Ming-Kai Chern

Synthesis and structure-activity relationship study of 8-hydroxyquinoline-derived Mannich bases as anticancer agents.

To continue our early study on the structural modifications of clioquinol, more 8-hydroxyquinoline-derived Mannich bases were synthesized and examined for growth-inhibitory effect. Taken Mannich base 1 as our lead compound, upon replacement of either sulfonyl group with methylene group or piperazine ring with ethylenediamine group resulted in an appreciable increase in potency. On the other hand, as 8-hydroxyquinoline was replaced with phenol, 3-hydroxypyridine and 1-naphthol, a dramatic decrease in activity was observed, indicating that 8-hydroxyquinoline is a crucial scaffold for activity. Further 3D-QSAR analysis on HeLa cells revealed that both steric and electronic effects contributed equally to growth inhibition. Taken together, the structure-activity relationships obtained from both in vitro data and CoMFA model warrant a valuable reference for further study.

Electroporation for three commonly used yeast strains for two-hybrid screening experiments

The efficiency of transformation by electroporation has been known to be compromised by strain dependency. A high efficiency protocol is still lacking for distinct two-hybrid yeast strains of diverse genetic features. Here, we used 0.5 M lithium acetate (LiAc) and 50 mM Tris-HCl with 5 mM EDTA (pH 7.5), i.e., fivefold the standard concentrations, and voltage at 1.0 to develop a protocol which, for the first time, is able to effect an average efficiency of 1.84×10(6)transformants/μg DNA for three commonly used yeast strains committed to two-hybrid screening experiments.

THE EFFECTS OF EXTENSIONAL STRESS ON RED BLOOD CELL HEMOLYSIS

Artificial prostheses create non-physiologic flow conditions with stress forces that may induce blood cell damage, particularly hemolysis. Earlier computational fluid dynamics (CFD) prediction models based on a quantified power model showed significant discrepancies with actual hemolysis experiments. These models used the premise that shear stresses act as the primary force behind hemolysis. However, additional studies have suggested that extensional stresses play a more substantial role than previously thought and should be taken into account in hemolysis models. We compared extensional and shear stress flow fields within the contraction of a short capillary with sharp versus tapered entrances. The flow field was calculated with CFD to determine stress values, and hemolysis experiments with porcine red blood cells were performed to correlate the effects of extensional and shear stress on hemolysis. Our results support extensional stress as the primary mechanical force involved in hemolysis, with a threshold value of 1000 Pa under exposure time less than 0.060 ms.