Tolerance Analysis Research Articles

Ultra-low-dose continuous combined estradiol and dydrogesterone in postmenopausal women: A pooled safety and tolerability analysis

Objective: To assess the safety and tolerability of ultra-low dose estradiol and dydrogesterone (E0.5 mg/D2.5 mg) among postmenopausal women. Methods: This pooled analysis of data from three clinical studies assessed the effects of continuous combined ultra-low-dose estradiol and dydrogesterone among postmenopausal women. Participants received E0.5 mg/D2.5 mg or placebo for 13 weeks (double-blind, randomized, European study), E0.5 mg/D2.5 mg or placebo for 12 weeks (double-blind, randomized, Chinese study), or E0.5 mg/D2.5 mg for 52 weeks (open-label, European study). Safety outcomes included treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment discontinuation due to a TEAE, and adverse events of special interest (AESIs). Results: Overall, 1027 women were included in the pooled analysis (E0.5 mg/D2.5 mg, n = 736; placebo, n = 291). Mean treatment exposure was 288.9 days in the E0.5 mg/D2.5 mg group and 86.6 days in the placebo group. The proportion of women experiencing ≥1 TEAE was similar in the E0.5 mg/D2.5 mg and placebo groups (50.1% vs 49.5%, respectively). TESAEs occurred in 12 (1.6%) women receiving E0.5 mg/D2.5 mg and 9 (3.1%) women receiving placebo. Discontinuation of study treatment was infrequent in both groups (E0.5 mg/D2.5 mg: 1.5%; placebo: 2.4%). The occurrence of breast pain was more common in the E0.5 mg/D2.5 mg group than in the placebo group (2.0% vs 0.3%) as was uterine hemorrhage (6.5% vs 2.4%). The incidence of acne, hypertrichoses and weight increased was similar between groups. Conclusions: Across three studies, ultra-low-dose estradiol plus dydrogesterone was well tolerated among postmenopausal women, with no increase in TEAEs or TESAEs compared with placebo.

Design of a 1 × 3 Power Splitter Based on Multimode Interference in a Parabolic-Type Slot-Waveguide Structure

Multimode interference (MMI) couplers based on silicon slot-waveguide structures have received widespread attention in recent years. The key issues that need to be addressed are the size and loss of such devices. This study introduces a 1 × 3 silicon-based slot-waveguide multimode interference power splitter. The device uses a gallium-nitride slot-waveguide structure to reduce the length of the coupling region and decrease additional losses. To reduce the width of the coupling region, the multimode interference coupling area is designed with a parabolic-shaped structure. The introduction of a tapered structure between the input/output waveguides and the coupling region improves additional losses and non-uniformity. Furthermore, we conducted an analysis of the fabrication tolerances of the coupling region. In this paper, we use mode solution to simulate the design of the device in the 1550 nm optical wavelength range. The eigenmode expansion method is used to simulate and optimize the parameters of the device. The device is simulated using the eigenmode expansion solver. The simulation results show that the total length of the coupling region for the device is only 4 μm. The normalized transmission of the device is 0.992, and its excess loss and imbalance are 0.036 dB and 0.003 dB, respectively. The proposed power splitter can be applied to integrated optical circuit design, optical sensing, and optical power measurement.

Expression of the alfalfa gene MsMDHAR in Arabidopsis thaliana increases water stress tolerance.

The ascorbate-glutathione pathway plays an essential role in the physiology of vascular plants, particularly in their response to environmental stresses. This pathway is responsible for regulating the cellular redox state, which is critical for maintaining cell function and survival under adverse conditions. To study the involvement of the alfalfa monodehydroascorbate reductase (MsMDHAR) in water stress processes, Arabidopsis thaliana plants constitutively expressing the sequence encoding MsMDHAR were developed. Transgenic events with low and high MsMDHAR expression and ascorbate levels were selected for further analysis of drought and waterlogging tolerance. Under water stress, Arabidopsis transgenic plants generated higher biomass, produced more seeds, and had larger roots than wild type ones. This higher tolerance was associated with increased production of waxes and chlorophyll a at the basal level, greater stomatal opening and stability in regulating the relative water content and reduced H2O2 accumulation under stress conditions in transgenic plants. Overall, these results show that MsMDHAR is involved in plant tolerance to abiotic stresses. The data presented here also emphasises the potential of the MsMDHAR enzyme as a plant breeding tool to improve water stress tolerance.

Economic Impact Assessment of Structural Health Monitoring Systems on the Lifecycle of a Helicopter Blade

Structural Health Monitoring Systems (SHMS) are currently widely investigated in the literature, however, their application to the aerospace industry is still limited. One of the reasons lies in the lack of methods aimed at evaluating their economic impact on the lifecycle of the structural element to be monitored [1]. In this work the economic impact of FBG-based SHMS was evaluated on a composite helicopter rotor blade, considering two perspectives: Beginning Of Life (BOL), concerning the blade production, and Middle Of Life (MOL), concerning its usage. The processes were modeled using the IDEF0 methodology, which allowed deriving the cost models for two scenarios: the current one, and the one including the SHMS. In BOL, the SHMS was supposed providing support to the development of new composite rotor blades, including the curing cycle definition and certification tests. In MOL the SHMS was supposed performing automatic scheduled inspections coupled with the traditional ones. The cost model was implemented in the Probabilistic Damage Tolerance Analysis [2] to compare the scenarios having the same blade Probability Of Failure and considering the performances of the SHMS in terms of Probability Of Detection and Probability of False Alarm. Results show that an economic benefit may be achieved using the SHMS in the development of new blades, potentially reducing the number of blades tested and number of autoclave cycles. Moreover, it was found that the traditional scheduled detailed inspection intervals could be extended if automatic SHMS inspections are performed in addition, maintaining the same Probability Of Failure. [1] Büchter, K. D. et al. (2022). Modeling of an aircraft structural health monitoring sensor network for operational impact assessment. Structural Health Monitoring, 21(1), 208-224. [2] Lin, K. Y., & Styuart, A. V. (2007). Probabilistic approach to damage tolerance design of aircraft composite structures. Journal of Aircraft, 44(4), 1309-1317.

Method for the consideration of statistically distributed geometrical deviations in the design of cylindrical roller bearing arrangements

Rolling bearings are of great importance in all areas of mechanical engineering due to their precise and low-friction guidance of rotating components at low cost. The design of rolling bearing arrangements is usually based on approximately ideal geometries of bearings and adjacent parts on which the bearing seats are located. However, real components inevitably show statistically distributed deviations from their nominal shapes, which are limited by tolerances. Tight tolerances result in high manufacturing costs while on the other hand their expansion leads to an increase of occurring geometrical deviations which cause changes in the bearing-internal contact and load conditions and can thus impair the operating behavior of the bearing, e.g. with regard to fatigue life, frictional torque or vibration behavior. By taking these effects into account in the design stage, potential problems in operation can be identified early during development and countermeasures can be taken, e.g. by adjusting bearing and seat tolerances. This enables an improvement of overall product quality and a reduction of costs. This paper presents a method for the integration of component deviations in the computation of the fatigue life (Lnmr) and dynamic behavior of cylindrical roller bearing arrangements—both of which are crucial design criteria—based on a combination of statistical tolerance analysis and multi-body simulations. The method is applied to an exemplary use case for illustration.

Prospective study on stereotactic body radiotherapy for small pancreatic neuroendocrine tumors: tolerance and effectiveness analysis.

Surgery is the standard treatment for pancreatic neuroendocrine tumors (pNETs), obtaining favorable results but associating high morbidity and mortality rates. This study assesses stereotactic body radiation therapy (SBRT) as a radical approach for small (< 2cm) nonfunctioning pNETs. From January 2017 to June 2023, 20 patients with small pNETs underwent SBRT in an IRB-approved study. Endpoints included local control, tolerance, progression-free survival, and overall survival (OS). Diagnostic assessments comprised endoscopy, CT scans, OctreScan or PET-Dotatoc, abdominal MRI, and histological confirmatory samples. In a 30-month follow-up of 20 patients (median age 55.5years), SBRT was well-tolerated with no grade > 2 toxicity. 40% showed morphological response, 55% remained stable. Metabolically, 50% achieved significant improvement. With a median OS of 41.5months, all patients were alive without local or distant progression or need for surgical resection. SBRT is a feasible and well-tolerated approach for small neuroendocrine pancreatic tumors, demonstrating effective local control. Further investigations are vital for validation and extension of these findings.

Design of a zoom head-up display optical system based on a nodal aberration theory

We propose a zoom dual-path augmented reality head-up display optical system. The system uses two image generation units to display the basic and interactive information. Based on the node aberration theory, the aberration evaluation function was constructed. By solving the optimal solution of the aberration evaluation function, the initial structure of the interactive information display optical path was obtained. In order to solve the vergence-accommodation conflict in the process of vehicle speed change, the interactive information optical path was designed as a zoom optical path. The zoom distance is 10–20 m, and the basic information optical path will not be interfered with in the process. In addition, the tolerance analysis of the system was carried out to prove the machinability and stability of the system. This study makes the imaging of the augmented reality head-up display system more in line with the characteristics of the human eye and improves driving comfort.

Fault Tolerance Analysis and Optimization of Centralized Control Platform Based on Artificial Intelligence and Optimization Algorithm

To enhance the reliability and self-healing of the system, the research on fault tolerance of the reconfigurable modular centralized control center is its development trend. Most of the previous research has focused on hardware redundancy. Improving fault tolerance performance is an essential topic in the research of centralized control platforms. Firstly, the problem of centralized fault tolerance in the working configuration of a reconfigurable manipulator is studied. The effect of each hinge on fault tolerance in the existing configuration is studied with the criterion of manoeuvrability and tolerable space. The fault module was first modelled to represent the system architecture information. A modular motion rule based on autonomous recombination technology is proposed. A self-organizing deformation algorithm with fault tolerance is studied. The fault tolerance of the motion pairs is compensated by adding a small number of motion pairs to ensure the configuration characteristics. With the addition of a failure compensation device, the joint’s range of motion was reduced, and the fault tolerance rate was enhanced. After the failure of the robot arm, the fault tolerant control method can still ensure that the robot arm can perform work in its tolerable working space. The test results show that the fault tolerance analysis method is practical and feasible. It lays a theoretical foundation for the application in aerospace, industry and other fields.

A Lung-Expressing mRNA Delivery Platform with Tunable Activity in Hypoxic Environments.

Messenger RNA (mRNA) delivery platforms often facilitate protein expression in the liver following intravenous injection and have been optimized for use in normally oxygenated cells (21% O2 atmosphere). However, there is a growing need for mRNA therapy in diseases affecting non-liver organs, such as the lungs. Additionally, many diseases are characterized by hypoxia (<21% O2 atmosphere), a state of abnormally low oxygenation in cells and tissues that can reduce the efficacy of mRNA therapies by upwards of 80%. Here, we report a Tunable Lung-Expressing Nanoparticle Platform (TULEP) for mRNA delivery, whose properties can be readily tuned for optimal expression in hypoxic environments. Briefly, our study begins with the synthesis and characterization of a novel amino acrylate polymer that can be effectively complexed with mRNA payloads into TULEPs. We study the efficacy and mechanism of mRNA delivery using TULEP, including analysis of the cellular association, endocytosis mechanisms, endosomal escape, and protein expression in a lung cell line. We then evaluate TULEP under hypoxic conditions and address hypoxia-related deficits in efficacy by making our system tunable with adenosine triphosphate (ATP). Finally, we conclude our study with an in vivo analysis of mRNA expression, biodistribution, and tolerability of the TULEP platform in mice. In presenting these data, we hope that our work highlights the utility of TULEPs for tunable and effective mRNA delivery while more broadly highlighting the utility of considering oxygen levels when developing mRNA delivery platforms.

Stochastic evaluation of quasi-zero stiffness magnetic spring using a reluctance-corrected analytical model

—In state of the art high-precision motion systems, which utilize magnetic levitation, a quasi-zero stiffness gravity compensation is one of the essentials to improve dynamic performance, eliminate position dependency and thus simplify controller design. Special configurations of permanent magnets, such as Halbach magnet arrays, can realize magnetic levitation as a form of magnetic spring. However, unlike conventional permanent magnet machines with large stiffness, the quasi-zero stiffness magnetic spring requires higher modeling accuracy for force estimation, which is affected by the nonlinear reluctance effect of permanent magnets. In this study, we propose an accurate magnetic modeling method for the quasi-zero stiffness magnetic spring. By correcting the reluctance effect of magnets, the proposed magnetic model achieves superior accuracy estimating levitation force and stiffness to the conventional surface current model. Using the reluctance-corrected magnetic model, tolerance analysis was performed to identify dominant geometric parameters affecting the uncertainty of the Halbach array magnetic spring performance. A Monte-Carlo simulation was used to estimate the overall tolerance of magnetic forces and stiffness. The experimental results fit in the tolerances.

Use of hydroponics-based evaluation for phenotyping tolerance/susceptibility to the aphid, Uroleucon compositae and inheritance analysis of aphid tolerance in a global germplasm collection of Carthamus tinctorius L. (Safflower).

The online version contains supplementary material available at 10.1007/s12298-024-01467-0.

Tolerance analysis of slat gear rotary actuator in civil aircraft

Abstract The slat gear rotary actuator of civil aircraft needs to meet the requirements of small space and large transmission ratio. The planetary gear system based on triple teeth is a common actuator design, and the design structure is complex, so its tolerance control is also strict. In order to meet the design requirements of its internal structure, this paper presents a deviation analysis method for the internal structure design of a typical civil aircraft slat gear rotary actuator. The results of preliminary tolerance distribution and improved tolerance distribution are analyzed using the Jacobi-based assembly deviation model. By comparing the standard deviation of the analysis results, the validity of this deviation analysis method is verified, which proves that this method can be used to analyze the internal structure deviation of the rotary actuator of slat gear in civil aircraft.

Meta-QTL and Candidate Gene Analyses of Agronomic Salt Tolerance and Related Traits in an RIL Population Derived from Solanum pimpinellifolium.

Breeding salt-tolerant crops is necessary to reduce food insecurity. Prebreeding populations are fundamental for uncovering tolerance alleles from wild germplasm. To obtain a physiological interpretation of the agronomic salt tolerance and better criteria to identify candidate genes, quantitative trait loci (QTLs) governing productivity-related traits in a population of recombinant inbred lines (RIL) derived from S. pimpinellifolium were reanalyzed using an SNP-saturated linkage map and clustered using QTL meta-analysis to synthesize QTL information. A total of 60 out of 85 QTLs were grouped into 12 productivity MQTLs. Ten of them were found to overlap with other tomato yield QTLs that were found using various mapping populations and cultivation conditions. The MQTL compositions showed that fruit yield was genetically associated with leaf water content. Additionally, leaf Cl- and K+ contents were related to tomato productivity under control and salinity conditions, respectively. More than one functional candidate was frequently found, explaining most productivity MQTLs, indicating that the co-regulation of more than one gene within those MQTLs might explain the clustering of agronomic and physiological QTLs. Moreover, MQTL1.2, MQTL3 and MQTL6 point to the root as the main organ involved in increasing productivity under salinity through the wild allele, suggesting that adequate rootstock/scion combinations could have a clear agronomic advantage under salinity.

Power Enhancement and Spot Homogenization Design for Arrayed Semiconductor Lasers.

Improving the spot brightness and uniformity of arrangement of the array laser is conducive to ensuring the beam quality of the fiber laser. Based on the light tracing principle, the optical model performance of two common fiber lasers was first analyzed. Then, a novel rotationally polarized optical model with high power and spot uniformity was designed and optimized on the basis of the aforementioned analysis. The results of the evaluation metrics of the multi-indicator optical model show that the spot uniformity of our proposed model improved by 24.03%, the power improved by 0.55%, and the maximum light distance was shortened from 120 mm to 82.58 mm. Further, the results of the coupling tolerance analysis of the optical elements show that the total coupling efficiency was 89.04%. The coupling power and tolerance relationships did not produce degradation compared with the traditional model. Extensive comparative results show that the designed rotationally polarized optical path model can effectively improve the optical coupling efficiency and spot uniformity of arrayed semiconductor lasers.

Isolation, identification, and tolerance analysis of yeast during the natural fermentation process of Sidamo coffee beans.

Yeast, which plays a pivotal role in the brewing, food, and medical industries, exhibits a close relationship with human beings. In this study, we isolated and purified 60 yeast strains from the natural fermentation broth of Sidamo coffee beans to screen for indigenous beneficial yeasts. Among them, 25 strains were obtained through morphological characterization on nutritional agar medium from Wallerstein Laboratory (WL), with molecular biology identifying Saccharomyces cerevisiae strain YBB-47 and the remaining 24 yeast strains identified as Pichia kudriavzevii. We investigated the fermentation performance, alcohol tolerance, SO2 tolerance, pH tolerance, sugar tolerance, temperature tolerance, ester production capacity, ethanol production capacity, H2S production capacity, and other brewing characteristics of YBB-33 and YBB-47. The results demonstrated that both strains could tolerate up to 3% alcohol by volume at a high sucrose mass concentration (400g/L) under elevated temperature conditions (40 ℃), while also exhibiting a remarkable ability to withstand an SO2 mass concentration of 300g/L at pH 3.2. Moreover, S. cerevisiae YBB-47 displayed a rapid gas production rate and strong ethanol productivity. whereas P. kudriavzevii YBB-33 exhibited excellent alcohol tolerance. Furthermore, this systematic classification and characterization of coffee bean yeast strains from the Sidamo region can potentially uncover additional yeasts that offer high-quality resources for industrial-scale coffee bean production.

QTL analysis of low-temperature tolerance in maize germination by SLAF-seq and BSA technique

BackgroundCold damage of maize during germination is a global problem; it occurs frequently in northeast China, and leads to a large-scale reduction in yield. Low temperature tolerance of maize in germination is a complex quantitative trait controlled by multigenes, and no major QTLs or key genes have been identified. ResultsAn F2 isolation population with S319 and R144 as parents was constructed. The bulked segregant analysis (BSA) and specific-locus amplified fragment-sequencing (SLAF-seq) methods were applied to locate the chromosomal association regions related to low-temperature tolerance of maize during germination. Sequencing obtained 221.72 Gbp clean data, with an average sequencing depth of 25.96X. Four candidate regions associated with low-temperature tolerance trait of maize in germination were obtained, with a total length of 25.71 Mb and 1513 annotated genes, including 456 nonsynonymous mutant genes and 111 frameshift mutant genes. ConclusionsThis study aimed to lay the foundation for the mining of candidate genes of low-temperature tolerance in maize during germination, and accelerate the process of targeted improvement of maize low-temperature tolerance molecular marker-assisted breeding.How to cite: Yu T, Zhang J, Cao J, et al. QTL analysis of low temperature tolerance in maize germination by SLAF-seq and BSA technique. Electron J Biotechnol 2024;70. https://doi.org/10.1016/j.ejbt.2024.04.003.

Balanced travelling-wave parametric amplifiers for practical applications

The development of superconducting travelling-wave parametric amplifiers (TWPAs) over the past decade has highlighted their potential as low-noise amplifiers for use in fundamental physics experiments and industrial applications. However, practical challenges, including signal-idler contamination, complex pump injection and cancellation, impedance mismatch, and the reciprocal nature of the device, have made it challenging to deploy TWPAs in real-world applications. In this paper, we introduce an innovative solution to these issues through phase-controlled balanced-TWPA architectures. These architectures involve placing two TWPAs in parallel between a pair of broadband couplers. By carefully controlling the phases of the tones propagating along the TWPAs, we can effectively separate the signal and idler tones, as well as the pump(s), using a straightforward injection and cancellation mechanism. The balanced-TWPA architecture offers versatility and flexibility, as it can be reconfigured either intrinsically or externally to suit different application needs. In this manuscript, we provide a comprehensive discussion of the working principles of the balanced-TWPA, including various configurations designed to meet diverse application requirements. We also present the expected gain-bandwidth products in comparison to traditional TWPAs and conduct tolerance analysis to demonstrate the feasibility and advantages of the balanced-TWPA architecture. By addressing the practical challenges associated with TWPAs, the balanced-TWPA architecture represents a promising advancement in the field, offering a more practical and adaptable solution for a wide range of applications.

Comparative stress physiological analysis of aluminium stress tolerance of indigenous maize (Zea mays L.) cultivars of eastern Himalaya

Yield potential of maize having distinct genetic diversity in Eastern Himalayan Region (EHR) hill ecologies is often limited by Al toxicity caused due to soil acidity. Stress physiological analysis of local check exposed to 0–300 μM Al under sand culture revealed that 150 μM Al as critical and 200 μM Al as tolerable limit. Increase in Al from 0 to 300 μM reduced total chlorophyll, carotenoids by 74.8 % and 44.7 % respectively and enhanced anthocyanin by 35.3 % whereas LA, SLW and SL have reduced by 81.3%, 21.3 % and 47.8 % respectively. R/S ratio was 51.0 and 13.7 % higher at lower Al levels (50 μM and 100 μM) and photosynthetic, transpiration rate and TDM were 62.5 %, 42.9 % and 78.6 % lower at higher Al (300 μM) as compared to control. TRL, RSA, RDW and RV at higher Al (300 μM) were 92.6 %, 98.7 %, 78.7 and 97.5 % lower over control respectively. Root and shoot Al and PUpE at higher Al (300 μM) was 194.0, 69.2 and 830 % higher whereas PUE decreased to 88.5 % over control. Evaluation of 31 indigenous maize cultivars at 0, 150, and 250 μM Al in sand culture, alongside tolerance scoring and assessment, revealed that Megha-9, Megha-10, and MZM-19 exhibits high Al tolerance, Megha-1, MZM-22, and MZM-42 demonstrated moderate tolerance, whereas Uruapara, Sublgarh, and BRL Para were identified as Al-sensitive. Stress physiological parameters like SDW, TDM, TRL, SL and LA contributed 46.02 % of variability to PC1, whereas A, RV, RSA, anthocyanin and Chlorophyll_b, contributed 13.56 % of variability to PC2. Highest values of CMS, SL, LP, LA, TRL and anthocyanin were recorded in cluster I having sensitive cultivars while highest CMS, SL, LA, LP, TRL and RSA were found in cluster II having moderately tolerant cultivars and highest mean values for TRL, RSA, LP, LA, CMS and SL were recorded in cluster III having highly Al stress tolerant cultivars. The traits viz., A, RV, RSA, anthocyanin and Chlorophyll_b, total chlorophyll and TDM were emanated as physio-morphological for assessing Al toxicity stress tolerance in Maize with high divergence values. Tolerant cultivars showing 63.4 % and 22.4 % higher anthocyanin at 150 μM Al and 250 μM Al than moderately tolerant one in acid soil experiment with increased root Al, shoot Al, root P and shoot P by 42.6 %, 11 %, 95.1 % and 34 % respectively were emerged as promising for novel maize improvement under acid soils of EHR.

Design, analysis, and manufacturing of a glass-plastic hybrid minimalist aspheric panoramic annular lens

We propose a high-performance glass-plastic hybrid minimalist aspheric panoramic annular lens (ASPAL) to solve several major limitations of the traditional panoramic annular lens (PAL), such as large size, high weight, and complex system. The field of view (FoV) of the ASPAL is 360° × (35° ∼ 110°) and the imaging quality is close to the diffraction limit. This large FoV ASPAL is composed of only 4 lenses. Moreover, we establish a physical structure model of PAL using the ray tracing method and study the influence of its physical parameters on compactness ratio. In addition, for the evaluation of local tolerances of annular surfaces, we propose a tolerance analysis method suitable for ASPAL. This analytical method can effectively analyze surface irregularities on annular surfaces and provide clear guidance on manufacturing tolerances for ASPAL. Benefiting from high-precision glass molding and injection molding aspheric lens manufacturing techniques, we finally manufactured 20 ASPALs in small batches. The weight of an ASPAL prototype is only 8.5 g. Our framework provides promising insights for the application of panoramic systems in space and weight-constrained environmental sensing scenarios such as intelligent security, micro-UAVs, and micro-robots.

1964: Prostate Cancer ultra-hypofractionation: single-center late tolerance analysis, two-years data

1964: Prostate Cancer ultra-hypofractionation: single-center late tolerance analysis, two-years data