Time-space evolution and volcanological features of the Late Miocene-Quaternary Calimani-Gurghiu-Harghita Volcanic Range, East Carpathians, Romania. A Review.

The Carpathian-Pannonian Region (CPR) hosts one of the major Cainozoic volcanic provinces of Europe extending in space over 6 eastern European countries.The lithospheric evolution of this large area governed by large-scale asthenospheric processes is recorded by products of volcanic activity occurred during a time interval of more than 21 million years. According to their surface occurrence areas, ages and composition the Neogene volcanics of CPR were systematized in three main groups: 1) mostly explosive products of felsic magmas generated at the beginning of volcanism in the whole CPR and in their particular occurrence areas (21-12 Ma) developed in the actual intra-Carpathian Pannonian Basin, 2) mostly intermediate calc-alkaline rocks emplaced in both the intra-Carpathian areas and along the arcuate Carpathian fold-and-thrust belt, and 3) Na- and K- alkaline and ultra-alkaline products clustered in a number of monogenetic volcanic fields across the whole intra-Carpathian realm developed in the final stages of volcanic activity of the CPR as a whole and of their particular occurrence areas. The ca. 160 km long Călimani-Gurghiu-Harghita volcanic range (CGH) developed as part of the intermediate calc-alkaline volcanism closely related in space with the fold-and-thrust belt of the Carpathians, representing the south-eastern segment of the CPR. Although its map view and general petrochemical and volcanological characteristics are quite similar with those of other segments of the orogene belt- tied calc-alkaline volcanic segments, at a closer look CGH displays a number of unique features. The time-space evolution of CGH is particular not only in that it is the youngest (10.5 to < 0.05 Ma) dominantly calc-alkaline segment in CPR but also it shows a transient character. Unlike other segments along which volcanism occurred simultaneously forming true subduction-related 400 to 800 km long volcanic fronts which were stable in time for millions of year, in CGH volcanic activity migrated continuously along the range from NW to SE. So, during any given 1 Ma time interval active volcanism was restricted to very limited areas and to just a few active volcanic centers. The along-range shift of volcanic foci was concurrent with progressively lower volumes of magma erupted and decreasing magma output rates. As a result, gradually lower-volume and less complex volcanic edifices were built up. Moreover, at the range-ending and youngest South Harghita sub-segment, magma compositions gradually changed from normal calc-alkaline to high-K calc-alkaline and shoshonitic, and adakitic features emerged at the end of volcanic activity, after a time gap of 0.5 Ma. This marks a major geodynamic event in the development of the East Carpathians themselves. During the transient volcanism of CGH, edifices of varying volume and complexity were built up forming a row of tightly- packed adjoining stratovolcanoes/composite volcanoes whose peripheral volcaniclastic aprons complexly juxtaposed, overlapped and merged with each other. The largest ones (Călimani caldera, and Fâncel-Lăpuşna) developed until caldera stage. Some of them (Rusca-Tihu in the Călimani Mts., Vârghiş in the North Harghita Mts.) became unstable during their growth and collapsed, generating widespread large-volume debris avalanche deposits. Edifice instability was solved by volcano-basement interaction processes, such as volcano spreading, at some large-volume volcanoes (in particular those in the Gurghiu Mts.). Volcano typology changed at the smaller-volume constructs toward the southeastern terminus of the range in the South Harghita Mts. from typical large stratovolcanoes to smaller composite volcanoes, dome clusters and isolated domes and simpler internal structures. As a whole, CGH displays an extremely particular evolutionary pattern strongly suggesting a transient character and decreasing to extinguishing volcanic activity along its length from NW to SE

Impact of copper and iron binding properties on the anticancer activity of 8-hydroxyquinoline derived Mannich bases.

The anticancer activity of 8-hydroxyquinolines relies on complex formation with redox active copper and iron ions. Here we employ UV-visible spectrophotometry and EPR spectroscopy to compare proton dissociation and complex formation processes of the reference compound 8-hydroxyquinoline (Q-1) and three related Mannich bases to reveal possible correlations with biological activity. The studied derivatives harbor a CH2-N moiety at position 7 linked to morpholine (Q-2), piperidine (Q-3), and chlorine and fluorobenzylamino (Q-4) substituents. Solid phase structures of Q-3, Q-4·HCl·H2O, [(Cu(HQ-2)2)2]·(CH3OH)2·Cl4·(H2O)2, [Cu(Q-3)2]·Cl2 and [Cu(HQ-4)2(CH3OH)]·ZnCl4·CH3OH were characterized by single-crystal X-ray diffraction analysis. In addition, the redox properties of the copper and iron complexes were studied by cyclic voltammetry, and the direct reaction with physiologically relevant reductants (glutathione and ascorbic acid) was monitored. In vitro cytotoxicity studies conducted with the human uterine sarcoma MES-SA/Dx5 cell line reveal the significant cytotoxicity of Q-2, Q-3, and Q-4 in the sub- to low micromolar range (IC50 values 0.2-3.3 μM). Correlation analysis of the anticancer activity and the metal binding properties of the compound series indicates that, at physiological pH, weaker copper(ii) and iron(iii) binding results in elevated toxicity (e.g.Q4: pCu = 13.0, pFe = 6.8, IC50 = 0.2 μM vs.Q1: pCu = 15.1, pFe = 13.0 IC50 = 2.5 μM). Although the studied 8-hydroxyquinolines preferentially bind copper(ii) over iron(iii), the cyclic voltammetry data revealed that the more cytotoxic ligands preferentially stabilize the lower oxidation state of the metal ions. A linear relationship between the pKa (OH) and IC50 values of the studied 8-hydroxyquinolines was found. In summary, we identify Q-4 as a potent and selective anticancer candidate with significant toxicity in drug resistant cells

Inverse monoids and immersions of 2-complexes

It is well known that under mild conditions on a connected topological space $\mathcal X$, connected covers of $\mathcal X$ may be classified via conjugacy classes of subgroups of the fundamental group of $\mathcal X$. In this paper, we extend these results to the study of immersions into 2-dimensional CW-complexes. An immersion $f : {\mathcal D} \rightarrow \mathcal C$ between CW-complexes is a cellular map such that each point $y \in {\mathcal D}$ has a neighborhood $U$ that is mapped homeomorphically onto $f(U)$ by $f$. In order to classify immersions into a 2-dimensional CW-complex $\mathcal C$, we need to replace the fundamental group of $\mathcal C$ by an appropriate inverse monoid. We show how conjugacy classes of the closed inverse submonoids of this inverse monoid may be used to classify connected immersions into the complex