Running ground reaction forces across footwear conditions are predicted from the motion of two body mass components.

Although running shoes alter foot-ground reaction forces, particularly during impact, how they do so is incompletely understood. Here, we hypothesized that footwear effects on running ground reaction force-time patterns can be accurately predicted from the motion of two components of the body's mass (mb): the contacting lower-limb (m1 = 0.08mb) and the remainder (m2 = 0.92mb). Simultaneous motion and vertical ground reaction force-time data were acquired at 1,000 Hz from eight uninstructed subjects running on a force-instrumented treadmill at 4.0 and 7.0 m/s under four footwear conditions: barefoot, minimal sole, thin sole, and thick sole. Vertical ground reaction force-time patterns were generated from the two-mass model using body mass and footfall-specific measures of contact time, aerial time, and lower-limb impact deceleration. Model force-time patterns generated using the empirical inputs acquired for each footfall matched the measured patterns closely across the four footwear conditions at both protocol speeds (r2 = 0.96 ± 0.004; root mean squared error = 0.17 ± 0.01 body-weight units; n = 275 total footfalls). Foot landing angles (θF) were inversely related to footwear thickness; more positive or plantar-flexed landing angles coincided with longer-impact durations and force-time patterns lacking distinct rising-edge force peaks. Our results support three conclusions: 1) running ground reaction force-time patterns across footwear conditions can be accurately predicted using our two-mass, two-impulse model, 2) impact forces, regardless of foot strike mechanics, can be accurately quantified from lower-limb motion and a fixed anatomical mass (0.08mb), and 3) runners maintain similar loading rates (ΔFvertical/Δtime) across footwear conditions by altering foot strike angle to regulate the duration of impact. NEW & NOTEWORTHY Here, we validate a two-mass, two-impulse model of running vertical ground reaction forces across four footwear thickness conditions (barefoot, minimal, thin, thick). Our model allows the impact portion of the impulse to be extracted from measured total ground reaction force-time patterns using motion data from the ankle. The gait adjustments observed across footwear conditions revealed that runners maintained similar loading rates across footwear conditions by altering foot strike angles to regulate the duration of impact.

(Z)-1-aryl-3-arylamino-2-propen-1-ones, highly active stimulators of tubulin polymerization: synthesis, structure-activity relationship (SAR), tubulin polymerization, and cell growth inhibition studies.

Tubulin, the major structural component of microtubules, is a target for the development of anticancer agents. A series of (Z)-1-aryl-3-arylamino-2-propen-1-one (10) were synthesized and evaluated for antiproliferative activity in cell-based assay. The most active compound (Z)-1-(2-bromo-3,4,5-trimethoxyphenyl)-3-(3-hydroxy-4-methoxyphenylamino)prop-2-en-1-one (10ae) was tested in 20 tumor cell lines including multidrug resistant phenotype and was found to induce apoptosis in all these cell lines with similar GI(50) values. Flow cytometry studies showed that 10ae arrested the cells in G2/M phase of cell cycle. In addition to G2/M block, these compounds caused microtubule stabilization like paclitaxel and induced apoptosis via activation of the caspase family. The observations made in this investigation demonstrate that (Z)-1-Aryl-3-arylamino-2-propen-1-one (10) represents a new class of microtubule-stabilizing agents.