimization algorithm with differential evolution hybridization (CPSO-DE), to include constrained optimization in it, named Ts-CPD. It is implemented as a kernel of electronic design automation (EDA) tool capable of sizing circuit components considering a single-objective design with restrictions and constraints. The aim is to improve the optimization solutions in the sizing of analog circuits. To evaluate our proposal’s performance, we present the design of three analog circuits: a deferential amplifier, a two-stage operational amplifier, and a folded cascode operational transconductance amplifier. Numerical simulation results indicate that Ts-CPD can find better solutions, in terms of the design objective and the accomplishment of constraints, than those reported in previous works.

Semi-supervised consensus clustering is a promising strategy to compensate for the subjectivity of clustering and its sensitivity to design factors, with various techniques being recently proposed to integrate domain knowledge and multiple clustering partitions. In this article we present a new approach that makes double use of domain knowledge, namely to build the initial partitions as well as to combine them. In particular, we show how to model and integrate must-link and cannot-link constraints into the objective function of a generic consensus clustering (??) framework that maximizes the similarity between the consensus partition and the input partitions, which have, in turn, been enriched with the same constraints. In addition, borrowing from the theory of functional dependencies, the integrated framework exploits the notions of deductive closure and minimal cover to take full advantage of the logical implication between constraints. Using standard UCI benchmarks, we found that the resulting algorithm, termed ??? (double-Constrained Consensus Clustering), was more effective than plain ?? at combining base constrained partitions. We then argue that ??? is especially well-suited to profiling counterfeit e-commerce websites, because constraints can be acquired by leveraging specific domain features, and demonstrate its potential for detecting affiliate marketing programs. Taken together, our experiments suggest that ??? makes the process of clustering more robust and able to withstand changes in clustering algorithms, datasets, and features, with a remarkable improvement of average performance.

Locomotor impairment is a high-prevalent and significant source of disability and significantly impacts a large population’s quality of life. Despite decades of research in human locomotion, the challenges of simulating human movement to study the features of musculoskeletal drivers and clinical conditions remain. Most recent efforts in utilizing reinforcement learning (RL) techniques are promising to simulate human locomotion and reveal musculoskeletal drives. However, these simulations often failed to mimic natural human locomotion because most reinforcement strategies have yet to consider any reference data regarding human movement. To address these challenges, in this study, we designed a reward function based on the trajectory optimization rewards (TOR), and bio-inspired rewards, which includes the rewards obtained from reference motion data captured by a single Intertial Moment Unit (IMU) sensor. The sensor was equipped on the participants’ pelvis to capture reference motion data. Also, we adapted the reward function by leveraging previous research in walking simulation for TOR. The experimental results showed that the simulated agents with the modified reward function performed better in mimicking the collected IMU data from participants, which means the simulated human locomotion was more realistic. Also, as this bio-inspired defined cost, IMU data enhanced the agent’s capacity to converge during the training process. As a result, the models’ convergence is faster than those developed without reference motion data. Consequently, human locomotion can be simulated more quicker and in a broader range of environments with a better simulation performance.

Recently, the Hypervolume Newton method (HVN) has been proposed as fast and precise indicator-based method for solving unconstrained bi-objective optimization problems with objective functions that are at least twice continuously differentiable. The HVN is defined on the space of (vectorized) fixed cardinality sets of decision space vectors for a given multi-objective optimization problem (MOP) and seeks to maximize the hypervolume indicator adopting the Newton-Raphson method for deterministic numerical optimization. To extend its scope to non-convex optimization problems the HVN method was hybridized with a multi-objective evolutionary algorithm (MOEA), which resulted in a competitive solver for continuous unconstrained bi-objective optimization problems. In this paper, we extend the HVN to constrained MOPs with in principle any number of objectives. We demonstrate the applicability of the extended HVN on a set of challenging benchmark problems and show that the new method can be readily be applied to solve equality constraints with a high precision problems, and to some extend also inequalities. We finally use HVN as local search engine within a MOEA and show the benefit of this hybrid method on several benchmark problems.

Transketolase (TKT) is an essential thiamine diphosphate (ThDP)-dependent enzyme of the non-oxidative branch of pentose phosphate pathway, with the glucose-6P flux through the pathway regulated in various medically important conditions. Here, we characterize the brain TKT regulation by acylation in rats with perturbed thiamine-dependent metabolism, known to occur in neurodegenerative diseases. The perturbations are modelled by administration of oxythiamine inhibiting ThDP-dependent enzymes in vivo, or by reduced thiamine availability in the presence of metformin and amprolium, inhibiting intracellular thiamine transporters. Compared to control rats, chronic administration of oxythiamine does not significantly change the modification level of the two detected TKT acetylation sites (K6 and K102), but doubles malonylation of TKT K499, concomitantly decreasing 1.7-fold the level of demalonylase sirtuin 5. The inhibitors of thiamine transporters do not change average levels of TKT acylation or sirtuin 5. TKT structures indicate that the acylated residues are distant from the active sites. The acylations-perturbed electrostatic interactions may be involved in conformational shifts and/or formation of TKT complexes with other proteins or nucleic acids. Acetylation of K102 may affect the active site entrance/exit and subunit interactions. Correlation analysis reveals that the action of oxythiamine is characterized by significant negative correlations of K499 malonylation or K6 acetylation with TKT activity, not observed upon the action of the inhibitors of thiamine transport. However, the transport inhibitors induce significant negative correlations between the TKT activity and K102 acetylation or TKT expression, absent in the oxythiamine group. Thus, perturbations in the ThDP-dependent catalysis or thiamine transport manifest in the insult-specific patterns of the brain TKT malonylation and acetylations.

Day-ahead forecasting of electricity prices is important in deregulated electricity markets for all the stakeholders: energy wholesalers, traders, retailers, and consumers. Electricity price forecasting is an inherently difficult problem due to its special characteristic of dynamicity and non-stationarity. In this paper, we present a robust price forecasting mechanism that shows resilience towards aggregate demand response effect and provides highly accurate forecasted electricity prices to the stakeholders in a dynamic environment. We employ an ensemble prediction model in which a group of different algorithms participate in predicting the price for each hour of a day. We propose two different strategies, namely, Fixed Weight Method (FWM) and Varying Weight Method (VWM), for selecting each hour's expert algorithm from the set of participating algorithms. In addition, we utilize a carefully engineered set of features selected from a pool of features derived from information such as past electricity price data, weather data, and calendar data. The proposed ensemble model offers better results than both the Pattern Sequence-based Forecasting (PSF) method and our own previous work using Artificial Neural Networks (ANN) alone do on the datasets for New York, Australian, and Spanish electricity markets.

The SK model proposed by Sherrington and Kirkpatrick is an important mean field model for spin glasses. The dependence structure of Hamiltonians of the SK model is considered in this paper. We have investigated the covariance matrix of Hamiltonians of the SK model, and establish a relationship between the rank of the corresponding covariance matrix and the dimension of the space spanned by the Hamiltonians. Finally, we also give an upper bound for the rank of the covariance matrix, which might be the best.

This study addresses the implementation of the International Financial Reporting Standard 9 (IFRS 9) in the European Union as of January 1, 2018, replacing the International Accounting Standard 39 (IAS 39) to introduce a new model for recognizing Loan Loss Provisions (LLP) based on Expected Credit Loss (ECL). This model responds to criticisms of the former Incurred Credit Loss (ICL) system for its inability to reflect credit losses in a timely manner, potentially exacerbating the effects of financial crises (Bushman &amp; Williams, 2015; Gebhardt &amp; Novotny-Farkas, 2011). The study focuses on the effects of adopting the ECL model on the level of Loan Loss Allowances (LLA) in loans, own equity, and the Common Equity Tier 1 (CET1) ratio across 13 Portuguese commercial banks. A mean comparison test is used to evaluate scenarios before and after the application of the ECL model, highlighting the importance of regulator actions and the adequacy of loss recognition policies, including the effects of Regulation (EU) 2017/2395 of December 12. The results obtained demonstrate significant negative impacts on the net values of loans, own equity, and the CET1 ratio upon adopting the IFRS 9 ECL model, due to the widespread increase in LLAs.

Generation of unique identifiers extracted from the physical characteristics of the underlying hardware ensures the protection of electronic devices against counterfeiting and provides security to the data they store and process. This work describes the design of an efficient Physical Unclonable Function (PUF) based on the differences in the frequency of Ring Oscillators (ROs) with identical layout due to variations in technological processes involved in the manufacture of the integrated circuit. The logic resources available in the Xilinx Series-7 programmable devices are exploited in the design to make it more compact and achieve an optimal bit-per-area rate. On the other hand, the design parameters can also be adjusted to provide a high bit-per-time rate for a particular target device. The PUF has been encapsulated as a configurable Intellectual Property (IP) module, providing it with an AXI4-Lite interface to ease its incorporation into embedded systems in combination with soft- or hard-core implementations of general-purpose processors. The capability of the proposed RO-PUF to generate implementation-dependent identifiers has been extensively tested, using a series of metrics to evaluate its reliability and robustness for different configuration options. Finally, in order to demonstrate its utility to improve system security, the identifiers provided by RO-PUFs implemented on different devices have been used in a Helper Data Algorithm (HDA) to obfuscate and retrieve a secret key.

This paper proposes a method based on genetic algorithm (GA) for the security-constrained optimal dispatch of integrated natural gas and electricity networks, considering operating scenarios in both energy systems. The mathematical formulation of the optimization problem consists of a multi-objective function which aims to minimize both cost of thermal generation (diesel and natural gas) as well as the production and transportation of natural gas. The joint gas-electricity system is modeled by two separate groups of nonlinear equation, which are solved by the combination of Newton's method with the GA. The applicability of the proposed method is tested in the Belgian gas network integrated with the IEEE 14-bus test system and a 15-node natural gas network integrated with the IEEE 118-bus test system. The results demonstrate that the proposed method provides efficient and secure solutions for different operating scenarios in both energy systems.

The assortment of low-cost 3D printers for “in-practice” use, e.g., for clear aligner therapies, is ever increasing. To address concerns about the accuracy of orthodontic models produced on such printers when cost efficient modes of 3D printing are employed, this study examined the effect of print model body type and print angulation on accuracy. Six printing-configuration groups were included: 2 model types (solid or hollow shell) combined with 3 print angles (0°, 70°, or 90°) with 10 models/group; all models were printed with 100-µm layer thickness using a digital light processing-based 3-dimensional printer. Eleven selected structures and distances were measured on the printed models with a digital microscope and compared to the same measures on a digitized master model. The clinically-acceptability range was set at ±0.25 mm difference from the master model for single tooth measurements (intra-tooth) and ±0.5 mm for cross-arch measurements (inter-tooth). For individual measurements across all models, 98% fell within clinical acceptability. For mean measurements within each model group, only canine height for the shell-0° model had a mean difference (0.26 mm ± 0.03) outside the clinically acceptable range for intra-tooth measurements. Standard deviations for all intra-tooth measurements were within 0.07 mm. While none of the mean inter-tooth measurements exceeded the acceptability range, the standard deviations were larger (0.04 to 0.30 mm). Accuracy of orthodontic models for clear aligner therapies was not impacted beyond the clinically acceptable range when altering model body type and print angulation to improve efficiency of 3D printing. These findings suggest greater flexibility of the practitioner to alter print settings to address time and cost efficiency in various clinical scenarios and still maintain clinically acceptable model accuracy.

By introducing environmental mediator, for avoiding randomness in selecting indicators and subjectivity in deciding interaction path coefficients to reveal interaction mechanism among forest industry, ecology and environmental capacity, structural Pressure–State–Impact–Response (PSIR) and quantitative Structural Equation Modeling (SEM) are utilized with data on thirty–one provinces of China. We can find that: (i) forest industry has a negative influence on ecology, whereas ecology has a positive influence on industry; (ii) the destructive influence that industry has on ecology is much greater than the positive effect ecology has on industry; and (iii) environmental capacity plays a partial mediating role between industry and ecology. According to these results we can conclude that: (i) forest industry and ecology are not in a symbiotic relationship and have not reached a level of ecological security; (ii) the interaction between industry and ecology is in a period of transition from antagonistic to beneficial; and (iii) industry dominates ecology. However, we prospect the following advice: (i) methods of forest industry should be changed; (ii) new modes of industrial integration and circular economy should be developed; and (iii) the ability of the environment to sustain itself should be enhanced. The level of forest ecological security to discuss the symbiotic mechanism of industry and ecology will propose to be measured in future.

Employing low tensor rank decompositions in image inpainting has attracted increasing attention. This paper exploits a novel tensor-augmentation schemes to transform an image (a low-order tensor) to a higher-order tensor without changing the total number of pixels. The developed augmentation schemes enhance the low-rankness of an image under three tensor decompositions: matrix SVD, tensor train (TT) decomposition, and tensor singular value decomposition (t-SVD). By exploiting the schemes, we solve the image inpainting problem with three low-rank con-strained models which use the matrix rank, TT rank, and tubal rank as constrained priors re-spectively. The tensor tubal rank and tensor train multi-rank are developed from t-SVD and TT decomposition respectively. We exploit efficient ADMM algorithms for solving the three models. Experimental results demonstrate that our methods are effective for image inpainting and supe-rior to numerous close methods.

Classifying network flow subsequences in an Industrial IoT gateway is an effective method for identifying Industrial IoT faults. This paper proposes a subsequence classification algorithm SSGBUL-IKNN based on unsupervised learning encoding to address the problem of low classification accuracy. Firstly, we built a network module based on unsupervised learning to encode the flow sequence of the Industrial IoT gateway. In the encoding module, a subsequence calibration algorithm controls the increasing error during the coding process. Then, the specific fault type is obtained through an improved KNN classification algorithm based on the indication distance source from the integrated coding sequences converted by multi-dimensional network flow sequences. The test result on three Industrial IoT datasets of a sewage treatment plant shows that the accuracy of SSGBUL-IKNN in this paper exceeds 92%, significantly higher than the algorithm DTW and TSF. It reaches the classification requirements of Industrial IoT fault diagnosis.

Immobilization of enzymes is a good field of study to expand the life of enzyme in and lowering the cost of the chemical processes such as separation processes. Urease is an important enzyme with medical and industrial applications. The aim of the present study is to prepare an immobilized urease on a strong cation exchange resin (Amberlite IR120 -Na) and study of its activity and stability. We monitored the liberation of Na ions in the collected fractions and searching for protein in the fractions as an indicators of immobilization by ion exchange phenomenon. Sodium is measured using atomic absorption spectroscopy techniques, while protein tested by Bradford’s method. Immobilized urease activity was evaluated by salicylate-hypochlorite method. The results indicated a complete immobilization of urease enzyme on the resin surface with reserving 92% of the activity of free enzyme. The immobilized urease enzyme on resin showed good stability and it has a 62% of its activity after 154 days of storage at room temperature. It is concluded that a new immobilized urease enzyme system is prepared with good enzyme activity and stability.

Extracellular enzymes catalyze biogeochemical reactions in soil, cycling carbon and nutrients in agricultural systems. Enzymes respond quickly to soil management, including organic amendment inputs, such as biochar, a charcoal-like solid byproduct of bioenergy production. In a previous agricultural field trial, a pine biochar amendment caused an approximately 40% decrease in the enzyme activities of β-glucosidase (BG) and phosphatase (PHOS). The large surface area of the pine biochar has the potential to sorb nutrients and other organic molecules. To test if sorption caused decreased enzyme activity, we used a laboratory assay to quantify the activity of two sorbed enzymes: BG and acid PHOS, involved in the cycling of carbon and phosphorous. The enzymes were incubated with three solid phases: (1) the high surface area pine biochar, (2) the agricultural soil, and (3) a low surface area grass biochar, for an additional comparison. We quantified the sorbed enzymes at pH 6, 7, and 8, using a Bradford protein assay, and measured the immobilized enzyme activities via high-throughput fluorometric analysis. After sorption onto pine biochar, detectable BG and PHOS activity levels dropped by over 95% relative to the soil, supporting direct sorption as one mechanism that reduces enzyme activity in biochar amended soil. This laboratory assay demonstrated that sorption could account for the lack of priming of native soil organic matter and changes in soil phosphorous cycling after pine biochar addition.

Soil enzyme activity can be affected by both production and degradation, as enzymes can be degraded by proteases. However, the impact of nutrient addition on enzyme activity is often solely attributed to changes in enzyme production without fully considering degradation. Here, we demonstrated that the activities of β-1,4-glucosidase (BG), β-D-cellobiohydrolase (CBH), β-1,4-Xylosidase (BX), and β-1,4-N-acetyl-glucosaminnidase (NAG) were comparable in nitrogen (N) and phosphorus (P) fertilized soils and the unfertilized control under field conditions, but the reduction in activity was substantially greater in the fertilized soils during short-term laboratory incubation. The results show that the interruption of the natural, continuous supply of organic matter or non-soil microbial-derived enzymes, which typically occurs under field conditions, leads to a more significant reduction in apparent enzyme activities in fertilized soils compared to unfertilized control. This may be attributed to the higher abundance of protease in fertilized soils, resulting in faster enzyme degradation. Interestingly, P fertilization alone did not have a similar effect, indicating that N fertilization is likely the main cause of the larger decreases in enzyme activity during incubation in fertilized soils compared to unfertilized control soils, despite our study site being poor in P and rich in N. These findings highlight the importance of considering enzyme degradation when investigating material dynamics in forest ecosystems, including the impact of nutrient addition on enzyme activity, as enzyme production alone may not fully explain changes in apparent enzyme activity.

Enzymes are in high demand for very diverse biotechnological applications. However, natural biocatalysts often need to be engineered for fine-tuning their properties towards the end applications, such as the activity, selectivity, stability to temperature or co-solvents, and solubility. Computational methods are increasingly used in this task, providing predictions that narrow down the space of possible mutations significantly and can enormously reduce the experimental burden. Many computational tools are available as web-based platforms, making them accessible to non-expert users. These platforms are typically user-friendly, contain walk-throughs, and do not require deep expertise and installations. Here we describe some of the most recent outstanding web-tools for enzyme engineering and formulate future perspectives in this field.

Considering characteristics of high river density, special underlying surface in plain river network region, and municipal drainage system function, river network drainage unit model is proposed, which is defined as a region surrounded by main river or embankment. Flood storage variety and control projects regulation of small rivers in each unit is simulated. With drainage catchment as an object, according to its drainage capacity, simplified municipal drainage model was developed. Coupling river network drainage unit model, simplified municipal drainage model and 2D flood routing model, urban flood analysis model for plain tidal river network region was developed, which could be applied to analyzing flood from upstream river, storm surge and local rainfall. Demonstration research was carried out in Puxi flood protected area in Shanghai.

Attribute reduction is a core technique in the rough set domain and an important step in data preprocessing. Researchers have proposed numerous innovative methods to enhance the capability of attribute reduction, such as the emergence of multi-granularity rough set models, which can effectively process distributed and multi-granularity data. However, these innovative methods still have many shortcomings, such as how to deal with complex constraints and how to perform multi-angle effectiveness evaluations. Based on the multi-granularity model, this study proposes a new method of attribute reduction, namely using multi-granularity neighborhood information gain ratio as the measurement criterion. This method combines both supervised and unsupervised perspectives, and by integrating multi-granularity technology with neighborhood rough set theory, constructs a model that can adapt to multi-level data features. This model can select the optimal granularity level or attribute set according to the requirements. Finally, the proposed method is experimented with on 15 UCI datasets against six other attribute reduction algorithms. The experimental outcomes, upon analysis and comparative review, substantiate the reliability and consistency of the attribute reduction approach introduced in this study.

By repeated unloading and loading of the excavation dynamic and static loads, repeated train dynamic and static loads of multi-factors, the underpass tunnel, cross tunnel engineering influence area rock layer, the existing tunnel structure of the three constitutes a multifaceted structure, multi-factor interaction system. Existing tunnels into the prediction theory model of the new tunnel excavation process of dynamic and static loads, dynamic and static loads of existing tunnels are mostly analyzed individually, the results of synergistic analysis needs to be improved. Based on the theory of the current layer method, the paper comprehensively considers the stiffness of the existing tunnel, the stiffness of the new tunnel, the excavation method load and the existing tunnel load, coupled with Peck's empirical formula, the theoretical model of deformation prediction for excavation of a two-lane highway tunnel under the tunnel through the existing railroad is proposed, and verified and optimized by numerical calculations and monitoring data, which proves the applicability and reliability of the theoretical model in the similar strata and the project promotion.

Turbo-roundabouts are one of the most frequently recommended road junction design options when it comes to increasing traffic capacity and traffic safety. This is in particular true of suburban areas, with dominant traffic flow on the main road and moderate traffic flow on the side road. Other intersections handling local traffic and considerably constricting the availability of space are usually located in the vicinity of such intersections. Another factor contributing to less availability of land for construction in these locations is the presence of surrounding residential housing. Then choosing the suitable turbo-roundabout type becomes the main issue. The article presents a case study for the selection of a type of turbo roundabout under the conditions of considerably constricted land availability, based on analyses of provision of swepth path for the chosen design vehicles. The article considers the typical Egg type turbo roundabouts, "flattened" turbo roundabouts and ellipse based roundabouts, with unconventional geometries of the truck apron and central island. For each of the analysed roundabout types setting out methods were described in detail, which enable designers to quickly select a type of roundabout suitable for specific constrained site conditions.

This paper presents a novel algorithm, the multi-objective nonlinear interval PageRank (MONIPR) Algorithm. This algorithm extends the conventional PageRank (PR) algorithm, integrating nonlinear interval computation and multi-objective considerations into the computation process. The MONIPR algorithm bridges a research gap in integrating nonlinear interval approaches and multi-objective problems into the PR algorithm, which were traditionally treated separately. In addition, this research adopts the constrained interval arithmetic proposed to address the limitations of the conventional PR algorithm, which tends to overlook uncertainties and results in deterministic outcomes. In addition, we use a numerical example to demonstrate the proposed algorithm, contrasting it with the conventional approaches. A numerical example demonstrates the algorithm's performance by comparing the rank intervals obtained with the traditional crisp Markov chain and PR algorithm. The results highlight the ability of the proposed algorithm to provide a range of possible rank intervals, considering both uncertainty and multi-objectives. The findings suggest potential applications in decision-making, uncertainty quantification, and systems analysis.

Real-world optimization problems are often governed by one or more constraints. Over the last few decades, extensive research has been performed in Constrained Optimization Problems (COPs) fueled by advances in computational intelligence. In particular, Evolutionary Algorithms (EAs) are a preferred tool for practitioners for solving these COPs within practicable time limits. We propose an ensemble of multi- method hybrid EA framework with four mutation operators, two crossover operators, multi-search [Differential Evolution (DE) & Gaining Sharing Knowledge (GSK)] optimization algorithm, and ensemble of constraint handling techniques to solve global real- world constrained optimization problem. The proposed frame- work FEPEA has an ascendancy of multiple adaptation strategies concerning the control parameters, search mechanisms, two sub-populations as well as uses knowledge sharing mechanism between junior and senior phases. The algorithm also combines the power of four popular constraint handling techniques (CHT) and uses a voting mechanism to select any particular CHT. On top of that, this algorithm also uses both linear and non- linear population size reduction in every step of the evolutionary process. We test our method on 57 real-world problems provided as part of the CEC 2020 special session & competition on real- world constrained optimization benchmark suite. Experimental results indicate that FEPEA is able to achieve state-of-the- art performance on real-world constrained global optimization when compared against other well-known real-world constrained optimizers.

Currently, in some domestic and foreign mines, the backfill drilling pipeline experience a rupture phenomenon even when the wear degree is low. This results in a delay in production due to the filling becoming 'sick'. This paper presents, for the first time, the damage mechanism from a mechanical perspective and re-derives the anti-extrusion strength model of the backfill drilling pipeline. We investigate the influence of law on the anti-extrusion strength of pipelines from the perspective of stratum and cement ring. We then verify the theoretical and simulation results through engineering examples. The results demonstrate that the Mises stress criterion is a suitable modification principle for the anti-extrusion strength model of the backfill drilling pipeline. The anti-extrusion strength of the pipeline is related to the elastic modulus and Poisson's ratio of the stratum, and the thickness of the cement ring. It is negatively affected by the depth of the stratum. For hard strata, a cement ring with a smaller elastic modulus is suitable, while for soft stratum, a cement ring with a larger elastic modulus is recommended. When the missing angle of the cement ring is less than 60°, the stress concentration factor increases up to 2.2. The stress unloading capacity of the cement ring ranges from 32.7% to 37.8%, and optimal performance of the cement ring is achieved when it has high strength and low rigidity. The backfill filling pipeline of a copper mine abroad was destroyed due to external extrusion force exceeding its anti-extrusion strength value. The modified pipeline anti-extrusion strength model is 18.2% higher than the casing API strength value. This finding can inform the design of the backfill filling pipeline for China's kilometer-deep wells in the future.

Concrete is more stable than filler as a false roof in a downward approach type infill quarry, but the mechanical model of a concrete false roof is not clear. As a result, there has been limited application. Therefore, it is necessary to establish the mechanical model of a concrete artificial false roof to enhance the stability of the downward approach infill quarry. This paper combines theoretical analysis, model derivation, finite element analysis and field application methods. Firstly, the basic assumptions of thin plate theory and elasticity mechanics are used as the premise to establish the differential equations of the deflection curve of the concrete thin plate false roof. Then, the three types of bending moment generation of the concrete thin plate false roof are explored. Secondly, the relationship between the location of dangerous surface and dangerous point in hard-supported weak-slab structure and soft-supported weak-slab structure is analyzed, and the type of uniform load and calculation model of concrete thin-slab false roof are improved. Finally, according to the established mechanical model of thin slab false roof, finite element analysis and field application were carried out. The results show that there are three types of deflection curve differential equations in the concrete thin slab false roof perpendicular to the strike, and three extreme points exist in the middle section of the thin slab and on both sides of the surrounding rock. The hazardous surface of the hard-supported weak-slab structure is present at the intersection of the encircling rock and the thin-slab fake ceiling, with the perilous point situated on the top of this surface. The hazardous surface of the soft-supported weak-slab structure can be found in the centre section of the thin-slab fake ceiling, with the perilous point being located at the bottom of this surface. Moreover, the damage mode for both structures is that of maximum tensile stress damage. Upon conducting a finite element analysis, the results indicate that the concrete's maximum tensile stress is significantly high.

Periodontitis is a chronic inflammatory disease which results in the destruction of the tooth’ s supporting tissues and the alveolar bone resorption. The complement becomes a major link between infection and inflammatory pathology including periodontitis. Gingipians as important virulence factors of P. gingivalis have the activity of C5 convertase, could cleave C5 into fully functional C5a to activate C5aR. The above process could be blocked by the C5aR antagonist (PMX-53) to suppress local periodontal inflammation, and then achieves the purpose of treatment of periodontitis. Nanoparticles incorporated within gelatin are promising carrier system for drug delivery in recent years. This study aimed to investigate whether gelatin nanoparticles loaded with PMX-53 prevents alveolar bone resorption in miniature swines model of periodontitis. Four miniature swines were placed ligatures around the maxillary and mandibular fourth premolar and first molar on both sides for seven weeks to induce periodontitis. Then, animals were assigned randomly to four groups: minocycline-treated group, gelatin with PMX53-treated group, gelatin-treated group and a sham control group. They were treated with 1ml related drugs respectively, into gingival sulcusl for 4 times at one-week intervals. We showed that local treatments with gelatin nanoparticles loaded with PMX-53 could inhibit alveolar bone loss of periodontitis. Our study revealed that gelatin nanoparticles loaded with PMX-53 prevented alveolar bone resorption miniature swines model of periodontitis. In addition, provided proof-of-concept for local targeting of gelatin nanoparticles loaded with PMX-53 as a powerful candidate for the treatment of periodontitis.

Demand response flexible loads can provide fast regulation and ancillary services as reserve capacity in power systems. This paper proposes a joint optimization dispatch control strategy for source-load system with stochastic renewable power injection and flexible thermostatically controlled loads (TCLs) and plug-in electric vehicles (PEVs). Specifically, the optimization model is characterized by a chance constraint look-ahead programming to maximal the social welfare of both units and load agents. By solving the chance constraint optimization with sample average approximation (SAA) method, the optimal power scheduling for units and TCL/PEV agents can be obtained. Secondly, two demand response control algorithms for TCLs and PEVs are proposed respectively based on the aggregate control models of the load agents. The TCLs are controlled by its temperature setpoints and PEVs are controlled by its charging power such that the DR control objective can be fulfilled. The effectiveness of the proposed dispatch and control algorithm has been demonstrated by the simulation studies on a modified IEEE 39 bus system with a wind farm, a photovoltaic power station, two TCL agents and two PEV agents.

There is limited data on pregnancy outcomes in Pompe Disease (PD) resulting from deficiency of the lysosomal enzyme acid alpha-glucosidase. Late-onset PD is characterized by progressive proximal muscle weakness and decline of respiratory function secondary to the involvement of the respiratory muscles. In a cohort of twenty-five females, the effects of both PD on the course of pregnancy and the effects of pregnancy on PD were investigated. Reproductive history, course of pregnancy, use of Enzyme replacement therapy (ERT), PD symptoms, and outcomes of each pregnancy were obtained through a questionnaire. Among 20 subjects that reported one or more pregnancies, one subject conceived while on ERT and continued therapy through two normal pregnancies with worsening of weakness during pregnancy and improvement postpartum. While fertility was not affected, pregnancy may worsen symptoms, or cause initial symptoms to arise. Complications with pregnancy or birth were not higher, except for an increase in the rate of stillbirths (3.8% compared to the national average of 0.2-0.7%). Given small sample size and possible bias of respondents being only women who have been pregnant, further data may be needed to better analyze the effects of pregnancy on PD, and the effects of ERT on pregnancy outcomes.

In this work model of mirror elements equilibrium of the micromechanical components is developed, the behavior analysis of the mirror element of micromechanical mirrors in case changing of control voltages of electrostatic actuators is carried out, an expression for determining the maximum value of deflection voltage at which the snap-down effect will take the following form is obtained in case of the influence of the coefficient of the electrostatic rigidity of electrostatic actuators. The developed equilibrium model of mirror elements and the obtained results of modeling can be used at design of micromechanical mirrors with internal suspensions.

In this paper, a semi-empirical model of air waves induced by falling rock is described. The model is composed of a uniform motion phase (velocity close to 0 m·s^-1) and an acceleration movement phase. The uniform motion phase was determined based on experimentally and the acceleration movement phase was derived by theoretical analysis. A series of experiments were performed to verify the semi-empirical model and elucidated the law of the uniform motion phase. The acceleration movement phase accounted for a larger portion with a greater height of the falling rock. Experimental results of different falling heights of the goaf showed close agreement with theoretical analysis values. The semi-empirical model could accurately and conveniently estimate the velocity of air wave induced by falling rock. Thus, the semi-empirical model can provide a reference and basis for estimating the speed of air waves and designing protective measures in mines.

In bacteria, enzymes usually comprise of enzymatic domains only. In eukaryotes/mammals, and here particularly in context of signal transduction, proteins with enzymatic functions contain additional modules promoting interactions with cooperating signaling proteins. Often such protein-protein interaction domains, such as SH2- and SH3-domains, help to localize the enzymatic function (e.g. kinase, phosphatase) to another protein, cellular compartment, or membrane nanodomain. In such cases, the interaction domain(s) serve(s) the enzymatic function. However, there are molecular situations in which an interaction domain fulfills its task completely independent of the protein´s enzymatic function and in this review, we call such function the adapter function of an enzyme. Though many stories can be told, we will concentrate on several proteins playing crucial roles in cells of the immune system, such as BTK, PI3K, and SHIP1, as well as in cancer cells, such as proteins of the RAS/ERK MAPK pathway. We will also discuss how these adaptor functions of enzymes determine or even undermine the efficacy of targeted therapy compounds, such as ATP-competitive kinase inhibitors, thereby highlighting the need to develop pharmacological approaches, such as PROTACs, that eliminate the entire protein. We also review how genetic kock-out and knock-in approaches can be leveraged to identify adaptor functions of signaling proteins.

The catalytic parameters describing enzyme catalysis are discussed in the context of the design of de novo enzymes. It is shown that high values of the catalytic efficiency may in some cases reflect tight substrate binding and lead to an immediate levelling-off of rates to reach a low plateau, an undesirable scenario for many industrial applications. It is argued that increasing the catalytic rate constant should be a main target in de novo enzyme engineering.

Determining halal product of fermented foods and bevearages becomes important for muslim consumers due to religious codification of halal. In order to help on site analysis, an alcohol biosensor was under development. The biosensor was constructed using bacteria producing alcohol oxidase (AOX). Bacteria from apple juice was isolated in advance to obtain pure bacteria. The bacteria was cultured in two solid media. Bacteria on the Acetobacter media had a resistance in a solution containing alcohol with a higher concentration. Acetobacter was cultured on solid and liquid media for measuring at various ethanol concentrations (0.01%-3%) with different absorbance value. Bacteria with absorbance value 0.500 had the highest oxidation current peak. Later, it was used as bioreceptor for measuring ethanol by cyclic voltammetry method. The linearity of measurement later was compared with spectrophotometric measurement. By using cyclic voltammetry the linearity had higher R² value than spectrophotometric method. However, it only had stability for two days, there fore it needs more improvement for lasting its lifetime. Basically, electrochemical method has potency for further being improved fur as an alternative method of ethanol on-site measurement.

This paper addresses the input coupling problem for the shape memory alloy (SMA) actuated parallel platform with completely unknown nonlinear dynamics. The problem means that in a parallel platform with multiple SMA actuators acting together, the displacement of one of the actuators will simultaneously affect the remaining actuators to change. Due to the coupling problem and nonlinear characteristics of the SMA actuators, it is not easy to control the platform to achieve bi-directional swing with completely unknown nonlinear dynamics. Therefore, a model-free adaptive sliding mode control method is proposed to improve the control accuracy of the complex motion of the platform, avoiding the complex modeling process of the SMA actuated parallel platform. Based on the model-free adaptive control (MFAC) theory, a multiple input and multiple output (MIMO) dynamic linearized mathematical model of the parallel platform is established using the online input and output data of the system. Then, a sliding mode controller is designed based on the dynamic model. A rigorous theoretical analysis proves that the proposed model-free adaptive sliding mode controller is able to stably control the SMA actuated parallel platform, and its tracking error is uniformly ultimately bounded (UUB). Finally, experiments are conducted on the established SMA actuated parallel platform. The results show that the proposed model-free controller is feasible and effective, and can control the system well to achieve the complex motion of bi-directional swing.

The paper presents an error model of a measurement chain containing link performing discrete wavelet transform algorithm which is most often the last stage of measurement signal processing. The goal is to determine the uncertainty budget of the input quantities of the wavelet transform algorithm. The error model takes into account parts of analog, analog-to-digital and digital processing, describing the properties of subsequent fragments of the chain using their transmittance and processing functions. The proposed model enables the description of both deterministic and non-deterministic properties of signal errors. The proposed model was validated using an example measurement chain created for this purpose.

Although, promotion of urbanization culture in recent decades has made inevitable development of cities in the world, however, the development can be guided in a direction that leave, to the extent possible, minimum socioeconomic and environmental impacts. For this, it is required to first forecast auto-spreading orientation of cities and suburbs in rural areas over time and then avoid shapeless growth of cities. This paper is an attempt to develop a dynamic hybrid model based on logistic regression (LR), Markov chain (MC), and cellular automata (CA) for prediction of future urban sprawl in fast-growing cities. The model was developed using 12 widely-used urban development criteria, whose significant coefficient was determined by logistic regression, and validated by relative operating characteristic (ROC) analysis. The validated model was run in Guilan, a tourist province in northern Iran with a very high rate of urban development. For this, changes in the area of urban land use were detected over the period of 1989 to 2013 and then, future sprawl of the province was forecasted by the years 2025 and 2037. The analysis results revealed that the area of urban land use was increased by more than 1.7 % from 36012.5 ha in 1989 to 59754.8 ha in 2013, and the area of Caspian Hyrcanian forestland was reduced by 31628 ha. The results also predicted an alarming increase in the rate of urban development in the province by the years 2025 and 2037, during which urban land use is predicted to develop 0.9 % and 1.38 %, respectively. The development pattern is expected to be uneven and scattered, without following any particular direction. The development will occur close to the existing or newly-formed urban basements as well as around major roads and commercial areas. This development, if not controlled, will lead to the loss of 13863 ha of Hyrcanian forests and if the trend continues, 21013 ha of Hyrcanian forests and 20208 ha of Barren/open lands are expected to be destroyed by the year 2037. In general, the proposed model is an efficient tool for the support of urban planning decisions and facilitates the process of sustainable development of cities by providing decision-makers with an overview on future development of cities where the growth rate is very fast.

Nonlinear optimization (NOPT) is a meaningful tool for solving complex tasks in fields like engineering, economics, and operations research, among others. However, NOPT has problems when it comes to dealing with data variability and noisy input measurements that lead to incorrect solutions. Furthermore, nonlinear constraints may result in outcomes that are either infeasible or suboptimal, such as non-convex optimization. This paper introduces a novel regularized physics-informed neural network (RPINN) framework as a new NOPT tool for both supervised and unsupervised data-driven scenarios. By using custom activation functions and regularization penalties in an artificial neural network (ANN), RPINN can handle data variability and noisy inputs. Besides, it uses physics principles to build the network architecture, computing the optimization variables based on network weights and learned features. In addition, it uses automatic differentiation training to make the system scalable and cut down on computation time through batch-based back-propagation. The test results for both supervised and unsupervised NOPT tasks show that our RPINN can provide solutions that are competitive compared to state-of-the-art solvers. In turn, RPINN’s robustness against noisy input measurements makes it particularly valuable in environments with fluctuating information. Additionally, RPINN’s ANN-based foundation offers significant flexibility and scalability.

In this paper, the optimal approximation algorithm is proposed to simplify non-linear functions and/or discrete data as piecewise polynomials by using the constrained least squares. In time-sensitive applications or in embedded systems with limited resources, the runtime of the approximate function is as crucial as its accuracy. The proposed algorithm search to find the Optimal Piecewise Polynomial (OPP) with minimum computational cost while ensuring the error below a specified threshold. This was accomplished by using smooth piecewise polynomials with optimal order and number of intervals. The computational cost only depends on polynomial complexity, i.e., the order and the number of intervals at runtime function call. For optimal approximation, computational costs for all the possible combinations of piecewise polynomials were calculated and tabulated as ascending order for the specific target CPU off-line. Each combination was optimized through constrained least squares and random selection method for given sample points. Afterward, whether the approximation error is below the predetermined value is examined. When the error is permissible, the combination is selected as the optimal approximation or the next combination was examined. To verify the performance, several representative functions were examined and analyzed.

Land Surface Temperature (LST) is routinely retrieved from remote sensing instruments using semi-empirical relationships between top of atmosphere (TOA) radiances and LST, using ancillary data such as total column water vapor or emissivity. These algorithms are calibrated using a set of forward radiative transfer simulations that return the TOA radiances given the LST and the thermodynamic profiles. The simulations are done in order to cover a wide range of surface and atmospheric conditions and viewing geometries. This work analyses calibration strategies, considering some of the most critical factors that need to be taken into account when building a calibration dataset, covering the full dynamic range of relevant variables. A sensitivity analysis of split-windows and single channel algorithms revealed that selecting a set of atmospheric profiles that spans the full range of surface temperatures and total column water vapor combinations that are physically possible seems beneficial for the quality of the regression model. However, the calibration is extremely sensitive to the low-level structure of the atmosphere indicating that the presence of atmospheric boundary layer features such as temperature inversions or strong vertical gradients of thermodynamic properties may affect LST retrievals in a non-trivial way. This article describes the criteria established in the EUMETSAT Land Surface Analysis – Satellite Application Facility to calibrate its LST algorithms applied both for current and forthcoming sensors.

In this research, catalytic steam reforming acetic acid derived from the aqueous portion of bio-oil for hydrogen production was investigated by using different Ni/ATC (Attapulgite Clay) catalysts prepared by precipitation, impregnation and mechanical blending methods. The fresh and reduced catalysts were characterized by XRD, N₂ adsorption-desorption, TEM and H₂-TPR. The comprehensive results demonstrated that the interaction between active metallic Ni and ATC carrier was significantly improved in Ni/ATC catalyst prepared by precipitation method, and in which the mean Ni particle size was the smallest (~13 nm) resulted in the highest metal dispersion (7.5%). The catalytic performance of the three catalysts was evaluated through the process of steam reforming of acetic acid in a fixed-bed reactor under atmospheric pressure at two different temperatures, such as 550 ℃ and 650 ℃. Results showed that the Ni/ATC (PM-N/ATC) prepared by precipitation method, achieved the highest H₂ yield of ~82% and little lower acetic acid conversion efficiency of ~85% than that (~95%) of Ni/ATC (IM-NATC) prepared by impregnation method. In addition, the deactivation catalysts after reaction for 4 h were analyzed by XRD, TGA-DTG and TEM, which demonstrated that the catalyst deactivation was not caused by the amount of carbon deposition, but owed to the significant agglomeration and sintering of Ni particles in the carrier.

Smart manufacturing encompasses a category of manufacturing that employs computer-integrated capabilities and technologies to enhance supply chain optimization, production efficiency, and recyclability. Yet limited studies have been conducted to optimize these prospects from the perspective of low resource countries where such innovative studies have not been adequately explored. This paper aims to examine the implications of smart manufacturing practices (Smart Procurement, Smart Supply Chain, Smart Production Planning and Control, Automation and Industrial Robot, and Supply Chain Configuration) on pro-environmental behaviour and develop a baseline moderated mediation model to explain the relationship between smart manufacturing and pro-environmental behaviour with a role of green dynamic capability, and environmental orientation. This study is anchored on quantitative research approach, deductive reasoning, and explanatory design. Cross – sectional survey data have been obtained from 382 manufacturing companies in Ghana. Our hypotheses have been tested using Structural Equation Modelling and SMART-PLS version 3.8.9. The study has revealed that smart manufacturing practices significantly and positively relate to pro-environmental behaviour. Moreover, green dynamic capability and environmental orientation moderate the relationship between smart manufacturing and pro-environmental behaviour. The implications of the study include the emergence of a baseline model to guide policymakers, practitioners, and academicians to explain the relationship between smart manufacturing and sustainable manufacturing in the context of developing countries. Again, the social implication of the study includes the realisation of decent job and economic growth, responsible consumption and production as well as actions taken to combat climate change.

A comprehensive kinetic model of the Fischer-Tropsch synthesis (FTS) is developed in a fixed bed reactor under operating conditions (temperature, 230–235°C, pressure, 20–25 bar, gas hourly space velocity, 4000–5000 cm³(STP)/h/g_catalyst ,H₂/CO feed molar ratio, 2.1) over a Co based catalyst. Reaction rate equations based on Eley-Rideal (ER) type model for initiation step and Langmuir-Hinshelwood-Hougen-Watson (LHHW) type model for propagation and termination steps of the FTS reactions have been considered and the readsorption of olefins were taken into account. The model that was reported in the literature was modified in order to explain many significant deviations from the ASF distribution. Optimum parameters have been obtained by Genetic Algorithms (GA). The calculated activation energies to produce n-paraffins and 1-olefins were in the range of 82.24 to 90.68 kJ/mol and 100.66 to 105.24 kJ/mol, respectively. The hydrocarbon distribution in FTS reactions was satisfactorily predicted particularly for paraffins.

Wolfenden and his coworkers observed the astronomical numbers for the catalytic proficiency of some enzymes. We connected that pinnacle of biological evolution to the universal thermodynamic evolution. We added or multiplied a random noise with chosen rate constants to explore the correlation between dissipation and enzyme efficiency for ten enzymes: beta-galactosidase, glucose isomerase, β-lactamases from three bacterial strains, ketosteroid isomerase, triosephosphate isomerase, and carbonic anhydrase I, II, and T200H. The turnover number kcat and catalytic efficiency kcat/KM are proportional to the overall entropy production – the main parameter from irreversible thermodynamics. For most enzymes with the Michaelis-Menten type cycle kinetics, the best increase in the forward kcat/KM follows after increasing the equilibrium constant of substrate-enzyme association. The Discussion section emphasizes the role of biological evolution in harvesting order (high enzyme efficiency) from disorder (high noise and dissipation). It also connects the applications of the maximum partial entropy production theorem in optimizing enzyme kinetics (D. Juretić "Bioenergetics - A Bridge across Life and Universe") with the present total entropy production role analysis. De novo enzyme design and various attempts to speed up the rate-limiting catalytic steps may profit from our theoretical insights.

Electrochemical biosensors based on immobilized enzymes are among the most popular and commercially successful biosensors. Literature in this field suggests that modification of electrodes with nanomaterials is an excellent method for enzyme immobilization, which can greatly improve the stability and sensitivity of the sensor. However, the poor stability, weak reproducibility, and limited lifetime of the enzyme itself still limit the requirements for the development of enzyme electrochemical biosensors for food production process monitoring. Therefore, constructing sensing technologies based on enzyme electrochemical biosensors remains a great challenge. This article outlines the construction principles of four generations of enzyme electrochemical biosensors and discusses the applications of single-enzyme systems, multi-enzyme systems and nano-enzyme systems developed based on these principles. The article further describes methods to improve enzyme immobilisation by combining different types of nanomaterials such as metals and their oxides, graphene-related materials, metal-organic frameworks, carbon nanotubes and conducting polymers. In addition, the article highlights the challenges and future trends of enzyme electrochemical biosensors, providing theoretical support and future perspectives for further research and development of high-performance enzyme chemical biosensors.

Background: Bacterial infections constantly have a large impact on public health, because of increased rates of resistance and reduced frequency of development of novel antibiotics. The utility of conventional antibiotics for treating bacterial infections has become increasingly challenging. The aim of the study was to assess the antibacterial effect of β -Lapachone, a novel synthetic compound. Methods: The antibacterial activity of the β -Lapachone compound was examined against laboratory strains by agar well diffusion method, minimal inhibitory concentration (MICs), and minimal bactericidal concentration (MBCs). Growth kinetics inhibition in presence of β -Lapachone on Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa (ATCC 27853) was assessed by MABA. Crystal violet blue assay was used for biofilm inhibition assays, biofilm eradication assay and for molecular modeling PyMOL was used. Results: β -Lapachone exhibited potent antimicrobial activity against laboratory strains of bacteria with MIC of 0.2 mM for S. saprophyticus and Staphylococcus aureus, and 0.04 mM for Staphylococcus epidermidis and Pseudomonas aeruginosa ATCC 27853. The inhibition of catalase enzyme was found to be the cause for its antibacterial activity. Molecular modeling predicted the binding of β -Lap at active site and heme binding site of catalase, KatA. The activity of some commercial antibiotics was enhanced in association with β -Lap. In addition, β -Lap inhibited the biofilm formation and eradicated the already formed and ultra-mature biofilms of aforesaid bacterial strains.

This paper addresses a new micromechanical model to predict biaxial tensile moduli of plain weave fabric (PWF) composites by considering the interaction between the orthogonal interlacing strands. The two orthogonal yarns in micromechanical unit cell (UC) were idealized as the curved beams with a path depicted by using sinusoidal shape functions. The biaxial tensile moduli of PWF composites were derived by means of the minimum total complementary potential energy principle founded on micromechanics. The biaxial tensile tests were respectively conducted on the RTM-made EW220/5284 PWF composites at five biaxial loading ratios of 0, 1, 2, 3 and ∞ to validate the new model. The predictions from the new model were compared with experimental data and good correlation was achieved between the predictions and actual experiments, demonstrating the practical and effective use of the proposed model. Using the new model, the biaxial tensile moduli of plain weave fabric (PWF) composites could be predicted based only on the properties of basic woven fabric.

Background: This study aimed to identify the association between occupational stress and depression-well-being by proposing a comprehensive and flexible job burden-capital model with its corresponding hypotheses. Methods: For this research, 1618 valid samples were gathered from the electronic manufacturing service industry in Hunan Province, China; self-rated questionnaires were administered to participants for data collection after obtaining their written consent. The proposed model was fitted and tested through structural equation model analysis. Results: Single-factor correlation analysis results indicated that coefficients between all items and dimensions had statistical significance. The final model demonstrated satisfactory global goodness of fit (CMIN/DF=5.37, AGFI=0.915, NNFI=0.945, IFI=0.952, RMSEA=0.052). Both the measurement and structural models showed acceptable path loadings. Job burden and capital were directly associated with depression and well-being or indirectly related to them through personality. Multi-group structural equation model analyses indicated general applicability of the proposed model to basic features of such a population. Gender, marriage and education led to differences in the relation between occupational stress and health outcomes. Conclusions: The job burden-capital model of occupational stress-depression and well-being was found to be more systematic and comprehensive than previous models.

Insulin-degrading enzyme (IDE) is a highly conserved metalloprotease mainly localized in the cytosol. Although IDE can degrade insulin and some other low molecular weight substrates efficiently, its ubiquitous expression suggests additional functions supported by experimental findings, such as a role in stress responses, cellular protein homeostasis. Translation of full-length (Met1) IDE transcripts has reported to result in targeting to mitochondria but the role of IDE in this compartment is unknown. To obtain initial leads on the function of IDE in mitochondria, here we used a proximity biotinylation approach to identify proteins interacting with wild-type and protease-dead IDE targeted to the mitochondrial matrix. We find that mitochondrial IDE interacts strongly with mitochondrial ribosomes as well as with proteins of the respiratory chain. The mitochondrial interactomes of wild type and mutant IDE are highly similar and do not reveal any proteolytic IDE substrates. We speculate that IDE could adopt similar functions in mitochondria as in the cytosol, acting as a chaperone and contributing to protein homeostasis and stress responses.

Assessment of extreme events and climate change on reservoir inflow is important for water and power stressed countries. Projected climate is subject to uncertainties related to climate change scenarios and Global Circulation Models (GCMs’). Extreme climatic events will increase with the rise in temperature as mentioned in the AR5 of the IPCC. This paper discusses the consequences of climate change that include extreme events on discharge. Historical climatic and gauging data were collected from different stations within a watershed. The observed flow data was used for calibration and validation of SWAT model. Downscaling was performed on future GCMs’ temperature and precipitation data, and plausible extreme events were generated. Corrected climatic data was applied to project the influence of climate change. Results showed a large uncertainty in discharge using different GCMs’ and different emissions scenarios. The annual tendency of the GCMs’ is bi-vocal: six GCMs’ projected a rise in annual flow, while one GCM projected a decrease in flow. The change in average seasonal flow is more as compared to annual variations. Changes in winter and spring discharge are mostly positive, even with the decrease in precipitation. The changes in flows are generally negative for summer and autumn due to early snowmelt from an increase in temperature. The change in average seasonal flows under RCPs’ 4.5 and 8.5 are projected to vary from -29.1 to 130.7% and -49.4 to 171%, respectively. In the medium range (RCP 4.5) impact scenario, the uncertainty range of average runoff is relatively low. While in the high range (RCP 8.5) impact scenario, this range is significantly larger. RCP 8.5 covered a wide range of uncertainties, while RCP 4.5 covered a short range of possibilities. These outcomes suggest that it is important to consider the influence of climate change on water resources to frame appropriate guidelines for planning and management.

In this paper, we propose an efficient numerical computation method of reduced-order controller design for linear time-invariant systems. The design problem is described by linear matrix inequalities (LMIs) with a rank constraint on a structured matrix, due to which the problem is NP-hard. Instead of the heuristic method that approximates the matrix rank by the nuclear norm, we propose a numerical projection onto the rank-constrained set based on the alternating direction method of multipliers (ADMM). Then the controller is obtained by alternating projection between the rank-constrained set and the LMI set. We show the effectiveness of the proposed method compared with existing heuristic methods, by using 95 benchmark models from the COMPLeib library.

This paper aims to develop a hierarchical risk assessment model using the newly-developed evidential reasoning (ER) rule, which constitutes a generic conjunctive probabilistic reasoning process. In this paper, we first provide a brief introduction to the basics of the ER rule and emphasize the strengths for representing and aggregating uncertain information from multiple experts and sources. Further, we discuss the key steps of developing the hierarchical risk assessment framework systematically, including (1) formulation of risk assessment hierarchy, (2) representation of both qualitative and quantitative information, (3) elicitation of attribute weights and information reliabilities, (4) aggregation of assessment information using the ER rule and (5) quantification and ranking of risks using utility-based transformation. The proposed hierarchical risk assessment framework can potentially be implemented to various complex and uncertain systems. A case study on the fire/explosion risk assessment of marine vessels demonstrates the applicability of the proposed risk assessment model.

In current transportation hubs, it is a common phenomenon that passengers travel with necessary wheeled-luggage or suitcases. Due to the fact that most luggage occupies certain space within dense passenger crowds with giant mass inertia, its abnormal motions, such as drifting, frequently trig unavoidable local disturbances and turbulence in surrounding pedestrian flows, further increasing security risk. While, current researches primarily concentrate on examining the impact of luggage on crowd evacuation efficiency through scenario-based experiments and analyzing the spatial characteristics of crowd distribution in surveillance videos. There still lacks of the dynamic disturbance mechanisms and crowd stability associated with the combined motion of passengers and luggage. Therefore, this study considers the luggage-laden passenger as a deformable particle, the resulting disturbance on surrounding non-luggage passengers is analyzed and quantified into a nonlinear pressure term. Subsequently, the disturbance propagation model of passenger-luggage is developed by adapting the classical Aw-Rascle traffic flow model with incorporation of the pressure term. Simulation experiments of disturbances caused by luggage drifting and retrograding validate that the proposed propagation model aligns with real-world situations in transportation hubs. Quantitively, when luggage-laden passenger drifted left, the disturbing force of left side crowd can reach a peak of 238N in the passenger density of 3.0 p/m2, and the maximum difference between the left and right sides disturbing force can reach 153N. Furthermore, it is recommended that the proposed model can be applied to crowd flow analysis and risk assessment.

Antioxidant, anti-inflammatory and chemo-preventive features have been reported for the carotenoid diatoxanthin. Diatoxanthin is only produced by a few groups of microalgae where it functions in photoprotection. Its large-scale production in microalgae is currently not feasible. In fact, rapid conversion into the inactive pigment diadinoxanthin is triggered when the cells are removed from the high-intensity light source, which will be the case during large-scale harvesting of microalgae biomass. Zeaxanthin epoxidase (ZEP) 2 and/or ZEP3 have been suggested to be responsible for the back-conversion of high-light accumulated diatoxanthin to diadinoxanthin in low light in diatoms. Using the CRISPR/Cas9 gene editing technology we knocked out the ZEP2 and ZEP3 genes in the already commercially used marine diatom Phaeodactylum tricornutum to investigate their role in the diadinoxanthin-diatoxanthin cycle, and to determine if one of the mutant strains could function as a diatoxanthin production line. Light shift experiments proved that ZEP3 encodes the enzyme converting diatoxanthin to diadinoxanthin in low light. Loss of ZEP3 caused the high-light accumulated diatoxanthin to be stable for several hours after the cultures had been returned to low light, suggesting that zep3 mutant strains could be suitable as commercial production lines of diatoxanthin.

The organic fraction of municipal solid waste (OFMSW) is a significant environmental threat, and an economic and social challenge to manage. As such, the efficient treatment of OFMSW is a significant key factor in achieving sustainable waste management. Decentralized Composting (DC) develops a new framework of waste management. The DC Analysis Model (DCAM), proposed in our previous study, provides a powerful tool for decision makers, based on the quantification of the DC project characteristics. In this paper, we focus on the qualitative analysis as a complementary tool to support decision making, in cases where quantitative analysis is unequivocal. The qualitative analysis identifies the main players in the field, the critical stakeholders and the potential conflicts between them. It also reveals the root problems and the core competencies for the project's implementation. DCAM qualitative analysis in Shefa-Amr (case study) indicates that unresolved root problems, such as the “lack of national regulation”, “clear ownership of the project” and “lack of ongoing budget” can result in an unsustainable composting system. Countering that, “the commitment of the municipality”, together with “economic viability” and securing “suitable areas for placing composters” are among the most important core competencies for the effective implementation of DC projects.

Gestational diabetes mellitus (GDM) pathophysiology comprises clinical and genetic factors. In fact, GDM has been associated with several single nucleotide polymorphisms (SNPs). This study aimed to build a prediction model of GDM combining clinical and genetic risk factors. A total of 1588 pregnant women from the San Carlos Cohort participated in the present study, 1069 (67.3%) Caucasian (CAU) and 519 (32.7%) Latin American (LAT), 255 (16.1%) with GDM. The incidence of GDM was similar in both groups (16.1% CAU and 16.0% LAT). Genotyping was performed by IPLEX Mass ARRAY PCR selecting 110 SNPs based on literature references. The SNPs showing the strongest likelihood of GDM development were the rs10830963, rs7651090 and rs1371614 in CAU and rs1387153 and the rs9368222 in LAT. Clinical variables including age, pre-pregnancy body mass index and fasting plasma glucose (FPG) at 12 gestational weeks predicted the risk of GDM (AUC 0.648, 95%CI 0.601-0.695 in CAU; AUC 0.688, 95%CI 0.628-9.748 in LAT) and adding the SNPs modestly improved prediction (AUC 0.722, 95%CI 0.680-0.764 in CAU; AUC 0.769, 95%CI 0.711-0.826 in LAT). In conclusion, adding genetic variants enhanced the prediction model of GDM risk in CAU and LAT pregnant women. An RCT is underway to demonstrate its usefulness

Motivated for improving the efficiency and reliability of wind turbine energy conversion, this paper presents an advanced control design that enhances the power regulation efficiency and re-liability. The constrained behaviour of the wind turbine is taken into account, by using the barrier Lyapunov function in the analysis of the Lyapunov direct method. This, consequently, guarantees that the generated power remains within the desired bounds to satisfy the grid power demand. Moreover, a Nussbaum-type function is utilized in the control scheme, to cope with the unpre-dictable wind speed. This eliminates the need for accurate wind speed measurement or estimation. Furthermore, via properly designed adaptive laws, a robust actuator fault-tolerant capability is integrated into the scheme, handling the model uncertainty. Numerical simulations are performed on a high-fidelity wind turbine benchmark model, under different fault scenarios, to verify the effectiveness of the developed design. Also, a Monte-Carlo analysis is exploited for the evaluation of the reliability and robustness characteristics against the model-reality mismatch, measurement errors and disturbance effects.

Due to the increasing global importance of decarbonizing human activities, especially the production of electricity, the optimal deployment of renewable energy technologies will play a crucial role in future energy systems. To accomplish this, particular attention must be accorded to the geospatial and temporal distribution of variable renewable energy sources (VRES) such as wind and solar radiation in order to match electricity supply and demand. This study presents a techno-economical assessment of four energy technologies in the hypothetical context of Mexico in 2050, namely: onshore and offshore wind turbines, and open-field and rooftop photovoltaics. A land eligibility analysis incorporating physical, environmental, and socio-political eligibility constraints and individual turbine and photovoltaic park simulations, drawing on 39 years of climate data, is performed for individual sites across the country in an effort to determine the installable potential and the associated levelized costs of electricity. The results reveal that up to 54 PWh of renewable electricity can be produced as a cost of less than 70 EUR/MWh. Around 91% (49 PWh) of this would originate from 23 TW of open-field photovoltaic parks that could occupy up to 578,000 km2 of eligible land across the country. The remaining 9% (4.8 PWh) could be produced by 1.9 TW of onshore wind installations allocated to approximately 68,500 km2 of eligible land that is almost fully adjacent to three mountainous zones. The combination of rooftop photovoltaic and offshore wind turbines account for a very small share of less than 0.03% of the overall techno-economical potential.

In order to further clarify the growth-promoting effect of non-core Metarhizium spp. M. marquandii on plants, M. marquandii SGSF043, which was obtained from the pre-screening in the laboratory, was selected as a test strain, and the effects of the fungus fermentation broth during the stabilization period of the growth of this strain on the growth and growth of maize seeds were investigated by using fermentation broth as a submerged seed. germination, seedling growth, and inter-root soil enzyme activity of seedlings. The results are as follows: In the seed germination test, M. marquandii SGSF043 fermentation liquid had a certain inhibitory effect on the germination of maize seeds, and the 10-times dilution of the fermentation liquid significantly promoted the seed germination, and the effect was the best; After the germination test, the growth of maize germ was promoted by the treatment groups of 10 times and 1,000 times diluent; In the field plot experiment, the 100-fold dilution had the best growth promotion effect, which could promote the growth of cabbage seedlings and increase the seedling biomass. The results show that M. marquandii SGSF043 has the potential to promote the growth of maize and improve the soil environment, which provides a theoretical basis for the research and application of M. marquandii in farmland.

Analysing the human body by direct observation can lead to misinterpretation of underlying trends, whereas in vitro organ models facilitate their understanding. Likewise, in vitro organ models serve as valuable tools for assessing the toxicity of compounds. However, none of the existing models had the features we considered critical for toxicity assessment, so we developed an in vitro liver model for toxicity assessment. We used four different types of primary liver cells: Hepatic sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells and hepatocytes. We cultured them in different combinations of composition and volume of cell medium, hepatocyte proportion of total cells, and addition of extracellular matrix. We added rifampicin, ibuprofen and 5-fluorouracil to this model and observed the microanatomy and physiology changes for a week with preclinical and clinical instruments. Among the different model configurations, we selected the feature combination of the in vitro model that had similar biomarker values to those measured by the clinical instruments used in clinical diagnostics. When we exposed the selected model configuration to rifampicin, ibuprofen and 5-fluorouracil, the viability of Kupffer cells and liver sinusoidal endothelial cells was significantly lower than in the untreated samples. In contrast, we observed negligible viability of hepatocytes compared to the untreated samples. We have built an in vitro liver model that resembles the liver microenvironment and we have analysed it with clinical instrumentation to facilitate the data translation. In this sense, we have established that Kupffer and LSEC cells are suitable candidates for the search for clinical diagnostic markers of liver function.

Distributed/semi-distributed models are considered to be sensitive to the spatial resolution of the data input. In this paper, we take a small catchment in high urbanized Yangtze River Delta, Qinhuai catchment as study area, to analyze the impact of spatial resolution of precipitation and the potential evapotranspiration (PET) on the long-term runoff and flood runoff process. The data source includes the TRMM precipitation data, FEWS download PET data, and the interpolated metrological station data. GIS/RS technique was used to collect and pre-process the geographical, precipitation and PET series, which were then served as the input of CREST (Coupled Routing and Excess Storage) model to simulate the runoff process. The results clearly showed that, the CREST model is applicable to the Qinhuai catchment; the spatial resolution of precipitation had strong influence on the modelled runoff results and the metrological precipitation data cannot be substituted by the TRMM data in small catchment; the CREST model was not sensitive to the spatial resolution of the PET data, while the estimation fourmula of the PET data was correlated with the model quality. This paper focused on the small urbanized catchment, suggesting the influential explanatory variables for the model performance, and providing reliable reference for the study in similar area.

Cardiovascular diseases (CVD) are chronic diseases associated with a high risk of mortality and morbidity. Early detection of CVD is crucial to initiating timely interventions, such as appro- priate counseling and medication, which can effectively manage the condition and improve patient outcomes. Preventive measures should be implemented at the general public level, promoting a healthy lifestyle, and at the individual level, that is, in people with moderate to high risk of CVD or patients already diagnosed with CVD by addressing an unhealthy lifestyle. Personalized early diagnostic systems based on artificial intelligence (AI), ontologies, and other medical information processing systems may prove to be a great preventive measure. In this paper, we focus on the use of ontology-inspired database models in the diagnosis of cardiovascular disease, as well as their potential for use in web application development.

The primary contributor to global warming has been the careless usage of fossil fuels. Urbanization's threat to the depletion of these resources has made it necessary to find alternatives due to the rising demand. Four different forms of biofuels are now available and constitute a possible replacement for fossil fuels. The first generation of biofuels is generated from the edible portion of biomass, the second generation is made from the non-edible portion of biomass, the third generation is made from algal biomass, and the fourth generation is made using molecular biology to improve the algal strain. Second generation biofuels are extremely important because they are derived from non-edible biomass, such as agricultural and agro-industrial wastes rich in cellulose, hemicellulose, pectin, and starch impregnated with lignin, and are hydrolyzed after delignification by physio-chemical or biological pretreatments using ligninases. There has been a lot of research on their production using chemical and enzymatic hydrolysis, but it has not been economically viable in comparison to first generation biofuels due to the formation of several inhibitors with chemical hydrolysis and the high cost of the enzymes. Furthermore, the need for multiple enzymes due to the various types of carbohydrates in the feedstocks makes the enzymatic process too expensive. This article examines the enzymes involved in the hydrolysis of feedstocks for the production of second generation bioethanol, a highly acceptable biofuel.

Some cancer cells rely heavily on non-essential biomolecules for survival, growth, and proliferation. Enzyme based therapeutics can eliminate these biomolecules, thus specifically targeting neoplastic cells; however, enzyme therapeutics are susceptible to immune clearance, exhibit short half-lives, and require frequent administration. Encapsulation of therapeutic cargo within biocompatible and biodegradable poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) is a strategy for controlled release. Unfortunately, PLGA NPs exhibit burst release of cargo shortly after delivery or upon introduction to aqueous environments where they decompose via hydrolysis. Here we show the generation of hybrid silica-coated PLGA (SiLGA) NPs as viable drug delivery vehicles exhibiting sub-200 nm diameters, a metastable Zeta potential, and high loading efficiency and content. Compared to uncoated PLGA NPs, SiLGA NPs offer greater retention of enzymatic activity and slow the burst release of cargo. Thus, SiLGA encapsulation of therapeutic enzymes, such as asparaginase, could reduce frequency of administration, increase half-life, and improve efficacy for patients with a range of diseases.

Accurate diagnosis for the 400 million people with rare diseases is critical for healthcare decisions, prognosis, understanding disease mechanisms, and identification of treatments. Despite advances in genome sequencing, barriers such as high interpretation costs, diagnostic expertise, throughput associated delays, and uncertain variant classifications persist, with demand exceeding capacity. Many variant classification methods focus narrowly on specific consequences, leading to the use of complex integrative pipelines that often overlook transcript variability and lack prediction transparency. To overcome these limitations, we introduce DITTO. This transparent, transcript-aware machine-learning method demonstrates superior overall performance in accuracy, recall, and precision when compared to existing tools. DITTO is publicly available at https://github.com/uab-cgds-worthey/DITTO

The Imbalance Cost Pass-Through (ICPT) is a flexible component of the Incentive Regulation (IBR) that empowers power producers to adjust tariffs in response to variable fuel prices, thereby enhancing the economic resilience of electricity generation. However, the cost of electricity generation is significantly influenced by the volatility of commodity prices, including coal, gas and LNG. In Malaysia, the Energy Commission has conducted biannual reviews of fuel and other generation costs. Any cost savings or increases identified during these reviews will be passed on to customers in the form of rebates or surcharges. Due to that reason, this study proposes ICPT price forecasting for the electricity market in Peninsular Malaysia. The study aims to construct an ICPT-related baseline model for the peninsular generation data by employing three forecasting methods. The forecasting performance is analysed by a Mean Absolute Percentage Error (MAPE). In findings, the ARIMA method is one of the most accurate forecasting methods for fuel prices compared to the Moving Average (MA) and LSSVM methods. The observed price differences between the ARIMA and LSSVM models for ICPT are minimal. The ICPT price for July-December 2022 and January-June 2023 is MYR 0.21/ kWh for ARIMA and MYR 0.18/kWh for LSSVM, which are close to the actual TNB’s ICPT tariff. As for the forecasting, the ICPT price is expected to drop for the next announcement. The findings of this study may contribute to a positive impact on the sustainability of the energy sector in Malaysia.

Semi-continuous data are very common in the social science and economics. In this paper, a Bayesian variable selection procedure is developed to assess the influence of exogenous factors including observed and unobserved on the semi-continuous data. Our formulation is based on the two-part latent variable model with polytomous response. We consider two schemes for the penalties of regression coefficients and factor loadings: the Bayesian spike and slab bimodal prior and the Bayesian lasso prior. Within the Bayesian framework, we implement Markov Chains Monte Carlo sampling method to conduct posterior inference. To facilitate posterior sampling, we recast the logistic model in part one as the norm-like mixture model. Gibbs sampler is designed to draw observations from the posterior. Our empirical results show that with suitable hyper-parameters, the spike and slab bimodal method slightly outperforms the Bayesian lasso in the current analysis. Finally, a real example related to the China household finance survey is analyzed to illustrate the application of the methodology.. .

The paper examines the various uncertainties encountered in high-frequency trading (HFT) environments and delves into the multiple challenges faced by HFT firms in navigating the Dodd-Frank Wall Street Reform and Consumer Protection Act (referred to as the "Dodd-Frank Act"), particularly during the initial stages of its enactment. These challenges include the ambiguity surrounding the definition of HFT, the lack of clarity regarding regulatory requirements and boundaries, inconsistencies in enforcement resulting from deviations in understanding the content, and the absence of detailed descriptions of the Act’s provisions. These hurdles significantly impact not only the daily operations of HFT firms but also pose higher demands on their long-term strategic planning and risk management. Drawing upon the Data, Information, Knowledge, Wisdom, and Purpose (DIKWP) model, this study employs an innovative analytical framework. Through the comprehensive application of conceptual space, cognitive space, and semantic space, it provides a systematic methodology for identifying and analyzing the aforementioned issues. This approach not only aids firms in better comprehending and adhering to complex regulatory requirements but also enables them to explore new business opportunities and competitive advantages while ensuring compliance.

Smart living, a concept that has gained increasing attention in recent years, revolves around integrating advanced technologies in homes and cities to enhance the quality of life for citizens. Sensing and human action recognition are crucial aspects of this concept. Smart living applications span various domains, such as energy consumption, healthcare, transportation, and education, which greatly benefit from effective human action recognition. This field, originating from computer vision, seeks to recognize human actions and activities using not only visual data but also many other sensor modalities. This paper comprehensively reviews the literature on human action recognition in smart living environments, synthesizing the main contributions, challenges, and future research directions. This review selects five key domains: Sensing Technology, Multimodality, Real-time Processing, Interoperability, and Resource-Constrained Processing, as they encompass the critical aspects required for successfully deploying human action recognition in smart living. These domains highlight the essential role that sensing and human action recognition play in successfully developing and implementing smart living solutions. This paper serves as a valuable resource for researchers and practitioners seeking to explore further and advance the field of human action recognition in smart living.

Smart Internet of Vehicles (IoVs) combined with Artificial Intelligence (AI) will contribute to vehicle decision-making in the Intelligent Transportation System (ITS). Multi-Vehicle Pursuit games (MVP), a multi-vehicle cooperative ability to capture mobile targets, is becoming a hot research topic gradually. Although there are some achievements in the field of MVP in the open space environment, the urban area brings complicated road structures and restricted moving spaces as challenges to the resolution of MVP games. We define an Observation-constrained MVP (OMVP) problem in this paper and propose a Transformer-based Time and Team Reinforcement Learning scheme (T3OMVP) to address the problem. First, a new multi-vehicle pursuit model is constructed based on decentralized partially observed Markov decision processes (Dec-POMDP) to instantiate this problem. Second, by introducing and modifying the transformer-based observation sequence, QMIX is redefined to adapt to the complicated road structure, restricted moving spaces and constrained observations, so as to control vehicles to pursue the target combining the vehicle’s observations. Third, a multi-intersection urban environment is built to verify the proposed scheme. Extensive experimental results demonstrate that the proposed T3OMVP scheme achieves significant improvements relative to state-of-the-art QMIX approaches by 9.66%~106.25%. Code is available at https://github.com/pipihaiziguai/T3OMVP.

The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. We have now investigated all bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies with minodronate could be valuable.

In light of the hazardous effects of global warming brought on by climate change, bioethanol production is one of the key alternatives in which the world has expressed a great deal of interest. Two factors—indigenous production and price—are crucial for bioethanol to be appealing in Africa and, for that matter, Ghana. The objective of this research is to produce bioethanol from cheap lignocellulosic materials using onsite enzymes produced from cassava peels degrading fungi. Due to Ghana's prominent position as one of the leading cassava producers in the world, the study focused on utilizing cassava peels, which are underutilized in the country. The research was conducted in multiple stages. In the first stage, the peels were prepared by washing, drying, and manually crushing them using mortar and pestle. The second stage involved analyzing the chemical composition of the peels, including starch and insoluble fibre, which were determined as Acid Detergent Fiber (ADF), Neutral Detergent Fiber (NDF), and Acid Detergent Lignin (ADL). The results showed significant levels of cellulose (39.78%) and starch (31.21%), indicating that cassava peels are valuable raw materials for bioethanol production. The content of hemicellulose (21.11%) and lignin (3.84%) were also determined. In the third stage, using a Petri dish, three fungi (ICPF1, ICPF2, and ICPF3) were isolated from two different cassava peels. ICPF1 was only identified from fresh cassava peels (FCP), while all three fungi were identified from decayed cassava peels (DCP). Morphologically, these fungi were identified as Aspergillus niger, Aspergillus flavus, and Rhizopus stolonifer. The fourth stage focused on optimizing the enzyme activity of the three isolates for potential applications, with A. niger demonstrating the highest enzyme activity with a diameter of zone of clearance of 16 mm. Stage five involved optimizing the production of the onsite enzyme in a 50ml flask using A. niger, basal salt medium (BSM), and cassava peels as a substrate. The DNSA method was used to measure the absorbance of maltose and glucose at 540 nm for various substrate concentrations (1%, 3%, 5%, 8%, and 10%) at specific intervals of 2, 4, 6, 8, and 10 days with a spore concentration of 2.1 x 105 cells/ml. The maltose and glucose concentrations were calculated as 7.138mg/ml and 6.398 mg/ml, respectively, and the corresponding enzyme activity was determined as 4.759U/ml and 4.265U/ml. The optimal conditions of Day 4 and a substrate concentration of 10%, along with a fixed temperature of 30°C and a pH of 5.5, were used to prepare the onsite enzymes in a 500 ml flask for the fermentation process. The onsite enzymes were used for saccharification and Saccharomyces cerevisiae for fermentation under simultaneous saccharification and fermentation (SSF) process. A mixture of 20 ml of onsite enzymes and 1.5 g of S. cerevisiae were added to substrate concentrations of 5%, 10%, and 20%, and the ethanol concentration was analyzed daily for 7 days using Gas Chromatography (GC). The highest ethanol concentration (1.316%) was observed on Day 5 with a substrate concentration of 20%, while the lowest concentration (0.123%) was recorded on Day 1 with a substrate concentration of 5%.

A recent report from the American Heart Association in 2018 shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin-angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, heart failure among others. It has been suggested that ACE inhibitors can reduce the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that alterations in the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases. In mice, overexpression of ACE in the brain reduces symptoms of the AD-model systems. Thus, we find opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin-angiotensin system; (2) amyloid-degrading enzyme that can hydrolyze beta-amyloid and reduce amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to Alzheimer’s disease to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during the midlife, leading to age-related later events.

In this paper, an adaptive proportional and integral (PI) controller for speed control of electric drives is developed. The adaptive PI controller is designed based on model reference adaptive identification and the Lyapunov function so that the system stability can be proved. To identify the inertia, the viscous friction torque coefficient, and the load torque simultaneously and smoothly, sinusoidal speed reference is usually employed. A modified motion equation considering the low-pass filter for feedback speed and the Coulomb friction torque is introduced and the relationship between the identified parameters and their actual values are clarified. A high-precision digital simulation model is built based on MATLAB/Simulink. The effectiveness of the proposed method is verified by simulations under various conditions.

Meningitis is a severe disease associated with death in children under five with highest rates of infections under age of one. Vaccines for Neisseria meningitides and Haemophilus influenza are used to prevent the main causative agents of meningitis. Administration of H. influenzae type b (Hib) vaccine is recommended at 2, 4 and 6 months with a booster dose at 18 months. N. meningitidis has two commercially available vaccines, the pure polysaccharide is recommended at 24 months meanwhile the protein-conjugated vaccines at 12 months. We sought in this study to examine if coadministering the vaccines for the two main meningitis causing bacteria might be synergistic as a preliminary step towards the possibility of shuffling immunization schedule. So, we coadministered Hib vaccine with commercially available vaccines either quadrate (ACWY) polysaccharide meningococcal (Men) or conjugated meningococcal (Nim) vaccines in Balb/C mice (n = 6/group) and compared to each vaccine administered separately and controls. Thirty-five days post immunization, we measured specific antibodies titers. Hib vaccine increased Men antibody titers significantly for serotypes Y and W. When Hib vaccine was coadministrated with Nim, antibody titer for Y, W and A significantly increased. For serotype C, there was no significant difference in antibody titers among immunized groups. As for effect of meningococcal vaccines on Hib, Men significantly increased Hib antibody titers while Nim had no effect. Collectively, our data suggested that coadministration of Hib and Men or Nim vaccines was safe and had synergistic effect on immune responses elicited to both vaccines. Further studies are needed before immunization schedule modifications. Such immunization schedule recommendation should provide better protection against this life-threatening disease in young children.

Local food has continued to become more popular in both the home and as featured ingredients in all segments of food service. Numerous studies have explored the motivating factors for consumer purchasing motivators. However, no known study has explored if there is a correlation between ego and intent to buy local foods. This study adopted a modified version of the Theory of Trying and surveyed a sample of 237 food service buying agents in South Carolina to examine their perceptions of buying local. Results suggest that ego is a predictor of trying to purchase local foods for restaurants. It was also found that the modified model is an acceptable model for predicting buyer intent. These findings support the majority of the studies looking at ego-centric behaviors with green purchases and could potentially help local food suppliers to better market their products to foodservice establishments. This study could also act as the foundation for future studies to explore the full extent of ego’s motivational effect on purchasing intentions in the food service industry.

ESG (Environmental, Social, and Governance) responsibility fulfillment increasingly affects enterprise valuation. Although researchers debate about the precise effects, the prevailing view suggests a linear relationship between ESG performance and enterprise value. This study introduces a novel ESG responsibility performance metric through the Regulated Intermediary Model to delve into this relationship within the Chinese context. Our findings reveal an inverted U-shaped relationship between ESG performance and enterprise value, with financing constraints having a significant moderating effect. These findings remain robust after employing instrumental variables to mitigate potential endogeneity. Heterogeneity analysis demonstrates that this inverted U-shaped relationship is particularly pronounced in non-polluting and non-state-owned enterprises. Moreover, a comparison between equity and debt financing mechanisms underscores that improved ESG performance is associated with lower cost of equity financing, thereby enhancing enterprise value. Financial institutions are encouraged to leverage innovative financial instruments to diversify enterprise financing channels and alleviate financing constraints of enterprises that fulfill their ESG responsibilities.

The enhancement of early diagnosis of lung cancer is mandatory to improve prognosis. We observed the increase cancer stem cells (CSC) and circulating tumor cells (CTC) in blood of mice on d3 after Lewis lung carcinoma (LLC) cell implantation before disease symptom. Besides we have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). The rsCD8+T-cells were able to migrate to lung and were more resistant after the exhaustion in vitro in comparison with naïve sCD8+T-cells. In the orthotopic LLC model, the rsCD8+T-cells therapy increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung from mice. The amount of CSC decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.