Fast reconstruction of laser beam near-field and focal spot profiles using deep neural network and numerical propagation.

Inertial confinement fusion (ICF) experiments demand precise knowledge of laser beam parameters on high-power laser facilities. Among these parameters, near-field and focal spot distributions are crucial for characterizing laser beam quality. While iterative phase retrieval shows promise for laser beam reconstruction, its utility is hindered by extensive iterative calculations. To address this limitation, we propose an online laser beam reconstruction method based on deep neural network. In this method, we utilize coherent modulation imaging (CMI) to obtain labels for training the neural network. The neural network reconstructs the complex near-field distribution, including amplitude and phase, directly from a defocused diffraction pattern without iteration. Subsequently, the focal spot distribution is obtained by propagating the established complex near-field distribution to the far-field. Proof-of-principle experiments validate the feasibility of our proposed method.

Genetic characterization of plasmid-borne blaOXA-58 and blaOXA-72 in Acinetobacter pittii in Shaanxi, China.

OBJECTIVES: Acinetobacter pittii has emerged as an opportunistic nosocomial pathogen associated with hospital-acquired infections. The purpose of this study was to investigate the genetic structures of plasmids carrying carbapenemase genes blaOXA-58 and blaOXA-72 in A. pittii strains AR3676 and AR3651 isolated from patients. METHODS: Antimicrobial susceptibility testing was performed using broth microdilution. Whole-genome sequencing and bioinformatics analysis were performed to characterize the genome of A. pittii AR3676 and AR3651. Conjugation experiments were conducted to evaluate plasmid transferability. Phylogenetic and comparative genomic analysis were performed to explore the characteristics of carbapenem-resistant A. pittii isolates worldwide. RESULTS: The AR3676 strain showed resistance to imipenem. The 19 700-bp plasmid pAR3676-OXA-58 harboured blaOXA-58 with genetic contexts consisting of a truncated ISAba3-like-blaOXA58-ISAba3. Additionally, the AR3651 strain showed resistance to imipenem and meropenem. The AR3651 genome comprised one 9,837-bp RepA_AB plasmid pAR3651-OXA-72 harbouring blaOXA-72. This blaOXA-72 was flanked by XerC/XerD recombination sites. The conjugation of plasmids pAR3676-OXA-58 and pAR3651-OXA-72 from A. pittii to Acinetobacter baumannii ATCC 17978RIFR failed three independent times. Phylogenetic analysis of A. pittii strains AR3676, AR3651, and a further 504 A. pittii strains collected between 1966 and 2022 from various geographic localities revealed genetic diversity with a heterogeneous distribution of carbapenemase genes. CONCLUSIONS: A. pittii strains with a plasmid carrying blaOXA-58 or blaOXA-72 may serve as an important reservoir of carbapenemase genes. Carbapenemase genes on a single plasmid may facilitate their dissemination and persistence. Additionally, pdif sites and mobile elements play an important role in the mobilization of resistance genes and plasmid evolution.

JiaGaSongTang improves chronic cholestasis via enhancing FXR-mediated bile acid metabolism.

BACKGROUND: Bile acid (BA) enterohepatic circulation disorders are a main feature of chronic cholestatic diseases. Promoting BA metabolism is thus a potential method of improving enterohepatic circulation disorders, and treat enterohepatic inflammation, oxidative stress and fibrosis due to cholestasis. PURPOSE: To investigate the effect of JiaGaSongTang (JGST) and its blood-absorbed ingredient 6-gingerol on α-naphthylisothiocyanate (ANIT)-induced chronic cholestasis, as well as elucidate the underlying regulatory mechanism. METHODS: Chronic cholestasis was induced in mice via subcutaneous injection of ANIT (50 mg/kg) every other day for 14 d. Treatment groups were administered JGST orally daily. Damage to the liver and intestine was observed using histopathological techniques. Biochemical techniques were employed to assess total BA (TBA) levels in the serum, liver, and ileum samples. Liquid chromatograph-mass spectrometry/mass spectrometry (LC-MS/MS) was used to analyze fecal BA components. Bioinformatic methods were adopted to screen the core targets and pathways. The blood-absorbed ingredients of JGST were scrutinized via LC-MS/MS. The effects of the major JGST ingredients on farnesoid X receptor (FXR) transactivation were validated using dual luciferase reporter genes. Lastly, the effects of the FXR inhibitor, DY268, on JGST and 6-gingerol pharmacodynamics were observed at the cellular and animal levels. RESULTS: JGST ameliorated pathological impairments in the liver and intestine, diminishing TBA levels in the serum, liver and gut. Fecal BA profiling revealed that JGST enhanced the excretion of toxic BA constituents, including deoxycholic acid. Bioinformatic analyses indicated that JGST engaged in anti-inflammatory mechanisms, attenuating collagen accumulation, and orchestrating BA metabolism via interactions with FXR and other pertinent targets. LC-MS/MS analysis identified six ingredients absorbed to the bloodstream, including 6-gingerol. Surface plasmon resonance (SPR) and dual luciferase reporter gene assays confirmed the abilities of 6-gingerol to bind to FXR and activate its transactivation. Ultimately, in both cellular and animal models, the therapeutic efficacy of JGST and 6-gingerol in chronic cholestasis was attenuated in the presence of FXR inhibitors. CONCLUSION: The findings, for the first time, demonstrated that 6-gingerol, a blood-absorbed ingredient of JGST, can activate FXR to affect BA metabolism, and thereby attenuate ANIT-induced liver and intestinal injury in chronic cholestasis mice model via inhibition of inflammation, oxidative stress, and liver fibrosis, in part in a FXR-dependent mechanism.

Experimental and Numerical Study of Radioiodine Sorption and Transport in Hanford Sediments.

Radioiodine (129I) poses a potential risk to human health and the environment at several U.S. Department of Energy sites, including the Hanford Site, located in southeastern Washington State. Experimental studies and numerical modeling were performed to provide a technical basis for field-scale modeling of iodine sorption and transport behavior. The experiments were carried out using six columns of repacked contaminated sediments from the Hanford Site. Although iodate has been determined to be the dominant iodine species at the Hanford Site, the sorption and transport behaviors of different iodine species were investigated in a series of column experiments by first leaching sediments with artificial groundwater (AGW) followed by AGW containing iodate (IO3-), iodide (I-), or organo-iodine (2-iodo-5-methoxyphenol, C7H7IO2). Ferrihydrite amendments were added to the sediments for three of the columns to evaluate the impact of ferrihydrite on 129I attenuation. The results showed that ferrihydrite enhanced the iodate sorption capacity of the sediment and retarded the transport but had little effect on iodide or organo-I, providing a technical basis for developing a ferrihydrite-based remedial strategy for iodate under oxidizing conditions. Data from the column transport experiments were modeled using the linear equilibrium Freundlich isotherm model, the kinetic Langmuir adsorption model, and a distributed rate model. Comparisons of the experimental data and modeling results indicated that sorption was best represented with the distributed rate model with rates and maximum sorption extents varying by iodine species and ferrihydrite treatment. However, the linear Freundlich isotherm (Kd) model was also found to fit the laboratory experimental data relatively well, suggesting that the Kd model could also be used to represent iodine transport at the field scale.

Application of serum Raman spectroscopy combined with classification model for rapid breast cancer screening.

Introduction: This study aimed to evaluate the feasibility of using general Raman spectroscopy as a method to screen for breast cancer. The objective was to develop a machine learning model that utilizes Raman spectroscopy to detect serum samples from breast cancer patients, benign cases, and healthy subjects, with puncture biopsy as the gold standard for comparison. The goal was to explore the value of Raman spectroscopy in the differential diagnosis of breast cancer, benign lesions, and healthy individuals. Methods: In this study, blood serum samples were collected from a total of 333 participants. Among them, there were 129 cases of tumors (pathologically diagnosed as breast cancer and labeled as cancer), 91 cases of benign lesions (pathologically diagnosed as benign and labeled as benign), and 113 cases of healthy controls (labeled as normal). Raman spectra of the serum samples from each group were collected. To classify the normal, benign, and cancer sample groups, principal component analysis (PCA) combined with support vector machine (SVM) was used. The SVM model was evaluated using a cross-validation method. Results: The results of the study revealed significant differences in the mean Raman spectra of the serum samples between the normal and tumor/benign groups. Although the mean Raman spectra showed slight variations between the cancer and benign groups, the SVM model achieved a remarkable prediction accuracy of up to 98% for classifying cancer, benign, and normal groups. Discussion: In conclusion, this exploratory study has demonstrated the tremendous potential of general Raman spectroscopy as a clinical adjunctive diagnostic and rapid screening tool for breast cancer.

Mathematical uniqueness of multimode ptychographic imaging.

By writing diffracted intensities as a set of linear equations with the self-correlation of sample's Fourier components as unknown terms and the self-correlation of illumination's Fourier components as coefficients, it was found that the number of unknown terms to be determined is much larger in partially coherent PIE than that in purely coherent PIE. When a partially coherent illumination composed of N modes was applied a unique reconstruction can be determined by scanning the sample to at least 4N positions and recording 4N frames of diffraction patterns. While mathematically illustrating the physical mechanism of multimode ptychography and numerically demonstrating its capability in generating unique reconstruction under partially coherent illumination, this study showed for the first time that multimode ptychography could be an analytic imaging method.

Dual-view transport of intensity phase imaging flow cytometry.

In this work, we design multi-parameter phase imaging flow cytometry based on dual-view transport of intensity (MPFC), which integrates phase imaging and microfluidics to a microscope, to obtain single-shot quantitative phase imaging on cells flowing in the microfluidic channel. The MPFC system has been proven with simple configuration, accurate phase retrieval, high imaging contrast, and real-time imaging and has been successfully employed not only in imaging, recognizing, and analyzing the flowing cells even with high-flowing velocities but also in tracking cell motilities, including rotation and binary rotation. Current results suggest that our proposed MPFC provides an effective tool for imaging and analyzing cells in microfluidics and can be potentially used in both fundamental and clinical studies.

A patient with tumor necrosis factor receptor-associated periodic syndrome misdiagnosed as Kawasaki disease: A case report and literature review.

This article reports a case of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) misdiagnosed as Kawasaki disease and summarizes the clinical features and therapeutic progress of TRAPS and the relationship between its clinical manifestations and gene mutations. We retrospectively analyzed a patient with tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) -mutated auto-inflammatory disease who was misdiagnosed with Kawasaki disease in another hospital. The clinical features and therapeutic progress of TRAPS were analyzed by combining clinical features and gene reports of this case and literature review. TRAPS onset occurred in a female pediatric patient at the age of 4 months. The child and in his father at the age of 6 years, both of whom manifested periodic fever, and recurrent rash, as well as elevated leukocytes, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) during episodes but normal between episodes. This child carried a heterozygous mutation in TNFRSF1A located in the region 6442923-6442931 on chromosome 12. The nucleic acid alteration was: c.298 (exon3) _c.306 (exon3) 291 delCTCAGCTGC, resulting in a 3 amino acid deletion p.L100_C 102del 292 (p.Leu100_Cys102del) (NM_001065). After etanercept treatment, the symptoms of fever and rash disappeared, and the levels of ESR, CRP, interleukin (IL)-1, IL-6, and TNF-α levels were normal. Subsequently, no liver, kidney, or cardiac amyloidosis and severe etanercept-related adverse events were observed at 1-year follow-up. TRAPS pathogenesis is associated with TNFRSF1A mutation, which is characterized by periodic episodes of fever, mostly accompanied by recurrent rashes, periorbital edema, abdominal pain, and serious complications of organ amyloidosis. Moreover, etanercept can effectively alleviate the clinical symptoms and high inflammation level of TRAPS.

Prognostic value of cell division cycle-associated protein-3 in prostate cancer.

BACKGROUND: The study was aimed to explore cell division cycle-associated protein-3 (CDCA3) expression and its correlation with clinicopathological characteristics, and identification of co-expressed genes of CDCA3 in prostate cancer (PCa). METHODS: Data for CDCA3 mRNA expression in PCa were obtained from The Cancer Genome Atlas database. Furtherly, CDCA3 protein expression was examined by immunohistochemistry in 80 cases, including 20 normal prostate samples and 60 PCa samples. Then we used "survival" package to obtain the differentially expressed CDCA3 mRNA associated with prognosis of PCa patients. "pROC" package was used to analyze receiver operating characteristic of CDCA3. We used chi-square test, Kruskal-Wallis test and Wilcoxon rank sum test to identify clinicopathological parameters that correlated with CDCA3 expression. In order to determine the effects of CDCA3 expression and clinicopathological parameters on survival, univariate cox regression analysis was performed. Finally, the co-expressed genes of CDCA3 in PCa were explored by search tool for the retrieval of interacting genes, Kyoto encyclopedia of genes and genomes enrichment analysis and Spearman correlation analysis. RESULTS: In this study, we found that CDCA3 expression was increased in PCa. PCa patients with higher CDCA3 expression had poor outcomes. In terms of receiver operating characteristic, CDCA3 had an area under the curve of 0.857. High CDCA3 expression was positively correlated with advanced T stage, N stage, Gleason score, and served as an independent predictor of progress free interval in PCa patients. Then 20 proteins closely related to CDCA3 were screened through STRING website. Functional enrichment analysis revealed that, Kyoto encyclopedia of genes and genomes pathway was mainly enriched in cell cycle, including 6 genes, BUB1, CCNA2, CDK1, CDC20, TTK, and CCNB2. CONCLUSION: CDCA3 is significantly associated with the prognosis of PCa, which may be an indicator of the diagnosis and prognosis of PCa and a new therapeutic target.

Dual-channel binary diffuser-based coherent modulation imaging.

To improve the performance of binary diffuser-based coherent modulation imaging (CMI), a double-channel optical alignment was proposed. Two diffraction patterns formed by the reflection and transmission of a binary diffuser were simultaneously captured and adopted for iterative reconstruction in combination. The information involved in reflected light, not considered in the traditional single-channel optical alignment, was also reconstructed in this dual-channel binary diffuser-based coherent modulation imaging (DB-CMI). The reconstruction quality and speed were improved and verified by both numerical simulations and proof-of-principle experiments. Therefore, DB-CMI improves traditional CMI and provides a powerful tool for quantitative phase imaging.

Bone marrow mesenchymal stem cells response on collagen/hyaluronan/chondroitin scaffold enriched with gentamicin -loaded gelatin microparticles for skin tissue engineering.

The repair and functional reconstruction of large skin defects caused by burn remains an intractable clinical problem. Collagen type I (ColI) was extracted from carp scales and confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis ultraviolet adsorption spectra and automatic amino acid analyzer. Then the scaffolds containing the purified ColI, hyaluronic acid (HA) and chondroitin sulfate (CS) were constructed and examined. The results showed that the scaffold (ColI:CS:HA=9:1:1) had larger pore diameter, porosity, water absorption, degradation rate and tensile strength. gentamycin sulphate (GS) - gelatin microspheres (GMSs) were prepared by emulsion cross-linking method. The drug release study of the ColI-CS-HA-GS/GMSs scaffold with antibacterial property showed a prolonged, continuous, and sustained release of GS. The bone marrow mesenchymal stem cells (BMSCs) were extracted from rat and inoculated into the ColI-HA-CS-GS/GMSs scaffold. The results performed that the scaffold could accelerate proliferation of the BMSCs and wound healing.

sPhaseStation: a whole slide quantitative phase imaging system based on dual-view transport of intensity phase microscopy.

Whole slide imaging scans a microscope slide into a high-resolution digital image, and it paves the way from pathology to digital diagnostics. However, most of them rely on bright-field and fluorescence imaging with sample labels. In this work, we designed sPhaseStation, which is a dual-view transport of intensity phase microscopy-based whole slide quantitative phase imaging system for label-free samples. sPhaseStation relies on a compact microscopic system with two imaging recorders that can capture both under and over-focus images. Combined with the field of view (FoV) scan, a series of these defocus images in different FoVs can be captured and stitched into two FoV-extended under and over-focus ones, which are used for phase retrieval via solving the transport of intensity equation. Using a 10× micro-objective, sPhaseStation reaches the spatial resolution of 2.19 µm and obtains the phase with high accuracy. Additionally, it acquires a whole slide image of a 3m m×3m m region in 2 min. The reported sPhaseStation could be a prototype of the whole slide quantitative phase imaging device, which may provide a new perspective for digital pathology.

Phase flow cytometry with coherent modulation imaging.

Label-free imaging and identification of fast-moving cells is a very challenging task. A kind of phase flow cytometry using coherent modulation imaging was proposed to realize label-free imaging and identification on fast-moving cells with compact optical alignment and high accuracy. Phase image of cells under inspection could be computed qualitatively from their diffraction patterns at the accuracy of about 0.01 wavelength and the resolution of about 1.23 µm and the view field of 0.126 mm2 . Since the imaging system was mainly composed by a piece of random phase plate a detector without using commonly adopted reference beam and corresponding complex optical alignment, this method has much compacter optical structure and much higher tolerance capability to environmental instability in comparison with other kinds of phase flow cytometry. Current experimental results prove it could be an efficient optical tool for label-free tumor cell detection.

Three-wavelength digital photoelasticity.

A three-wavelength photoelasticity method is proposed to simplify the optical setup and speed up data acquisition. By recording six intensity images with circularly polarized illuminations of three close wavelengths, the phase retardation and corresponding inner stress can be computed accurately with a correspondingly developed computational algorithm. Since the mechanical rotations of wave plates and polarizers required by classic photoelasticity techniques are avoided, the data acquisition of this proposed method is very speedy, and measurement of a dynamic sample can be achieved with a very simple and compact optical setup. Besides theoretical analyses, numerical and experimental evidences are also used to confirm the feasibility of this suggested three-wavelength digital photoelasticity method.

Single-shot measurement of the near-field and focal spot profiles of a 351 nm laser beam for SGII-upgraded facility with multiple-focal-plane constraint coherent modulation imaging.

Inertial confinement fusion (ICF) places an urgent demand for precise measurement of 351 nm (3ω) laser beam parameters when performing physical experiments on high-power laser facilities. The near-field and focal spot distributions are the utmost important parameters to characterize the quality of the laser beam. Coherent modulation imaging (CMI) is a promising technique for online laser beam measurement, however, it fails to reconstruct the near-field and focal spot profiles when it is used to measure the beam quality of a 351 nm laser beam for SGII-upgrade facility. To solve this problem, a novel CMI reconstruction algorithm is proposed in this work, and the performance of the algorithm in 3ω laser beam measurement can be obviously improved. By adopting multiple-virtual-focal-plane constraint in the proposed algorithm, the near-field and focal spot profiles of the 3ω laser beam can be successfully reconstructed. Experiments have been conducted on SGII-upgrade facility to verify the feasibility of the proposed method.

Jia-ga-song-tang protection against alcoholic liver and intestinal damage.

Gut-liver axis and cellular homeostasis play key roles in alcohol liver disease (ALD). Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a stress-sensitive guarantor of cellular homeostasis. We investigated whether the beneficial effects and underlying mechanisms of Jia-ga-song Tang (JGST) against ALD were associated with gut-liver axis and cellular homeostasis. A predictive network depicting the relationship between Jia-Ga-Song-Tang (JGST) and alcoholic liver disease (ALD) was designed by Network pharmacology. Next, 5% v/v Lieber-DeCarli alcohol liquid diet was used to establish the ALD. JGST protected the liver damage, repaired the intestines to alleviate the Two-hit on the liver, and balanced the cellular homeostasis. It was manifested in repairing the liver and intestinal pathological structure, reducing serum ALT, AST, and liver TG, TC, MDA, CAT, and increasing liver GSH, and intestine GSH-Px. JGST mainly inhibited the liver mRNA levels of HO-1, NQO1, GCLC, FASN, and PPARα and activated the intestinal mRNA levels of HO-1 and NQO1, while inhibiting the liver protein levels of HO-1, NQO1. Furthermore, LPS and LBP in the plasma and the expression of inflammatory factors such as IL-1ß, TNF-α, IL-6, TGFß1, CD14, and Myd88 were reduced after treatment to prove that JGST protects the liver from Two-hit. Ethanol was used to intervene in HepG2 and IEC-6 to establish an ALD cell model and treated by Germacrone, ML385, and TBHQ. repaired the intestinal barrier, and inhibited Nrf2 in IEC-6, but protect the HepG2 by activating Nrf2 to balance cellular homeostasis. Our results reinforce that JGST provides an effective protective method for alcoholic liver disease (ALD) by regulating Gut-liver axis and cellular homeostasis.

Automatic whole blood cell analysis from blood smear using label-free multi-modal imaging with deep neural networks.

Whole blood cell analysis is widely used in medical applications since its results are indicators for diagnosing a series of diseases. In this work, we report automatic whole blood cell analysis from blood smear using label-free multi-modal imaging with deep neural networks. First, a commercial microscope equipped with our developed Phase Real-time Microscope Camera (PhaseRMiC) obtains both bright-field and quantitative phase images. Then, these images are automatically processed by our designed blood smear recognition networks (BSRNet) that recognize erythrocytes, leukocytes and platelets. Finally, blood cell parameters such as counts, shapes and volumes can be extracted according to both quantitative phase images and automatic recognition results. The proposed whole blood cell analysis technique provides high-quality blood cell images and supports accurate blood cell recognition and analysis. Moreover, this approach requires rather simple and cost-effective setups as well as easy and rapid sample preparations. Therefore, this proposed method has great potential application in blood testing aiming at disease diagnostics.

Research on Rice Yield Prediction Model Based on Deep Learning.

Food is the paramount necessity of the people. With the progress of society and the improvement of social welfare system, the living standards of people all over the world are constantly improving. The development of medical industry improves people's health level constantly, and the world population is constantly climbing to a new peak. With the continuous development of deep learning in recent years, its advantages are constantly displayed, especially in the aspect of image recognition and processing, it drives into the distance. Thanks to the superiority of deep learning in image processing, the combination of remote sensing images and deep learning has attracted more attention. To simulate the four key factors of rice yield, this article tries a regression model with a combination of various characteristic independent variables. In this article, the selection of the best linear and nonlinear regression models is discussed, the prediction performance and significance of each regression model are analyzed, and some thoughts are given on estimation of actual rice yield.

Safety and efficacy of telitacicept in refractory childhood-onset systemic lupus erythematosus: A self-controlled before-after trial.

OBJECTIVE: To observe the efficacy and safety of telitacicept in refractory childhood-onset systemic lupus erythematosus (cSLE). METHODS: A self-controlled before-after trial. Children with active SLE, aged 5-18 years, who cannot tolerate side effects of glucocorticoid, were enrolled in our study. Patients received subcutaneous injection of telitacicept weekly based on the standard treatment. SLE responder index-4 (SRI-4) was assessed before the first administration and at least 4 weeks after the first administration. RESULTS: Among the 15 cases of refractory cSLE, three were males (20%) and 12 were females (80%). The median age and weight were 13 years old and 52 kg, respectively. The median duration of disease was 30 months. 5-26 weeks (80 or 160 mg per week) after administration of telitacicept, 66.7% (n=10) reached SRI-4 response. 12 cases reduced their glucocorticoid intake from 40 mg/d to 17.5 mg/d. The urinary protein after treatment declined in 8 cases whose 24-h proteinuria was >0.5 g at baseline. The urinary protein in two of the eight cases turned negative and plasma albumin in five of the eight cases rose to normal. In addition, three of these eight cases demonstrated varying degrees of improvement in renal impairment, whose estimated glomerular filtration rate (eGFR, ml/min·1.73 m2) rose from 17.4 to 26.6, 40.7 to 48.2, and 63.2 to 146.0, respectively. There were mild to moderate adverse events after treatment. CONCLUSION: Telitacicept combined with the standard treatment may significantly increase the SRI-4 response rate and reduce the glucocorticoid dosage in refractory cSLE, and also shown efficacy on lupus nephritis. The related adverse drug events were controllable.

Laser-pulse-induced temperature, thermal stress, and crater morphology effect during multipulse nanosecond laser manufacturing.

We construct a numerical model for multipulse laser drilling. It is found that the previous laser-pulse-induced temperature accumulation, thermal stress occurrence, and crater morphology change promote subsequent pulse laser drilling. Among them, previous laser-pulse-induced temperature accumulation contributes significantly to the drilled crater depth when the workpiece temperature is higher than its melting point just before the subsequent laser pulse irradiation, especially in a short pulse interval condition. The crater morphology change becomes the main contributor when the workpiece temperature decreases below the melting point, often in a long pulse interval condition. Besides, the previous occurrence of laser-pulse-induced thermal stress always has had little influence on the drilled crater. This work can be a theoretical reference, especially for multipulse laser manufacturing.