General regularization schemes for signal detection in inverse problems

The authors discuss how general regularization schemes, in particular linear regularization schemes and projection schemes, can be used to design tests for signal detection in statistical inverse problems. It is shown that such tests can attain the minimax separation rates when the regularization parameter is chosen appropriately. It is also shown how to modify these tests in order to obtain (up to a $\log\log$ factor) a test which adapts to the unknown smoothness in the alternative. Moreover, the authors discuss how the so-called \emph{direct} and \emph{indirect} tests are related via interpolation properties

Effect of an Electrolyte Cation on Detecting DNA Damage with the Latch Constriction of α‑Hemolysin

The effect of an electrolyte cation on the unzipping of furan-containing double-stranded DNA in an α-hemolysin (αHL) nanopore is described. The current through an open αHL channel increases in proportion to the ion mobility. However, the ionic current measured during residence of a DNA duplex inside of the protein pore shows a more complex dependence on the choice of cation, indicating that the current measured during DNA residence in the pore is modulated by the specific interactions of the cations with the DNA and/or αHL. The residence time (stability) of the DNA duplex inside of the pore prior to unzipping is also highly dependent on the cation, in striking contrast to the small variation in duplex stability (as measured by the melting temperature) in bulk electrolyte solution. A missing base in DNA can be detected in the latch region of αHL with optimal current resolution in RbCl, while optimal time resolution is possible in LiCl

Base-excision repair activity of uracil-DNA glycosylase monitored using the latch zone of α-hemolysin

Nanopores have been investigated as a simple and label-free tool to characterize DNA nucleotides when a ssDNA strand translocates through the constriction of the pore. Here, a wild-type α-hemolysin protein nanopore was used to monitor DNA repair enzyme activity based on base-specific interactions of dsDNA with the vestibule constriction “latch”, a previously unrecognized sensing zone in α-hemolysin specific for dsDNA structure. The presence of a single abasic site within dsDNA that is in proximity to the latch zone (±2 nucleotides) results in a large increase in ion channel current, allowing accurate quantitation of the kinetics of base repair reactions involving an abasic site product. Taking advantage of the high resolution for abasic site recognition, the rate of uracil-DNA glycosylase hydrolysis of the N-glycosidic bond, converting 2′-deoxyuridine in DNA to an abasic site, was continuously monitored by electrophoretically capturing reaction substrate or product dsDNA in the ion channel vestibule. Our work suggests use of the nanopore as an enzymology tool and provides a means to identify single base structural changes in dsDNA