Search Results (758)

Remote photoplethysmography (rPPG) provides a contactless way to estimate cardiac activity from facial videos, but post-exercise recovery remains difficult because the heart rate changes rapidly and motion artifacts are often pronounced. This work focuses on rPPG-based heart rate estimation under these non-stationary conditions. We introduce a Recovery-Aware Learning framework in which a subject-specific recovery time is used only during training to guide window sampling and auxiliary supervision. Early recovery windows are sampled more frequently to reduce the imbalance between the short rapid-transition phase and the longer stable phase, while a soft recovery-progress target provides additional temporal guidance. We further propose ResPulseNet, a 1D convolutional encoder–decoder network designed to reconstruct rPPG waveforms from multi-ROI RGB traces while sharing temporal representations with the auxiliary recovery-progress task. On the MCD-rPPG dataset, ResPulseNet achieves an overall MAE of $2.20\pm 0.36$ bpm and an MAE of $2.48\pm 0.37$ bpm on post-exercise recordings, compared with 4.89 and 5.41 bpm, respectively, for the strongest evaluated baseline. These results show that combining recovery-aware training with dedicated temporal modeling improves rPPG estimation during post-exercise physiological transitions. Full article

To probe a possibility of symmetry breaking within chainlike σ-conjugated polymers, we investigated the preservation of P-odd/T-even and P-odd/T-odd symmetries in semiflexible poly(n-butyl-isobutylsilane) (C4-iBS), which lacks point chirality. Using circular dichroism (CD) and circularly polarized luminescence (CPL) spectroscopy in various achiral solvents, we recorded three sets of temperature-dependent CD generation and inversion at the Siσ–Siσ* transitions, which were assigned to 11₄-, 8₃-, and 7₃-helices, respectively. In n-hexadecane-h₃₄, C4-iBS exhibited a CD inversion due to an 8₃-helix reversal from g_abs = −1.3 × 10⁻³ (40 °C) to +0.7 × 10⁻³ (20 °C). The observed H/D isotope effects in n-hexadecane-h₃₄ and -d₃₄ suggest that ¹H and ²H nuclei contribute differently to the temperature-dependent 8₃-helicity. Remarkably, photoexcited C4-iBS at 20 °C displayed dynamic CPL oscillations at 330 nm, alternating between g_lum = −7 × 10⁻² and +9 × 10⁻² at ~20 s intervals. These CD and CPL results suggest a mixing of P-odd and P-even states in both S₀- and S₁-states. Furthermore, magnetic circular dichroism (MCD) and magnetochiral dichroism (MChD) under a reversing H₀ = ±0.45 T at 23 °C produced non-mirror-image MCD/MChD spectra and their non-identical unpolarized MUV/MChUV spectra. These observations and analysis imply the simultaneous mixing of P-odd/P-even and T-odd/T-even terms in the S₀- and S₁-states of C4-iBS. Full article

Trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite, is a known risk factor for cardiovascular disease. We previously showed that TMAO induces NLRP3 inflammasome activation and contributes to endothelial dysfunction. However, the upstream mechanisms linking TMAO to inflammasome activation and barrier injury remain unclear. In the present study, we examined whether membrane raft (MR) redox signaling contributes to TMAO-induced NLRP3 inflammasome activation and endothelial dysfunction. MR clustering, colocalization of MRs with NADPH oxidase subunits, inflammasome formation, and junction protein expression were assessed by Western blot analysis. RT-qPCR was performed to further assess the mRNA expression of junctional genes. Superoxide production was measured by electron spin resonance (ESR), caspase-1 activity was determined using a biochemical assay kit, IL-1β production was measured by ELISA, and endothelial permeability was evaluated using an FITC-dextran assay. TMAO increased MR clustering in endothelial cells in a dose-dependent manner. TMAO also enhanced the colocalization of MRs with p47phox and gp91phox, indicating the formation of an MR-associated redox signaling axis. In addition, TMAO increased superoxide production; promoted NLRP3 inflammasome formation; elevated caspase-1 activity and IL-1β production; reduced the expression of ZO-2, ZO-1, VE cadherin and occludin; and increased endothelial permeability. Pretreatment with the MR disruptor MCD, the NADPH oxidase inhibitor DPI, or the caspase-1 inhibitor WEHD significantly attenuated these TMAO-induced effects. These findings demonstrate that TMAO-mediated endothelial injury is dependent on the MR-associated redox signaling axis. TMAO promotes MR-associated redox signaling, leading to NADPH oxidase activation, superoxide generation, NLRP3 inflammasome activation, disruption of endothelial junction proteins, and barrier dysfunction. Targeting MR-associated signaling pathways may offer a novel therapeutic strategy to mitigate TMAO-induced vascular inflammation and endothelial dysfunction. Full article

Water-lubricated seal interfaces are particularly vulnerable to fluid-film instability, which accelerates interfacial friction and wear and compromises the reliability and service life of underwater equipment. Here, a novel graphite-microcrystalline diamond (Graphite-MCD) soft–hard seal-face tribopair was proposed and systematically benchmarked against SiC-SiC and Graphite-SiC tribopairs under high-pressure water lubrication. Their sealing capacity, friction and wear behavior, and interfacial evolution were evaluated. The polished Graphite-MCD pair achieved the highest limiting PcV (90.73 MPa·m·s⁻¹) and the lowest wear rate, markedly outperforming the SiC-SiC and Graphite-SiC pairs. Multiscale interfacial characterization showed that the SiC-SiC pair failed primarily through adhesive instability after breakdown of the water film. Although the Graphite-SiC pair reduced interfacial shear resistance, sliding generated a continuous triboreaction layer accompanied by third-body wear. In contrast, the Graphite-MCD pair preserved interfacial structural integrity and suppressed the formation of an unstable continuous reaction layer and abundant abrasive debris. This behavior enabled a synergistic combination of a low-shear lubricating interface and a stiff load-bearing counterface. These results demonstrate that improving the limiting PcV of mechanical seals cannot be achieved by reducing the friction coefficient alone; rather, it requires simultaneous control of lubricity and interfacial stability. The findings provide a mechanistic basis for designing soft–hard tribopairs for high-pressure, water-lubricated mechanical seals. Full article

The Berca–Arbănași region of Buzău County (Romania) is of exceptional geochemical interest due to diapiric structures, active mud volcanoes, and historical subsurface hydrocarbon deposits. This study presents the first comprehensive geochemical assessment of surface soils from the Berca–Arbănași Subcarpathian zone, based on the analysis of 27 soil samples collected along three north–south transects and the determination of 12 potentially toxic elements (As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, V, Zn) using aqua regia digestion and ICP-MS. The local geochemical background was calculated using the iterative median ± 2MAD method. Twelve pollution and ecological risk indices were computed: the Pollution Index (PI), Contamination Factor (CF), Geoaccumulation Index (Igeo), Enrichment Factor (EF), Pollution Load Index (PLI), Modified Degree of Contamination (mCd), Nemerow Integrated Pollution Index (PINemerow), Ecological Risk Factor (E_rⁱ), Ecological Risk Index (RI), Mean Effect Range-Median Quotient (MERMQ), Degree of contamination (Cdeg), and the V/Ni petroleum origin indicator. Results show that 66.7% of samples are classified as polluted (PLI ≥ 1; mean = 1.102), with moderate enrichment in Cd, Cu, Hg, Pb, and Zn, attributable to diffuse anthropogenic sources. The ecological risk index (RI) remains low across all samples (mean = 35.96; all < 150), indicating that, despite moderate pollution, ecological risk is currently low. The V/Ni ratio (0.391–0.884, mean = 0.608) is below 1.0 for all samples, indicating a lithogenic (not petroleum) origin of vanadium and nickel and confirming a negligible geochemical impact of mud volcanoes and hydrocarbon extraction activities in the area at the sampled locations. The study establishes baseline geochemical reference values for the Berca–Arbănași area and provides data for sustainable land management, environmental monitoring, and evidence-based policymaking. These results directly support the objectives of the EU Soil Strategy 2030 and align with the United Nations Sustainable Development Goals on food security (SDG 2), good health and well-being (SDG 3), and life on land (SDG 15). Full article

Surface urban heat island (SUHI) behavior in dryland cities can reverse sign when hot, bare peripheral surfaces exceed urban-core temperatures, yet long monthly records across contrasting climates remain scarce. This study reconstructs land surface temperature (LST) and standardized urban-core–periphery thermal contrasts for five Moroccan cities from 1995 to 2024 using Landsat, ERA5-Land, NDVI, and the annual MODIS MCD12Q1 land-cover product. The diagnostic analysis of SUHI and Urban Heat Sink (UHS) occurrence is explicitly separated from the forecasting component: SARIMA, Random Forest, XGBoost, and LSTM models predict monthly LST rather than UHI intensity. Tangier exhibits a persistent positive SUHI (mean: 4.6 °C; UHS frequency: 3.0%), whereas Béni Mellal, Ifrane, Laayoune, and Taza have negative mean contrasts of −1.4, −2.4, −1.0, and −0.7 °C, respectively; Ifrane records the highest UHS frequency (90.5%). No city shows a statistically significant monotonic UHI trend, and Sen’s slopes remain close to zero. Forecasting skill is city-dependent: SARIMA performs best in Ifrane and Tangier (R² = 0.94 and 0.93), while Random Forest performs best in Taza and Laayoune (R² = 0.90 and 0.79). Approximate 95% empirical uncertainty half-widths derived from held-out RMSE range from ±3.78 to ±15.48 °C, indicating substantial model- and city-specific uncertainty. The results support the hypothesis that local climate and peripheral land-cover context can outweigh urban fraction as controls on SUHI sign and amplitude. Generalization is limited by fixed reference distances, possible urbanization of the outer ring, clear-sky satellite sampling, the distinction between LST and air temperature, and the 36-month recursive forecasting chain used to display the 2026–2027 outlook. Full article

Objectives: This study focuses on exploring the mechanism by which Schisandrin B (Sch B) regulates metabolic dysfunction-associated steatotic liver disease (MASLD) mice induced by a high-fat methionine–choline-deficient (MCD) diet through the activation of peroxisome proliferator-activated receptor γ (PPARγ). Methods: Male C57BL/6 mice were fed a high-fat MCD diet for 8 weeks to establish a mouse MASLD model, and the effects of Sch B on MASLD and the mechanisms were investigated. PPARγ overexpression (OE) was induced by adeno-associated virus (AAV) administration via intrahepatic portal vein injection in mice, and a negative control (NC-OE) was also established. Body weight; wet liver weight; hepatic index; serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β); and hepatic triglyceride (TG) levels were measured in the mice. The histopathology and lipid deposition were observed by hematoxylin and eosin (H&E) staining and Oil Red O staining, while the fibrosis was assessed using Masson staining. Western blot was employed to detect the expression levels of PPARγ, sterol regulatory element-binding protein 1c (SREBP-1c), carnitine palmitoyltransferase 1A (CPT1A), transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMA), collagen type I (collagen I), Smad family members 2/3 (Smad2/3), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38), and extracellular signal-regulated kinase 1/2 (ERK1/2), along with the phosphorylation activation status of these kinases. Results: It was confirmed that Sch B caused effects similar to those induced by PPARγ overexpression, reducing the hepatic index, AST, and ALT levels while alleviating lipid accumulation and fibrosis; and upregulating PPARγ and CPT1A while inhibiting SREBP-1c; and the phosphorylation of the TGF-β/Smad and MAPK pathways were involved in the mechanisms. Conclusions: Sch B can alleviate high-fat MCD-induced MASLD by activating PPARγ in mice. Full article

Background/Objectives: IgA nephropathy (IgAN) is a highly heterogeneous glomerular disease with variable clinical presentation and response to therapy. Standard histopathology provides a static assessment and may not fully reflect dynamic podocyte injury. The objective of this case series was to characterize distinct clinical phenotypes of IgAN and explore the relationship between urinary protein composition assessed by the urine albumin-to-protein ratio (uAPR) and ultrastructural glomerular injury. Methods: We retrospectively analyzed three patients with distinct clinical phenotypes of biopsy-proven IgA nephropathy to examine the relationship between urinary protein composition (uAPR), ultrastructural findings, treatment response, and clinical outcomes. Results: Case 1 demonstrated a podocytopathic phenotype resembling minimal change disease (MCD) with steroid sensitivity. Case 2 showed progression to focal segmental glomerulosclerosis (FSGS) despite stable renal function. Case 3 revealed persistent predominantly non-albumin proteinuria (uAPR 0.07–0.13) preceding biopsy-proven IgAN and resistance to multiple immunosuppressive regimens. Conclusions: Differences in uAPR were observed alongside distinct clinicopathological and ultrastructural phenotypes of IgA nephropathy. These observations suggest that urinary protein composition may provide complementary information on disease phenotype; however, its relationship with specific mechanisms of glomerular injury requires prospective validation. Full article

Introduction: The fetal ganglionic eminence (GE) is a transient brain structure involved in interneuron development; its abnormalities may be associated with malformations of cortical development (MCD). This systematic review evaluated the feasibility and clinical value of transvaginal neurosonography for fetal GE assessment. Material and Methods: PubMed, Scopus, and Web of Science were searched from January 2015 to June 2026. Human in vivo ultrasound studies of the fetal GE were included. Results: Thirteen studies comprising 890 fetuses were included. GE visualization ranged from 71% to 100%, with highest rates using dedicated three-dimensional transvaginal neurosonography at 9–22 weeks. Measurement reproducibility was good to excellent. GE cavitation and enlargement were associated with MCD in selected high-risk cohorts, but reported frequencies varied substantially. Conclusions: Transvaginal neurosonography permits feasible and reproducible visualization of the fetal GE in experienced hands. Small studies, heterogeneous protocols, and limited long-term outcome data preclude routine GE assessment at present. Full article

The increasing complexity of cyber–physical manufacturing systems demands simulation architectures that scale with the physical plant without a proportional growth in engineering effort. This paper introduces a formal, symmetry-based framework for behavioral reuse in arbitrary cyber–physical manufacturing systems, implemented within the Siemens NX Mechatronic Concept Designer (MCD), version NX 2506, environment. Symmetry is treated rigorously, as an equivalence relation induced by a symmetry-group action over the set of plant components, and three exploitable classes are defined on this basis: structural symmetry, arising from replicated kinematic configurations; functional symmetry, arising from shared behavioral specifications across instances of a common component class; and temporal symmetry, arising from synchronized cyclic behavior across concurrent actors. From these definitions, a four-condition behavioral inheritance protocol is derived, specifying the prerequisites under which a single behavioral library template is correctly instantiated across an arbitrary number of interchangeable components. The framework is demonstrated on a production cell comprising ten conveyor sections, nine CNC machining centers (5-axis, X/Y/Z/A/B/SP), and two COMAU NJ420-3.0 manipulators—each a 6-axis articulated arm extended by an external linear rail to seven controlled axes—governed through Siemens Sinumerik RunMyRobot/Direct Control and exercised in a co-simulation environment that integrates a Create MyVirtual Machine (CMVM) Software-in-the-Loop (SiL) controller, a Simit Model-in-the-Loop (MiL) communication layer, and MCD for kinematic and behavioral emulation. Using the number of independent behavioral configuration operations as the effort metric, the symmetry-driven approach reduces machining-center configuration effort by 88.9% (from nine independent configurations to one template instantiated nine times) and robot behavioral configuration effort by 100% (both manipulators inherit from a single seven-axis library entry), while preserving full kinematic and signal-level fidelity. The inheritance mechanism is shown to tolerate heterogeneous kinematic substitution: a COMAU NJ420-3.0 may be replaced by any kinematically equivalent 6-axis manipulator in the RunMyRobot database without behavioral reconfiguration. The component and capability mapping matrix (CCMM) introduced in prior work is extended with a symmetry-annotation layer that explicitly encodes instance relationships and inheritance chains, providing a structured input to automated behavioral-deployment workflows. The results establish symmetry-based modular simulation as a principled and scalable methodology for industrial digital-twin development in multi-robot manufacturing environments. Full article

Agricultural soils in arid regions require assessment approaches that separate local element enrichment from actual ecological and human health relevance. Here, a site-prioritization framework is applied to potentially toxic elements (PTEs) in agricultural soils from Onaizah, central Saudi Arabia. The approach combines contamination indices, ecological-risk screening, deterministic health-risk estimates, Monte Carlo resampling, and relative ranking of management priorities. A total of 33 surface-soil samples collected from cultivated farms were examined for As, Co, Cr, Cu, Mn, Ni, Pb, V, and Zn. The measured concentration ranges (mg/kg) were 1–5 (As), 1–12 (Co), 10–53 (Cr), 4–38 (Cu), 107–541 (Mn), 6–54 (Ni), 2–23 (Pb), 8–47 (V), and 11–168 (Zn). Based on their mean concentrations, the investigated elements decreased in the following sequence: Mn > Zn > Cr > Ni > V > Cu > Pb > Co > As. The P_N values ranged from 0.127 to 1.339, indicating 27 safe sites, 2 warning-line sites, and 4 slightly polluted sites, mainly controlled by localized Zn enrichment and, in one case, Pb. In contrast, mCd values of 0.099–0.676 indicated nil to very low contamination, while RI values of 2.743–15.701 confirmed low ecological risk across all samples. Non-carcinogenic risk was generally below the threshold of concern, with HI values of 0.204–1.018 for children and 0.024–0.119 for adults. Only one site showed a marginal child HI exceedance, emphasizing localized rather than widespread health concern. Children showed approximately 8.6-fold higher non-carcinogenic risk than adults, with Mn, Cr, As, and V as the main contributors. The total LCR values for As, Cr, and Pb ranged from 7.79 × 10⁻⁶ to 4.07 × 10⁻⁵ for children and from 3.48 × 10⁻⁶ to 1.82 × 10⁻⁵ for adults, within the commonly tolerable range of 1 × 10⁻⁶ to 1 × 10⁻⁴. Chromium was the dominant contributor to LCR. Monte Carlo resampling supported the deterministic risk classification, with only a 3.1% probability of child HI exceeding 1 and no simulated exceedance of the LCR threshold for either children or adults. From the standpoint of sustainable soil management, site 7 should undergo further health-risk assessment, while sites 30 and 33 require source verification and periodic monitoring before any remediation action is considered. Full article

Photosynthetically active radiation (PAR) is a fundamental driver of terrestrial photosynthesis and a key input for light use efficiency-based estimates of gross primary productivity (GPP). However, existing PAR products are typically designed for regional to global applications and often remain spatially mismatched with the finer-resolution land surface variables now commonly derived from optical satellite observations. In this study, we present a semi-empirical framework for deriving daily clear-sky and all-sky PAR from Sentinel-2 Level-2A imagery. The approach combines solar geometry, daily extraterrestrial radiation, and simplified atmospheric transmittance parameterizations using Sentinel-2 aerosol, water vapor, and scene classification information to estimate clear-sky PAR, and further extends this formulation to all-sky conditions through a cloud-transmission factor derived from cloud probability to generate a spatially explicit PAR product aligned with Sentinel-2 observations. The resulting estimates are evaluated against flux tower observations from 172 AmeriFlux sites across North and South America for the period 2017–2024 and compared with MODIS MCD18, VIIRS VNP18, and CERES SYN1deg PAR products. The clear-sky Sentinel-2 formulation showed a moderate positive bias of 6.38 W m⁻², while the all-sky cloud adjustment reduced the mean bias to −1.44 W m⁻² with an RMSE of 23.53 W m⁻² and correlation of r = 0.87. The largest improvements occurred in spring and summer seasons, when atmospheric attenuation has the strongest influence on the clear-sky estimates. MODIS and CERES all-sky PAR products achieved lower overall errors with RMSE of 17.60 W m⁻² and 15.56 W m⁻², respectively, but at substantially coarser spatial resolution. The proposed framework therefore provides a practical high-resolution approximation of daily PAR that is spatially consistent with Sentinel-2 observations. Rather than replacing dedicated radiative transfer-based products, the method is intended to support analyses in which PAR needs to be evaluated together with Sentinel-2 bands, vegetation indices, and other Sentinel-2-derived variables within a common observational framework. Full article

Floating Offshore Wind (FOW) enables offshore wind deployment in deeper waters not suitable for bottom-fixed turbines, unlocking new areas for renewable energy generation. Most major cost contributors to FOW have clear pathways for cost reduction however mooring systems are the exception due to the pre-existing market maturity. Solutions to lower mooring costs include Mechanical Compliance Devices (MCDs) aimed at reducing the high peak and snatch loads in mooring lines and thus driving down the capital, operations and maintenance costs. In this paper, a comparison of a physical tank testing campaign and corresponding numerical analysis, for an MCD is described and analysed. The objective of the testing campaign was to validate the component-only tank results with the modelling of an MCD, namely Dublin Offshore’s Load Reduction Device (LRD) using a multi-body dynamics (MBD) approach. The paper presents analysis of the experimental testing and numerical modelling and compares the results with the validated Load–Extension Curve (LEC). Experimental testing was carried out at 1:38.5 scale using bespoke mooring test apparatus at Lír, Ireland’s National Ocean Test Facility. The results of testing are presented for all of the MCD model scales tested and compared with the modelled LEC. The correlation between the experimental and numerical data and with the LEC, characterised by Pearson Correlation Coefficient (R) in the range of 0.952 to 0.999, demonstrates the ability to model the LRD using the MBD approach. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive immunometabolic liver disorder involving lipid dysregulation, inflammation, fibrosis, and extrahepatic immune–neural responses, yet therapies capable of modulating these interconnected processes remain limited. Berberine (BBR), an isoquinoline alkaloid derived from traditional medicinal plants including Coptis chinensis Franch. (Coptidis Rhizoma), has shown metabolic and anti-inflammatory activities; however, its effects on hepatic inflammation and the liver–brain inflammatory axis in MASH remain unclear. Here, network pharmacology and molecular docking were used to predict BBR targets and pathways, followed by in vivo validation in a methionine- and choline-deficient diet-induced mouse model. Liver injury and metabolic alterations were assessed using serum biochemistry and lipid profiles, histological changes by hematoxylin and eosin and Sirius Red staining, and hepatic and hypothalamic inflammation by qRT-PCR, flow cytometry, and Iba-1/GFAP immunostaining. SREBF1, AKT1, and TGFB1 were identified as core BBR targets, with pathways linked to lipid metabolism, oxidative stress, inflammation, and fibrogenesis. BBR attenuated liver injury, steatosis, steatohepatitis, and fibrosis, suppressed SREBF1-associated lipogenic signaling and fibrogenic gene expression, remodeled circulating monocyte subsets, reduced Kupffer cell accumulation, and inhibited hypothalamic microglial activation. These findings suggest that BBR alleviates MCD-induced steatohepatitis through multi-target regulation of hepatic metabolic dysfunction, immune remodeling, and hypothalamic neuroinflammation. Full article

In aerospace manufacturing, validating heavy-duty automated production tooling and Ground Support Equipment (GSE) traditionally requires costly and time-consuming physical proof load testing. This study proposes a novel Virtual Certification framework that utilizes a high-fidelity Multiphysical Digital Twin driven by a Software-in-the-Loop (SiL) co-simulation architecture (integrating Siemens NX MCD, SIMIT, and TIA Portal) to retroactively diagnose mechanical failures and virtually validate design modifications prior to physical manufacturing. The dual-focus methodology is rigorously applied to a physical case study: an over-constrained (hyperstatic) 4-point aerospace lifting system designed for a 26.48 kN fuselage section that suffered a catastrophic mechanical stall during a 39.24 kN physical proof load verification. While conventional static dimensioning models erroneously predicted a nominal drive torque of only 4.56 Nm, the high-fidelity dynamic twin (incorporating a non-linear exponential Stribeck friction model) calculated the transient mechanical resistance causing the stall, capturing a peak load of 46.2 Nm at the motor shaft. The SiL co-simulation revealed that the rigid positional synchronization logic enforced by the PLC inadvertently amplified localized boundary friction, driving the actuators beyond their rated 6.4 Nm capacity. Based on this forensic diagnosis, a remedial powertrain featuring an 8.0 Nm stepper motor coupled with a 16:1 planetary gearbox was integrated and virtually certified. The framework confirmed that the upgraded architecture successfully attenuated the hyperstatic resistance, reflecting a peak load of only 3.0 Nm at the motor shaft and guaranteeing a stable Safety Factor of 2.66. By bridging the reality gap without iterative physical prototyping, this framework establishes a scalable, “First-Time-Right” validation paradigm for multi-point automated manufacturing mechanisms. Full article