Multiple Testing for Detecting Efficient Dose Steps

In the comparison of various dose levels it can often be assumed that the parameters to be tested follow an order restriction. Two closed multiple test procedures for detecting the highest dose level still providing a shift in the response distribution as compared to the adjacent lower dose level is proposed. One is based on one sided comparisons between neighbouring doses, the other uses Helmert-type contrast statistics. If a sequence of testing is fixed in advance the multiple test can be suitably modified. The power of the procedures is simulated under the assumption of normally distributed responses for various constellations of the dose means. It is compared with the power of a general Holm-type procedure discussed in BUDDE & BAUER (1989).     

Apoptosis induction by miR-19b inhibition: does it show therapeutic potential for leukemia?

Abstract

High levels of miR-19 play an important role in malignant diseases of the hematopoietic system. Therefore the treatment with corresponding microRNA antagonists seems to be an interesting therapeutic approach. We found a significant increase of apoptosis in Jurkat cells which were transfected with a miR-19b inhibitor. The rise of apoptosis in transfected human monocuclear cells (MNCs) was significant as well, but the unspecific miRNA control induced apoptosis in MNCs to a similar extend. A closer look at the MNC subpopulations revealed higher specific apoptosis in B cells whereas T cell apoptosis was lower and induced by unspecific miRNA interference.     

Partial purification and characterization of pyruvate, orthophosphate dikinase from Rhodospirillum rubrum.

We confirmed an earlier report (B. B. Buchanan, J. Bacteriol. 119:1066-1068, 1974) that the nonsulfur purple photosynthetic bacterium Rhodospirillum rubrum contains pyruvate, orthophosphate dikinase (EC 2.7.9.1) activity that is absolutely dependent upon all three substrates by performing enzyme assays in both the forward (phosphoenolpyruvate formation) and reverse (ATP formation) directions. Of the various carbon sources tested, photoheterotrophic growth on DL-lactate plus bicarbonate proved to be best for the production of dikinase activity units. A four-step protocol, which included batch DEAE-cellulose processing, ammonium sulfate fractionation, and chromatography on hydroxylapatite and Blue A Dyematrex gels, was devised for partially purifying the enzyme from such cells. The protein was purified about 80-fold to an apparent electrophoretic purity of about 60% and a final specific activity of 3.6 U/mg of protein, with about a 35% overall recovery of activity units. Estimations of native and monomeric relative molecular weights by sucrose density gradient centrifugation, high-pressure liquid chromatography-based size exclusion chromatography, denaturing electrophoresis, and immunoblotting suggested that the holoenzyme was most likely a homodimer of 92.7-kilodalton subunits. The results are compared with related previous data on the nonphotosynthetic bacterial dikinase and the C4 mesophyll chloroplast enzyme.     

Aldolase stability in the presence of organic solvents

Rabbit muscle aldolase (RAMA) and trout muscle aldolase (TRMA) retained 100% activity in the presence of hexane, cyclohexane and toluene. Both enzymes retained greater than 80% activity in the presence of 20% (v/v) methanol. In the presence of 20% (v/v) N,N-dimethylformamide RAMA and TRMA were inactive, but at least 50% activity could be restored by returning the enzymes to an aqueous environment.