Material modeling using modern numerical methods accelerates the design process and reduces the costs of developing new products. However, for multiscale modeling of heterogeneous materials, the ...well-established
homogenization techniques
remain
computationally expensive
for high accuracy levels. In this contribution, a machine learning approach, convolutional neural networks (CNNs), is proposed as a computationally efficient solution method that is capable of providing a high level of accuracy. In this work, the data-set used for the training process, as well as the numerical tests, consists of artificial/real microstructural images (“input”). Whereas, the output is the homogenized stress of a given representative volume element
RVE
. The model performance is demonstrated by means of examples and compared with traditional homogenization methods. As the examples illustrate, high accuracy in predicting the homogenized stresses, along with a significant reduction in the computation time, were achieved using the developed CNN model.
Sorghum damping-off, caused by Fusarium solani (Mart.) Sacc., is a serious disease which causes economic loss in sorghum production. In this study, antagonistic activity of lavender essential oil ...(EO) at 0.5, 0.75, 1.0, 1.25, 1.5, and 1.6% against F. solani was studied in vitro. Their effects on regulation of three SbWRKY transcription factors, the response factor JERF3 and eight defense-related genes, which mediate different signaling pathways, in sorghum were investigated. Effects of application under greenhouse conditions were also evaluated. The results showed that lavender EO possesses potent antifungal activity against F. solani. A complete inhibition in the fungal growth was recorded for lavender EO at 1.6%. Gas chromatography-mass spectrometric analysis revealed that EO antifungal activity is most likely attributed to linalyl anthranilate, α-terpineol, eucalyptol, α-Pinene, and limonene. Observations using transmission electron microscopy revealed many abnormalities in the ultrastructures of the fungal mycelium as a response to treating with lavender EO, indicating that multi-mechanisms contributed to their antagonistic behavior. Results obtained from Real-time PCR investigations demonstrated that the genes studied were overexpressed, to varying extents in response to lavender EO. However, SbWRKY1 was the highest differentially expressed gene followed by JERF3, which suggest they play primary role(s) in synchronously organizing the transcription-regulatory-networks enhancing the plant resistance. Under greenhouse conditions, treating of sorghum grains with lavender EO at 1.5% prior to infection significantly reduced disease severity. Moreover, the growth parameters evaluated, the activities of antioxidant enzymes, and total phenolic and flavonoid contents were all enhanced. In contrast, lipid peroxidation was highly reduced. Results obtained from this study support the possibility of using lavender EO for control of sorghum damping-off. However, field evaluation is highly needed prior to any usage recommendation.
MYC is one of the most important oncogenes and is overexpressed in the majority of cancers. G-Quadruplexes are noncanonical four-stranded DNA secondary structures that have emerged as attractive ...cancer-specific molecular targets for drug development. The G-quadruplex formed in the proximal promoter region of the MYC oncogene (MycG4) has been shown to be a transcriptional silencer that is amenable to small-molecule targeting for MYC suppression. Indenoisoquinolines are human topoisomerase I inhibitors in clinical testing with improved physicochemical and biological properties as compared to the clinically used camptothecin anticancer drugs topotecan and irinotecan. However, some indenoisoquinolines with potent anticancer activity do not exhibit strong topoisomerase I inhibition, suggesting a separate mechanism of action. Here, we report that anticancer indenoisoquinolines strongly bind and stabilize MycG4 and lower MYC expression levels in cancer cells, using various biochemical, biophysical, computer modeling, and cell-based methods. Significantly, a large number of active indenoisoquinolines cause strong MYC downregulation in cancer cells. Structure–activity relationships of MycG4 recognition by indenoisoquinolines are investigated. In addition, the analysis of indenoisoquinoline analogues for their MYC-inhibitory activity, topoisomerase I-inhibitory activity, and anticancer activity reveals a synergistic effect of MYC inhibition and topoisomerase I inhibition on anticancer activity. Therefore, this study uncovers a novel mechanism of action of indenoisoquinolines as a new family of drugs targeting the MYC promoter G-quadruplex for MYC suppression. Furthermore, the study suggests that dual targeting of MYC and topoisomerase I may serve as a novel strategy for anticancer drug development.
This study was conducted to provide comprehensive information on the anatomical and histological features of the upper (UL) and lower (LL) lips of Rahmani sheep by gross examination, morphometric ...analysis in addition to Light and scanning electron microscope (SEM). Samples from normal healthy adult male sheep heads were collected directly after slaughtering. UL and LL were dissected, and specimens were collected for both light and SEM. The UL was longer approximately by one‐fold and thicker by one‐fold at the median and the oral angle areas, and by one‐ and half‐folds at the paramedian area than the LL. The free border of both lips was characterized rostrally by the presence of labial projections. By SEM the edges of the inner aspect of the lips and of the philtrum were distinguished by labial projections. These projections which surrounding the philtrum subdivided into polygonal areas with numerous keratinized scales especially at the apical parts which increased dorsally toward the nostril. Most of the openings of the upper labial salivary glands were volcanic crater‐shaped while that of the lower labial salivary glands were various shapes; round folded margin, rosette and whirlpool shaped. Histologically, the shape of the projection or papillae differs at the median and paramedian areas of the UL than the LL. However, there was no differences near the oral angle area. In conclusion, the shape, size and amount of keratinization of the papillae may offer efficiency to the lips during feeding process.
The present study compared the morphology and histology of the UL and LL of Rahmani sheep. The UL was longer and thicker at the median, paramedian and oral angle areas than the LL.
By SEM, most of the openings of the upper labial salivary glands were volcanic crater‐shaped while the lower labial salivary glands were various in shapes; round folded margin, rosette and whirlpool shaped.
The Histological investigation revealed that the shape of the labial papillae differs at the median and paramedian areas of the UL than the LL.
Our results suggest a high level of functional adaptation in Rahmani sheep to their diet. These adaptations may paly essential role in increase the efficiency of food intake and protection of oral mucosa.
Microorganisms living inside plants can promote plant growth and health, but their genomic and functional diversity remain largely elusive. Here, metagenomics and network inference show that fungal ...infection of plant roots enriched for Chitinophagaceae and Flavobacteriaceae in the root endosphere and for chitinase genes and various unknown biosynthetic gene clusters encoding the production of nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs). After strain-level genome reconstruction, a consortium of
and
was designed that consistently suppressed fungal root disease. Site-directed mutagenesis then revealed that a previously unidentified NRPS-PKS gene cluster from
was essential for disease suppression by the endophytic consortium. Our results highlight that endophytic root microbiomes harbor a wealth of as yet unknown functional traits that, in concert, can protect the plant inside out.
Periodic truss-based lattice materials, a particular subset of cellular solids that generally have superior specific properties as compared to monolithic materials, offer regularity and ...predictability that irregular foams do not. Significant advancements in alternative technologies-such as additive manufacturing-have allowed for the fabrication of these uniquely complex materials, thus boosting their research and development within industries and scientific communities. However, there have been limitations in the comparison of results for these materials between different studies reported in the literature due to differences in analysis approaches, parent materials, and boundary and initial conditions considered. Further hindering the comparison ability was that the literature generally only focused on one or a select few topologies. With a particular focus on the crashworthiness of lattice topologies, this paper presents a comprehensive study of the impact performance of 24 topologies under dynamic impact loading. Using steel alloy parent material (manufactured using Selective Laser Melting), a numerical study of the impact performance was conducted with 16 different impact energy-speed pairs. It was possible to observe the overarching trends in crashworthiness parameters, including plateau stress, densification strain, impact efficiency, and absorbed energy for a wide range of 3D lattice topologies at three relative densities. While there was no observed distinct division between the results of bending and stretching topologies, the presence of struts aligned in the impact direction did have a significant effect on the energy absorption efficiency of the lattice; topologies with struts aligned in that direction had lower efficiencies as compared to topologies without.
Hypoalbuminemia (HA) is frequently observed in systemic inflammatory diseases and in liver disease. However, the influence of HA on the pharmacokinetics and toxicity of compounds with high plasma ...albumin binding remained insufficiently studied. The ‘
lack-of-delivery-concept
’ postulates that HA leads to less carrier mediated uptake of albumin bound substances into hepatocytes and to less glomerular filtration; in contrast, the ‘
concept-of-higher-free-fraction
’ argues that increased concentrations of non-albumin bound compounds facilitate hepatocellular uptake and enhance glomerular filtration. To address this question, we performed intravital imaging on livers and kidneys of anesthetized mice to quantify the spatio-temporal tissue distribution of the mycotoxin ochratoxin A (OTA) based on its auto-fluorescence in albumin knockout and wild-type mice. HA strongly enhanced the uptake of OTA from the sinusoidal blood into hepatocytes, followed by faster secretion into bile canaliculi. These toxicokinetic changes were associated with increased hepatotoxicity in heterozygous albumin knockout mice for which serum albumin was reduced to a similar extent as in patients with severe hypoalbuminemia. HA also led to a shorter half-life of OTA in renal capillaries, increased glomerular filtration, and to enhanced uptake of OTA into tubular epithelial cells. In conclusion, the results favor the ‘
concept-of-higher-free-fraction
’ in HA; accordingly, HA causes an increased tissue uptake of compounds with high albumin binding and increased organ toxicity. It should be studied if this concept can be generalized to all compounds with high plasma albumin binding that are substrates of hepatocyte and renal tubular epithelial cell carriers.
Cellular materials offer industries the ability to close gaps in the material selection design space with properties not otherwise achievable by bulk, monolithic counterparts. Their superior specific ...strength, stiffness, and energy absorption, as well as their multi-functionality, makes them desirable for a wide range of applications. The objective of this paper is to compile and present a review of the open literature focusing on the energy absorption of periodic three-dimensional cellular materials. The review begins with the methodical cataloging of qualitative and quantitative elements from 100 papers in the available literature and then provides readers with a thorough overview of the state of this research field, discussing areas such as parent material(s), manufacturing methods, cell topologies, cross-section shapes for truss topologies, analysis methods, loading types, and test strain rates. Based on these collected data, areas of great and limited research are identified and future avenues of interest are suggested for the continued maturation and growth of this field, such as the development of a consistent naming and classification system for topologies; the creation of test standards considering additive manufacturing processes; further investigation of non-uniform and non-cylindrical struts on the performance of truss lattices; and further investigation into the performance of lattice materials under the impact of non-flat surfaces and projectiles. Finally, the numerical energy absorption (by mass and by volume) data of 76 papers are presented across multiple property selection charts, highlighting various materials, manufacturing methods, and topology groups. While there are noticeable differences at certain densities, the graphs show that the categorical differences within those groups have large overlap in terms of energy absorption performance and can be referenced to identify areas for further investigation and to help in the preliminary design process by researchers and industry professionals alike.
•The rs1042044 C > A polymorphism may influence PTC risk and invasion by affecting GLP-1R expression.•Upregulation of GLP-1R expression was correlated with prognostic markers in PTC patients.•GLP-1R ...mRNA expression analysis could diagnose PTC with 95% sensitivity and 97% specificity.•The rs1042044 SNP and tissue GLP-1R expression might be employed as genetic markers for PTC incidence and invasion.
Glucagon like peptide-1 receptor (GLP-1R) agonist usage has previously been linked to an elevated incidence of thyroid cell adenomas and carcinomas in animals.
The goal of this study was to determine if there was an association between GLP-1R gene polymorphism and expression with the risk of papillary thyroid carcinoma (PTC) and its clinical characteristics among the Egyptian population.
A total of eighty PTC patients and eighty healthy controls were included in the study. Real-time polymerase chain reaction (real-time PCR) and immunohistochemistry were used to determine GLP-1R expression in tumor tissue. The polymorphisms rs1042044 and rs6923761 in the GLP-1R gene were determined using PCR -restriction fragment length polymorphism (PCR-RFLP).
PTC patients exhibited considerably greater frequencies of rs1042044 AA genotypes and A allele than controls (OR (95% CI) = 4.5 (1.75–11.8), P < 0.001; OR (95% CI) = 2.032 (1.301–3.17), P < 0.001 respectively). GLP-1R mRNA and protein expressions were higher in tumor samples than normal thyroid tissues among PTC patients. In addition, high GLP-1R expressions were more common in rs1042044 AA genotype carriers than CC carriers (P < 0.001). GLP-1R mRNA expression showed 95 % sensitivity and 97% specificity for PTC diagnosis. Moreover, GLP-1R expression was closely associated with LN metastasis, tumor size, tumor stage, and multifocality in PTC patients.
This research provides new evidence linking the GLP-1R genetic polymorphism and tissue expression to PTC risk and invasiveness among the Egyptian population.
An intramolecular version of the Catellani reaction was optimized for one-step synthesis of bulky N-substituted benzo1,6naphthyridinones with good to excellent yields. The optimized reaction of ...N-substituted o-bromobenzamides with 4-bromoquinolines features a wide substrate scope and yields of up to 98%. The employment of aryl bromides under carefully optimized conditions instead of the usual aryl iodides enhances the scope of the reaction.
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![Synthesis of Benzo[1,6]naph...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1523-7060/small "Synthesis of Benzo[1,6]naphthyridinones Using the Catellani Reaction")