On model for Darcy–Forchheimer 3D nanofluid flow subject to heat flux boundary condition

Journal of Thermal Analysis and Calorimetry - This paper provides a theoretical study of 3D nanofluid flow with zero nanoparticles mass and constant heat fluxes conditions. An incompressible...     

Deciphering the Role of Filamin B Calponin-Homology Domain in Causing the Larsen Syndrome,Boomerang Dysplasia,and Atelosteogenesis Type I Spectrum Disorders via a Computational Approach

Filamins (FLN) are a family of actin-binding proteins involved in regulating the cytoskeleton and signaling phenomenon by developing a network with F-actin and FLN-binding partners. The FLN family comprises three conserved isoforms in mammals: FLNA, FLNB, and FLNC. FLNB is a multidomain monomer protein with domains containing an actin-binding N-terminal domain (ABD 1–242), encompassing two calponin-homology domains (assigned CH1 and CH2). Primary variants in FLNB mostly occur in the domain (CH2) and surrounding the hinge-1 region. The four autosomal dominant disorders that are associated with FLNB variants are Larsen syndrome, atelosteogenesis type I (AOI), atelosteogenesis type III (AOIII), and boomerang dysplasia (BD). Despite the intense clustering of FLNB variants contributing to the LS-AO-BD disorders, the genotype-phenotype correlation is still enigmatic. In silico prediction tools and molecular dynamics simulation (MDS) approaches have offered the potential for variant classification and pathogenicity predictions. We retrieved 285 FLNB missense variants from the UniProt, ClinVar, and HGMD databases in the current study. Of these, five and 39 variants were located in the CH1 and CH2 domains, respectively. These variants were subjected to various pathogenicity and stability prediction tools, evolutionary and conservation analyses, and biophysical and physicochemical properties analyses. Molecular dynamics simulation (MDS) was performed on the three candidate variants in the CH2 domain (W148R, F161C, and L171R) that were predicted to be the most pathogenic. The MDS analysis results showed that these three variants are highly compact compared to the native protein, suggesting that they could affect the protein on the structural and functional levels. The computational approach demonstrates the differences between the FLNB mutants and the wild type in a structural and functional context. Our findings expand our knowledge on the genotype-phenotype correlation in FLNB-related LS-AO-BD disorders on the molecular level, which may pave the way for optimizing drug therapy by integrating precision medicine.     

Insights on the Synthesis of N-Heterocycles Containing Macrocycles and Their Complexion and Biological Properties

Macrocyclic chemistry has been extensively developed over the past several decades. In fact, the architecture of new macrocyclic models has undergone exponential growth to offer molecules with specific properties. In this context, an attempt is made in this study to provide an overview of some synthetic methods allowing the elaboration of N-heterocycles containing macrocycles (imidazole, triazole, tetrazole, and pyrazole), as well as their applications in the complexation of metal cations or as pharmacological agents.     

The reaction of vicinal triketones with cumulative phosphorus ylides. Synthesis of phosphoranylidenecyclobutanes

1,2,3-Indantrione ( 1 ), diphenylpropanetrione( 6 ), and alloxan ( 8 ) can be converted by reactions with ketenylidene-( 2a ) and thioketenylidenetriphenylphosphorane ( 2b ) into phosphoranylidenecyclobutanes ( 5 , 7 , and 9 ). The structures of the new cyclic compounds were confirmed on the basis of elemental analysis and spectral studies.     

2-Hydroxyestradiol Overcomes Mesenchymal Stem Cells-Mediated Platinum Chemoresistance in Ovarian Cancer Cells in an ERK-Independent Fashion

Ovarian cancer (OC) is the second most common type of gynecological malignancy. Platinum (Pt)-based chemotherapy is the standard of care for OC, but toxicity and acquired chemoresistance has proven challenging. Recently, we reported that sensitivity to platinum was significantly reduced in a co-culture of OC cells with MSC. To discover compounds capable of restoring platinum sensitivity, we screened a number of candidates and monitored ability to induce PARP cleavage. Moreover, we monitored platinum uptake and expression of ABC transporters in OC cells. Our results showed that 2-hydroxyestradiol (2HE2), a metabolite of estradiol, and dasatinib, an Abl/Src kinase inhibitor, were significantly effective in overcoming MSC-mediated platinum drug resistance. Dasatinib activity was dependent on ERK1/2 activation, whereas 2HE2 was independent of the activation of ERK1/2. MSC-mediated platinum drug resistance was accompanied by reduced intracellular platinum concentrations in OC cells. Moreover, MSC co-cultured with OC cells resulted in downregulation of the expression of cellular transporters required for platinum uptake and efflux. Exposure to 2HE2 and other modulators resulted in an increase in intracellular platinum concentrations. Thus, 2HE2 and dasatinib might act as sensitizers to restore platinum drug sensitivity to OC cells and thus to limit TME-mediated chemoresistance in OC.     

Dislocation density crystalline plasticity modeling of lath martensitic microstructures in steel alloys

A three-dimensional multiple-slip dislocation density-based crystalline formulation, specialized finite-element formulations and Voronoi tessellations adapted to martensitic orientations were used to investigate large strain inelastic deformation modes and dislocation density evolution in martensitic microstructures. The formulation is based on accounting for variant morphologies and orientations, retained austenite and initial dislocation densities that are uniquely inherent to martensitic microstructures. The effects of parent austenite orientation and retained austenite were also investigated for heterogeneous fcc/bcc crystalline structures. Furthermore, the formulation was used to investigate microstructures mapped directly from SEM/EBSD images of martensitic steel alloys. The analysis indicates that variant morphology and orientations have a direct effect on dislocation density accumulation and inelastic localization in martensitic microstructures, and that lath directions, orientations and arrangements are critical characteristics of high strength martensitic deformation and behavior.     

Application of Fast Grey RA to the spectrophotometric determination of copper in liver of Egyptian camels

The ortho-orthohydroxyazo dye 15690-Solochromate Fast Grey RA, CI mordant Black 19 (reddish navy-blue black) has been used as a reagent for the spectrophotometric determination of copper in liver of Egyptian camels. To determine copper digest, 1-g dry liver samples with 5 ml of each of 50% v/v sulfuric and concentrated nitric followed by 3 ml hydrogen peroxide, get rid of excess acid by repeated evaporation and washing, transfer quantitatively to 100 ml flask, make with water up to volume, to 1 ml add 2 ml 0.05 N nitric, 2 ml 0.2 M ascorbic acid, 3 ml 0.005% FG make up with water to 10 ml. Measure extinction at 555 mμ. Such a procedure gave satisfactory results as compared to the DEDTC procedure and a recovery of 98.8%.     

First synthesis and structure of beta-ketoimine calix[4]arenes: complexation and extraction studies

The synthesis of a new series of beta-ketoimine calix[4]arene derivatives is described. The reaction of calix[4]arene or p-tert-butylcalix[4]arene with bromoacetonitrile or bromobutyronitrile afforded di-, tri-, and tetranitrile calixarene derivatives (3-8, 3a), which were then reduced into the corresponding amine (9-13, 3b). The condensation of these aminocalixarenes with acetylacetone led to six beta-ketoimine calix[4]arene derivatives (14-18, 3c) as a class of selective receptors toward transition metals. Molecular structures of 4, 7, and 17 have been determined by X-ray diffraction. The packing of 17 revealed a network of intramolecular and intermolecular hydrogen bonds. The complexation properties of receptors 15, 17, and 3c toward different metal ions have been investigated by UV-vis titrations in organic media. The stoichiometries of complexes with 17 were determined by both the mole ratio method and Job plots. These novel receptors selectively complex Cu2+, Hg2+, and Ag+. Moreover, the extraction properties of 17 toward cations have been studied by liquid-liquid extraction and atomic absorption spectrometry. Compound 17 has good affinity and selectivity toward Pb2+.