Corrigendum: Towards automatic pulmonary nodule management in lung cancer screening with deep learning.

This corrects the article DOI: 10.1038/srep46479.

Cloning, purification and characterisation of the lipase from Staphylococcus epidermidis--comparison of the substrate selectivity with those of other microbial lipases.

On the chromosome of Staphylococcus epidermidis RP62A the lipase gene (gehSE1) is immediately flanked by the icaAA'BC operon, which is involved in biofilm formation. Since lipase production might play a role in staphylococcal skin colonisation as well, we studied the biochemical properties of the staphylococcal lipases more closely. The DNA sequence and the deduced protein sequence revealed that gehSE1 is very similar to the lipase sequence of S. epidermidis strain 9. Like other staphylococcal lipases, gehSE1 is organised as a preproenzyme. The part of gehSE1 coding for the mature lipase was cloned and overexpressed as a fusion protein with an N-terminal histidine tag in Escherichia coli. The lipase was purified to homogeneity using a combination of precipitation techniques, metal-affinity chromatography and gel filtration. Biochemical characterisation showed that this lipase is closely related to the lipase from Staphylococcus aurelis NCTC8530. Both enzymes have a pH optimum around 6, are very stable at low pH, and need calcium as a cofactor for catalytic activity. The preferred substrates are small triacylglycerols, with a maximum activity toward tributyrylglycerol. Comparison of the substrate selectivity with those of other microbial lipases showed that phospholipids are generally poor substrates for lipases. An exception is the lipase from Staphylococcus hyicus, which prefers phospholipids as a substrate, distinguishing this staphylococcal lipase from other microbial lipases. These results are discussed in view of the structure/function relationships of staphylococcal lipases, and the possible involvement of these enzymes in biological processes such as skin colonisation and pathogenesis.

Iontophoretic delivery of nonpeptide drugs: formulation optimization for maximum skin permeability.

Although the technique of transdermal iontophoretic drug delivery has been known for many years, its use has been limited clinically to those applications for which a brief drug delivery period is adequate (e.g., delivery of pilocarpine in the diagnosis of cystic fibrosis). For most therapeutic applications, however, it is necessary to have an extended, if not continuous, drug delivery regimen. The use of iontophoresis has been limited in these applications by side effects, primarily skin trauma, associated both with the current density and the total amount of current passed. A mechanism for these side effects will be proposed and techniques to mitigate them will be presented. Many of these techniques involve ways in which the drug formulation can be designed to maximize the fraction of current carried by the drug species. These methods include the following: control of the pH in the bulk solution and in the boundary layer without using conventional buffers; taking advantage of polarization effects; and enhancing the permselectivity of skin. In this way, the therapeutic dose or optimal infusion rate of drug can be achieved with the minimum current and, therefore, the minimum number of side effects.