Despite nearly 85 years of successful antibacterial chemotherapy, bacterial infections still pose a serious threat to human health. Continually emerging drug-resistant bacteria make existing agents less effective, and a paucity of new agents and decreased development effort from the pharmaceutical industry provide little hope of replenishing the arsenal (1, 2). Complications and mortality due to bacterial infections continue to increase, already reaching epidemic proportions in some areas of the world. If humans are to regain the upper hand in fighting bacterial infections, then innovation, investment, and new antibacterial agents will be needed. Although some of the barriers to the discovery and approval of new compounds are economic or policy related, there is also a desperate need for new targets and new mechanisms of action. A renewed effort to expand our knowledge of bacterial physiology and to translate discoveries into the clinic will be needed to address these challenges and to reinvigorate antibiotic development pipelines.Recent advances in our understanding of how bacteria maintain physiological homeostasis revealed a promising class of potential antibiotic targets called riboswitches-noncoding mRNAs that form a structured receptor (or aptamer) which can directly bind to a specific small-molecule ligand or ion and thereby regulate gene expression (3-5). Ligand binding to a riboswitch aptamer stabilizes a conformationally distinct architecture in the mRNA that modulates the expression of the adjacent coding region(s) (4-8). To date, more than 35 riboswitch classes have been discovered and characterized (7). Three of these riboswitch classes have been revealed as important cellular targets of antibacterial small molecules whose mechanism of action had not been previously defined (9-13). More recently, several publications have demonstrated that novel small molecules that bind to selected riboswitch aptamers with affinities comparable to that of the cognate ligand can be rationally identified and optimized (14-21).In some cases, synthetic or natural riboswitch ligand analogs have demonstrated potent antibacterial activity (12-15, 20, 22). For example, the phosphorylated form of roseoflavin (RoF) (
The superconducting RF linac for LCLS-II calls for 1.3 GHz 9-cell cavities with an average intrinsic quality factor Q0 of 2.7×10 10 at 2.0 K and 16 MV/m accelerating gradient. Two niobium 9 cell cavities, prepared with nitrogen-doping at Fermilab, were assembled into the Cornell Horizontal Test Cryomodule (HTC) to test cavity performance in a cryomodule that is very similar to a full LCLS-II cryomodule. The cavities met LCLS-II specifications with an average quench field of 17 MV/m and an average Q0 of 3×10 10 . The sensitivity of the cavities' residual resistance to ambient magnetic field was determined to be 0.5 nΩ/mG during fast cool down. In two cool downs, a heater attached to one of the cavity beam tubes was used to induce large horizontal temperature gradients.Here we report on the results of these first tests of nitrogen-doped cavities in a cryomodule, which provide critical information for the LCLS-II project.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.