Although carbapenem use is prohibited in animals in China, carbapenem-resistant Escherichia coli (CREC), especially New Delhi metallo-β-lactamase (NDM)-producing strains, are widely prevalent in foodproducing animals. At present, the impact of livestock-associated CREC strains on human populations at the national level is unknown. Here, we conduct a retrospective cross-sectional study to investigate the prevalence of CREC from clinical settings across 22 Chinese provinces or municipalities and analyze anthropogenic factors associated with their presence. We also ascertain the blaNDM and blaKPC abundance among pig and chicken farms and present a detailed genomic framework for CREC of animal and human origin. Overall, 631/29799 (2.1%) clinical Escherichia coli (E. coli) isolates were identified as CREC. Multivariable analysis revealed that being male, an age below 1, an age between 13 and 18, provinces with greater chicken production, and provinces with higher pig production were associated with higher odds of CREC infection. In general, 73.8% (n = 45/61) of pig farms and 62.2% (n = 28/45) of chicken farms had a blaNDM abundance of 1×10－5 to 1×10－3 and 1×10－3 to 1×10－2, respectively. Among all the Chinese NDM-positive E. coli (n = 463) available at the National Center for Biotechnology Information (NCBI), the genomic analysis revealed that blaNDM-5 and IncX3 were the predominant carbapenemase gene-plasmid combination, while a highly homogeneous relationship between NDM-positive isolates from humans and animals was demonstrated at the plasmid and core genome levels. All the findings suggest frequent CREC transmission between humans and animals, indicating that further discussions on the use of antibiotics in animals and humans are needed, both in China and across the globe.
Salmonella enterica serovar 4,[5],12:i:- (S. 4,[5],12:i:-) is a monophasic variant of Salmonella enterica serovar Typhimurium that has emerged as a global serovar causing public health concern. To date, the epidemiology and genomic characterization of this pathogen in China have not been well described. We investigated the prevalence, antimicrobial resistance (AMR) phenotypes, and population genomics of sequence type 34 (ST34) S. 4,[5],12:i:- among cases of human salmonellosis in Henan Province, China. A total of 100 ST34 S. 4,[5],12:i:- isolates were studied from 2008 to 2017 and found mostly resistant to ampicillin (AMP), streptomycin (STR), sulfonamides (SUL), and tetracycline (TET) (ASSuT). Bayesian phylogenetic analysis demonstrated that isolates identified in China were mostly related to the European lineage and evolved into two major clades with different resistance genes and plasmid profiles. Notably, clade 1 showed a significantly higher rate of mutations in gyrA and plasmid-mediated quinolone resistance genes. The carrying of the resistance-containing region (encoding R-type ASSuT), including blaTEM-1B (conferring resistance to AMP), strAB (STR), sul2 (SUL), and tet(B) (TET) inserted into the fljBA operon, was responsible for most of the monophasic variants in clade 2. IncHI2 plasmids were the dominant multi-drug resistance mobile genetic elements accounting for the transmission of acquired resistance genes in this serovar, and these were more prevalent in clade 1. Our findings highlighted the increasing prevalence of multi-drug resistant S. 4,[5],12:i:- in China, along with the differential characteristics of resistance gene acquisition among various lineages. Based on our data, control measures are required to address the spread of this zoonotic pathogen. Further owing to its potential origin in food-producing animals, a ″One Health″ approach, should be implemented to support surveillance whilst informing interventional strategies.
This study was designed to investigate the molecular epidemiology of mobile colistin resistance (mcr) using a ″One-Health″ approach in Laos and to predict whether any dominant plasmid backbone and/or strain type influences the dissemination of mcr. We collected 673 samples from humans (rectal normal flora), poultry, and the environment (water, flies, birds, etc.) in Vientiane, Lao People's Democratic Republic (Laos), from May to September 2018. A total of 238 Escherichia coli (E. coli) isolated from nonduplicative samples, consisting of 98 MCR-positive E. coli (MCRPEC) (″mcr″ denotes the gene encoding mobile colistin resistance, and ″MCR″ denotes the subsequent protein encoded by mcr) and 140 MCRnegative E. coli (MCRNEC), were characterized by phenotype and Illumina sequencing. A subset of MCRPEC was selected for MinION sequencing, conjugation assay, plasmid stability, and growth kinetics in vitro. The prevalence of MCRPEC was found to be 14.6% (98/673), with the highest prevalence in human rectal swabs (45.9% (45/98), p < 0.0001, odds ratio (OR): 0.125, 95% confidence interval (CI): 0.077–0.202). The percentages of MCRPEC from other samples were 14.3% (2/14) in dog feces, 12.0% (24/200) in flies, 11.0% (11/100) in chicken meat, 8.9% (8/90) in chicken cloacal, 8.0% (4/50) in chicken caeca, and 7.5% (4/53) in wastewater. MCRPEC was significantly more resistant to co-amoxiclav, sulfamethoxazoletrimethoprim, levofloxacin, ciprofloxacin, and gentamicin than MCRNEC (p < 0.05). Genomic analysis revealed the distribution of MCRPEC among diverse clonal types. The putative plasmid Inc types associated with mcr-1 were IncX4, IncHI2, IncP1, IncI2, and IncFIA, and those associated with mcr-3 were IncFII, IncFIA, IncFIB, IncP1, and IncR. Recovery of highly similar plasmids from both flies and other sampling sectors implied the role of flies in the dissemination of mcr-1. mcr-positive plasmids were shown to be conjugative, and a significantly high transfer rate into a hypervirulent clone ST1193 was observed. Plasmids containing mcr irrespective of Inc type were highly stable and invariably did not exert a fitness effect upon introduction into a new host. These findings signify the urgent need for a standard infection control program to radically decontaminate the source of resistance.
Antibiotic treatment failure against life-threatening bacterial pathogens is typically caused by the rapid emergence and dissemination of antibiotic resistance. The current lack of antibiotic discovery and development urgently calls for new strategies to combat multidrug-resistant (MDR) bacteria, especially those that survive in host cells. Functional nanoparticles are promising intracellular drug delivery systems whose advantages include their high biocompatibility and tunable surface modifications. Inspired by the fact that the rigidity of nanoparticles potentiates their cellular uptake, rigidity-functionalized nanoparticles (RFNs) coated with bacteria-responsive phospholipids were fabricated to boost endocytosis, resulting in the increased accumulation of intracellular antibiotics. Precise delivery and high antibacterial efficacy were demonstrated by the clearing of 99% of MDR bacteria in 4 h using methicillin-resistant Staphylococcus aureus (MRSA) and pathogenic Bacillus cereus as models. In addition, the subcellular distribution of the RFNs was modulated by altering the phospholipid composition on the surface, thereby adjusting the electrostatic effects and reprograming the intracellular behavior of the RFNs by causing them to accurately target lysosomes. Finally, the RFNs showed high efficacy against MRSA-associated infections in animal models of wound healing and bacteremia. These findings provide a controllable rigidity-regulated delivery platform with responsive properties for precisely reprograming the accumulation of cytosolic antibiotics, shedding light on precision antimicrobial therapeutics against intracellular bacterial pathogens in the future.
New therapeutic strategies for the rapid and effective treatment of drug-resistant tuberculosis are highly desirable, and their development can be drastically accelerated by facile genetic manipulation methods in Mycobacterium tuberculosis (M. tuberculosis). Clustered regularly interspaced short palindromic repeat (CRISPR) base editors allow for rapid, robust, and programmed single-base substitutions and gene inactivation, yet no such systems are currently available in M. tuberculosis. By screening distinct CRISPR base editors, we discovered that only the unusual Streptococcus thermophilus CRISPR associated protein 9 (St1Cas9) cytosine base editor (CBE)—but not the widely used Streptococcus pyogenes Cas9 (SpCas9) or Lachnospiraceae bacterium Cpf1 (LbCpf1) CBEs—is active in mycobacteria. Despite the notable C-to-T conversions, a high proportion of undesired byproducts exists with St1Cas9 CBE. We therefore engineered St1Cas9 CBE by means of uracil DNA glycosylase inhibitor (UGI) or uracil DNA glycosylase (UNG) fusion, yielding two new base editors (CTBE and CGBE) capable of C-to-T or C-to-G conversions with dramatically enhanced editing product purity and multiplexed editing capacity in Mycobacterium smegmatis (M. smegmatis). Because wild-type St1Cas9 recognizes a relatively strict protospacer adjacent motif (PAM) sequence for DNA targeting, we engineered a PAM-expanded St1Cas9 variant by means of structureguided protein engineering for the base editors, substantially broadening the targeting scope. We first developed and characterized CTBE and CGBE in M. smegmatis, and then applied CTBE for genome editing in M. tuberculosis. Our approaches significantly reduce the efforts and time needed for precise genetic manipulation and will facilitate functional genomics, antibiotic-resistant mechanism study, and drugtarget exploration in M. tuberculosis and related organisms.
Fermentation-based antibiotic production results in abundant nutrient-rich fermentation residue with high potential for recycling, but the high antibiotic residual concentration restricts its usefulness (e.g., in land application as organic fertilizer). In this study, an industrial-scale hydrothermal facility for the treatment of erythromycin fermentation residue (EFR) was investigated, and the potential risk of the long-term soil application of treated EFR promoting environmental antibiotic resistance development was evaluated. The treatment effectively removed bacteria and their DNA, and an erythromycin removal ratio of up to approximately 98% was achieved. The treated EFR was utilized as organic fertilizer for consecutive field applications from 2018 to 2020, with dosages ranging from 3750 to 15 000 kg∙hm－2, resulting in sub-inhibitory levels of erythromycin (ranging from 0.83–76.00 μg∙kg－1) in soils. Metagenomic shotgun sequencing was then used to characterize the antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and bacterial community composition of the soils. The soil ARG abundance and diversity did not respond to the treated EFR application in the first year, but gradually changed in the second and third year of application. The highest fold change in relative abundance of macrolide-lincosamidestreptogramin (MLS) and total ARGs were 12.59 and 2.75 times, compared with the control (CK; without application), respectively. The soil MGEs and taxonomic composition showed similar temporal trends to those of the ARGs, and appeared to assist in driving increasing ARG proliferation, as revealed by correlation analysis and structural equation models (SEMs). The relative abundance of particular erm resistance genes (RNA methyltransferase genes) increased significantly in the third year of treated EFR application. The close association of erm with MGEs suggested that horizontal gene transfer played a critical role in the observed erm gene enrichment. Metagenomic binning results demonstrated that the proliferation of mac gene-carrying hosts was responsible for the increased abundance of mac genes (efflux pump genes). This study shows that sub-inhibitory levels of erythromycin in soils had a cumulative effect on soil ARGs over time and emphasizes the importance of long-term monitoring for assessing the risk of soil amendment with treated industrial waste.
The human gut microbiome has primarily been studied through the use of fecal samples, a practice that has generated vital knowledge on the composition and functional capacities of gastrointestinal microbial communities. However, this reliance on fecal materials limits the investigation of microbial dynamics in other locations along the gastrointestinal tract (in situ), and the infrequent availability of fecal samples prevents analysis at finer temporal scales (e.g., hours). In our study, we utilized colonic transendoscopic enteral tubing, a technology originally developed for fecal microbiota transplantation, to sample the ileocecal microbiome twice daily; metagenomic and metatranscriptomic analyses were then conducted on these samples. A total of 43 ileocecal and 28 urine and fecal samples were collected from five healthy volunteers. The ileocecal and fecal microbiomes, as profiled in the five volunteers, were found to be similar in metagenomic profiling, yet their active genes (metatranscriptome) were found to be highly distinct. Both microbiomes were perturbed after laxative exposure; over time, they exhibited reduced dissimilarity to their pre-treatment state, thereby demonstrating resilience as an innate property of the gut microbiome, although they did not fully recover within our observation time window. Sampling of the ileocecal microbiome during the day and at night revealed the existence of diurnal rhythms in a series of bacterial species and functional pathways, particularly those related to short-chain fatty acid production, such as Propionibacterium acnes and coenzyme A biosynthesis II. Autocorrelation analysis and fluctuations decomposition further indicated the significant periodicity of the diurnal oscillations. Metabolomic profiling in the fecal and urine samples mirrored the perturbance and recovery in the gut microbiome, indicating the crucial contribution of the gut microbiome to many key metabolites involved in host health. This study provides novel insights into the human gut microbiome and its inner resilience and diurnal rhythms, as well as the potential consequences of these to the host.
Patient-derived tumor xenografts (PDXs) are a powerful tool for drug discovery and screening in cancer. However, current studies have led to little understanding of genotype mismatches in PDXs, leading to massive economic losses. Here, we established PDX models from 53 lung cancer patients with a genotype matching rate of 79.2% (42/53). Furthermore, 17 clinicopathological features were examined and input in stepwise logistic regression (LR) models based on the lowest Akaike information criterion (AIC), least absolute shrinkage and selection operator (LASSO)-LR, support vector machine (SVM) recursive feature elimination (SVM-RFE), extreme gradient boosting (XGBoost), gradient boosting and categorical features (CatBoost), and the synthetic minority oversampling technique (SMOTE). Finally, the performance of all models was evaluated by the accuracy, area under the receiver operating characteristic curve (AUC), and F1 score in 100 testing groups. Two multivariable LR models revealed that age, number of driver gene mutations, epidermal growth factor receptor (EGFR) gene mutations, type of prior chemotherapy, prior tyrosine kinase inhibitor (TKI) therapy, and the source of the sample were powerful predictors. Moreover, CatBoost (mean accuracy = 0.960; mean AUC = 0.939; mean F1 score = 0.908) and the eight-feature SVM (mean accuracy = 0.950; mean AUC = 0.934; mean F1 score = 0.903) showed the best performance among the algorithms. Meanwhile, application of the SMOTE improved the predictive capability of most models, except CatBoost. Based on the SMOTE, the ensemble classifier of single models achieved the highest accuracy (mean = 0.975), AUC (mean = 0.949), and F1 score (mean = 0.938). In conclusion, we established an optimal predictive model to screen lung cancer patients for NOD/Shi-scid, interleukin-2 receptor (IL-2R) γnull (NOG)/PDX models and offer a general approach for building predictive models.
Due to the worldwide epidemic of allergic disease and a cure nowhere in sight, there is a crucial need to explore its pathophysiological mechanisms. As allergic disease has been associated with gut dysbiosis, we searched for a possible mechanism from the perspective of the molecular interface between host and microbiota with concurrent metabolomics and microbiome composition analysis. Sprague-Dawley rats were injected with Artemisia pollen extract to stimulate a hyper reaction to pollen. This hyper reaction decreased the circulation of valine, isoleucine, aspartate, glutamate, glutamine, indole-propionate (IPA), and myo-inositol, and reduced short-chain fatty acids (SCFAs) in feces. Several beneficial genera belonging to Ruminococcaceae, Lachnospiraceae, and Clostridiales declined in the model group, whereas Helicobacter and Akkermansia were only expressed in the model group. Furthermore, the expression of intestinal claudin-3 and liver fatty acid binding protein was downregulated in the model group and associated with metabolic changes and bacteria. Our results suggest that alterations in amino acids as well as their derivatives (especially valine, and IPA which is the reductive product of tryptophan) , SCFAs, and the gut microbiome (specifically Akkermansia and Helicobacter) may disrupt the intestinal barrier function by inhibiting the expression of claudin proteins and affecting the mucus layer, which further results in hay fever.
By providing a means of separating the airborne emissions of patients from the air breathed by healthcare workers (HCWs), vented individual patient (VIP) hoods, a form of local exhaust ventilation (LEV), offer a new approach to reduce hospital-acquired infection (HAI). Results from recent studies have demonstrated that, for typical patient-emitted aerosols, VIP hoods provide protection at least equivalent to that of an N95 mask. Unlike a mask, hood performance can be easily monitored and HCWs can be alerted to failure by alarms. The appropriate use of these relatively simple devices could both reduce the reliance on personal protective equipment (PPE) for infection control and provide a low-cost and energy-efficient form of protection for hospitals and clinics. Although the development and deployment of VIP hoods has been accelerated by the coronavirus disease 2019 (COVID-19) pandemic, these devices are currently an immature technology. In this review, we describe the state of the art of VIP hoods and identify aspects in need of further development, both in terms of device design and the protocols associated with their use. The broader concept of individual patient hoods has the potential to be expanded beyond ventilation to the provision of clean conditions for individual patients and personalized control over other environmental factors such as temperature and humidity.
A novel compression-induced twisting (CIT)-compliant mechanism was designed based on the freedom and constraint topology (FACT) method and manufactured by means of laser powder bed fusion (LPBF). The effects of LPBF printing parameters on the formability and compressive properties of the laserprinted CIT-compliant mechanism were studied. Within the range of optimized laser powers from 375 to 450 W and with the densification level of the samples maintained at above 98%, changes in the obtained relative densities of the LPBF-fabricated CIT-compliant mechanism with the applied laser powers were not apparent. Increased laser power led to the elimination of residual metallurgical pores within the inclined struts of the CIT mechanism. The highest dimensional accuracy of 0.2% and the lowest surface roughness of 20 μm were achieved at a laser power of 450 W. The deformation behavior of the CIT-compliant mechanism fabricated by means of LPBF exhibited four typical stages: an elastic stage, a heterogeneous plastic deformation stage, a strength-destroying stage, and a deformation-destroying stage (or instable deformation stage). The accumulated compressive strain of the optimally printed CIT mechanism using a laser power of 450 W went up to 20% before fracturing, demonstrating a large deformation capacity. The twisting behavior and mechanical properties were investigated via a combination of finite-element simulation and experimental verification. An approximately linear relationship between the axial compressive strain and rotation angle was achieved before the strain reached 15% for the LPBF-processed CIT-compliant mechanism.
The “Grain-for-Green” project on the Loess Plateau is the largest revegetation program in the world. However, revegetation-induced land use changes can influence both water and carbon cycles, and the diverse consequences were not well understood. Therefore, the reasonability and sustainability of revegetation measures are in question. This study quantifies the impacts of revegetation-induced land use conversions on the water and carbon cycles in a typical watershed on the Loess Plateau and identifies suitable areas where revegetation of forest or grassland could benefit both soil and water conservation and carbon sequestration. We used a coupled hydro-biogeochemical model to simulate the changes of a few key components in terms of water and carbon by designing a variety of hypothetical land use conversion scenarios derived from revegetation policy. Compared to the baseline condition (land use in 2000), both sediment yield and water yield decreased substantially when replacing steep cropland with forest or grassland. Converting cropland with slopes larger than 25°, 15°, and 6° to forest (CTF) would enhance the carbon sequestration with a negligible negative effect on soil water content, while replacing cropland with grassland (CTG) would result in a decline in net primary production but with a substantial increase in soil water content (3.8%–14.9%). Compared to the baseline, the soil organic carbon would increase by 0.9%–3.2% in CTF and keep relatively stable in CTG. Through testing a variety of hypothetical revegetation scenarios, we identified potential priority areas for CTF and CTG, where revegetation may be appropriate and potentially beneficial to conserving soil and water and enhancing carbon sequestration. Our study highlights the challenges in future water and carbon coupling management under revegetation policy, and our quantitative results and identification of potential areas for revegetation could provide information to policy makers for seeking optimal management on the Loess Plateau.
Chlorine is usually applied in the process of urban water treatment to deactivate pathogens and prevent waterborne diseases. As a pre-treatment during water treatment, it remains unclear whether chlorinated water can effectively alleviate the fouling of membranes during ultrafiltration (UF). In this study, tap water was investigated with respect to its impacts on biofilm formation and biofouling in a gravity-driven membrane (GDM) filtration system. For comparison, the biofilm/biofouling with untreated surface (lake) water was studied in parallel. It was found that more severe membrane fouling occurred with the filtration of tap water than lake water, and larger quantities of polysaccharide and eDNA were present in the tap-water biofilm than in lake-water biofilm. The tap-water biofilm had a densely compact morphology, whereas a porous, spider-like structure was observed for the lake-water biofilm, which was assumed to be associated with the bacteria in the biofilm. The hypothesis was verified by the 16S ribosomal RNA (rRNA) sequencing results which demonstrated that Xanthobacter was the dominant taxon in the tap-water biofilm. Additionally, membrane hydrophobicity/hydrophilicity played a minor role in affecting the membrane fouling properties and microbial community. Overall, these findings have revealed the significant role of chlorine-resistant bacteria in biofouling formation and provided a deeper understanding of membrane fouling, which can potentially aid the search for effective ways of controlling membrane fouling.
Hydrated cement is one of the complex composite systems due to the presence of multi-scale phases with varying morphologies. Calcium silicate hydrate (C–S–H), which is the principal binder phase in the hydrated cement, is responsible for the stiffness, strength, and durability of Portland cement concrete. To understand the mechanical and durability behavior of concrete, it is important to investigate the interactions of hydrated cement phases with other materials at the nanoscale. In this regard, the molecular simulation of cement-based materials is an effective approach to study the properties and interactions of the cement system at the fundamental scale. Recently, many studies have been published regarding atomistic simulations to investigate the cement phases to define/explain the microscopic physical and chemical properties, thereby improving the macroscopic performance of hardened binders. The research in molecular simulation of cementitious systems involves researchers with multidisciplinary backgrounds, mainly in two areas: ① cement chemistry, where the hydration reactions govern most of the chemical and physical properties at the atomic scale; and ② computational materials science and engineering, where the bottom-up approach is required. The latter approach is still in its infancy, and as such, a study of the prevailing knowledge is useful, namely through an exhaustive literature review. This state-of-the-art report provides a comprehensive survey on studies that were conducted in this area and cites the important findings.
Uncertain security threats caused by vulnerabilities and backdoors are the most serious and difficult problem in cyberspace. This paper analyzes the philosophical and technical causes of the existence of so-called “dark functions” such as system vulnerabilities and backdoors, and points out that endogenous security problems cannot be completely eliminated at the theoretical and engineering levels; rather, it is necessary to develop or utilize the endogenous security functions of the system architecture itself. In addition, this paper gives a definition for and lists the main technical characteristics of endogenous safety and security in cyberspace, introduces endogenous security mechanisms and characteristics based on dynamic heterogeneous redundancy (DHR) architecture, and describes the theoretical implications of a coding channel based on DHR.
With the increasing penetration rate of electric vehicles (EVs), EV demand response holds great significance for promoting the optimal and secure operation of the power system. This paper proposes an EV response capability assessment method that considers EV users' travel demands and the reliability of the cyber systems integrated into both the power grid and the transportation network. A novel framework for an integrated cyber–power–transportation system is proposed for the first time, and a reliability model for the cyber system is provided. A method is further proposed to calculate the state of an EV when it is plugged in, considering the reliability of traffic guidance information and the reliability of the release of such information. The degree of relaxation in the EV charging demand is proposed to reflect the user's travel demand, based on which the EV response capability can be assessed. Extensive test results on a cyber–power–transportation system containing RBTS BUS6 and the Beijing transportation network are conducted to show the efficiency of the proposed method. The impact of cyber reliability on the EV trip and response capability is analyzed.
Three-dimensional (3D)-printed magnetic soft architectures have attracted extensive attention and research from the engineering and material fields. The force-driven shape deformation of such architectures causes a change in the magnetic field distribution, indicating the capability to convert mechanical energy to electricity. Herein, we fabricate a flexible superhydrophobic and magnetic device by integrating two kinds of 3D printing approaches. The 3D-printed magnetic device (3DMD) exhibits a long-term stable mechanoelectrical conversion capacity under consecutive water droplet dripping. The output current of the 3DMD is higher than that of records in the existing literature. Combined with Maxwell numerical simulation, the mechanoelectrical conversion mechanism of the 3DMD is investigated, further guiding regulation of the diverse parameters. Moreover, three 3DMDs are integrated to light up a commercial light-emitting diode (LED) by a stream of collected rainwater. Such a combined design incorporating energy conversion is believed to promisingly motive advances in the 3D printing field.
Three-dimensional (3D) profile scanning plays a crucial role in the inspection of assembled large aircraft. In this paper, to achieve noncontact automatic measurements of the high-reflective profiles of large-scale curved parts and components, an automated noncontact system and method with high accuracy and high efficiency are presented. First, a hybrid 3D coordinate measurement system based on proximity sensors and cameras is proposed to obtain noncontact measurements while avoiding the influence of high reflection on the measurement accuracy. A hybrid measurement model that combines the one-dimensional distances measured by the proximity sensors and the 3D information obtained by cameras is proposed to determine high-accuracy 3D coordinates of the measured points. Then, a profile-driven 3D automated scanning method and strategy are designed to rapidly scan and reconstruct the profile within the effective range without scratching the profile or exceeding the measurement range of the proposed system. Finally, experiments and accuracy analyses are performed in situ on an assembled tailplane panel (approximately 1760 mm × 460 mm). The automated scanning process is completed in a timeframe of 208 s with an average error of less than 0.121 mm for profile reconstruction. Therefore, the proposed method is promising considering both the high accuracy and high efficiency requirements of profile inspections for large aircraft.