23 research outputs found
Do Loading Path and Specimen Thickness Affect the Brittle Compressive Failure of Ice?
Compressive experiments were performed on square (160 mm × 160 mm) prismatic specimens of columnar-grained, S2 freshwater ice, biaxially loaded across the columns at −10°C. The work focused on brittle behavior, achieved by deforming the specimens at an applied strain rate of 4.5 ± 1.2 × 10 3s 1 in the direction of shortening. The results show that the specimen thickness (25–150 mm) has no detectable effect on the terminal failure strength of the ice. Likewise, the strength of the ice when loaded under proportional loading, where the minor stress varies during the test, was similar to that when loaded under a constant minor stress, implying that terminal failure depends only on the stress state and not on the path taken
The novel choline kinase inhibitor ICL-CCIC-0019 reprograms cellular metabolism and inhibits cancer cell growth.
The glycerophospholipid phosphatidylcholine is the most abundant phospholipid species of eukaryotic membranes and essential for structural integrity and signaling function of cell membranes required for cancer cell growth. Inhibition of choline kinase alpha (CHKA), the first committed step to phosphatidylcholine synthesis, by the selective small-molecule ICL-CCIC-0019, potently suppressed growth of a panel of 60 cancer cell lines with median GI50 of 1.12 μM and inhibited tumor xenograft growth in mice. ICL-CCIC-0019 decreased phosphocholine levels and the fraction of labeled choline in lipids, and induced G1 arrest, endoplasmic reticulum stress and apoptosis. Changes in phosphocholine cellular levels following treatment could be detected non-invasively in tumor xenografts by [18F]-fluoromethyl-[1,2–2H4]-choline positron emission tomography. Herein, we reveal a previously unappreciated effect of choline metabolism on mitochondria function. Comparative metabolomics demonstrated that phosphatidylcholine pathway inhibition leads to a metabolically stressed phenotype analogous to mitochondria toxin treatment but without reactive oxygen species activation. Drug treatment decreased mitochondria function with associated reduction of citrate synthase expression and AMPK activation. Glucose and acetate uptake were increased in an attempt to overcome the metabolic stress. This study indicates that choline pathway pharmacological inhibition critically affects the metabolic function of the cell beyond reduced synthesis of phospholipids
Low-speed friction and brittle compressive failure of ice: fundamental processes in ice mechanics
Atomistic simulations of friction at an ice-ice interface
Even though the slipperiness of ice is important both technologically and environmentally and often experienced in everyday life, the nanoscale processes determining ice friction are still unclear. We study the friction of a smooth ice-ice interface using atomistic simulations, and especially consider the effects of temperature, load, and sliding velocity. At this scale, frictional behavior is seen to be determined by the lubricating effect of a liquid premelt layer between the sliding ice sheets. In general, increasing temperature or load leads to a thicker lubricating layer and lower friction, while increasing the sliding velocity increases friction due to viscous shear