Search Results (2,289)

Supported Pt catalysts are highly active for the selective catalytic oxidation of ammonia (NH₃-SCO), but their practical use is limited by poor N₂ selectivity and insufficient hydrothermal durability under high-temperature exhaust conditions. Herein, we report a composition-regulated high-entropy oxide interface strategy to stabilize Pt–Cu dual sites and steer NH₃ oxidation toward selective N₂ formation. A series of fluorite-type Ce-based high-entropy oxides, including CeZrLaPrYO_x, CeSmLaPrYO_x, and CeSnLaPrYO_x, were constructed as thermally robust supports for Pt and Cu loading. Among them, PtCu/HEO-Zr calcined at 1000 °C exhibits the best NH₃-SCO performance, achieving 90% NH₃ conversion at 260 °C while maintaining N₂ selectivity above 80% over a broad temperature window of 100–300 °C under a high weight hourly space velocity of 100,000 mL·g⁻¹·h⁻¹. More importantly, after harsh hydrothermal aging at 800 °C with 10 vol% H₂O for 12 h, the catalyst shows negligible activity loss and nearly unchanged N₂ selectivity, demonstrating exceptional structural and catalytic robustness. Structural and surface analyses reveal that Zr incorporation optimizes the fluorite high-entropy lattice, increases oxygen vacancy concentration, promotes lattice oxygen mobility, strengthens surface acidity, and enriches active Cu²⁺ species, thereby enhancing the interfacial cooperation between NH₃ activation and oxygen-assisted intermediate conversion. In situ DRIFTS further reveals that PtCu/HEO-Zr favors an O_lat-assisted internal selective catalytic reduction pathway, in which adsorbed NH₃ is activated to -NH₂ species and subsequently reacts with lattice oxygen-derived intermediates to form N₂O₂²⁻-like species that decompose into N₂ and H₂O. Meanwhile, the formation of nonselective NO_x and N₂O products is suppressed. This work highlights high-entropy oxide-supported Pt–Cu interfaces as a promising platform for designing hydrothermally durable and N₂-selective NH₃-SCO catalysts. Full article

Background/Objectives: Prostate cancer is one of the most common non-skin solid malignancies among male solid organ transplant recipients (SOTRs), in whom radical prostatectomy is technically demanding. We report the first use of indocyanine green (ICG) fluorescence for simultaneous transplanted-ureter identification and renal graft vascular mapping during robot-assisted radical prostatectomy (RARP), and the first use of the CMR Versius^® platform in a SOTR. Methods: Retrospective case series of four consecutive male SOTRs (two renal [RTRs], two hepatic) undergoing RARP. In both RTRs, a dual-route ICG protocol was used on the da Vinci Xi with Firefly^® imaging: pre-docking intraureteral ICG via a ureteral catheter for ureter identification, plus an intravenous ICG bolus for graft vascular mapping and cortical perfusion. One hepatic recipient was operated with the CMR Versius^® system using an infra-umbilical port configuration to avoid the chevron transplant scar. Results: All four procedures were completed robotically without conversion. Median operative time was 176 min and median estimated blood loss 350 mL. Surgical margins were negative (R0) in all four; final pathology was pT3aN0 in three and pT2N0 in one, although in the renal recipients nodal staging reflected a contralateral-only dissection. PSA was undetectable at three months in all patients. One hepatic recipient later developed biochemical recurrence, managed with salvage radiotherapy and androgen deprivation therapy, with subsequent undetectable PSA. One hepatic recipient had a Clavien–Dindo IIIa complication. No graft dysfunction occurred. Conclusions: ICG-guided RARP and the CMR Versius^® platform appear technically feasible in carefully selected solid organ transplant recipients treated at an experienced multidisciplinary centre, with no graft-related complications observed in this small initial series. These preliminary findings require validation in larger, multicenter studies before general safety and oncological efficacy can be established. Full article

Background: This study investigates the psychophysiological stress profiles of professional basketball players by simultaneously analyzing two distinct neuroendocrine pathways: the sympathetic–adrenal–medullary (SAM) system, via salivary alpha-amylase (AA), and the hypothalamic–pituitary–adrenal (HPA) axis, via salivary cortisol (C). While competitive environments are known to elicit significant stress, the interaction between game-specific variables—such as playing time (PT) and tactical position—and those biomarkers remains insufficiently explored in real-time, official match settings. Methods: Twelve professional male basketball players were monitored across four official matches. Salivary samples were collected, and stress biomarkers (AA and C) were analyzed at three timepoints: pre-match, half-time, and post-match. Results: Results indicate that stress responses are non-uniform and highly context-dependent. A significant spike in AA was observed during the first match (p < 0.001; ES = 0.82; 95% CI −0.01–1.66), where concentrations rose from a pre-match mean of 247.9 ± 232.59 U/mL to a post-match peak of 674.39 ± 693.33 U/mL. Cortisol responses did not vary significantly across matches but exhibited a strong positive correlation with PT (p = 0.01; R = 0.76), identifying that C may serve as a primary marker of individual physical workload. Positional analysis revealed significant divergence in HPA activation; guards (0.55 ± 0.31 µg/dL) and centers (0.51 ± 0.22 µg/dL) exhibited higher cortisol levels compared to forwards (0.24 ± 0.18 µg/dL), reflecting the high cognitive/decision-making load of guards and the mechanical/physical contact load of centers. Conclusions: The observed differences in AA and C liberation suggest that stress responses during matches are influenced by a complex interaction of physiological and psychological stimuli characteristic of competitive basketball. Consequently, these findings indicate the importance and value of a dual-biomarker approach which might provide a framework for optimized training load management and recovery protocols in elite basketball. Full article

Background/Objectives: Prostate cancer (PCa) remains a leading cause of cancer-related mortality in men. While localized PCa carries a favorable prognosis, progression to locally advanced disease substantially worsens outcomes. There is an unmet need for molecular markers that reliably distinguish indolent from aggressive tumors. MicroRNAs (miRNAs), small non-coding RNAs that post-transcriptionally regulate gene expression, are implicated in cancer development and progression, and their expression profiles may serve as putative biomarkers of disease stage. Methods: We performed small RNA sequencing on formalin-fixed paraffin-embedded (FFPE) prostate tumor tissues from nine patients (five localized, four locally advanced-stage). Differentially expressed miRNAs were identified using a bioinformatics pipeline (fold-change ≥ 2, p < 0.05). Target gene prediction, KEGG pathway enrichment, and miRNA–mRNA interaction network analyses were conducted, followed by in silico validation using two independent public mRNA datasets (GSE46602 and GSE21034, a subseries of GSE21032). Results: Seven unique mature miRNAs were differentially expressed between localized and locally advanced PCa. Five miRNAs (miR-145-5p, miR-205-5p, miR-206, miR-24-1-5p, and hsa-miR-3648) were downregulated in locally advanced tumors, while hsa-miR-625-3p and miR-324-5p were upregulated. Network analysis identified CLTC and CDK6 as putative downstream targets co-targeted by multiple downregulated miRNAs. Independent validation using GSE46602 and GSE21034 consistently demonstrated significantly higher expression of CLTC and CDK6 in locally advanced prostate cancer following Benjamini–Hochberg correction. Conclusions: This exploratory pilot analysis identified several miRNAs that differ between localized (pT2) and locally advanced (pT3–T4/N+) prostate cancer. Independent validation across two publicly available mRNA cohorts supports CLTC and CDK6 as candidate stage-associated genes. However, these findings remain hypothesis-generating and require validation in larger prospective cohorts together with functional confirmation before biomarker or therapeutic claims can be made. Full article

Background: The molecular changes associated with the progression of intraductal papillary mucinous neoplasm (IPMN) to pancreatic ductal adenocarcinoma (PDAC) and distant metastasis remain incompletely understood. Case Presentation: A man in his late 70s underwent pancreaticoduodenectomy and partial hepatectomy for a pancreatic head tumor with synchronous liver metastasis. Histology showed a 4.5 cm moderately differentiated PDAC arising in an IPMN with high-grade dysplasia (pT3N1M1). Genomic analysis of the IPMN, PDAC, and liver metastasis identified KRAS p.G12D, CDKN2A deletion, and GNAS p.R201H in the IPMN; additional SMAD4 p.R361C in the PDAC; and KRAS p.G12D, CDKN2A deletion, SMAD4 p.R361C, and APC p.R1450Ter in the liver metastasis. The APC alteration was confirmed by targeted sequencing and was accompanied by loss of heterozygosity at the APC locus. β-Catenin showed membranous expression in the IPMN and PDAC, but nuclear accumulation in the liver metastasis. Discussion: The shared KRAS, CDKN2A, and SMAD4 alterations support a common clonal origin of the PDAC and metastatic tumors. The absence of a detectable GNAS alteration in the liver metastasis and the presence of a metastasis-specific APC alteration are compatible with, but do not prove, branching evolution and selection of a metastatic subclone. Conclusions: This case shows a metastasis-specific heterozygous APC truncating alteration with loss of heterozygosity, accompanied by nuclear β-catenin accumulation, in an IPMN-associated PDAC. Full article

Background: Thyroid function tests are frequently requested, but manufacturer reference intervals often lack age- or sex-based stratification. This study established indirect reference intervals for thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3) in a large adult population. We evaluated unsupervised algorithms and conventional partitioning to identify subgroups, compared multiple limit estimation methods, and assessed the diagnostic performance of the derived intervals against an independent, clinically defined external validation cohort. Methods: Data from 37,255 adults (age ≥ 18) collected between 2022 and 2024 were analyzed; a reference population of 5870 individuals was established following standardized exclusion criteria. Age-based subgroups were identified through hierarchical clustering with the Elbow method, and variable importance was assessed using Random Forest analysis. Reference intervals were calculated using non-parametric, Bhattacharya, refineR, and reflimR algorithms, applied to three population frameworks: (1) the total population without stratification, (2) subgroups derived from hierarchical clustering and (3) subgroups defined by the conventional Harris–Boyd partitioning method. Diagnostic performance was subsequently evaluated in an independent external cohort (National Health and Nutrition Examination Survey [NHANES]; N = 2297) for all estimated reference intervals. Three classification scenarios were assessed: TSH-only, fT4-only, and combined TSH + fT4, with sensitivity, specificity, Youden index, and decision curve analysis performed for each. Results: Random Forest analysis identified age as the dominant variable influencing TSH, fT4 and fT3 distributions (mean decrease in accuracy: TSH 41.62, fT4 44.18, fT3 43.7), while sex showed the lowest impact. Clustering yielded six age-based subgroups for analytes. Harris–Boyd partitioning yielded six age-based subgroups for TSH, two sex-based subgroups for fT4, and six combined age-and-sex subgroups for fT3. TSH limits were broadly concordant across all three approaches (six-subgroup partitioning: 0.36–0.68 to 4.75–5.67 mIU/L). For fT4, conventional (sex-based) and clustering (age-based) partitioning produced similar ranges (11.33–20.08 pmol/L), except reflimR’s notably lower limit (10.90 pmol/L). For fT3, conventional (age + sex) and clustering (age-only) partitioning showed comparable ranges (3.36–7.03 pmol/L), with clustering revealing a clearer age-related decline in the oldest group. Diagnostic performance varied markedly by analyte. TSH-only classification achieved positive discrimination across all 13 methods (Youden index: 0.173–0.239). In contrast, fT4-only and combined TSH + fT4 classifications performed at or below chance for most methods, with 75% of the cohort falling outside fT4 reference intervals, indicating an inter-platform harmonization issue rather than a partitioning failure. Decision curve analysis confirmed TSH-only classification’s superiority, exceeding universal testing from pt ≈ 0.20 onward across all methods. Conclusions: Age-stratified reference intervals combined with limit estimation showed potential diagnostic advantages over manufacturer and non-stratified intervals; however, an independent external validation using a clinically defined outcome indicated that this advantage was not consistently reproduced and was dependent on the clinical decision threshold considered. These results suggest that age stratification and algorithm choice merit further clinically adjudicated validation before broad clinical adoption, and that unsupervised clustering offers a practical, objective alternative to manual subgrouping for laboratories pursuing this approach. Full article

We demonstrate an integrated eight-wavelength high-power laser source on a 4H-silicon carbide (SiC)-based optical integration platform. Eight discrete Fabry–Perot laser diodes emitting at 445 nm, 637 nm, 789 nm, 806 nm, 846 nm, 978 nm, 1316 nm, and 1552 nm are integrated on a single SiC chip, each delivering ≥100 mW continuous-wave output power. A complete fabrication process is developed, including lift-off metallization (Ni/Ti/Pt/Au), surface hydrophilic activation bonding, and multi-step blade dicing to form SiC waveguides with a width of 500 μm and a thickness defined by the ~510 μm dicing depth, matching the output aperture of the multimode laser diodes. The resulting waveguides exhibit a facet misorientation of <1° and an approximate facet mean surface roughness of ~2 nm. The laser diodes are directly butted against the waveguide facets for edge coupling, and fixed using In₅₂Sn₄₈ solder bonding with pulse temperature control. Under controlled temperature, all eight channels operate stably with measured peak wavelengths matching the design targets. This work provides a scalable and practical solution for multi-wavelength, high-power on-chip light source integration on the SiC platform, addressing critical thermal and integration challenges for dense wavelength division multiplexing. Full article

Pt-Sn/C and Pt-Ru/C electrocatalysts were synthesized by a polyol method at nominal atomic ratios of 1:1, 2:1, and 3:1, and evaluated for the ethanol oxidation reaction (EOR) and ethylene glycol oxidation reaction (EGOR) in alkaline media. EDS confirmed compositions close to the nominal values, XRD evidenced fcc Pt-M alloy formation, and ADF-STEM revealed well-dispersed nanoparticles below 3 nm. Cyclic voltammetry showed that both Sn and Ru enhance activity relative to Pt/C: Pt-Sn_1:1 delivered the highest forward current density in the Sn series (1486 mA mg⁻¹_Pt for EOR; 2583 mA mg⁻¹_Pt for EGOR), whereas Pt-Ru shifted the onset to more negative potentials (down to −539 mV vs. SHE for EOR), with Pt-Ru_3:1 reaching 1858 (EOR) and 2434 mA mg⁻¹_Pt (EGOR). Chronoamperometry revealed higher current retention during EGOR than EOR for all catalysts, indicating fewer poisoning intermediates from ethylene glycol. DFT calculations of CO adsorption on 1:1 and 3:1 model surfaces rationalize the distinct roles of the two metals: Sn excludes CO from Sn sites at both compositions and weakens the Pt-CO bond by 0.602 eV at 1:1, while Ru weakens it moderately yet binds CO strongly at both compositions; the bifunctional supply of OH_ads by Ru, inferred from the more negative onset potentials, accounts for its higher activity. PDOS analysis links these trends to distinct Pt d-band modifications. Full article

Peripheral facial palsy is often attributed to idiopathic Bell’s palsy, but secondary structural causes should be considered when local red flags are present. A 61-year-old man with a 40-pack-year smoking history and former betel quid chewing presented with a verrucous-appearing mass involving the left oral commissure and buccal mucosa, intermittent purulent discharge from the lesion, progressive left facial swelling, and ipsilateral lower-motor-neuron facial palsy with lagophthalmos. Magnetic resonance imaging demonstrated a left buccal/oral-cavity lesion with ipsilateral parotid duct obstruction. He underwent tracheostomy, wide excision, left supraomohyoid neck dissection, and radial forearm free-flap reconstruction. Pathology confirmed squamous cell carcinoma, pT2N0, cM0 (stage II), with perineural invasion; surgical margins were negative, and lymphovascular invasion was not identified. At follow-up, wound healing was satisfactory and purulent discharge had resolved, but lower-motor-neuron facial palsy persisted; adjuvant radiotherapy was recommended. This case emphasizes that lower-motor-neuron facial palsy with an oral mass, purulent discharge, facial swelling, or salivary-duct obstruction should prompt careful oral examination and head-and-neck imaging. Full article

This study evaluated a cost-effective UAV-based multi-sensor approach for characterizing river corridor conditions during and after moderate floods in two mountain river corridors in Northern Utah, USA: the Logan River and Blacksmith Fork River. These study reaches included urban, rural, and agricultural areas, hydraulic structures and bridges, and fish passage structures. A DJI Matrice 300 UAV was used with two separate payloads: an AgEagle Altum-PT multispectral camera and an R3 Pro V2 two-return LiDAR system. The workflow included UAV flight planning and data collection, post-processing of the multi-spectral and LiDAR sensor data, spatial resolution and accuracy assessment, and interpretation of the resultant data. The multi-spectral post-processing produced pansharpened orthomosaics with a spatial resolution of 0.0432 m, while the UAV LiDAR produced DSM/DTM products at 0.05 m resolution. LiDAR accuracy assessment showed vertical RMSE values of approximately 0.0602 m for the Blacksmith Fork and 0.0782 m for the Logan River. The results showed that multispectral imagery and 2-band LiDAR provided a cost-effective means for detailed remote sensing with each sensor providing complementary information for flood and river corridor assessment. Multispectral imagery supported interpretation of flood extent, vegetation condition, relative turbidity, and thermal patterns, while LiDAR captured terrain and surface features such as banks, levees, floodplain surfaces, channel modifications, and structures. The integrated datasets supported maximum flood extent mapping and flood-level estimation. These datasets can support reach-scale hydraulic modeling, catchment hydrology, river corridor ecology, floodplain conditions, and real-time monitoring of floods, in addition to quantification of flood hazards or post-flood impacts for municipalities and insurers. Full article

Optical remote sensing object detection faces challenges such as large variations in scale, slender and direction-sensitive targets, complex backgrounds, and limited deployment resources. This paper proposes a lightweight geometrically decoupled student network with a dynamic multi-teacher distillation framework. Based on YOLO11n, the student detector keeps the original classification branch while redesigning the regression branches at different scales. Lightweight regression towers are used for the shallow and deep branches, whereas a geometrically decoupled regression tower is introduced only at the intermediate branch to enhance localization for slender and orientation-sensitive objects with limited extra cost. A geometry-adaptive box loss is further employed to stabilize localization training. For knowledge transfer, three specialized teachers are constructed for semantic classification, geometric regression, and structural topology supervision. A branch-decoupled adaptive weighting strategy dynamically integrates their complementary knowledge for classification and regression distillation. Experiments on DIOR show that the proposed model reduces parameters by 6.8% and GFLOPs by 13.9%, while improving mAP50 by 0.23 percentage points over YOLO11n. Validation on NWPU VHR-10 and deployment tests using PT, ONNX, and TensorRT further demonstrate improved accuracy–efficiency trade-offs and practical inference acceleration. Full article

The rhabdocoel family Trigonostomidae has been the subject of recent phylogenetic revisions. However, due to the limited number of sequenced taxa, questions regarding intrafamilial and intrageneric relationships remain unresolved. To address these gaps, we collected trigonostomids from the North Sea, the Mediterranean, and the Atlantic Ocean, and examined them using an integrative approach. Nineteen specimens, representing ten species, were sequenced for phylogenetic analyses. Eight species were sequenced for the first time, including the first molecular data for Lutheriella. All genera were recovered as monophyletic; however, Ceratopera falcata (type species of Messoplana) and a new closely related species were found to cluster with species of Beklemischeviella, while the remaining species of Ceratopera formed a distinct clade. Based on these findings, we propose the resurrection of Messoplana, which had previously been synonymised with Ceratopera. Notably, genetic divergence and differences in the bursal mouthpiece between specimens of M. falcata suggest the possible presence of cryptic diversity or geographical isolation within this taxon. The inclusion of Trigonostomum breitfussi provided molecular support for its morphologically defined group. Furthermore, L. diplostyla was found to be closely related to species of Ptychopera. In addition to phylogenetic analyses, we describe four new species: Ceratopera bransoni sp. nov., Messoplana judithae sp. nov., Parapharyngiella scotti sp. nov., and Ptychopera woodyi sp. nov. The discussion of the new species of Parapharyngiella and Ptychopera motivated the reclassification of Pt. scutulifera as Pa. scutulifera comb. nov. We record for the first time eight species from Florida, seven from the Indian River Lagoon, and two from the Florida Keys National Marine Sanctuary, in the USA. This study refines the phylogenetic framework and internal classification of Trigonostomidae by providing new molecular evidence for previously unsampled taxa and by re-evaluating generic boundaries within the family. Full article

This work reports the design and validation of a reusable platinum (Pt) electrode platform (ST-E) for green electrochemical analysis. The device integrates Pt working and counter electrodes with an external Ag/AgCl reference and is engineered for repeated regeneration and refunctionalization. Surface renewal by alumina polishing followed by electrochemical activation in 0.5 M H₂SO₄ restores a clean, reproducible Pt surface, as confirmed by diffusion-controlled, reversible ferricyanide voltammetry over 5–150 mV s⁻¹ with near-Nernstian peak separation and i_pa/ipc ≈ 1. Platform versatility is demonstrated in two applications. First, ST-E is functionalized with PFOA-selective molecularly imprinted nanoparticles on an APTES layer, enabling trace determination of perfluorooctanoic acid (1–5 pg mL⁻¹), with a detection limit of 0.50 pg mL⁻¹ and sensitivity of 3.16 μA (pg mL⁻¹)⁻¹. Responses correlate with an equivalently modified commercial screen-printed electrode (r = 0.990, p < 0.005), with Bland–Altman analysis confirming concordance. Second, after regeneration, electropolymerization of o-phenylenediamine yields an insulating poly(o-phenylenediamine) film that attenuates redox currents and increases ΔE_p, illustrating compatibility with diverse surface chemistries. Green metrics (AGREE, AGREEprep ≈ 0.80; BAGI = 75.0) highlight reduced waste and solvent use versus single-use transducers and compatibility with portable potentiostats, supporting circular electrochemical sensing. Full article

Reliable and sustainable access to energy continues to pose a significant challenge for rural farms in African underprivileged areas, where traditional diesel generators are both economically and environmentally unfeasible. This research explores the potential of pumped thermal energy storage (PTES) systems utilizing a Rankine cycle for the preservation of farm produce, analyzing four configurations of reversible heat pump–organic Rankine cycle (HP–ORC) systems that employ R1234ze(E) as the working fluid: hot-storage cooled HP mode, air-cooled HP mode, basic ORC mode, and ORC mode with integrated electrical heaters. Despite the exploration of hybrid HP–ORC and reversible PTES configurations in the existing literature, there remains a significant lack of research focusing on their feasibility for energy services in rural agriculture, and the literature data remains insufficient for comprehensive decision-making on deployment for small-scale applications in rural settings. To bridge this gap, the thermodynamic performance was evaluated for the PTES configurations through exergy analysis, to measure system irreversibility and component losses. Also, an exergoeconomic assessment was conducted using the Specific Exergy Costing (SPECO) method, while environmental impacts were examined with Eco-Indicator 99, aimed primarily at decision-making for real-life application. The results indicate that the ORC mode with electric heater achieved the highest exergy efficiency at 31.7%, surpassing the hot-storage cooled HP mode by approximately 11 percentage points. The air-cooled ORC with electric heaters exhibited a thermal efficiency of 26.6% and reduced economic losses, while also demonstrating significantly lower environmental degradation compared to the hot-storage HP mode (1327 mpts/s). These results suggest that air-cooled HP-ORC configurations provide an optimal balance of technical, economic, and environmental performance, thereby promoting sustainable, localized energy solutions for rural agricultural practices. Full article

This paper introduces a novel method for producing planar electrochemical devices by combining multi-material 3D printing with metal leaves (3D-MLEs). The fabrication process is based on the use of two polymeric materials, polylactic acid (PLA) and polycaprolactone (PCL), leveraging their different melting points. The approach exploits the thermoadhesive properties of polyesters, which can act as bonding layers upon heating, enabling a direct-writing and low-step fabrication strategy. The device was fabricated using a dual-extruder 3D printer to produce a PLA support containing PCL tracks, followed by selective thermal adhesion of the metal leaf onto the PCL. This process exploits the different melting temperatures of the two polymers: PCL softens and becomes adhesive at the selected temperature, while the PLA support remains structurally unaffected. A final brushing step enables the definition of a well-controlled three-electrode geometry. Following optimization of the fabrication parameters, a platinum leaf-based device (3D-PtLE) was assembled and evaluated using potassium hexacyanoferrate(II) and hexaammineruthenium(III) chloride as redox probes. The optimized device was subsequently applied to hydrogen peroxide detection in phosphate buffer (pH 7), exhibiting a linear response in the concentration range of 0.25–5 mM, with a limit of detection of 67 μM and good repeatability (RSD = 4.2%). The analytical applicability of the device was further demonstrated through the analysis of a real sample consisting of washing water prepared from a sodium percarbonate-based cleaning tablet, with good agreement (98 ± 6%) with the standard titration method. The proposed strategy provides a simple, low-cost, and customizable approach for fabricating planar electrochemical platforms based on pure metal electrodes, combining high analytical performance with straightforward manufacturing. Full article