Numerical Investigations through ANNs for Solving COVID-19 Model

The current investigations of the COVID-19 spreading model are presented through the artificial neuron networks (ANNs) with training of the Levenberg-Marquardt backpropagation (LMB), i.e., ANNs-LMB. The ANNs-LMB scheme is used in different variations of the sample data for training, validation, and testing with 80%, 10%, and 10%, respectively. The approximate numerical solutions of the COVID-19 spreading model have been calculated using the ANNs-LMB and compared viably using the reference dataset based on the Runge-Kutta scheme. The obtained performance of the solution dynamics of the COVID-19 spreading model are presented based on the ANNs-LMB to minimize the values of fitness on mean square error (M.S.E), along with error histograms, regression, and correlation analysis.

General soliton and (semi-)rational solutions of the partial reverse space y-non-local Mel’nikov equation with non-zero boundary conditions

General soliton and (semi-)rational solutions to the y-non-local Mel’nikov equation with non-zero boundary conditions are derived by the Kadomtsev–Petviashvili (KP) hierarchy reduction method. The solutions are expressed in N × N Gram-type determinants with an arbitrary positive integer N . A possible new feature of our results compared to previous studies of non-local equations using the KP reduction method is that there are two families of constraints among the parameters appearing in the solutions, which display significant discrepancies. For even N , one of them only generates pairs of solitons or lumps while the other one can give rise to odd numbers of solitons or lumps; the interactions between lumps and solitons are always inelastic for one family whereas the other family may lead to semi-rational solutions with elastic collisions between lumps and solitons. These differences are illustrated by a thorough study of the solution dynamics for N = 1, 2, 3. Besides, regularities of solutions are discussed under proper choices of parameters.

Medicago Sativa Defensin 1 (MsDef1), A Natural Tumor Targeted Sensitizer for Improving Chemotherapy: Translation from Anti-Fungal Agent to Potential Anti-Cancer Agent

IntroductionMsDef1, a 45-amino acid cysteine-rich peptide from the seed of Medicago sativa is an antifungal defensin small protein. It exhibits broad-spectrum antifungal activity against fungal pathogens of plants at low micromolar concentrations. The common vulnerability of fungal and cancer cells determines the utility of MsDef1 as a potential anti-tumor agent.ResultsThe solution dynamics of 15N-labeled MsDef1, 15N longitudinal relaxation (T1) and 15N-1H Nuclear Overhauser Effect (NOE) shows that GlcCer binds at two sites on the peptide molecule, i.e., Asp36-Cys39 and amino acids between 12-20 and 33-40. MsDef1 interacts with drug resistant breast cancer MCF-7R cells, permeates GlcCer-rich plasma membrane and releases apoptotic ceramide. This results in the activation of ceramide pathway involving interaction of the peptide with intracellular thioredoxin (Trx), another tumor specific biomarker. MsDef1 oxidizes Trx through four S-S bonds and in the process, gets reduced to thiols. Oxidation of Trx is correlated with the activation of Apoptosis Stimulating Kinase 1 (ASK1) which is known to sensitize cancer cells to chemotherapeutics including front-line drug Doxorubicin. A combination of MsDef1 and Doxorubicin exhibits 5-10-fold greater apoptosis in vitro in MDR triple negative breast cancer (TNBC) cells compared to either MsDef1 or Doxorubicin alone.ConclusionAn antifungal plant defensin MsDef1 is shown to be a cell permeating peptide (CPP) for MDR cancer cells targeted to two tumor specific targets activating two cell death pathways. That makes MsDef1, potentially a tumor targeted sensitizer neoadjuvant to cancer therapy.

Synthesis, solution dynamics and chemical vapour deposition of heteroleptic zinc complexes via ethyl and amide zinc thioureides

Ethyl and amide zinc thioureides [L1ZnEt]2 (1), [L1*ZnEt]2 (2) and [L1Zn(N(SiMe3)2)]2 (3) have been synthesised from the equimolar reaction of thiourea ligands (HL1 = iPrN(H)CSNMe2 and HL1* = PhN(H)CSNMe2) with diethyl zinc and zinc...

Structural effects of the highly protective V127 polymorphism on human prion protein

Prion diseases, a group of incurable, lethal neurodegenerative disorders of mammals including humans, are caused by prions, assemblies of misfolded host prion protein (PrP). A single point mutation (G127V) in human PrP prevents prion disease, however the structural basis for its protective effect remains unknown. Here we show that the mutation alters and constrains the PrP backbone conformation preceding the PrP β-sheet, stabilising PrP dimer interactions by increasing intermolecular hydrogen bonding. It also markedly changes the solution dynamics of the β2-α2 loop, a region of PrP structure implicated in prion transmission and cross-species susceptibility. Both of these structural changes may affect access to protein conformers susceptible to prion formation and explain its profound effect on prion disease.