ing host, our immunofluorescence data suggests that possible mechanisms contributing to the longer tumor growth delay observed with a sequential regimen may include reductions in tumor vascularity and mitotic rate beyond those achievable with a concurrent regimen or either modality alone. Regardless of the specific mechanism of action, both our in vitro and in vivo data suggest that the most effective combination schedule for these agents is a sequential one. The ideal combinedmodality approach to treating unresectable HCC may prove to involve radiotherapy administered concurrently with a radiosensitizing agent followed by maintenance sorafenib therapy. Although no targeted agents with well-established radiosensitizing activity against HCC have yet been identified, promising candidates include inhibitors of heat-shock proteins, EGFR, and the PI3K-AKT-mTOR pathway. In summary, our study presents evidence that concurrent schedules of LY3039478 chemical information sorafenib-radiation may result in tumor control that is equal to or worse than with radiation alone. Moreover, sequential treatment with radiation followed by sorafenib appears to be more efficacious against HCC both in vitro and in vivo than either agent given alone or concurrently. These results have implications for clinical decision making as well as current and future trial design in HCC. ~~ Tuberculosis is an international health concern with little foreseeable relief. With the emergence of multi-drug resistance of the causative agent, Mycobacterium tuberculosis, comes the need to understand the molecular basis of resistance acquisition. Antibiotic penetration of the notoriously impermeable mycobacterial outer membrane requires further exploration. Several mycobacterial efflux pumps have already been associated with reduced susceptibility to anti-tuberculous agents such as isoniazid, tetracycline, fluoroquinolones and aminoglycosides. Antibiotic uptake processes, however, are less clearly understood. Fluoroquinolones form a recent class of drugs increasingly used in the fight against tuberculosis, with members such as moxifloxacin, ofloxacin and levofloxacin being used as second-line treatment agents. While Rv2686-Rv2687-Rv2688c and LfrA have been associated with fluoroquinolone efflux activity in mycobacteria, it remains unclear how fluoroquinolone 
uptake occurs. The observation that the activity of fluoroquinolones against mycobacteria increases with the hydrophobicity of the drug indicates the preference for direct diffusion across lipid membranes. However, a study of M. smegmatis mutants carrying deletions of mspA and mspC, which code for the porins MspA and MspC respectively, showed a 4-fold decrease in intracellular accumulation of norfloxacin compared to the wild-type. It was concluded that porins play an important role in the 15315719 uptake of hydrophilic fluoroquinolones in mycobacteria. Polyamines are naturally-occurring organic molecules with at least two primary amino-groups. Endogenous to both prokaryotic and eukaryotic cell types, these polycations are produced via complex pathways involving the decarboxylation of ornithine, arginine and lysine. Although their exact functions are unclear, they are understood to play pleiotropic roles in cell growth and survival. The effects of four polyamines on the activity of E. coli porins OmpC and OmpF have been documented. These polyamines were 17251021 shown to suppress channel opening, enhance channel closure as well as promote the inactive state. It has been sugges