High immunogenicity and systemic toxicity are the main obstacles limiting the clinical use of the therapeutic agents based on Pseudomonas aeruginosa exotoxin A. In this work, we studied the immunogenicity, general toxicity and antitumor effect of the targeted toxin DARPin-LoPE composed of HER2-specific DARPin and a low immunogenic exotoxin A fragment lacking immunodominant human B lymphocyte epitopes. The targeted toxin has been shown to effectively inhibit the growth of HER2-positive human ovarian carcinoma xenografts, while exhibiting low non-specific toxicity and side effects, such as vascular leak syndrome and liver tissue degradation, as well as low immunogenicity, as was shown by specific antibody titer. This represents prospects for its use as an agent for targeted therapy of HER2-positive tumors.
The formation of snow-dirt sludge (SDS) via the mixing of snow and surface-deposited sediment by vehicles and pedestrians is one of the least studied sedimentation processes in urban areas. The aim of this study was to analyse the material, mineral, particle size, and chemical compositions of the SDS solid phase. The study was conducted using Ekaterinburg, Russia, as an example city with an intense anthropogenic impact and a long cold snowy period. The average content of the SDS solid phase was approximately 35 g L−1 of meltwater on heavy traffic roads, of which the dust fraction (<0.1 mm) accounted for 23 g L−1. On driveways and lawns, the contents of the SDS solid phase were 12 and 6.6 g L−1, respectively. The mineral composition of the SDS solid phase was generally similar to the geology of the surrounding area, which is composed of a mosaicked combination of felsic and mafic complexes. The presence of building material fragments and other anthropogenic particles confirms the significant anthropogenic impact. The chemical composition contained major and minor elements specific to the minerals and materials that constitute the SDS solid phase. There was significant variability in the concentrations of Pb, Cu, and Zn in the granulometric fractions, indicating pollution. Intensive melting of SDS with a high particulate matter (PM) content is an important factor influencing the environmental quality of the urban environment.
The alteration of platinum group minerals (PGM) of eluval, proximal, and distal placers associated with the Ural-Alaskan type clinopyroxenite-dunite massifs were studied. The Isovsko-Turinskaya placer system is unique regarding its size, and was chosen as research object as it is PGM-bearing for more than 70 km from its lode source, the Ural-Alaskan type Svetloborsky massif, Middle Urals. Lode chromite-platinum ore zones located in the Southern part of the dunite "core" of the Svetloborsky massif are considered as the PGM lode source. For the studies, PGM concentrates were prepared from the heavy concentrates which were sampled at different distances from the lode source. Eluvial placers are situated directly above the ore zones, and the PGM transport distance does not exceed 10 m. Travyanistyi proximal placer is considered as an example of alluvial ravine placer with the PGM transport distance from 0.5 to 2.5 km. The Glubokinskoe distal placer located in the vicinity of the Is settlement are chosen as the object with the longest PGM transport distance (30-35 km from the lode source). Pt-Fe alloys, and in particular, isoferroplatinum prevail in the lode ores and placers with different PGM transport distance. In some cases, isoferroplatinum is substituted by tetraferroplatinum and tulameenite in the grain marginal parts. Os-Ir-(Ru) alloys, erlichmanite, laurite, kashinite, bowieite, and Ir-Rh thiospinels are found as inclusions in Pt-Fe minerals. As a result of the study, it was found that the greatest contribution to the formation of the placer objects is made by the erosion of chromite-platinum mineralized zones in dunites. At a distance of more than 10 km, the degree of PGM mechanical attrition becomes significant, and the morphological features, characteristic of lode platinum, are practically not preserved. One of the signs of the significant PGM transport distance in the placers is the absence of rims composed of the tetraferroplatinum group minerals around primary Pt-Fez alloys. The sie of the nuggets decreases with the increasing transport distance. The composition of isoferroplatinum from the placers and lode chromite-platinum ore zones are geochemically similar.
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