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The control problem for quadrotor UAVs is difficult and challenging due to the complex nonlinear dynamics and ever-changing disturbances. In this paper, a supplementary controller based on reinforcement learning (RL) is proposed to improve the control performance of quadrotor UAVs. The proposed RL method is constructed by an actor-critic structure and some improved technologies, e.g., Q-learning, temporal difference, and experience replay. With the proposed method, the speed and stability of training can be improved greatly. On one hand, the supplementary controller can work together with the traditional controller online, which can guarantee the stability of the system. On the other hand, the model uncertainties and external disturbances could be restrained through online RL training. The Lyapunov theory is used to prove the convergence of the RL controller's weights theoretically. Finally, three simulations are provided to illustrate the effectiveness of the proposed controller.

In this paper, a nonlinear robust control method is developed for trajectory tracking of a quadrotor aircraft. The proposed approach combines the robust signal compensation method and the backstepping technique. First, the quadrotor dynamic system with multiple disturbances and uncertainties is divided into four subsystems. Then, the nominal controllers are constructed for the subsystems without disturbance terms, while the robust signal compensators are introduced to compensate for the effect of nonlinearities and uncertainties. Furthermore, the Lyapunov analysis has shown that the proposed controller can achieve stable tracking in the presence of violent discontinuous disturbances and uncertainties. The tracking error converges to an arbitrarily small neighborhood of zero. Finally, the proposed control design is validated with real flight experiments. The results show superior trajectory tracking performance of the quadrotor system affected by external disturbances.

We first report the results from analyzing the GRACE satellite data for the coseismic and long-term post-seismic changes in the Earth’s gravity field and geoid height induced by the 2004 Sumatra-Andaman earthquake (Mw 9.2) and the 2012 Indian-Ocean earthquake (Mw 8.6). The results suggest that the two earthquakes have changed the gravity field and geoid height irreversibly (as opposed to cyclically). We next use satellite ocean altimetry measurements to search for the geoid height change induced by the Sumatra-Andaman earthquake, employing an effective method of extracting coherent space-temporal signals, namely the empirical orthogonal functions (EOF) analysis. Our results demonstrate that the sea level variation in the studied (tropical) area during the studied (10-year) period is dominated by the strong steric changes related to ENSO, to the point that the earthquake-induced signals, even using EOF for the largest earthquakes, are obscured and thus undetectable by ocean altimetry. However, this also means that steric and non-steric changes can be observed separately from artificial satellites.

The Cre-loxP system produces structural variations, such as deletion, duplication, inversion and translocation, at specific loci and induces chromosomal rearrangements in the genome. To achieve chromosomal rearrangements in Kluyveromyces marxianus, the positions and sequences of centromeres were identified in this species for the first time. Next, a Cre-loxP system was established in K. marxianus. In this system, the Cre recombinase was expressed from a leaky LAC4 promoter in a plasmid to alleviate the cytotoxicity of Cre, and the unstable plasmid contained a panARS element to facilitate the clearance of the plasmid from the cells. By using LAC4 as a reporter gene, the recombination frequencies between loxP sites or loxPsym sites were 99% and 73%, respectively. A K. marxianus strain containing 16 loxPsym sites in the genome was constructed. The recombination frequency of large-scale chromosomal rearrangements between 16 loxPsym sites was up to 38.9%. Our study provides valuable information and tools for studying chromosomal structures and functions in K. marxianus.

Rice blast is one of the main diseases in rice and can occur in different rice growth stages. Due to the complicated procedure of panicle blast identification and instability of panicle blast infection influenced by the environment, most cloned rice resistance genes are associated with leaf blast. In this study, a rice panicle blast resistance gene, Pb2, was identified by genome-wide association mapping based on the panicle blast resistance phenotypes of 230 Rice Diversity Panel 1 (RDP1) accessions with 700,000 single-nucleotide polymorphism (SNP) markers. A genome-wide association study identified 18 panicle blast resistance loci (PBRL) within two years, including 9 reported loci and 2 repeated loci (PBRL2 and PBRL13, PBRL10 and PBRL18). Among them, the repeated locus (PBRL10 and PBRL18) was located in chromosome 11. By haplotype and expression analysis, one of the Nucleotide-binding domain and Leucine-rich Repeat (NLR) Pb2 genes was highly conserved in multiple resistant rice cultivars, and its expression was significantly upregulated after rice blast infection. Pb2 encodes a typical NBS-LRR protein with NB-ARC domain and LRR domain. Compared with wild type plants, the transgenic rice of Pb2 showed enhanced resistance to panicle and leaf blast with reduced lesion number. Subcellular localization of Pb2 showed that it is located on plasma membrane, and GUS tissue-staining observation found that Pb2 is highly expressed in grains, leaf tips and stem nodes. The Pb2 transgenic plants showed no difference in agronomic traits with wild type plants. It indicated that Pb2 could be useful for breeding of rice blast resistance.

Port environmental problems have gradually become the primary concern of port authorities. The future trend of port carbon emissions is crucial to port authorities and managers in formulating regulations and optimizing operation schedules. Owing to the limitations of current prediction methods and the complex social–environmental impact, the estimation results of port carbon emissions have insufficient accuracy to support port development in the future. In this work, the stochastic impacts by regression on population, affluence, and technology (STIRPAT)–long short-term memory (LSTM)–autoregressive integrated moving average with explanatory variable (ARIMAX) integrated model is proposed for the estimation of the carbon emission of Port of Los Angeles to improve the reliability of emission prediction. Macroeconomic indicators that affect port throughput are selected using the principal component analysis—multiple linear regression model. The chosen indicators are then combined with long-term historical port throughput data as the input of the multivariate autoregressive integrated moving average (ARIMAX) model to predict port throughput. Indicators related to port carbon emissions are verified by the STIRPAT model. The LSTM–ARIMAX integrated model is then applied to estimate the emission tendency, which can be useful in developing corresponding carbon reduction strategies and further understanding port emissions. Results show that the proposed method can significantly improve the estimation accuracy for port emission by 11% compared with existing techniques. Energy conservation strategies are also put forward to assist port authorities in achieving the peak clipping of port carbon emission.

ABSTRACT Background: the esophagogastric junction contractile integral (EGJ-CI) is a novel high-resolution manometry (HRM) tool designed to assess EGJ barrier function. This study assessed whether changes in EGJ-CI values reflect a disruption of the EGJ in achalasia patients undergoing per-oral endoscopic myotomy (POEM). Methods: patients with HRM performed both before and after POEM were identified over a three year period and were compared to healthy controls. EGJ-CI was calculated using the St Louis method, where EGJ vigor is assessed independently of respiration and referenced to the gastric baseline. It is reported as mmHg.cm. Pre- and post-POEM EGJ-CI, conventional lower esophageal sphincter pressure (LESP) metrics (end expiratory LESP and mean basal LESP) and integrated relaxation pressure (IRP) were compared between groups. The correlation between EGJ-CI and conventional LESP metrics was also assessed and compared to controls. Results: fifteen achalasia patients (35.2 ± 2.5 years, 73% female) fulfilled the inclusion criteria and were compared to 20 healthy volunteers (26.6 ± 1.1 years, 50% female). The Eckardt score was significant lower after POEM (1.5 ± 0.3 vs 7.0 ± 0.5, p < 0.001). Baseline conventional LESP metrics, EGJ-CI and IRP were higher in achalasia cases compared to controls (p < 0.001). Both conventional LESP metrics and EGJ-CI decreased significantly following POEM (p < 0.001) and approximated the values recorded in controls (p ≥ 0.1). However, IRP remained higher post-POEM compared to controls (p = 0.011). EGJ-CI correlated with conventional LESP metrics at baseline (Pearson's r = 0.75-0.79; Spearman's rho = 0.84-0.85, p < 0.001) and following POEM (0.55-0.70 and 0.5-0.77, respectively; p ≤ 0.03). Conclusions: EGJ-CI complements the assessment of the EGJ barrier and may be a useful metric to follow barrier function after per-oral myotomy.

Kluyveromyces marxianus is a promising host for producing bioethanol and heterologous proteins. It displays many superior traits to a conventional industrial yeast species, Saccharomyces cerevisiae, including fast growth, thermotolerance and the capacity to assimilate a wider variety of sugars. However, little is known about the mechanisms underlying the fast-growing feature of K. marxianus. In this study, we performed a comparative genomic analysis between K. marxianus and other Saccharomycetaceae species. Genes involved in flocculation, iron transport, and biotin biosynthesis have particularly high copies in K. marxianus. In addition, 60 K. marxianus specific genes were identified, 45% of which were upregulated during cultivation in rich medium and these genes may participate in glucose transport and mitochondrion related functions. Furthermore, the transcriptomic analysis revealed that under aerobic condition, normalized levels of genes participating in TCA cycles, respiration chain and ATP biosynthesis in the lag phase were higher in K. marxianus than those in S. cerevisiae. Levels of highly copied genes, genes involved in the respiratory chain and mitochondrion assembly, were upregulated in K. marxianus, but not in S. cerevisiae, in later time points during cultivation compared with those in the lag phase. Notably, during the fast-growing phase, genes involved in the respiratory chain, ATP synthesis and glucose transport were co-upregulated in K. marxianus. A few shared motifs in upstream sequences of relevant genes might result in the co-upregulation. Specific features in the co-regulations of gene expressions might contribute to the fast-growing phenotype of K. marxianus. Our study underscores the importance of genome-wide rewiring of the transcriptional network during evolution.

Cerebral edema is a severe complication of acute ischemic stroke with high mortality but limited treatment. Although parameters such as brain water content and intracranial pressure may represent the global assessment of edema, optical properties can appear heterogeneously throughout the cerebral tissue relative to the site of injury. In this study, we have monitored the edema formation and progression in both permanent and transient middle cerebral artery occlusion models in rats. Edema was reflected by the decrease of optical attenuation coefficient (OAC) value in OCT system. By utilizing swept-source optical coherence tomography (SS-OCT), we found that in photochemically induced permanent focal stroke model, both the edema size and edema index, steadily developed until the end of monitor (7h). Comparatively, when transient ischemia was introduced with endothelin-1 (ET-1), the edema was detected as early as 15min, and began to recover after 30min until monitor was finished (3h). Despite the majority of the edema being recovered to some extent, the condition of a small region within the edema kept deteriorating, presumably due to the reperfusion damage which might result in serious clinical outcomes. Our study has compared the edema characteristics from two different acute ischemic stroke situations. This work not only confirms the capability of OCT to temporal and spatial monitor of edema but is also able to locate focal conditions at some areas that might highly determine the prognosis and treatment decisions.

Segmentation of layers in retinal images obtained by optical coherence tomography (OCT) has become an important clinical tool to diagnose ophthalmic diseases. However, due to the susceptibility to speckle noise and shadow of blood vessels etc., the layer segmentation technology based on a single image still fail to reach a satisfactory level. We propose a combination method of structure interpolation and lateral mean filtering (SI-LMF) to improve the signal-to-noise ratio based on one retinal image. Before performing one-dimensional lateral mean filtering to remove noise, structure interpolation was operated to eliminate thickness fluctuations. Then, we used boundary growth method to identify boundaries. Compared with existing segmentations, the method proposed in this paper requires less data and avoids the influence of microsaccade. The automatic segmentation method was verified on the spectral domain OCT volume images obtained from four normal objects, which successfully identified the boundaries of 10 physiological layers, consistent with the results based on the manual determination.

This paper presents the research results of detecting gastric polyps with deep learning object detection method in gastroscopic images. Gastric polyps have various sizes. The difficulty of polyp detection is that small polyps are difficult to detect from the background. We propose a feature extraction and fusion module and combine it with the YOLOv3 network to form our network. This method performs better than other methods in the detection of small polyps because it can fuse the semantic information of high-level feature maps with low-level feature maps to help small polyps detection. In this work, we use a dataset of gastric polyps created by ourselves, containing 1433 training images and 508 validation images. We train and validate our network on our dataset. In comparison with other methods of polyps detection, our method has a significant improvement in precision, recall rate, F1, and F2 score. The precision, recall rate, F1 score, and F2 score of our method can achieve 91.6%, 86.2%, 88.8%, and 87.2%.

Backgrounds. The prevalence of diabetes has increased with the increase of obesity, and finding indicators to predict diabetes risk has become an urgent need. The purpose of this study is to compare the correlation between four anthropometric indices and the prevalence of diabetes. Methods. A total of 4052 participants aged 40 years and above were selected in Dehui City, Jilin Province, using a multistage stratified whole group sampling method. Face-to-face interviews and physical examinations were conducted. Multivariate logistic analysis was used. The values of BMI, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were divided into quartiles (Q1:

Human/humanized IgG4 antibodies have reduced effector function relative to IgG1 antibodies, which is desirable for certain therapeutic purposes. However, the developability and biophysical properties for IgG4 antibodies are not well understood. This work focuses on the head-to-head comparison of key biophysical properties, such as self-interaction and viscosity, for 14 human/humanized, and chimeric IgG1 and IgG4 S228P monoclonal antibody pairs that contain the identical variable regions. Experimental measurements showed that the IgG4 S228P antibodies have similar or higher self-interaction and viscosity than that of IgG1 antibodies in 20 mM sodium acetate, pH 5.5. We report sequence and structural drivers for the increased viscosity and self-interaction detected in IgG4 S228P antibodies through a combination of experimental data and computational models. Further, we applied and extended a previously established computational model for IgG1 antibodies to predict the self-interaction and viscosity behavior for each antibody pair, providing insight into the structural characteristics and differences of these two isotypes. Interestingly, we observed that the IgG4 S228P swapped variants, where the CH3 domain was swapped for that of an IgG1, showed reduced self-interaction behavior. These domain swapped IgG4 S228P molecules also showed reduced viscosity from experiment and coarse-grained simulations. We also observed that experimental diffusion interaction parameter (kD) values have a high correlation with computational diffusivity prediction for both IgG1 and IgG4 S228P isotypes.Abbreviations: [Formula: see text], constant region Hamaker constant; [Formula: see text], variable region Hamaker constant; CDRs, Complementarity-determining regions; CG, Coarse-grained model; CH1, Constant heavy chain 1; CH2 Constant heavy chain 2; CH3 Constant heavy chain 3; chgCH3 Effective charge on the CH3 region; CL Constant light chain; cP, Centipoise; DLS, Dynamic light scattering; Fab, Fragment antigen-binding; Fc, Fragment crystallizable; Fv, Variable domaing; (r) Radial distribution function; H1 CDR1 of Heavy Chain; H2 CDR2 of Heavy Chain; H3 CDR3 of Heavy Chain; HVI, High viscosity index; IgG1 human immunoglobulin of IgG1 subclass; IgG4 human immunoglobulin of IgG4 subclass; kD, Diffusion interaction parameter; L1 CDR1 of Light Chain; L2 CDR2 of Light Chain; L3 CDR3 of Light Chain; mAb, Monoclonal antibody; MD, Molecular dynamics; PPI Protein–protein interactions; SCM, Spatial charge map; UP-SEC, Ultra-high-performance size-exclusion chromatography; VH, Variable domain of Heavy Chain; VL, Variable domain of Light Chain

Ports offer an effective way to facilitate the global economy. However, massive carbon emission during port operating aggravates the atmospheric pollution in port cities. Capturing characteristics of port carbon emission is vital to reduce GHG (greenhouse gas) in the maritime realm as well as to achieve China’s carbon neutral objective. In this work, an integrated framework is proposed for exploring the driving factors of China ports’ emissions combined with stochastic effects on population, affluence and technology regression (STIRPAT), Global Malmquist-Luenberger (GML) and multiple linear regression (MLR). The port efficiency is estimated for each port and the potential driving factors of carbon emission are explored. The results indicate that port carbon emissions have a strong connection with port throughput, productivity, containerization and intermodal transshipment. It is worth noting that the containerization ratio and port physical facility with fossil-free energy improvement have positively correlated with carbon emissions. However, the specific value of waterborne transshipment shows a complex impact on carbon dioxide emission as the ratio increases. The findings reveal that China port authorities need to improve containerization ratio and develop intermodal transportation; meanwhile, it is responsible for port authorities to update energy use and improve energy efficiency in ways to minimize the proportion of non-green energy consumption in accordance with optimizing port operation management including peak shaving and intelligent management systems under a new horizon of clean energy and automatic equipment.

Purpose: In this study, we aimed to investigate the differences in the intrinsic functional connectivity (iFC) of the primary visual cortex (V1), based on resting-state functional magnetic resonance imaging (rs-fMRI), between patients with proliferative diabetic retinopathy (PDR) and healthy controls (HCs). Methods: In total, 26 patients (12 males, 14 females) with PDR and 26 HCs (12 males, 14 females), matched for sex, age, and education status, were enrolled in the study. All individuals underwent rs-fMRI scans. We acquired iFC maps and compared the differences between PDR patients and the HCs. Results: The PDR group had significantly increased FC between the left V1 and the right middle frontal gyrus (RMFG), and significantly reduced FC between the left V1 and the cuneus/calcarine/precuneus. In addition, the PDR patients had significantly increased FC between the right V1 and the right superior frontal gyrus (RSFG), and significantly reduced FC between the right V1 and the cuneus/calcarine/precuneus. The individual areas under the curve (AUCs) of FC values for the left V1 were as follows: RMFG (0.871, p

Selenite and phosphate share similar uptake mechanisms, as a phosphate transporter is involved in the selenite uptake process. However, the mechanism by which selenium (Se) transformation in plants is mediated by phosphorus (P) remains unclear. In this hydroponic study, the absorption, translocation, and biotransformation of Se in selenite-treated rice (Oryza sativa L.) seedlings were investigated under varying P nutrient status. The results showed that P-deficient cultivation increased the Se concentration in roots with Se-only treatment by 2.1 times relative to that of the P-normal condition. However, co-treating roots with additional P caused the Se concentration to decline by 20 and 73% compared to Se treatment alone under P-normal and P-deficient cultivation, respectively. A similar pattern was also observed in Se uptake by rice roots. With an Se-transfer factor elevated by 4.4 times, the shoot Se concentration was increased by 44% with additional P supply compared to the concentration under Se-only treatment of P deficiency; however, no significant differences were observed regarding P-normal cultivation. P deficiency increased the Se percentage by 28% within the cell wall, but reduced it by 60% in the soluble fraction of Se-only treated roots relative to that of the P-normal condition. Contrarily, compared with the Se-only treatment under P deficiency, additional P supply enhanced Se storage in the root soluble fraction by 1.3 times. The opposite tendency was observed for rice shoots. Moreover, P deficiency reduced the proportion of SeMet by 22%, but increased MeSeCys by 1.3 times in Se-only treated roots compared to those under the P-normal condition. Interestingly, MeSeCys was not detected when additional P was added to the two cultivation conditions. Unlike in the roots, only SeMet was generally detected in the rice shoots. The results demonstrate that the P nutrient status strongly affects the Se biofortification efficiency in rice seedlings by altering the Se subcellular distribution and speciation.

Monoclonal antibodies play an increasingly important role for the development of new drugs across multiple therapy areas. The term ‘developability’ encompasses the feasibility of molecules to successfully progress from discovery to development via evaluation of their physicochemical properties. These properties include the tendency for self-interaction and aggregation, thermal stability, colloidal stability, and optimization of their properties through sequence engineering. Selection of the best antibody molecule based on biological function, efficacy, safety, and developability allows for a streamlined and successful CMC phase. An efficient and practical high-throughput developability workflow (100 s-1,000 s of molecules) implemented during early antibody generation and screening is crucial to select the best lead candidates. This involves careful assessment of critical developability parameters, combined with binding affinity and biological properties evaluation using small amounts of purified material (

Genome shuffling is a process to combine advantage traits by the recombination of the entire genome and it has been successfully applied in the laboratory evolution of various industrial microorganisms. However, genome shuffling has not been described in Kluyveromyces marxianus (KM), a promising yeast host for the expression of heterologous proteins. In this protocol, genome shuffling in KM is performed by sexual reproduction and is combined with high-throughput screening to obtain high-yielding strains. Notably, the screening of diploid clones risen from one mating mixture is carried out to improve the effectiveness of evolution. Mating-sporulation-mating cycles are repeated to obtain KM strain with ideal traits. • The method combines genome shuffling with high-throughput to achieve strains displaying high yielding of heterologous proteins. • This method can be applied to the genome shuffling of other species when only a few starting strains are available for sexual reproduction.

Time-varying output formation control problems for high-order time-invariant swarm systems are studied with nonlinear uncertainties and directed network topology in this paper. A robust controller which consists of a nominal controller and a robust compensator is applied to achieve formation control. The nominal controller based on the output feedback is designed to achieve desired time-varying formation properties for the nominal system. And the robust compensator based on the robust signal compensator technology is constructed to restrain nonlinear uncertainties. The time-varying formation problem is transformed into the stability problem. And the formation errors can be arbitrarily small with expected convergence rate. Numerical examples are provided to illustrate the effectiveness of the proposed strategy.

The explosion pressure and minimum explosible concentration (MEC) properties of metal sulfide ore dust clouds are valuable for the prevention and control of metal sulfide ore dust explosions. In this study, a 20 L explosion sphere vessel was used to investigate the effect of sulfur content, particle size, and concentration on the explosion pressure and minimum explosible concentration of metal sulfide ore dust clouds. Four samples with different sulfur contents were selected (30%–40%, 20%–30%, 10%–20%, and 0%–10%). Before and after the explosion, samples were tested by X-ray diffraction. The results indicate that the metal sulfide ore dust is explosive dust with St1 grade explosion pressure. With an increase in concentration, the maximum explosion pressure increased at first and then decreased. With an increase in sulfide content, the explosion pressure of metal sulfide ore dust increased, while the minimum explosible concentration decreased. As particle size decreased, the MEC also decreased. The sulfur content, particle size, and concentration of metal sulfide ore dust were the main factors affecting the explosion hazard.

Meloxicam (MLX) is a non-steroidal anti-inflammatory drug used to treat rheumatoid arthritis and osteoarthritis. However, its poor water solubility limits the dissolution process and influences absorption. In order to solve this problem and improve its bioavailability, we prepared it in nanocrystals with three different particle sizes to improve solubility and compare the differences between various particle sizes. The nanocrystal particle sizes were studied through dynamic light scattering (DLS) and laser scattering (LS). Transmission electron microscopy (TEM) was used to characterize the morphology of nanocrystals. The sizes of meloxicam-nanocrystals-A (MLX-NCs-A), meloxicam-nanocrystals-B (MLX-NCs-B), and meloxicam-nanocrystals-C (MLX-NCs-C) were 3.262 ± 0.016 μm, 460.2 ± 9.5 nm, and 204.9 ± 2.8 nm, respectively. Molecular simulation was used to explore the distribution and interaction energy of MLX molecules and stabilizer molecules in water. The results of differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) proved that the crystalline state did not change in the preparation process. Transport studies of the Caco-2 cell model indicated that the cumulative degree of transport would increase as the particle size decreased. Additionally, plasma concentration–time curves showed that the AUC0–∞ of MLX-NCs-C were 3.58- and 2.92-fold greater than those of MLX-NCs-A and MLX-NCs-B, respectively. These results indicate that preparing MLX in nanocrystals can effectively improve the bioavailability, and the particle size of nanocrystals is an important factor in transmission and absorption.

Cerebral edema is a serious complication of ischemic cerebrovascular disease and mannitol is a commonly used dehydrating agent for relieving cerebral edema. However, the edema state and surrounding vascular perfusion level during mannitol treatment remains unclear, which affects the clinical application of the medicine. In this paper, we demonstrated the role of swept-source optical coherence tomography (OCT) in the evaluation of mannitol efficacy using mouse models. The OCT-based angiography and attenuation imaging technology were used to obtain the cerebral vascular perfusion level and cerebral edema state at different times. Vascular parameters and edema parameters were quantified and compared. Experimental results show that mannitol can significantly reduce the water content in the central region of edema, effectively inhibiting the rapid growth of the edema area, and restoring cerebral blood flow. On average, the edema area decreased by 33% after 2 h, and the vascular perfusion density increased by 12% after 5 h. This work helps to provide a valuable theoretical basis and research ideas for the clinical treatment of cerebral edema.

Abstract Background The yeast Kluyveromyces marxianus is an emerging cell factory for heterologous protein biosynthesis and its use holds tremendous advantages for multiple applications. However, which genes influence the productivity of desired proteins in K. marxianus has so far been investigated by very few studies. Results In this study, we constructed a K. marxianus recombinant (FIM1/Est1E), which expressed the heterologous ruminal feruloyl esterase Est1E as reporter. UV-60Co-γ irradiation mutagenesis was performed on this recombinant, and one mutant (be termed as T1) was screened and reported, in which the productivity of heterologous Est1E was increased by at least tenfold compared to the parental FIM1/Est1E recombinant. Transcriptional perturbance was profiled and presented that the intracellular vesicle trafficking was enhanced while autophagy be weakened in the T1 mutant. Moreover, whole-genome sequencing combined with CRISPR/Cas9 mediated gene-editing identified a novel functional protein Mtc6p, which was prematurely terminated at Tyr251 by deletion of a single cytosine at 755 loci of its ORF in the T1 mutant. We found that deleting C755 of MTC6 in FIM1 led to 4.86-fold increase in the production of Est1E compared to FIM1, while the autophagy level decreased by 47%; on the contrary, when reinstating C755 of MTC6 in the T1 mutant, the production of Est1E decreased by 66% compared to T1, while the autophagy level increased by 124%. Additionally, in the recombinant with attenuated autophagy (i.e., FIM1 mtc6 C755Δ and T1) or interdicted autophagy (i.e., FIM1 atg1Δ and T1 atg1Δ), the productivity of three other heterologous proteins was also increased, specifically the heterologous mannase Man330, the β-1,4-endoxylanase XynCDBFV or the conventional EGFP. Conclusions Our results demonstrated that Mtc6p was involved in regulating autophagy; attenuating or interdicting autophagy would dramatically improve the yields of desired proteins in K. marxianus, and this modulation could be achieved by focusing on the premature mutation of Mtc6p target.

Abstract Background Taking into account its thermotolerance, high growth rate, and broad substrate spectrum, Kluyveromyces marxianus can be considered an ideal consolidated bioprocessing (CBP). A major obstacle to ethanol production using K. marxianus is the low production of lignocellulolytic enzymes, which reduces the cellulose hydrolysis and ethanol production. Thus, further improvement of enzyme expression and secretion is essential. Results To improve the expression of lignocellulolytic enzymes, the inulinase promoter and signal sequence from K. marxianus was optimized through mutagenesis. A T(-361)A mutation inside the promoter, a deletion of AT-rich region inside 5′UTR (UTR∆A), and a P10L substitution in the signal sequence increased the secretory expression of the feruloyl esterase Est1E by up to sixfold. T(-361)A and UTR∆A increased the mRNA expression, while the P10L substitution extended the hydrophobic core of signal sequence and promoted secretion of mature protein. P10L and T(-361)A mutations increased secretory expressions of other types of lignocellulolytic enzymes by up to threefold, including endo-1,4-β-glucanase RuCelA, endo-1,4-β-endoxylanase Xyn-CDBFV, and endo-1,4-β-mannanase MAN330. During the fed-batch fermentation of strains carrying optimized modules, the peak activities of RuCelA, Xyn-CDBFV, MAN330, and Est1E reached 24 U/mL, 25,600 U/mL, 10,200 U/mL, and 1220 U/mL, respectively. Importantly, higher yield of enzymes by optimized promoter and signal sequence were achieved in all tested carbon sources, including the major end products of lignocellulose saccharification and fermentation, with growth on xylose resulting in the highest production. Conclusions The engineered promoter and signal sequence presented increased secretory expressions of different lignocellulolytic enzymes in K. marxianus by means of various carbon resources. Activities of lignocellulolytic enzymes in fed-batch fermentation were the highest activities reported for K. marxianus so far. Our engineered modules are valuable in producing lignocellulolytic enzymes by K. marxianus and in constructing efficient CBP strains for cellulosic ethanol production.

Abstract Cancer is a major public health problem as one of the leading causes of death worldwide. Deciphering the molecular regulation mechanisms of tumor progression can make way for tumor diagnosis and therapy. Paternally expressed gene 10 (PEG10), located on human chromosome 7q21.3, has turned out to be an oncogene implicated in the proliferation, apoptosis and metastasis of tumors. PEG10 has been found to be positively expressed in a variety of cancers with seemingly complex expression regulation mechanisms. In this review, we focus on the most vital factors influencing PEG10 expression and recapitulate some of the currently known and potential mechanisms of PEG10 affecting tumor progression, as understanding the molecular regulatory mechanisms of tumor progression can provide potential PEG10 related diagnosis and biomarker specific targeted therapies.

In view of problems that fault signal of centrifugal pump is easily submerged by noise and data analysis is difficult, a wear fault analysis method of centrifugal pump impeller based on multi-source signal fusion was proposed. Three vibration signals of volute, outlet and base of centrifugal pump, and electrical signals of prime mover terminal are collected when centrifugal pump impeller is in normal condition and wear state. Wavelet packet decomposition is used to extract characteristic frequency bands of the vibration signals, it is determined that the base can be used as the best detection point by laterally comparing energy values of each frequency band, and frequency analysis range is narrowed by longitudinally comparing the energy values of each frequency band. Based on narrowed frequency analysis range, chirp Z transform is used to analyze electrical signals of prime mover terminal and separate fault characteristics frequency and the third harmonic frequency, so as to extract fault characteristic frequency accurately. Test result verifies effectiveness of the method.

As strategic emerging mineral resources supported by the state, niobium and tantalum are the functional and structural materials needed for the development of emerging industries. Therefore, conducting research on the determination of niobium and tantalum in related materials is of great significance. Unfortunately, niobium and tantalum have similar physical and chemical properties, making it difficult to separate them. However, they are easy to hydrate. Geological samples are difficult to be decomposed, thus the determination of niobium and tantalum has always been a difficult issue. Sample pre-treatment technology and modern analytical techniques are reviewed in this paper. Sample pre-treatment is the key step for niobium and tantalum analysis, therefore a suitable sample digestion and preconcentration method combined with analytical methods and sample characteristics is the premise of accurate determination of niobium and tantalum. Instrument analysis is the mainstream of modern analytical technology. Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) are the most widely used methods for the determination of niobium and tantalum, but it is necessary to solve problems such as coexisting component interference, matrix effects and salt influence. Laser Ablation (LA), X-ray Fluorescence Spectrometry (XRF), and Neutron Activation Analysis (NAA) are the development direction of tantalum and niobium analysis, due to the fact that they avoid the complicated sample pre-treatment and addition of impurities by solid sample introduction.

Intrusion detection system (IDS) is emerging as a technology to improve the security of vehicular ad hoc network. However, the recent research on performance of IDS indicates that monitoring overhead is still a significant issue and challenge. The fundamental problem is caused by the fact that each node repeatedly detects adjacent nodes during operation. At the same time, monitoring results are sent to other nodes in the form of control packets, resulting in the decline of the network throughput. In this paper, we focus on selecting a bunch of monitoring nodes and propose a cross-layer security monitoring selection algorithm based on traffic prediction (CLSM-TP). Instead of repeatedly detection for each node, we select the monitoring node whose idle degree is relatively high by predicting the node's traffic based on a cross-layer vehicular ad hoc network. Moreover, the proposed algorithm leverages the mutual information and residual energy to optimize the node selection through social network analysis. The noteworthy contributions are that CLSM-TP can balance the resource consumption among all nodes and prolong the lifetime of vehicular ad hoc network to some extent. Our experimental results show that, the monitoring nodes selected by the algorithm proposed in this paper with higher idle degree preform good enough to monitor the whole vehicular ad hoc network.

In this paper, a target person tracking method based on the ultra-wideband (UWB) technology is proposed for the implementation of the human-tracking robots. For such robots, the detection and calculation of the position and orientation of the target person play an essential role in the implementation of the human-following function. A modified hyperbolic positioning algorithm is devised to overcome the challenge of the measurement errors. In addition, a modified virtual spring model is implemented in the robot to track the target person. One important advantage of such a UWB-based method compared with the computer vision-based methods lies in its robustness against the environment condition. In fact, the computer vision methods can be very sensitive to lighting conditions which make them suffer from the unconstrained outdoor environment. The robust performance of our methods is illustrated by the experimental results on a real-world robot.

With the prosperity of wireless networks, vehicular networks (VNs) have been extensively studied in recent years. It is deployed to ensure road safety, enhance the driving experience, and reduce traffic congestion. However, VNs are vulnerable to various attacks, especially Distributed Denial of Service (DDoS) that attackers control a large number of compromise nodes inside the networks to occupy the network resources of legitimate users and impact the communication among vehicles and between vehicles and infrastructure. In this paper, we design a platform to efficiently detect and rapidly respond to the DDoS attack in VNs based on software-defined networking (SDN). The proposed platform not only contains the trigger mechanism based on the message of OpenFlow protocol (i.e., PACKET_IN message) for a response not timely but also involves a flow feature extraction strategy based on the multi-dimensional information. Moreover, we construct an effective global network flow table feature values based on OpenFlow flow table feature and the entropy feature of flow table entry. We determine all flow table entry by the trained SVM. By analyzing the simulation results, we verify that the detection scheme effectively reduces the time for starting attack detection and classification recognition and has a lower false alarm rate.

Infectious bursal disease (IBD), caused by the infectious bursal disease virus (IBDV), is a highly contagious and immunosuppressive disease in chickens worldwide. The novel variant IBDV (nvIBDV) has been emerging in Chinese chicken farms since 2017, but there are no available vaccines that can provide effective protection. Herein, the capsid protein VP2 from nvIBDV strain FJ-18 was expressed in Kluyveromyces marxianus with the aim to produce nvIBDV subviral particles (SVPs). Two recombinant strains constructed for expression of nvIBDV VP2 (nvVP2) and His-tagged VP2 (nvHVP2) formed two types of nvIBDV subviral particles (SVPs), namely nvVP2-SVPs and nvHVP2-SVPs. TEM scans showed that both SVPs were about 25 nm in diameter, but there was a large portion of nvVP2-SVPs showing non-spherical particles. Molecular dynamics simulations indicate that an N-terminal His tag strengthened the interaction of the nvHVP2 monomer and contributed to the assembly of SVPs. Vaccination of chicks with the nvHVP2-SVPs provided 100% protection against novel variant IBDV infection when challenged with the FJ-18 strain, as well as the classical strain BC6/85. By contrast, vaccination with the nvVP2-SVPs only provided 60% protection against their parent FJ-18 strain, suggesting that the stable conformation of subviral particles posed a great impact on their protective efficacy. Our results showed that the nvHVP2-SVPs produced by the recombinant K. marxianus strain is an ideal vaccine candidate for IBDV eradication.

A thermoelectric module is a device that converts electrical energy into thermal energy through a mechanism known as the Peltier effect. A Peltier device has hot and cold sides/substrates, and heat can be pumped from the cold side to the hot side under a given voltage. By applying it in buildings and attaching it to building envelope components, such as walls, as a heating and cooling device, the heating and cooling requirements can be met by reversing the voltage applied on these two sides/substrates. In this paper, we describe a novel, panelized, ground source, radiant system design for space heating and cooling in buildings by utilizing the Peltier effect. The system is equipped with water pipes that are attached to one side of the panel and connected with a ground loop to exchange heat between the cold/hot sides of the thermoelectric module and the underground region. The ground loop is inserted in boreholes, similar to those used for a vertical closed-loop Ground Source Heat Pump (GSHP) system, which could be more than a hundred meters deep. Experiments were conducted to evaluate the feasibility of the developed panel system applied in buildings. The results show that: (1) the average cooling Coefficients Of Performance (COP) of the system are low (0.6 or less) even though the ground is used as a heat sink, and thus additional studies are needed to improve it in the future, such as to arrange the thermoelectric modules in cascade and/or develop a new thermoelectric material that has a large Seebeck coefficient; and (2) the developed system using the underground region as the heat source has the potential of meeting heating loads of a building while maintaining at a higher system coefficient of performance (up to ~3.0) for space heating, compared to conventional heating devices, such as furnaces or boilers, especially in a region with mild winters and relatively warm ground.

The objective of this study was to investigate the physico-chemical properties of concrete made with recycled brick-concrete aggregate, which was the mixture from waste concrete and waste clay brick in a 7:3 ratio. Specifically, this paper investigated the mechanical properties, freeze-thaw resistance, and distribution of water-soluble chloride ions of concrete containing RBCA and fly ash (FA) against combined freeze-thaw and sodium chloride attack. Concrete containing RBCA replacement of natural coarse aggregate and fly ash replacement of Portland cement was subjected to 45 freeze-thaw cycles containing sodium chloride solution. It was discovered that the mechanical properties and freeze-thaw resistance to sodium chloride attack gradually decreased with increasing RBCA content. At the same time, a replacement level of 15% FA by weight resulted in significant improvements in compressive strength and resistance to combined freeze-thaw and chloride attack. Furthermore, using a replacement of 30% FA by weight markedly improved the resistance to chloride ion penetration of concrete due to the lowest water-soluble chloride content.

In this paper, ZnO-TiO2-rGO nanocomposites were successfully synthesized by the hydrothermal method. The morphology and structure of the synthesized nanomaterials were characterized by SEM, XRD, HRTEM, and XPS. Butanone is a typical ketone product. The vapors are extremely harmful once exposed, triggering skin irritation in mild cases and affecting our breathing in severe cases. In this paper, the gas-sensing properties of TiO2, ZnO, ZnO-TiO2, and ZnO-TiO2-rGO nanomaterials to butanone vapor were studied. The optimum operating temperature of the ZnO-TiO2-rGO sensor is 145 °C, which is substantially lower than the other three sensors. The selectivity for butanone vapor is greatly improved, and the response is 5.6 times higher than that of other organic gases. The lower detection limit to butanone can reach 63 ppb. Therefore, the ZnO-TiO2-rGO sensor demonstrates excellent gas-sensing performance to butanone. Meanwhile, the gas-sensing mechanism of the ZnO-TiO2-rGO sensor to butanone vapor was also analyzed.