Anti-influenza Drug Discovery: Identification of an Orally Bioavailable Quinoline Derivative through Activity- and Property-Guided Lead Optimization

From a high-throughput screening (HTS) hit with inhibitory activity against virus-induced cytophathic in the low micromolar range, we have developed a potent anti-influenza lead through careful optimization without compromising the drug-like properties of the compound. An orally bioavailable compound was identified as a lead agent with nanomolar activity against influenza, representing a 140-fold improvement over the initial hit.     

Thermal degradation analysis of the isocyanate polyhedral oligomeric silsequioxanes (POSS)/sulfone epoxy nanocomposite

The sulfone epoxy (SEP)/polyhedral oligomeric silsesquioxane (POSS) nanocomposite contains bulky POSS side chains was studied in this research. Its glass transition temperature (T_g) decreases with the bulky POSS content, indicating that the bulky POSS side chains could not only generate the oligomers but also interrupt the network architectures of SEP. Homogeneous and uniform dispersion of POSS in SEP matrix can be obtained through the carbamate/oxazolidon covalent linkage, which is evidenced by scanning electron microscopy. The increasing concentration of POSS into SEP exhibits an increase of char yield in the nanocomposites, indicating that the POSS segments provide the antithermal‐oxidation effect for SEP/POSS, thereby inhibiting thermal degradation under open air at high temperatures. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Roles of Nitric Oxide and Asymmetric Dimethylarginine in Pregnancy and Fetal Programming

Nitric oxide (NO) regulates placental blood flow and actively participates in trophoblast invasion and placental development. Asymmetric dimethylarginine (ADMA) can inhibit NO synthase, which generates NO. ADMA has been associated with uterine artery flow disturbances such as preeclampsia. Substantial experimental evidence has reliably supported the hypothesis that an adverse in utero environment plays a role in postnatal physiological and pathophysiological programming. Growing evidence suggests that the placental nitrergic system is involved in epigenetic fetal programming. In this review, we discuss the roles of NO and ADMA in normal and compromised pregnancies as well as the link between placental insufficiency and epigenetic fetal programming.     

Coarse-grained modeling of model poly(urethane urea)s: Microstructure and interface aspects

Poly(urethane urea) elastomers are versatile and can be tailored to exhibit a broad range of mechanical response under high strain rate deformation. In this work, we utilize coarse-grained molecular dynamics simulations to elucidate the molecular mechanisms, particularly the effects of hard segment content, intermolecular interaction, and rigidity of the interface between the hard and soft segments on local morphology and rate-dependent stress-strain behavior in the ballistic regime. Simulation results qualitatively agree with available experimental data, where analysis of hard segment orientation during tensile and compression deformation and dynamic strain rate sensitivity was also performed. Further study of the intermolecular interaction on the stress-strain behavior reveals that it has a strong effect on strain hardening, particularly for a rigid interface, once the hard segment content reaches the percolation threshold. Simulation results also show that interface intermolecular interaction could become more dominant over interface rigidity in the initial stress-strain response, particularly below percolation.     

Mechanistic Insights and Photodegradation of Heterostructure Graphene Oxide/Titanium Dioxide

Topics in Catalysis - In this study, the electrospinning method was used to prepare graphene oxide/titanium dioxide (GO/TiO2) nanofibers with different contents of GO as photocatalysts used to...     

Moisture sorption on the wetting behavior of poly(p-phenylene terephthalamide) fibers in water and epoxy resin

The moisture sorption of poly(p-phenylene terephthalamide) (PPTA) fibers and the effects of moisture on the wetting behavior of these fibers in water and in an epoxy resin were studied. The moisture regains in the Kevlar 149 fibers followed a third order polynomial dependency on increasing relative humidity at 23°C. When preconditioned at 0% relative humidity (R.H.), water wettability of Kevlar 49 fibers was superior to that of Kevlar 149 fibers. Resin wettability of the dried Kevlar 49 fibers, on the other hand, was lower than that of Kevlar 149 fibers. Wettability in water and resin of these two fiber types was affected differently by moisture. Exposure to 97% R.H. moisture level significantly lowered water wettability of Kevlar 49 fibers but did not affect the wettability of Kevlar 149 fibers in water. Resin wettability of Kevlar 49 fibers was improved upon exposure to moisture, but the opposite was observed on Kevlar 149 fibers.     

Influence of dietary long-chain PUFA on premature baboon lung FA and dipalmitoyl PC composition

One of the major survival challenges of premature birth is production of lung surfactant. The lipid component of surfactant, dipalmitoyl PC (DPPC), increases in concentration in the period before normal term birth via a net shift in FA composition away from unsaturates. We investigated the influence of dietary DHA and arachidonic acid (AA) on lung FA composition and DPPC concentration in term and preterm baboons. Pregnant animals/neonates were randomized to one of four groups: breast-fed (B), term formula-fed (T⁻), preterm formulafed (P⁻), and preterm fed formula supplemented with DHA-AA (P⁺). Breast milk contained 0.68%wt DHA and the P⁺ group formula contained 0.61%wt DHA. In the preterm groups (P⁻ and P⁺), pregnant females received a course of antenatal corticosteroids. At the adjusted age of 4 wk, neonate lung tissue was harvested, and FA composition and DPPC were analyzed. Palmitate was ∼28%wt of lung total FA and no significant differences were found among the four treatment groups. In contrast, DPPC in the B group lung tissue was significantly greater than DPPC in the unsupplemented groups, but not compared with the P⁺ group. The B and P⁺ groups were not significantly different in DHA and AA, but were different compared with the unsupplemented (T, P⁻) groups. These results indicate that LCP supplementation increases lung DHA and AA, without compromising overall lung 16∶0 or DPPC. The shift in FA composition toward greater unsaturation in the groups consuming LCP supported improved surfactant lipid concentration in preterm neonate lungs.     

Shrinkage and warpage prediction of injection‐molded thin‐wall parts using artificial neural networks

This study demonstrates the successful use of back‐propagation artificial neural networks (BPANNs) in predicting the shrinkage and warpage of injection‐molded thin‐wall parts. The effects of structural parameters of a BPANN on the predictionaccuracy and the capability of a BPANN in determining the optimal process condition are also discussed. The training and testing data are obtained experimentally based on a Taguchi L₂₇ (3¹³) test schedule. The results show that the trained BPANN can successfully predict the shrinkage and warpage of injection‐molded thin‐wall parts. Comparing the prediction accuracies of the trained BPANN and C‐Mold software, it is noted that the trained BPANN predicts more accurately. In terms of determining the optimal process condition for minimizing the shrinkage and warpage of injected thin‐wall parts, the trained BPANN is also shown to give a better optimal process condition than Taguchi's method. Polym. Eng. Sci. 44:2029–2040, 2004. © 2004 Society of Plastics Engineers.     

Efficient Dispersants for TiO2 Nanopowder in Organic Suspensions

This article discusses the appropriate dispersant for titania (TiO₂) nanopowder in organic‐based suspensions. Four types of oleyl‐based dispersants, namely, oleyl alcohol, oleic acid, oleylamine, and oleyl phosphate, which have the functional groups hydroxyl (–OH), carboxyl (–COOH), amino (–NH₂), and phosphorous [–P(=O)(OH)₂], respectively, were compared for their ability to disperse TiO₂. Experimental results for zeta potential, adsorption, FT‐IR spectroscopy, and rheology, as well as theoretical calculations, indicate that dispersants with –P(=O)(OH)₂ and –NH₂ were more efficient than those with –COOH or –OH. The primary reason for this difference is related to the different interactions of TiO₂ with various dispersants and to different dispersion mechanisms. In addition to the major functional groups, –OH in the chemical structure of dispersants was important, as it might have other effects such as destabilization of the suspensions.     

VEGF and FGF2 Improve Revascularization,Survival, and Oocyte Quality of Cryopreserved,Subcutaneously-Transplanted Mouse Ovarian Tissues

This study was conducted to investigate the effect of the vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) on revascularization, survival, and oocyte quality of cryopreserved, subcutaneously-transplanted mouse ovarian tissue. Autologous subcutaneous transplantation of vitrified-thawed mouse ovarian tissues treated with (experimental group) or without (control group) VEGF and FGF2 was performed. After transplantation to the inguinal region for two or three weeks, graft survival, angiogenesis, follicle development, and oocyte quality were examined after gonadotropin administration. VEGF coupled with FGF2 (VEGF/FGF2) promoted revascularization and significantly increased the survival rate of subcutaneously-transplanted cryopreserved ovarian tissues compared with untreated controls. The two growth factors did not show long-term effects on the ovarian grafts. In contrast to the untreated ovarian grafts, active folliculogenesis was revealed as the number of follicles at various stages and of mature oocytes in antral follicles after gonadotropin administration were remarkably higher in the VEGF/FGF2-treated groups. Although the fertilization rate was similar between the VEGF/FGF2 and control groups, the oocyte quality was much better in the VEGF/FGF2-treated grafts as demonstrated by the higher ratio of blastocyst development. Introducing angiogenic factors, such as VEGF and FGF2, may be a promising strategy to improve revascularization, survival, and oocyte quality of cryopreserved, subcutaneously-transplanted mouse ovarian tissue.