Multiscale mathematical modeling to support drug development

It is widely recognized that major improvements are required in the methods currently being used to develop new therapeutic drugs. The time from initial target identification to commercialization can be 10-14 years and incur a cost in the hundreds of millions of dollars. Even after substantial investment, only 30-40% of the candidate compounds entering clinical trials are successful. We propose that multiscale mathematical pathway modeling can be used to decrease time required to bring candidate drugs to clinical trial and increase the probability that they will be successful in humans. The requirements for multiple time scales and spatial scales are discussed, and new computational paradigms are identified to address the increased complexity of modeling.     

Modeling of the Extraction Equilibrium of Copper from Sulfate Solutions with Acorga M5640

The extraction equilibrium of copper from sulfate media with the aldoxime Acorga M5640 in ShellSol D70 has been investigated. The distribution results were interpreted by taking into account the nonideality of the aqueous phase. The activity of copper and hydrogen ions in the target systems CuSO₄/H₂SO₄/Na₂SO₄ and CuSO₄/H₂SO₄/Fe₂(SO₄)₃/ZnSO₄ were calculated through the speciation of the aqueous solutions and by applying the Pitzer model. The experimental pH values were found in good agreement with the predicted pH values. A model considering the dimerization of the aldoxime extractant was proposed to predict the distribution ratio and the copper loading isotherms. The extraction constant at infinite dilution and the apparent dimerization constant were evaluated from the experimental data and were found to be 10^{3.06 ± 0.07} and 51 ± 9 M^?1, respectively, at 25°C.     

A novel ratiometric fluorescent Yb3+ sensor based on a N′-(1-oxoacenaphthylen-2(1H)-ylidene)furan-2-carbohydrazide as a suitable fluorophore

N′-(1-oxoacenaphthylen-2(1H)-ylidene)furan-2-carbohydrazide (L) was synthesized for the first time and used as a ratiometric fluorescent chemosensor for high selective recognition of Yb³⁺ ions in acetonitrile (MeCN) solution. The L–Yb³⁺ complexation quench the fluorescence of L at 420 nm and induces new fluorescent enhancement at 516 nm. Due to the formation of a 2:1 metal ligand complex in acetonitrile solution, the red shift of fluorescent emission spectrum occurred. The sensor shows a linear response toward Yb³⁺ ion concentration in the range of 3.3 × 10^? 7 M to 1.0 × 10^? 4 M with detection limit of 1.2 × 10^? 7 M. The fluorescent probe exhibits high selectivity for Yb³⁺ ion over the other common mono-, di-, and trivalent cations.     

用激光多普勒测速计（LDA）分析粘弹性对Metzner和Otto系数的影响

The Metzner and Otto correlation is the single practical method for incorporating non-Newtonian effects in the mixing process. In this article, the Metzner and Otto' s idea, the role of viscoelasticity on the Metzner and Otto coefficient, ks, effects of flow regime on ks and the determination of ks for Rushton turbine impeller have been studied using the direct method of the laser Doppler anemometry (LDA) velocity measurement for the case of viscoelastic liquids. The normalized mean tangential velocity profiles are independent of Rushton turbine impeller speeds. Contrary to literature findings, it is shown that the variation of local shear rate against the impeller speed is better correlated by the power equation, i.e. γ= ks' · Nb' , in the transition region, i. e. ～ 30 < Re <～ 2000. Also, a correlation between improved coefficient, ks', and the elasticity number of viscoelastic liquids is given which is very helpful in designing of the mixing of both viscoelastic and inelastic non-Newtonian fluids t     

P75 and S100 gene expression induced by cell-imprinted substrate and beta-carotene to nerve tissue engineering

Here we aimed to differentiate adipose derived stem cells (ADSCs) to Schwann cells (SCs), as one of the major and instrumental cell sources in nerve regeneration, by synergistic application of imprinting method and β-carotene. Accordingly, the topography of Schwann cells was imprinted on poly dimethyl siloxane (PDMS) substrates via mold casting and human ADSCs seeded on substrates; moreover, β-carotene was added to induce hADSCs differentiation. Physiochemical evaluations of PDMS by FTIR spectra presented its silicon-methyl bond (Si CH₃) at 1260 cm⁻¹. Morphology analysis by crystal violet, picrosirus red staining, and SEM images illustrated that MSCs seeded on imprinted substrates have formed SC-like morphology. Furthermore, according to q-PCR and ICC evaluations, SCs specific markers; S100 and P75 in addition of 5 μl β-carotene (BC) were upregulated (p-value<0.001). Also, the expression was detected on the imprinted surfaces without β-carotene to a lesser degree. Our study revealed that Schwann cell imprinted substrates can mimic the morphology and topography of SCs and induce differentiation signals in mesenchymal stem cells (MSCs). In addition, the potency of β-carotene as an organic substance in boosting and stimulating the neural differentiation was demonstrated. Relevantly, the reports have confirmed the synergistic pivotal roles of β-carotene and patterned surfaces in directing MSCs into SC-like cells differentiation without applying expensive and less safe chemical growth factors.     

Thermodynamic and Electrochemical Studies of Aniline and Phenylhydrazine and Their Derivatives Substituted POCl3-Based Compounds as Corrosion Inhibitor for Mild Steel in Hydrochloric Acid Solution

Protection of Metals and Physical Chemistry of Surfaces - The achievement of high corrosion inhibition performances by manipulating the molecular structure of organic substances has gained much...