Purpose: We have previously identified solute-linked carrier family A1 member 5 (SLC1A5) as an overexpressed protein in a shotgun proteomic analysis of stage I non-small cell lung cancer (NSCLC) when compared with matched controls. We hypothesized that overexpression of SLC1A5 occurs to meet the metabolic demand for lung cancer cell growth and survival.Experimental Design: To test our hypothesis, we first analyzed the protein expression of SLC1A5 in archival lung cancer tissues by immunohistochemistry and immunoblotting (N ¼ 98) and in cell lines (N ¼ 36). To examine SLC1A5 involvement in amino acid transportation, we conducted kinetic analysis of L-glutamine (Gln) uptake in lung cancer cell lines in the presence and absence of a pharmacologic inhibitor of SLC1A5, gamma-L-Glutamyl-p-Nitroanilide (GPNA). Finally, we examined the effect of Gln deprivation and uptake inhibition on cell growth, cell-cycle progression, and growth signaling pathways of five lung cancer cell lines.Results: Our results show that (i) SLC1A5 protein is expressed in 95% of squamous cell carcinomas (SCC), 74% of adenocarcinomas (ADC), and 50% of neuroendocrine tumors; (ii) SLC1A5 is located at the cytoplasmic membrane and is significantly associated with SCC histology and male gender; (iii) 68% of Gln is transported in a Na þ -dependent manner, 50% of which is attributed to SLC1A5 activity; and (iv) pharmacologic and genetic targeting of SLC1A5 decreased cell growth and viability in lung cancer cells, an effect mediated in part by mTOR signaling.Conclusions: These results suggest that SLC1A5 plays a key role in Gln transport controlling lung cancer cells' metabolism, growth, and survival.
We describe the design features that underlie the operation of iSprawl, a small (0.3 kg) autonomous, bio-inspired hexapod that runs at 15 body-lengths/second (2.3 m/s). These features include a tuned set of leg compliances for efficient running and a light and flexible power transmission system. This transmission system permits high speed rotary power to be converted to periodic thrusting and distributed to the tips of the rapidly swinging legs. The specific resistance of iSprawl is approximately constant at 1.75 for speeds between 1.25 m/s and 2.5 m/s. Examination of the trajectory of the center of mass and the ground reaction forces for iSprawl show that it achieves a stable, bouncing locomotion similar to that seen in insects and in previous (slower) bio-inspired robots, but with an unusually high stride frequency for its size.
Uni- and triaxial accelerometer outputs have a linear relationship with speed during walking. During running, uniaxial accelerometer outputs plateau because of the biomechanics of running, whereas triaxial accelerometer output has a linear relationship. The combined methodologies predict .VO2 better than either predictor alone; a subject's individually calibrated data further improves .VO2 estimation.
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