No abstract

Summary The lactate dehydrogenase-A (LDH-A) enzyme catalyzes the inter-conversion of pyruvate and lactate, is upregulated in human cancers and is associated with aggressive tumor outcomes. Here we use a novel inducible murine model and demonstrate that inactivation of LDH-A in mouse models of NSCLC driven by oncogenic K-RAS or EGFR leads to decreased tumorigenesis and disease regression in established tumors. We also show that abrogation of LDH-A results in reprogramming of pyruvate metabolism, with decreased lactic fermentation in vitro, in vivo, and ex vivo. This was accompanied by re-activation of mitochondrial function in vitro but not in vivo or ex vivo. Finally, using a specific small molecule LDH-A inhibitor, we demonstrated that LDH-A is essential for cancer initiating cell survival and proliferation. Thus, LDH-A can be a viable therapeutic target for NSCLC including cancer stem cell-dependent drug resistant tumors.

We compute loop corrections to the effective action of a field theory on a fivedimensional S 1 /Z 2 orbifold. We find that the quantum loop effects of interactions in the bulk produce infinite contributions that require renormalization by fourdimensional couplings on the orbifold fixed planes. Thus bulk couplings give rise to renormalization group running of brane couplings.

A method is described for establishing an upper bound on the spatial encoding capabilities of coil arrays in parallel MRI. Ultimate intrinsic signal-to-noise ratio (SNR), independent of any particular conductor arrangement, is calculated by expressing arbitrary coil sensitivities in terms of a complete set of basis functions that satisfy Maxwell's equations within the sample and performing parallel imaging reconstructions using these basis functions. The dependence of the ultimate intrinsic SNR on a variety of experimental conditions is explored and a physically intuitive explanation for the observed behavior is provided based on a comparison between the electromagnetic wavelength and the distance between aliasing points. Imaging at high field strength, with correspondingly short wavelength, is shown to offer advantages for parallel imaging beyond those already expected due to the larger available spin polarization. One-dimensional undersampling of k-space yields a steep drop in attainable SNR for more than a 5-fold reduction of scan time, while 2D undersampling permits access to much higher degrees of acceleration. Increased tissue conductivity decreases baseline SNR, but improves parallel imaging performance. A procedure is also provided for generating the optimal coil sensitivity pattern for a given acceleration, which will serve as a useful guide for future coil designs. Magn Reson Med 50: 1018 -1030, 2003.