Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection

Citation: Udukala, D. N., Wang, H. W., Wendel, S. O., Malalasekera, A. P., Samarakoon, T. N., Yapa, A. S., . . . Bossmann, S. H. (2016). Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection. Beilstein Journal of Nanotechnology, 7, 364-373. doi:10.3762/bjnano.7.33Additional Authors: Ortega, R.;Toledo, Y.;Bossmann, L.;Robinson, C.;Janik, K. E.;Koper, O. B.;Motamedi, M.;Zhu, G. H.Proteases, including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins (CTS) exhibit numerous functions in tumor biology. Solid tumors are characterized by changes in protease expression levels by tumor and surrounding tissue. Therefore, monitoring protease levels in tissue samples and liquid biopsies is a vital strategy for early cancer detection. Water-dispersable Fe/Fe3O4-core/shell based nanoplatforms for protease detection are capable of detecting protease activity down to sub-femtomolar limits of detection. They feature one dye (tetrakis(carboxyphenyl) porphyrin (TCPP)) that is tethered to the central nanoparticle by means of a protease-cleavable consensus sequence and a second dye (Cy 5.5) that is directly linked. Based on the protease activities of urokinase plasminogen activator (uPA), MMPs 1, 2, 3, 7, 9, and 13, as well as CTS B and L, human breast cancer can be detected at stage I by means of a simple serum test. By monitoring CTS B and L stage 0 detection may be achieved. This initial study, comprised of 46 breast cancer patients and 20 apparently healthy human subjects, demonstrates the feasibility of protease-activity-based liquid biopsies for early cancer diagnosis

Chlorophylls, ligands and assembly of light-harvesting complexes in chloroplasts

Chlorophyll (Chl) b serves an essential function in accumulation of light-harvesting complexes (LHCs) in plants. In this article, this role of Chl b is explored by considering the properties of Chls and the ligands with which they interact in the complexes. The overall properties of the Chls, not only their spectral features, are altered as consequences of chemical modifications on the periphery of the molecules. Important modifications are introduction of oxygen atoms at specific locations and reduction or desaturation of sidechains. These modifications influence formation of coordination bonds by which the central Mg atom, the Lewis acid, of Chl molecules interacts with amino acid sidechains, as the Lewis base, in proteins. Chl a is a versatile Lewis acid and interacts principally with imidazole groups but also with sidechain amides and water. The 7-formyl group on Chl b withdraws electron density toward the periphery of the molecule and consequently the positive Mg is less shielded by the molecular electron cloud than in Chl a. Chl b thus tends to form electrostatic bonds with Lewis bases with a fixed dipole, such as water and, in particular, peptide backbone carbonyl groups. The coordination bonds are enhanced by H-bonds between the protein and the 7-formyl group. These additional strong interactions with Chl b are necessary to achieve assembly of stable LHCs

Microstructural characterization of porous thermal barrier coatings by IR gas porosimetry and sintering forecasts

It is known that the thermal diffusivity of plasma sprayed coatings is quite sensitive to the operating conditions, namely the composition and pressure of the operating atmosphere. This makes it possible, in principle, to obtain information, in a non-destructive way, on the microstructure of thermal barrier coatings (TBCs) from thermal diffusivity measurements. An experimental assessment of this idea is presented in this paper. The microstructure of as-sprayed and sintered free-standing atmospheric plasma sprayed YPSZ TBC samples have been characterized by a new technique, named infrared (IR) gas porosimetry, as well as by mercury intrusion porosimetry and image analysis. The results from these different techniques have been compared. Furthermore, the microstructure and thermal diffusivity of sintered samples have been compared with the sintering forecasts produced by Cipitria’s sintering code coupled with the Bruggeman model for thermal diffusivity estimation. Sample-to-sample variations have been discussed and uncertainties in experimental techniques have been analysed. Conditions for accurate microstructural estimations have been obtained and suggestions on the reliability of the statistical evaluation are provide