Prediction of Critical Flashover Voltage of High Voltage Insulators Leveraging Bootstrap Neural Network

Understanding the flashover performance of the outdoor high voltage insulator has been in the interest of many researchers recently. Various studies have been performed to investigate the critical flashover voltage of outdoor high voltage insulators analytically and in the laboratory. However, laboratory experiments are expensive and time-consuming. On the other hand, mathematical models are based on certain assumptions which compromise on the accuracy of results. This paper presents an intelligent system based on Artificial Neural Networks (ANN) to predict the critical flashover voltage of High-Temperature Vulcanized (HTV) silicone rubber in polluted and humid conditions. Various types of learning algorithms are used, such as Gradient Descent (GD), Levenberg-Marquardt (LM), Conjugate Gradient (CG), Quasi-Newton (QN), Resilient Backpropagation (RBP), and Bayesian Regularization Backpropagation (BRBP) to train the ANN. The number of neurons in the hidden layers along with the learning rate was varied to understand the effect of these parameters on the performance of ANN. The proposed ANN was trained using experimental data obtained from extensive experimentation in the laboratory under controlled environmental conditions. The proposed model demonstrates promising results and can be used to monitor outdoor high voltage insulators. It was observed from obtained results that changing of the number of neurons, learning rates, and learning algorithms of ANN significantly change the performance of the proposed algorithm

Understanding the influence of applying plant extracts and microorganism culture filtrates against barley leaf rust disease

Rust fungi are devastating plant pathogens, and several Puccinia species have exerting substantial financial impacts on global barley cultivation. Fungicides are used on a large scale as an effective method for combating phytopathogenic fungi. The negative environmental impacts of fungicides are steadily escalating on a daily basis. Consequently, researchers are currently exploring alternative approaches to mitigate the use of fungicides, such as the utilization of plant extracts. This method has proven effective due to its incorporation of natural antifungal substances. Among the nine natural elicitors that were tested, the application of plant extracts on barley seedlings resulted in an increase in the incubation and latent periods of Puccinia hordei. These periods are integral components of partial and induced resistance, effectively mitigating the incidence of barley leaf rust disease by over 70% on mature plants. Similarly, the biochemical analyses demonstrated a notable augmentation in all the tested treatments’ overall phenolics and oxidative enzyme activities (peroxidase and polyphenol oxidase). Random amplified polymorphic DNA (SCoT) test serves as a viable approach for assessing the impact of plant extracts and microorganisms on barley plants. The results obtained from this study indicate that the detection of DNA polymorphism through SCoT analysis holds a significant potential powerful tool to evaluate genetic changes compared with untreated plants although some of them tested displayed high similarities at the morphological reaction

Combining Genome-Wide Gene Expression Analysis (RNA-seq) and a Gene Editing Platform (CRISPR-Cas9) to Uncover the Selectively Pro-oxidant Activity of Aurone Compounds Against Candida albicans

Candida albicans is the major fungal cause of healthcare-associated bloodstream infections worldwide with a 40% mortality rate. The scarcity of antifungal treatments due to the eukaryotic origin of fungal cells has challenged the development of selectively antifungal drugs. In an attempt to identify novel antifungal agents, aurones SH1009 and SH9051, as synthetically bioactive compounds, have been recently documented as anti-Candida agents. Since the molecular mechanisms behind the inhibitory activities of these aurones in C. albicans are unclear, this study aimed to determine the comprehensive cellular processes affected by these aurones and their molecular targets. Genome-wide transcriptional analysis of SH1009- and SH9051-treated C. albicans revealed uniquely repressed expression in different metabolic pathways, particularly trehalose and sulfur amino acid metabolic processes for SH1009 and SH9051, respectively. In contrast, the most commonly enriched process for both aurones was the up-regulation of RNA processing and ribosomal cleavages as an indicator of high oxidative stress, suggesting that a common aspect in the chemical structure of both aurones led to pro-oxidative properties. Additionally, uniquely induced responses (iron ion homeostasis for SH1009 and arginine biosynthesis for SH9051) garnered attention on key roles for the aurone functional groups. Deletion of the transcription factor for the trehalose biosynthesis pathway, Tye7p, resulted in an SH1009-resistant mutant, which also exhibited low trehalose content, validating the primary molecular target of SH1009. Aurone SH9051 uniquely simulated an exogenous supply of methionine or cysteine, leading to sulfur amino acid catabolism as evidenced by quantifying an overproduction of sulfite. Phenyl aurone, the common structure of aurones, contributed proportionally in the pro-oxidative activity through ferric ion reduction effects leading to high ROS levels. Our results determined selective and novel molecular mechanisms for aurone SH1009 and also elucidated the diverse cellular effects of different aurones based on functional groups.</jats:p

Prediction of Critical Flashover Voltage of High Voltage Insulators Leveraging Bootstrap Neural Network

Understanding the flashover performance of the outdoor high voltage insulator has been in the interest of many researchers recently. Various studies have been performed to investigate the critical flashover voltage of outdoor high voltage insulators analytically and in the laboratory. However, laboratory experiments are expensive and time-consuming. On the other hand, mathematical models are based on certain assumptions which compromise on the accuracy of results. This paper presents an intelligent system based on Artificial Neural Networks (ANN) to predict the critical flashover voltage of High-Temperature Vulcanized (HTV) silicone rubber in polluted and humid conditions. Various types of learning algorithms are used, such as Gradient Descent (GD), Levenberg-Marquardt (LM), Conjugate Gradient (CG), Quasi-Newton (QN), Resilient Backpropagation (RBP), and Bayesian Regularization Backpropagation (BRBP) to train the ANN. The number of neurons in the hidden layers along with the learning rate was varied to understand the effect of these parameters on the performance of ANN. The proposed ANN was trained using experimental data obtained from extensive experimentation in the laboratory under controlled environmental conditions. The proposed model demonstrates promising results and can be used to monitor outdoor high voltage insulators. It was observed from obtained results that changing of the number of neurons, learning rates, and learning algorithms of ANN significantly change the performance of the proposed algorithm.</jats:p

Chemogenomic profiling to understand the antifungal action of a bioactive aurone compound.

Every year, more than 250,000 invasive candidiasis infections are reported with 50,000 deaths worldwide. The limited number of antifungal agents necessitates the need for alternative antifungals with potential novel targets. The 2-benzylidenebenzofuran-3-(2H)-ones have become an attractive scaffold for antifungal drug design. This study aimed to determine the antifungal activity of a synthetic aurone compound and characterize its mode of action. Using the broth microdilution method, aurone SH1009 exhibited inhibition against C. albicans, including resistant isolates, as well as C. glabrata, and C. tropicalis with IC50 values of 4-29 μM. Cytotoxicity assays using human THP-1, HepG2, and A549 human cell lines showed selective toxicity toward fungal cells. The mode of action for SH1009 was characterized using chemical-genetic interaction via haploinsufficiency (HIP) and homozygous (HOP) profiling of a uniquely barcoded Saccharomyces cerevisiae mutant collection. Approximately 5300 mutants were competitively treated with SH1009 followed by DNA extraction, amplification of unique barcodes, and quantification of each mutant using multiplexed next-generation sequencing. Barcode post-sequencing analysis revealed 238 sensitive and resistant mutants that significantly (FDR P values ≤ 0.05) responded to aurone SH1009. The enrichment analysis of KEGG pathways and gene ontology demonstrated the cell cycle pathway as the most significantly enriched pathway along with DNA replication, cell division, actin cytoskeleton organization, and endocytosis. Phenotypic studies of these significantly enriched responses were validated in C. albicans. Flow cytometric analysis of SH1009-treated C. albicans revealed a significant accumulation of cells in G1 phase, indicating cell cycle arrest. Fluorescence microscopy detected abnormally interrupted actin dynamics, resulting in enlarged, unbudded cells. RT-qPCR confirmed the effects of SH1009 in differentially expressed cell cycle, actin polymerization, and signal transduction genes. These findings indicate the target of SH1009 as a cell cycle-dependent organization of the actin cytoskeleton, suggesting a novel mode of action of the aurone compound as an antifungal inhibitor

Multiple Brain Hemorrhages on Presentation in a Patient with Accelerated Phase Chronic Myeloid Leukemia and Subsequent CNS Blast Crisis Despite Systemic Complete Molecular Response: Possible Role of CNS Bleed in Leukemia Proliferation

Abstract Background Chronic myeloid leukemia (CML) is a myeloproliferative disorder which can present in one of the three disease phases; chronic phase, accelerated phase or blast crisis. Central nervous system (CNS) as a site of extramedullary blast crisis in CML is rare and when affected, it usually occurs concurrently with systemic relapse. In extremely rare cases, the blast phase can affect the CNS without bone marrow involvement. Tyrosine kinase inhibitors (TKI) have become the treatment of choice for CML. However, there is poor penetration of CNS by some of these drugs or their active metabolites. Therefore, CNS may act as a sanctuary site for malignant cells in CML patients treated with TKIs. Here we describe an unusual case of CML who presented in accelerated-phase and multiple intracranial hemorrhages, and developed isolated CNS blast crisis after one year in spite of being in systemic remission. Clinical presentation A previously healthy 27-years-old male presented with10 days history of fatigue, abdominal pain and vomiting. He also complained of weight loss and low grade fever. Abdominal examination revealed huge splenomegaly. Investigations showed a white cell count of 538Í 109/l, hemoglobin 7.2 g/dl and platelets 47Í 109/l. Blood film showed marked leukocytosis with left shift, blasts 9% and thrombocytopenia, consistent with accelerated-phase CML. A bone marrow (BM) aspirate confirmed the above findings. Cytogenetic analysis of the bone marrow revealed100% Philadelphia chromosome and BCR/ABL positivity. After admission, the patient developed headache and vomiting. MRI of brain showed multiple small hemorrhages in the supratentorial and infratentorial compartments (figure). The patient was diagnosed with accelerated-phase CML and leukostasis. Emergency leukapheresis was performed (two sessions) resulting in a decrease in his WBC count. He was also started on hydroxurea, nilotinib and cytarabine 100mg, which led to improvement of his general condition and control of leukocyte count. He was continued on nilotinib 400 mg twice daily. He achieved complete molecular remission. Brain radiotherapy was considered because of brain hemorrhages and fear of lodging of blasts in the brain but not given because of opinion against it by expert colleagues. He was also referred for allogeneic stem-cell-transplant (SCT) because of the above concerns but not considered because of excellent response to nilotinib. After 1year of initial diagnosis, he was readmitted with headache and bilateral visional loss. Fundoscopy showed retinal hemorrhages. His CBC, BM biopsy and brain MRI were normal. Lumbar puncture showed markedly increased CSF pressure (55cm) and leukocyte infiltration with many blast cells (42%). Patient was diagnosed as CNS blast crisis of CML with BM in molecular remission. He was stareted on intrathecal chemotherapy (ITC), triple regime (methotrexate 6mg, ARA-C 30 mg, hydrocortisone 30 mg) and nilotinib was changed to dasatinib. His CSF cleared after multiple sessions of ITC; unfortunately, significant visual impairment persisted. Patient also received radiotherapy to the brain. He went on to have a sibling SCT and remains well 8 months post transplant. Conclusion We describe a young male with accelerated-phase CML and multiple brain hemorrhages on presentation and subsequent isolated CNS blast crisis. We speculate that there was a possible link between the initial brain hemorrhages causing lodging and proliferation of blasts in the brain and subsequent isolated CNS blast crisis. We suggest that treatment options in such cases should include consideration of cranial irradiation initially, a tyrosine kinase inhibitor with better CNS penetration like dasatinib, and upfront allogeneic SCT as potential therapeutic modalities. Figure 1. MRI brain FLAIR images show multiple ring like foci of recent hemorrhages (arrows). Figure 1. MRI brain FLAIR images show multiple ring like foci of recent hemorrhages (arrows). Disclosures No relevant conflicts of interest to declare. </jats:sec

Evaluation of Haloxylon Persicum Leaves Ethanolic Extract for Phytochemical, Antioxidant, Anticancer, and Antimicrobial Properties

In the present work, we have examined the composition of phytochemicals in the ethanolic extract of Haloxylon persicum Bunge and its biological activities. The measurements of the biological activities included its antioxidant behavior; antimicrobial activities against pathogenic fungi, gram-positive, and gram-negative bacteria; and anticancerous activity against hepatocellular (HepG-2), lung (A-549), breast (MCF-7), and colon (HCT-116) cancer cells. The analysis of the chemical composition showed the highest preponderance of tannins and the lowest for flavonoids. There were wide variations in the antioxidant activities that were dependent on the measures used (scavenging of 2,2-Diphenyl-1-picrylhydrazyl free radical and superoxide radical anion, O· 2 −) compared to ascorbic acid or butylated hydroxyl anisole. The concentration of the extract needed to cause 50% growth inhibition varied about threefold among different cancer cells with HepG-2 being the most sensitive and A-549 the least. The test of the antimicrobial potential showed Candida albicans to be the most sensitive with no activity against Aspergillus fumigatus, Penicillium italicum, Streptococcus mutants, and Enterobacter cloacae. The measurement of the effect of extract on the liver and kidney markers in the rat serum revealed no change in the activities suggesting safety of the extract. Therefore, ethanolic extract of H. persicum Bunge need further investigation for its possible use in humans.</p

The CC₅₀ (cytotoxicity concentration of aurone SH1009 that causes 50% cell viability loss) ± the SEM and the selectivity index (SI) as a ratio between the CC₅₀ for the mammalian cells divided by the IC₅₀ against <i>C</i>. <i>albicans</i> SC5314.

The CC50 (cytotoxicity concentration of aurone SH1009 that causes 50% cell viability loss) ± the SEM and the selectivity index (SI) as a ratio between the CC50 for the mammalian cells divided by the IC50 against C. albicans SC5314.</p