Nitric Oxide: Perspectives and Emerging Studies of a Well Known Cytotoxin

The free radical nitric oxide (NO•) is known to play a dual role in human physiology and pathophysiology. At low levels, NO• can protect cells; however, at higher levels, NO• is a known cytotoxin, having been implicated in tumor angiogenesis and progression. While the majority of research devoted to understanding the role of NO• in cancer has to date been tissue-specific, we herein review underlying commonalities of NO• which may well exist among tumors arising from a variety of different sites. We also discuss the role of NO• in human physiology and pathophysiology, including the very important relationship between NO• and the glutathione-transferases, a class of protective enzymes involved in cellular protection. The emerging role of NO• in three main areas of epigenetics—DNA methylation, microRNAs, and histone modifications—is then discussed. Finally, we describe the recent development of a model cell line system in which human tumor cell lines were adapted to high NO• (HNO) levels. We anticipate that these HNO cell lines will serve as a useful tool in the ongoing efforts to better understand the role of NO• in cancer

Mechanistic investigation of CO2 hydroformylation methods

Tämän pro gradu – tutkielman kirjallisessa osassa on käsitelty perinteinen hydroformylaatioreaktio, jossa käytetään hiilimonoksidia reagenssina. Tämä sisältää useiden eri tutkimusryhmien tekemiä reaktioita. Esimerkit reaktioista ovat jaoteltu muun muassa eri lähtöaineiden, sekä erilaisten katalyyttikompleksien mukaan. Katalyyttikompleksien käyttäytymistä reaktiossa on kuvattu reaktiomekanismien avulla. Kirjallisuuskatsauksen tärkeimmässä osassa on käsitelty lukuisia esimerkkejä tähän asti tehdyistä hiilidioksidia käyttävistä hydroformylointireaktioista. Tämäkin osuus sisältää kuvauksen useimmiten käytetyistä katalyyttikomplekseista, ja niiden käyttäytymisen reaktiomekanismeista. Ioninesteitä ja niiden ominaisuuksia on kuvattu, sillä niitä on onnistuneesti käytetty liuottimina hydroformylointireaktiossa. Käänteistä vesi-kaasu siirtoreaktiota on myös käsitelty tarkasti, sillä se muuntaa hiilimonoksidin hiilidioksidiksi, joka toimii lähtoaineena hydroformylointireaktiossa. Tutkielman kokeellisen osan tavoitteena oli alun perin selvittää tarkemmin hiilidioksidia käyttävän hydroformylointireaktion mekanismia, tutkimalla kineettistä isotooppiefektiä (KIE) leimauskokeiden avulla. Tämän mahdollistamiseksi oli syntetisoitu leimatut lähtöaineet, 1-deuterium-syklohekseeni sekä 1,2,3,3-tetradeuterium-syklohekseeni, joiden saannot ja leimautumisprosentit saatiin melko suuriksi. Projektille annetun hyvin lyhyen ajan vuoksi näitä lähtöaineita ei kuitenkaan ehditty käyttämään hydroformylointireaktion mekanismin tutkimiseen.The theoretical part of the thesis describes the conventional hydroformylation reaction, which uses carbon monoxide, with many important reaction examples performed by several investigation groups. Reaction examples are divided by substances, and different homogeneous catalytic complexes, also different reaction mechanisms depending on used catalytic complex, are described. As a very important part, also several examples of hydroformylation reaction that uses carbon dioxide are described, together with mostly used homogeneous catalytic complexes, and reaction mechanisms. This contains reverse-water gas shift reaction, which converts carbon monoxide to carbon dioxide, and ionic liquids, which are successfully used as solvents in hydroformylation reaction. The experimental part aimed to investigate the mechanism of the carbon dioxide-based hydroformylation reaction through investigating the kinetic isotope effect (KIE). Based on that, deuterated substrates were synthesized with good yields and deuteration levels, 1-deuterio-cyclohexene and 1,2,3,3-tetradeuterio-cyclohexene. Unfortunately, the deuterated substrates could not be used in the KIE-experiments, due to the lack of time for this project

ЕФЕКТИВНІСТЬ ВИКОРИСТАННЯ ФІНАНСОВОГО ЛІЗИНГУ ДЛЯ ОНОВЛЕННЯ ОСНОВНОГО КАПІТАЛУ ПІДПРИЄМСТВ ЗАЛІЗНИЧНОЇ ГАЛУЗІ

In the article the dynamics of development and global structure of the leasing market are analyzed, the advantages of using the financial leasing for upgrading the fixed capital of railway industry are formulated.В статье проанализированы динамика развития и мировая структура рынка лизинга, сформулированы преимущества использования финансового лизинга для обновления основного капитала железнодорожной отрасли.У статті проаналізовано динаміку розвитку та світову структуру ринку лізингу, сформульовано переваги використання фінансового лізингу для оновлення основного капіталу залізничної галузі

THE USE EFFICIENCY OF FINANCIAL LEASING FOR THE RENEWAL OF FIXED CAPITAL OF THE RAILWAY INDUSTRY ENTERPRISES

In the article the dynamics of development and global structure of the leasing market are analyzed, the advantages of using the financial leasing for upgrading the fixed capital of railway industry are formulated

On the flexibility of the boundaries between the A-form and B-form sections in DNA molecule.

The degree of orientation of DNA in a flow has been studied within the interval of the B - A transition induced by ethanol. The orientation of the B DNA (60-65% ethanol, v/v) and that of the A DNA (80-82% ethanol) are nearly identical. This means that both conformations have similar persistence lengths and that there is no aggregation in the course of formation of the A form. Within the transition range (65-78% ethanol) the orientation attains a sharp minimum which coincides with the half-transition point (73% ethanol). The cooperative character of the B - A transition presupposes the existence of boundaries between the alternating sections of the A and B conformations that may entail an increased flexibility of the DNA molecule and a corresponding drop of orientation. Theory predicts an elliptical dependence of the number of boundaries on the proportion of the A form. The experimental degree of orientation follows the same pattern. Quantitative evaluation shows that the flexibility of a boundary is small, so that several dozen of boundaries are required to simulate free rotation

Distamycin-stabilized antiparallel-parallel-combination (APC) DNA

The formation of Antiparallel-Parallel-Combination (APC) DNA, a liner duplex with a segment of parallel-stranded (ps) helix flanked by conventional B-DNA, was tested with a number of synthetic oligonucleotides. The groove-binding ligand distamycin A (DstA) was used to stabilize the ps segment comprising five AT base pairs. Two drug molecules bound per APC, one in each of the two equivalent grooves characteristic of ps-DNA. APC-DNA, reference molecules and their complexes with DstA were analysed by several methods: circular dichroism and absorption spectroscopy, thermal denaturation, chemical modification, and molecular modeling. The dye binding stoichiometry differed significantly due to inherent structural differences in the groove geometries of ps-DNA (trans base pairs, similar grooves) and conventional antiparallel-stranded (aps) B-DNA (cis base pairs, distinct major and minor grooves). The data support the existence of APC folding in solution

The detection of B-form/A-form junction in a deoxyribonucleotide duplex.

The transition of the 14-meric deoxyoligonucleotide duplex d-(ACCCCCTTTTTTTG).d-(CAAAAAAAGGGGGT) from the B- to the A-conformation in water/trifluorethanol (TFE) solution was studied with the use of circular dichroism. An increase in the fraction of TFE induces a two-step B-A transition. In the first step, up to 73% TFE, the A-form is generated from the GC-rich part; in the second step, 73-82% TFE, the AT-rich part shifts to the A-form. By this we suggest the existence of a B/A junction near 73% TFE. Emergence of the B/A junction has been directly confirmed with the use of distamycin A and netropsin, ligands known to selectively bind to AT stretches of B-DNA. It can be shown that both ligands suppress formation of the A-form in the B-philic part. The free energy value for the B/A junction was estimated to be 2.1 kcal/mol, which agrees well with known data for polymeric DNAs. The obtained results may have biological relevance in connection with recently published x-ray data about the occurrence of the B/A junction in the complex of DNA with reverse transcriptase of HIV