THE SOUTH-EASTERN BORDER REGION OF THE HITTITE STATE

Tegarama was one of the eastern lands of the Hittite Kingdom. In the geographic sense it is part of the Armenian Highland that is why its history is of special interest to us. Taking into account the fact that the Armenian people had considerable ethnic ties with the Upper Euphrates region, specialists have traditionally tended to identify “Home of Torgom” in the Trans Euphrates region together with the city Tegarama (Assyrian Til-Garimmu) mentioned from the 2nd millennium BC. “Home of Torgom” literally repeats Bet-Togarma mentioned in the Bible. The study of the history of the country of Tegarama is also important because in Armenian historiography, starting from Movses Khorenatsi, Armenian ancestor Hayk is called “Son of Torgom”, and the Armenian people - “People of Torgom”. Most of the researchers located Tegarama in the place of the present settlement Gyurun. By comparing the “Cappadocian”, Hittite and Assyrian sources, Tegarama can be located in the Upper Euphrates valley, on the right bank of the river, to the north of Kargamis, to the west of Isuwa, to the south of Upper Land and to the east of Kanes. The territory of Tegarama was not far from Nesa - one of the initial centers of the Hittites; and it was also one of the initial places of inhabitance of the Hittites. Tegarama also occupied a strategically important position. On the one hand it bordered on the country of Mitanni, on the other hand - on Isuwa. Thus, the country of Tegarama occupied a significant geographic position: on the one hand roads led from here to other western districts of the Armenian Highland, to Tsopk, and on the other hand - to Northern Syria and Northern Mesopotamia. It was also one of the spiritual centers of Hatti

THE WESTERN REGIONS OF THE ARMENIAN HIGHLAND ACCORDING TO THE 20TH-18TH CC BC KANEŠ SOURCES

The city of Kaneš or Nesa was located in the east of Asia Minor. The city had been inhabited since the Chalcolite Age and flourished especially at the beginning of the second millennium (20th-18th centuries BC), when it was the center of the Assyrian merchants in the region and the capital of the state of Kaneš. For some time it was also the capital of the Hittite state (18th century BC). Invaluable sources for the history of Asia Minor and the surrounding areas are the so-called "Cappadocian tablets" from Kaneš, to be more precise from the Kültepe (Arm. Zrzort). These are tens of thousands of cuneiform tablets written in Akkadian, representing mainly the activities of Aššur trade colonies located in different regions of Asia Minor in the 20th-18th centuries BC. These are the earliest written documents that reveal the history of the region at that time and partially cover the history of the western regions of the Armenian Highland

Quantum impurity model for anyons

One of the hallmarks of quantum statistics, tightly entwined with the concept of topological phases of matter, is the prediction of anyons. Although anyons are predicted to be realized in certain fractional quantum Hall systems, they have not yet been unambiguously detected in experiment. Here we introduce a simple quantum impurity model, where bosonic or fermionic impurities turn into anyons as a consequence of their interaction with the surrounding many-particle bath. A cloud of phonons dresses each impurity in such a way that it effectively attaches fluxes or vortices to it and thereby converts it into an Abelian anyon. The corresponding quantum impurity model, first, provides a different approach to the numerical solution of the many-anyon problem, along with a concrete perspective of anyons as emergent quasiparticles built from composite bosons or fermions. More importantly, the model paves the way toward realizing anyons using impurities in crystal lattices as well as ultracold gases. In particular, we consider two heavy electrons interacting with a two-dimensional lattice crystal in a magnetic field, and show that when the impurity-bath system is rotated at the cyclotron frequency, impurities behave as anyons as a consequence of the angular momentum exchange between the impurities and the bath. A possible experimental realization is proposed by identifying the statistics parameter in terms of the mean-square distance of the impurities and the magnetization of the impurity-bath system, both of which are accessible to experiment. Another proposed application is impurities immersed in a two-dimensional weakly interacting Bose gas

A Quantum Impurity Model for Anyons

One of the hallmarks of quantum statistics, tightly entwined with the concept of topological phases of matter, is the prediction of anyons. Although anyons are predicted to be realized in certain fractional quantum Hall systems, they have not yet been unambiguously detected in experiment. Here we introduce a quantum impurity model, where bosonic (or fermionic) impurities turn into anyons as a consequence of their interaction with the surrounding many-particle bath. A cloud of phonons dresses each impurity in such a way that it effectively attaches fluxes/vortices to it and thereby converts it into an Abelian anyon. The corresponding quantum impurity model, first, provides a new approach to the numerical solution of the many-anyon problem, along with a new concrete perspective of anyons as emergent quasiparticles built from composite bosons or fermions. More importantly, the model paves the way towards realizing anyons using impurities in crystal lattices as well as ultracold gases. In particular, we consider two heavy electrons interacting with a two-dimensional lattice crystal in a magnetic field, and show that they behave as anyons when the impurity-bath system is rotated at the cyclotron frequency. A possible experimental realization is proposed by identifying the statistics parameter in terms of the mean square distance of the impurities and the magnetization of the impurity-bath system, both of which are accessible to experiment. Another proposed application are impurities immersed in a two-dimensional weakly interacting Bose gas

In vitro testing of cyto- and genotoxicity of new porphyrin water-soluble metal derivatives

Porphyrins and porphyrin derivatives have an outstanding potential for discovery of novel pharmacological agents due to their ability for numerous chemical modifications and a variety of mechanisms of biological effects. New water-soluble Ag and Zn derivatives of tetrachloride meso-tetra (4-N-oxiethylpyridyl) porphyne were synthesized. Cyto- and genotoxicity of these substances were tested in vitro by the vital dye (trypan blue) exclusion and the micronucleus tests, respectively. Both metalloporphyrins were shown to be cytotoxic for Cos-7 (fibroblast-like African green monkey kidney cells transformed by simian virus 40 [SV40]), DU 145 (epithelial-like cells of human prostate carcinoma), and K-562 (human chronic myeloid leukemia cells) cell lines. At the same time they did not cause chromosome fragmentation in K-562 cell line at as high concentrations as IC(50) (20 micromol/L for Ag and 70 micromol/L for Zn derivative). Thus, the metalloporphyrins tested meet at least two important demands to potential anticancer drugs as they combine the cytotoxicity with low genotoxicity. The three in vitro tumor models used are relevant to further in vitro and in vivo preclinical investigation of the studied metalloporphyrins as potential chemotherapeutics

Assessment of new cationic porphyrin binding to plasma proteins by planar microarray and spectroscopic methods

<div><p>Porphyrins have a unique aromatic structure determining particular photochemical properties that make them promising photosensitizers for anticancer therapy. Previously, we synthesized a set of artificial porphyrins by modifying side-chain functional groups and introducing different metals into the core structure. Here, we have performed a comparative study of the binding properties of 29 cationic porphyrins with plasma proteins by using microarray and spectroscopic approaches. The porphyrins were noncovalently immobilized onto hydrogel-covered glass slides and probed to bio-conjugated human and bovine serum albumins, as well as to human hemoglobin. The signal detection was carried out at the near-infrared fluorescence wavelength (800 nm) that enabled the effect of intrinsic visible wavelength fluorescence emitted by the porphyrins tested to be discarded. Competition assays on porphyrin microarrays indicated that long-chain fatty acids (FAs) (palmitic and stearic acids) decrease porphyrin binding to both serum albumin and hemoglobin. The binding affinity of different types of cationic porphyrins for plasma proteins was quantitatively assessed in the absence and presence of FAs by fluorescent and absorption spectroscopy. Molecular docking analysis confirmed results that new porphyrins and long-chain FAs compete for the common binding site FA1 in human serum albumin and meso-substituted functional groups in porphyrins play major role in the modulation of conformational rearrangements of the protein.</p> </div

Rational design of superoxide dismutase (sod) mimics: The evaluation of the therapeutic potential of new cationic Mn porphyrins with linear and cyclic substituents

Our goal herein has been to gain further insight into the parameters which control porphyrin therapeutic potential. Mn porphyrins (MnTnOct-2-PyP5+, MnTnHexOE-2-PyP5+, MnTE-2-PyPhP5+, and MnTPhE-2-PyP5+) that bear the same positive charge and same number of carbon atoms at meso positions of porphyrin core were explored. The carbon atoms of their meso substituents are organized to form either linear or cyclic structures of vastly different redox properties, bulkiness, and lipophilicities. These Mn porphyrins were compared to frequently studied compounds, MnTE-2-PyP5+, MnTE-3-PyP5+, and MnTBAP3-. All Mn(III) porphyrins (MnPs) have metal-centered reduction potential, E1/2 for MnIIIP/MnIIP redox couple, ranging from 194 to +340 mV versus NHE, log kcat(O2¢-) from 3.16 to 7.92, and log kred(ONOO-) from 5.02 to 7.53. The lipophilicity, expressed as partition between n-octanol and water, log POW, was in the range 1.67 to 7.67. The therapeutic potential of MnPs was assessed via: (i) in vitro ability to prevent spontaneous lipid peroxidation in rat brain homogenate as assessed by malondialdehyde levels; (ii) in vivo O2¢- specific assay to measure the efficacy in protecting the aerobic growth of SOD-deficient Saccharomyces cerevisiae; and (iii) aqueous solution chemistry to measure the reactivity toward major in vivo endogenous antioxidant, ascorbate. Under the conditions of lipid peroxidation assay, the transport across the cellular membranes, and in turn shape and size of molecule, played no significant role. Those MnPs of E1/2∼+300 mV were the most efficacious, significantly inhibiting lipid peroxidation in 0.5-10 M range. At up to 200 M, MnTBAP3- (E1/2 = 194 mV vs NHE) failed to inhibit lipid peroxidation, while MnTE-2-PyPhP5+ with 129 mV more positive E1/2 (65 mV vs NHE) was fully efficacious at 50 M. The E1/2 of MnIIIP/MnIIP redox couple is proportional to the log kcat(O2¢-), i.e., the SOD-like activity of MnPs. It is further proportional to kred(ONOO-) and the ability of MnPs to prevent lipid peroxidation. In turn, the inhibition of lipid peroxidation by MnPs is also proportional to their SOD-like activity. In an in vivo S. cerevisiae assay, however, while E1/2 predominates, lipophilicity significantly affects the efficacy of MnPs. MnPs of similar log POW and E1/2, that have linear alkyl or alkoxyalkyl pyridyl substituents, distribute more easily within a cell and in turn provide higher protection to S. cerevisiae in comparison to MnP with bulky cyclic substituents. The bell-shape curve, with MnTE-2-PyP5+ exhibiting the highest ability to catalyze ascorbate oxidation, has been established and discussed. Our data support the notion that the SOD-like activity of MnPs parallels their therapeutic potential, though species other than O2¢-, such as peroxynitrite, H2O2, lipid reactive species, and cellular reductants, may be involved in their mode(s) of action(s)