Search Results (60)

Background: Autism spectrum disorder (ASD) is a common condition with substantial personal and financial burdens of lifelong implication. Multiple twin studies have confirmed a genetic or inherited component at ~80%, higher than any other common condition. However, ASD’s rapidly accelerating prevalence, now at 1 in 31 in the USA, appears to defy a predominantly genetic basis and implicate our rapidly changing environment. A potential explanation for this paradox is a recent increase in de novo variants (DNVs), which are “new” mutations present in the patient yet absent in both parents. The present authors recently reported using trio whole-genome sequencing (trio-WGS) that DNVs highly likely to be highly disease-associated (“Principal Diagnostic Variants”, PDVs), mostly missense variants, were present in (25/50) 50% of the ASD patients clinically evaluated by our team. Methods: The current study was designed to support this observation with trio-WGS in 100 additional unrelated ASD patients. Results: De novo PDVs were identified in 47/100 (47%) of cases, in close approximation to our previous work. Using non-transcribed (up and downstream) variants for all genes as a control group, these DNV-PDVs were far more likely (p < 0.0001, OR 5.8, 95% C.I. 2.9–11) to be in SFARI-listed genes associated with ASD. Consistent with the emerging polygenic model, using the same analyses, inherited missense variants were also associated with ASD (p < 0.0001). Highly unexpectedly, silent variants, both inherited (p < 0.0001) and de novo (p < 0.007), were also statistically associated with ASD, and, among inherited variants, silent variants were more associated with ASD than were missense variants (p < 0.0001). Adding silent DNVs as PDVs increases the proportion of our subjects with at least one DNV-PDV to 55% of the subjects. Conclusions: Our proposed model for ASD, with prominent DNVs in most that are genetic yet not inherited, predicts the known predominant genetic pathogenesis and the accelerating prevalence of ASD, possibly from environmental factors, including insufficient nutrients and toxicant exposures, and/or the disrupted folate metabolism known to be associated with ASD. Limitations to this study include predominant inclusion of severely affected individuals and the lack of an unaffected control group and functional validation of variant pathogenicity. Full article

In order to correctly measure the shock wave pressure generated by a near-field explosion, and while considering the limitations of the measurement and calibration method of the current bar pressure sensor, an improved shock wave pressure measurement method was designed based on a bar pressure sensor combined with photon Doppler velocimetry (PDV) and strain measurement. By measuring the strain on the pressure bar and the particle velocity on the rear-end face, the shock wave pressure applied on the front-end face of the pressure bar was calculated based on one-dimensional stress wave theory. On the other hand, a calibration method was designed to validate the reliability of the test system. Based on the split-Hopkinson pressure bar (SHPB) loading experiment, the transmission characteristics of stress wave in the bar and the accuracy of the system test results were verified. The results indicated that the stress wave measurement results were consistent with the one-dimensional elementary theoretical calculation results of stress wave propagation in different wave-impedance materials, and the peak deviation measured by PDV and strain measurement method was less than 1.5%, which proved the accuracy of the test method and the feasibility of the calibration method. Full article

Plastid division regulatory genes play a crucial role in the morphogenesis of chloroplasts and amyloplasts. Chloroplasts are the main sites for photosynthesis and metabolic reactions, while amyloplasts are the organelles responsible for forming and storing starch granules. The proper division of chloroplasts and amyloplasts is essential for plant growth and yield maintenance. Therefore, this study aimed to examine the J175 (FtsZ2-2) gene, cloned from an ethyl methanesulphonate (EMS) mutant involved in chloroplast and amyloplast division in maize, through map-based cloning. We found that J175 encodes a cell division protein, FtsZ (filamentous temperature-sensitive Z). The FtsZ family of proteins is widely distributed in plants and may be related to the division of chloroplasts and amyloplasts. The J175 protein is localized in plastids, and its gene is expressed across various tissues. From the seedling stage, the leaves of the j175 mutant exhibited white stripes, while the division of chloroplasts was inhibited, leading to a significant increase in volume and a reduction in their number. Measurement of the photosynthetic rate showed a significant decrease in the photosynthetic efficiency of j175. Additionally, the division of amyloplasts in j175 grains at different stages was impeded, resulting in irregular polygonal starch granules. RNA-seq analyses of leaves and kernels also showed that multiple genes affecting plastid division, such as FtsZ1, ARC3, ARC6, PDV1-1, PDV2, and MinE1, were significantly downregulated. This study demonstrates that the maize gene j175 is essential for maintaining the division of chloroplasts and amyloplasts and ensuring normal plant growth, and provides an important gene resource for the molecular breeding of maize. Full article

Viral infections in stone fruit crops cause substantial economic losses across all sectors of production. Despite their significance, viruses affecting stone fruits remain under-investigated in Kazakhstan. Among these, plum pox virus (PPV, genus Potyvirus, family Potyviridae), commonly known as Sharka, is the most critical viral pathogen worldwide, severely threatening the sustainable cultivation of stone fruits and posing risks to food security. This study aimed to evaluate virus management strategies in stone fruit crops to facilitate the production of healthy planting material from valuable genotypes. Field surveys were conducted in plum and apricot orchards located in the Almaty region (Southeast Kazakhstan) and the Saryagash region (Southern Kazakhstan). Plant samples were tested for the presence of the following viruses: apple chlorotic leaf spot virus (ACLSV), apple mosaic virus (ApMV), PPV, prune dwarf virus (PDV), prunus necrotic ringspot virus (PNRSV), cherry green ring mottle virus (CGRMV), and myrobalan latent ringspot virus (MLRSV). Real-time RT-PCR diagnostics confirmed the presence of PPV in the ‘Stanley’ and ‘Ansar’ cultivars and Prunus armeniaca genotypes, while both PPV and ACLSV were detected in the ‘Ayana’ variety. Chemotherapy (Ribavirin), thermotherapy, cryotherapy, and shoot apical meristem (SAM) culture, both individually and in combination, were used to eliminate viruses and regenerate virus-free plants. Successful virus eradication was achieved for PPV and ACLSV. However, the ‘Stanley’ and ‘Ansar’ cultivars did not survive the treatment process, likely due to high thermo- or cryo-sensitivity. As a result of this research, an in vitro collection of virus-free plants was established, comprising eight rootstocks, six plum cultivars, and three apricot genotypes. Full article

This paper explores the use of explainable artificial intelligence (XAI) techniques in actuarial science to address the opacity of advanced machine learning models in financial contexts. While technological advancements have enhanced actuarial models, their black box nature poses challenges in highly regulated environments. This study proposes a protocol for selecting and applying XAI techniques to improve interpretability, transparency, and regulatory compliance. It categorizes techniques based on origin, target, and interpretative capacity, and introduces a protocol to identify the most suitable method for actuarial models. The proposed protocol is tested in a case study involving two classification algorithms, gradient boosting and random forest, with accuracy of 0.80 and 0.79, focusing on two explainability objectives. Several XAI techniques are analyzed, with results highlighting partial dependency variance (PDV) and local interpretable model-agnostic explanations (LIME) as effective tools for identifying key variables. The findings demonstrate that the protocol aids in model selection, internal audits, regulatory compliance, and enhanced decision-making transparency. These advantages make it particularly valuable for improving model governance in the financial sector. Full article

To investigate the energy transfer mechanisms during the micro-explosive initiator-driven flyer process and to guide the performance evaluation of micro-sized charges and the structural design of micro-initiators, a combined approach of numerical simulations and experimental tests was employed to study the detonation process of copper-based azide micro-charges driving a flyer. The output pressure and detonation velocity of the copper-based azide micro-charge were measured using the manganese–copper piezoresistive method and electrical probe technique, and the corresponding JWL equation of the state parameters was subsequently fitted. A simulation model for the micro-charge-driven flyer was established and validated using Photonic Doppler Velocimetry (PDV), and the influence of charge conditions, structural parameters, and other factors on the flyer velocity and morphology was investigated. The results indicate that the flyer velocity decreases as its thickness increases, whereas the specific kinetic energy of the flyer initially increases and then decreases with increasing thickness. The optimal flyer thickness was found to be in the range of 30 to 70 μm. The flyer velocity increases with the density and height of the micro-charge; however, when the micro-charge density exceeds a certain threshold, the flyer velocity decreases. The flyer velocity exhibits an exponential decline as the diameter of the acceleration chamber increases, whereas it shows a slight increase with the increase in the length of the acceleration chamber. The diameter of the acceleration chamber should not exceed the charge diameter and must be no smaller than the critical diameter required for detonation initiation of the underlying charge. The use of a multi-layer accelerating chamber structure leads to a slight reduction in flyer velocity and further increases in the transmission hole diameter while having no significant impact on the flyer velocity. Full article

A Pd-decorated V₂O₅/porous silicon (Pd-V₂O₅/PSi) composite was synthesized via magnetron sputtering for enhanced NO₂ gas sensing. The material’s morphology and composition were systematically characterized, and its gas sensing performance was evaluated through comprehensive experimental measurements and first-principles calculations. The decoration of Pd nanoparticles significantly improved the sensing capabilities of the V₂O₅/PSi composite, particularly enhancing sensitivity and response/recovery characteristics. Experimental results revealed a 3.1-fold increase in response to specific NO₂ concentrations (ppm level) compared to the undecorated V₂O₅/PSi sensor. The composite exhibited rapid NO₂ response at room temperature with excellent selectivity, reproducibility, and long-term stability. First-principles calculations elucidated the structural, electronic, and adsorption properties of the Pd-V₂O₅/PSi composite, uncovering the gas sensing mechanism in NO₂ environments. This combined experimental and theoretical study provides valuable insights for developing advanced gas sensors and lays a foundation for optimizing metal oxide-based sensing materials. Full article

Background: Women with a familial predisposition to breast cancer (BC) are offered screening at earlier ages and more frequently than women from the general population. Methods: We evaluated the effect of screening mammography in 1552 BC cases with a hereditary predisposition to BC unexplained by BRCA1 or BRCA2 and 1363 unrelated controls. Participants reported their lifetime mammography exposures in a detailed questionnaire. Germline rare deleterious or predicted deleterious variants (D-PDVs) in 113 DNA repair genes were investigated in 82.5% of the women and classified according to the strength of their association with BC. Genes with an odds ratio (OR) < 0.9 was assigned to the Gene Group “Reduced”, those with OR ≥ 0.9 and ≤1.1 to Group “Independent”, and those with OR > 1.1 to Group “Increased”. Results: Overall, having been exposed to mammograms (never vs. ever) was not associated with BC risk. However, an increase in BC risk of 4% (95% CI: 1–6%) per additional exposure was found under the assumption of linearity. When grouped according to D-PDV carrier status, mammograms doubled the BC risk of women carrying a D-PDV in Group “Reduced”, as compared to those carrying a D-PDV in Group “Increased”. Conclusions: Our study is the first to investigate the joint effect of mammogram exposure and variants in DNA repair genes other than BRCA1 and BRCA2 in women at high risk of BC; therefore, further studies are needed to verify our findings. Even though mammographic screening reduces the risk of mortality from BC, the identification of populations that are more or less susceptible to ionizing radiation may be clinically relevant. Full article

“GiSelA 17” (Prunus canescens × Prunus avium) is a novel cherry clonal rootstock with the ability to bear fruit early and resist replant situations, and it has a high tolerance to the menaces of Prunus dwarf virus (PDV) and Prunus necrotic ring spot virus (PNRSV). In this study, two kinds of explants were taken, i.e., shoot tip (E1) (10 mm) and nodal segment (E2) (15 mm) explants. Five different sterilant regimes using sodium hypochlorite, mercuric chloride, and ethyl alcohol were employed to assess surface sterilization. Two types of media, namely Murashige and Skoog (MS) and Woody Plant Medium (WPM), and twelve and six plant growth regulator combinations with benzyl amino purine (BAP) and indole-3-butyric acid (IBA) were used, respectively, for the establishment and proliferation steps. The results show that maximum culture asepsis (75.33%) was obtained with shoot tips (E1) using 0.05% HgCl₂ for 5 min + 70% ethanol for 10 s (S4), and maximum explant survival (80.33%) was observed in 0.1% HgCl₂ for 5 min (S1) for shoot tips (E1). The maximum establishment rate (83.33%) was found in shoot tips (E1) in MS medium with BAP + IBA (1 + 0.01 mg/L) during the establishment step, with a maximum proliferation rate of 92.00% obtained in MS and BAP (0.75 mg/L). Inferior establishment results (26.66%) were obtained in nodal segments (E2) using WPM and BAP + IBA (1.50 + 0.01 mg/L), with a low proliferation rate (68.66%) in WPM and BAP + IBA (0.25 + 0.01 mg/L). Nonetheless, our research is the first in vitro study on “GiSelA 17” rootstock that focuses on generating the best quality planting material for commercial cherry production. Full article

Small-scale impact welding may have several advantages over rivets: the strength can be higher, it can be applied right at the edges in lap joints, and it can be lighter and more easily installed if simple systems can be developed. Laser Impact Welding (LIW) is compact and simple, adapting the technologies of laser shock peening. It is limited in terms of the energy that can be delivered to the joint. Augmented Laser Impact Welding (ALIW) complements optical energy with a small volume of an exothermic detonable compound and has been shown to be an effective welding approach. The scope of this study is extended to build upon previous work by investigating varied augmentation chemistries and confinement layers, specifically borosilicate glass, sapphire, and water. The evaluation of these compositions involved the use of two aluminum alloys: Al 2024 and Al 6061. Photonic Doppler Velocimetry (PDV) was utilized to measure the flyer velocity and assess the detonation energy. The findings indicated that adding micro-air bubbles (GPN-3 scenario) to the original GPN-1 enhanced the flyer velocity by improving the sensitivity, which promoted gas release during detonation. Hence, employing 1 mm thick Al 2024 as a flyer with GPN-3 enhances the flyer velocity by 36.4% in comparison to GPN-1, thereby improving the feasibility of using 1 mm thick material as a flyer and ensuring a successful welded joint with the thickest flyer ever welded with laser impact welding. When comparing the confinement layers, sapphire provided slightly lower flyer velocities compared to borosilicate glass. However, due to its higher resistance to damage and fracture, sapphire is likely more suitable for industrial applications from an economic perspective. Furthermore, the lap shear tests and microstructural evaluations confirmed that GPN-3 provided higher detonation energy, as emphasized by the tendency of the interfacial waves to have a higher amplitude than the less pronounced waves of the original GPN-1. Consequently, this approach demonstrates the key characteristics of a practical process, being simple, cost-effective, and efficient. Full article

Sensitization to cross-reactive allergens complicates identifying the culprit insect in Hymenoptera venom allergy via diagnostic tests. This study evaluates sensitization to hyaluronidases (Api m 2 from honey bee (Apis mellifera) venom, HBV; Pol d 2 from European paper wasp (Polistes dominula) venom, PDV; and Ves v 2.0101 and Ves v 2.0201 from yellow jacket (Vespula vulgaris) venom, YJV) and their cross-reactivity in allergic patients from Italy, Spain, and Germany using ImmunoCAPs, ELISA, and basophil activation tests. Sensitization rates were 45% for Api m 2 in HBV-allergic subjects, 25% for Pol d 2 in PDV-allergic individuals, and 20% and 10% for Ves v 2.0201 and Ves v 2.0101 in YJV-allergic patients, respectively. Patients primarily sensitized to Api m 2 showed minimal cross-reactivity to vespid hyaluronidases, whereas those primarily sensitized to Pol d 2 or Ves v 2.0201 exhibited IgE reactivity to Api m 2. Neither Pol d 2 nor Ves v 2.0201 triggered basophil activation. Cross-reactivity of Api m 2, Pol d 2, and Ves v 2.0201 depends on the primary sensitizing venom. Sensitization to Pol d 2 and Ves v 2.0201 remains below 25%, yet these patients may exhibit cross-reactivity to Api m 2. Conversely, HBV-allergic patients sensitized to Api m 2 show minimal reactivity to Pol d 2 or Ves v 2.0201. Full article

Commercially cultivated Prunus species are commonly grown in adjacent or mixed orchards and can be infected with unique or commonly shared viruses. Apple (Malus domestica), another member of the Rosacea and distantly related to Prunus, can share the same growing regions and common pathogens. Pollen can be a major route for virus transmission, and analysis of the pollen virome in tree fruit orchards can provide insights into these virus pathogen complexes from mixed production sites. Commercial honey bee (Apis mellifera) pollination is essential for improved fruit sets and yields in tree fruit production systems. To better understand the pollen-associated virome in tree fruits, metagenomics-based detection of plant viruses was employed on bee and pollen samples collected at four time points during the peak bloom period of apricot, cherry, peach, and apple trees at one orchard site. Twenty-one unique viruses were detected in samples collected during tree fruit blooms, including prune dwarf virus (PDV) and prunus necrotic ringspot virus (PNRSV) (Genus Ilarvirus, family Bromoviridae), Secoviridae family members tomato ringspot virus (genus Nepovirus), tobacco ringspot virus (genus Nepovirus), prunus virus F (genus Fabavirus), and Betaflexiviridae family member cherry virus A (CVA; genus Capillovirus). Viruses were also identified in composite leaf and flower samples to compare the pollen virome with the virome associated with vegetative tissues. At all four time points, a greater diversity of viruses was detected in the bee and pollen samples. Finally, the nucleotide sequence diversity of the coat protein regions of CVA, PDV, and PNRSV was profiled from this site, demonstrating a wide range of sequence diversity in pollen samples from this site. These results demonstrate the benefits of area-wide monitoring through bee pollination activities and provide new insights into the diversity of viruses in tree fruit pollination ecosystems. Full article

American plum line pattern virus (APLPV) is the most infrequently reported Ilarvirus infecting stone fruit trees and is of sufficient severity to be classified as an EPPO quarantine A1 pathogen. In late spring, yellow line pattern symptoms were observed on leaves in a few flowering cherries (Prunus serrulata Lindl.) grown in a public garden in Northwest Italy. RNA extracts from twenty flowering cherries were submitted to Ilarvirus multiplex and APLPV-specific RT-PCR assays already reported or developed in this study. One flowering cherry (T22) with mixed prunus necrotic ringspot virus (PNRSV) and prune dwarf virus (PDV) infection also showed infection with APLPV. Blastn analysis of PCR products of the full coat protein (CP) and movement protein (MP) genes obtained from flowering cherry T22 showed 98.23% and 98.34% nucleotide identity with reference APLPV isolate NC_003453.1 from the USA. Then, a LAMP-specific assay was designed to facilitate the fast and low-cost identification of this virus either in the laboratory or directly in the field. The developed assay allowed not only the confirmation of APLPV (PSer22IT isolate) infection in the T22 flowering cherry but also the identification of APLPV in an asymptomatic flowering cherry tree (TL1). The LAMP assay successfully worked with crude flowering cherry extracts, obtained after manually shaking a single plant extract in the ELISA extraction buffer for 3–5 min. The developed rapid, specific and economic LAMP assay was able to detect APLPV using crude plant extracts rather that RNA preparation in less than 20 min, making it suitable for in-field detection. Moreover, the LAMP assay proved to be more sensitive in APLPV detection in flowering cherry compared to the specific one-step RT-PCR assay. The new LAMP assay will permit the estimation of APLPV geographic spread in the territory, paying particular attention to surrounding gardens and propagated flowering cherries in ornamental nurseries. Full article

The Precision Time Protocol (PTP) plays a pivotal role in achieving precise frequency and time synchronization in computer networks. However, network delays and jitter in real systems introduce uncertainties that can compromise synchronization accuracy. Three clock skew estimators designed for the PTP scenario were obtained in our earlier work, complemented by closed-form approximations for the Mean Squared Error (MSE) under the generalized fractional Gaussian noise (gfGn) model, incorporating the Hurst exponent parameter (H) and the a parameter. These expressions offer crucial insights for network designers, aiding in the strategic selection and implementation of clock skew estimators. However, substantial computational resources are required to fit each expression to the gfGn model parameters (H and a) from the MSE perspective requirement. This paper introduces new closed-form estimates that approximate the MSE tailored to match gfGn scenarios that have a lower computational burden compared to the literature-known expressions and that are easily adaptable from the computational burden point of view to different pairs of H and a parameters. Thus, the system requires less substantial computational resources and might be more cost-effective. Full article

Out-of-stock prediction refers to the activity of forecasting the time when a product will not be available for purchase because of an inventory deficiency. Due to difficulties, out-of-stock forecasting models now face certain challenges. Incorrect demand forecasting may result in a lack or excess of goods in stock, a factor that affects client satisfaction and the profitability of companies. Accordingly, the new approach BCHO-TCN LightGBM, which is based on Buzzard Coney Hawk Optimization with a deep temporal convolutional neural network and the Light Gradient-Boosting Machine framework, is developed to deal with all challenges in the existing models in the field of out-of-stock prediction. The role that BCHO plays in the LightGBM-based deep temporal CNNis rooted in modifying the classifier to improve both accuracy and speed. Integrating BCHO into the model training process allows us to optimize and adjust the hyperparameters and the weights of the CNN linked with the temporal DNN, which, in turn, makes the model perform better in the extraction of temporal features from time-series data. This optimization strategy, which derives from the cooperative behaviors and evasion tactics of BCHO, is a powerful source of information for the computational optimization agent. This leads to a faster convergence of the model towards optimal solutions and therefore improves the overall accuracy and predictive abilities of the temporal CNN with the LightGBM algorithm. The results indicate that when using data from Amazon India’s product listings, the model shows a high degree of accuracy, as well as excellent net present value (NPV), present discounted value (PDV), and threat scores, with values reaching 94.52%, 95.16%, 94.81%, and 95.76%, respectively. Likewise, in a k-fold 10 scenario, the model achieves values of 94.81%, 95.60%, 96.28%, and 95.86% for the same metrics. Full article