Biomimetic modeling of the nitrogen-centered radical postulated to occur during the inhibition of ribonucleotide reductases by 2'-azido-2'-deoxynucleotides

Ribonucleotide reductases (RNR) are essential enzymes that catalyze the reduction of ribonucleotides to 2'-deoxyribonucleotides, which is a critical step that produces precursors for DNA replication and repair. The inactivation of RNR, logically, would discontinue producing the precursors of the DNA of viral or cancer cells, which then would consequently end the cycle of DNA replication. Among different compounds that were found to be inhibitors of RNR, 2'-azido-2'-deoxynucleotide diphosphates (N3NDPs) have been investigated in depth as potent inhibitors of RNR. Decades of investigation has suggested that the inactivation of RNR by N3NDPs is a result of the formation of a nitrogen-centered radical (N·) that is covalently attached to the nucleotide at C3' and cysteine molecule C225 [3'-C(R-S-N·-C-OH)]. Biomimetic simulation reactions for the generation of the nitrogen-centered radicals similar to the one observed during the inactivation of the RNR by azionuclotides was investigated. The study included several modes: (i) theoretical calculation that showed the feasibility of the ring closure reaction between thiyl radicals and azido group; (ii) synthesis of the model azido nucleosides with a linker attached to C3' or C5' having a thiol or vicinal dithiol functionality; (iii) generation of the thiyl radical under both physiological and radiolysis conditions whose role is important in the initiation on RNR cascades; and (iv) analysis of the nitrogen-centered radical species formed during interaction between the thiyl radical and azido group by electron paramagnetic resonance spectroscopy (EPR). Characterization of the aminyl radical species formed during one electron attachment to the azido group of 2'-azido-2'-deoxyuridine and its stereospecifically labelled 1'-, 2'-, 3'-, 4'- or 5,6-[2H 2]-analogues was also examined. This dissertation gave insight toward understanding the mechanism of the formation of the nitrogen-centered radical during the inactivation of RNRs by azidonucleotides as well as the mechanism of action of RNRs that might provide key information necessary for the development of the next generation of antiviral and anticancer drugs.

Ab initio quantum chemical studies on neutral-radical reactions of ethynyl (C2H) and cyano (CN) with unsaturated hydrocarbons

An Ab Initio/RRKM study of the reaction mechanism and product branching ratios of neutral-radical ethynyl (C2H) and cyano (CN) radical species with unsaturated hydrocarbons is performed. The reactions studied apply to cold conditions such as planetary atmospheres including Titan, the Interstellar Medium (ISM), icy bodies and molecular clouds. The reactions of C2H and CN additions to gaseous unsaturated hydrocarbons are an active area of study. NASA's Cassini/Huygens mission found a high concentration of C2H and CN from photolysis of ethyne (C2H2) and hydrogen cyanide (HCN), respectively, in the organic haze layers of the atmosphere of Titan. The reactions involved in the atmospheric chemistry of Titan lead to a vast array of larger, more complex intermediates and products and may also serve as a chemical model of Earth's primordial atmospheric conditions. The C2H and CN additions are rapid and exothermic, and often occur barrierlessly to various carbon sites of unsaturated hydrocarbons. The reaction mechanism is proposed on the basis of the resulting potential energy surface (PES) that includes all the possible intermediates and transition states that can occur, and all the products that lie on the surface. The B3LYP/6-311g(d,p) level of theory is employed to determine optimized electronic structures, moments of inertia, vibrational frequencies, and zero-point energy. They are followed by single point higher-level CCSD(T)/cc-vtz calculations, including extrapolations to complete basis sets (CBS) of the reactants and products. A microcanonical RRKM study predicts single-collision (zero-pressure limit) rate constants of all reaction paths on the potential energy surface, which is then used to compute the branching ratios of the products that result. These theoretical calculations are conducted either jointly or in parallel to experimental work to elucidate the chemical composition of Titan's atmosphere, the ISM, and cold celestial bodies.<.

Ballots for Equality: An Approach to the Radical Tradition in U.S. Electoral Politics

Posing radical challenges to structural inequality is the defining quality of the Left. What role electoral politics might play in such processes is a dilemma of radical politics, the contours of which vary by historical and national contexts. For the U.S. Left there is a distinctive aspect of the dilemma directly related to the failure of a "Left" party of even the most moderate social democratic type to take root, creating a seemingly never ending debate over the value if any of "third party" progressive organizing. This debate is current, as illustrated by three divergent approaches; independent left electoral politics (Socialist Alternative), organizing within the less conservative of the dominant parties (Progressive Democrats of America), and a social movement focus outside the electoral process (Occupy Movement). The present day examples of alternative Left strategies noted here in passing are but three of many such specific organizational options for progressive politics. This article does not seek to advocate for any one of these options to the exclusion of the others but rather seeks to provide historical perspective.

The effects of biofeedback on the occurrence of urinary incontinence in patients following radical retropubic prostatectomy

Postprostatectomy incontinence can create a significant barrier to the attainment of optimal social and physical functioning postoperatively. The objective of this retrospective, descriptive study was to determine the effect of biofeedback on the incidence of urinary incontinence in men status post radical retropubic prostatectomy (RRP). All patients of a urologic practice who had a biofeedback session preoperatively, and two sessions postoperatively, were sent a survey to complete. Correlational analysis concluded that there was no significance (p > .05) between a subject's age, educational level, or adherence to biofeedback therapy, and their level of postprostatectomy incontinence. Of those subjects who participated (n = 46), 35% reported their urinary control as excellent, 50% reported good results, and 15% reported fair results. No subjects reported poor urinary control. Ninety-five percent of subjects said they would recommend the biofeedback treatment to a friend, and 88% felt that biofeedback had helped them attain their present level of urinary control.

Structure, energetics and reactions of metal cation complexes of dipeptides in the gas phase

Structure, energetics and reactions of ions in the gas phase can be revealed by mass spectrometry techniques coupled to ions activation methods. Ions can gain enough energy for dissociation by absorbing IR light photons introduced by an IR laser to the mass spectrometer. Also collisions with a neutral molecule can increase the internal energy of ions and provide the dissociation threshold energy. Infrared multiple photon dissociation (IRMPD) or sustained off-resonance irradiation collision-induced dissociation (SORI-CID) methods are combined with Fourier Transform Ion Cyclotron Resonance (FT-ICR) mass spectrometers where ions can be held at low pressures for a long time. The outcome of ion activation techniques especially when it is compared to the computational methods results is of great importance since it provides useful information about the structure, thermochemistry and reactivity of ions of interest. In this work structure, energetics and reactivity of metal cation complexes with dipeptides are investigated. Effect of metal cation size and charge as well as microsolvation on the structure of these complexes has been studied. Structures of bare and hydrated Na and Ca complexes with isomeric dipeptides AlaGly and GlyAla are characterized by means of IRMPD spectroscopy and computational methods. At the second step unimolecular dissociation reactions of singly charged and doubly charged multimetallic complexes of alkaline earth metal cations with GlyGly are examined by CID method. Also structural features of these complexes are revealed by comparing their IRMPD spectra with calculated IR spectra of possible structures. At last the unimolecular dissociation reactions of Mn complexes are studied. IRMPD spectroscopy along with computational methods is also employed for structural elucidation of Mn complexes. In addition the ion-molecule reactions of Mn complexes with CO and water are explored in the low pressures obtained in the ICR cell.

Crafting Radical Opposition or Reproducing Homonormativity? : Consociationalism and LGBT Rights Activism in Lebanon

Peer reviewed

Crafting Radical Opposition or Reproducing Homonormativity? : Consociationalism and LGBT Rights Activism in Lebanon

Peer reviewed

Different cation-protonation patterns in mol-ecular salts of unsymmetrical dimethyhydrazine : C2H9N2·Br and C2H9N2·H2PO3

Peer reviewed

A facile spin-cast route for cation exchange of multilayer perpendicularly-aligned nanorod assemblies

A facile spin cast route was developed to convert perpendicularly aligned nanorod assemblies of cadmium chalcogenides into their silver and copper analogues. The assemblies are rapidly cation exchanged without affecting either the individual rod dimensions or collective superlattice order extending over several multilayers.

Perpetuating sales: enabling incumbent survival of radical technological shifts

This paper examines an industry whose incumbents’ specialised complimentary assets were their operations management and distribution channels. This advantage was seriously undermined by the advent of digital distribution. Radical technological change theories dictate that if incumbents in an industry without specialised complimentary assets will be replaced by entrants. This did not happen, and extant theories of incumbent survival do not explain why the incumbents remained dominant in the industry. We propose that survival is due to the unique industry characteristic of perpetuating sales. This paper will explain what is a perpetuating sales model and why does it enable incumbent survival?

Low valence cation doping of bulk Cr2O3: Charge compensation and oxygen vacancy formation

The different oxidation states of chromium allow its bulk oxide form to be reducible, facilitating the oxygen vacancy formation process, which is a key property in applications such as catalysis. Similar to other useful oxides such as TiO2, and CeO2, the effect of substitutional metal dopants in bulk Cr2O3 and its effect on the electronic structure and oxygen vacancy formation are of interest, particularly in enhancing the latter. In this paper, density functional theory (DFT) calculations with a Hubbard + U correction (DFT+U) applied to the Cr 3d and O 2p states, are carried out on pure and metal-doped bulk Cr2O3 to examine the effect of doping on the electronic and geometric structure. The role of dopants in enhancing the reducibility of Cr2O3 is examined to promote oxygen vacancy formation. The dopants are Mg, Cu, Ni, and Zn, which have a formal +2 oxidation state in their bulk oxides. Given this difference in host and, dopant oxidation states, we show that to predict the correct ground state two metal dopants charge compensated with an oxygen vacancy are required. The second oxygen atom removed is termed "the active" oxygen vacancy and it is the energy required to remove this atom that is related to the reduction process. In all cases, we find that substitutional doping improves the oxygen vacancy formation of bulk Cr2O3 by lowering the energy cost.

De la prensa al libro : Radical libre de Manuel Vicent: El proceso compositivo de una antología

Fil: Macciuci, Raquel. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales (UNLP-CONICET); Argentina.

De la prensa al libro : Radical libre de Manuel Vicent: El proceso compositivo de una antología

Fil: Macciuci, Raquel. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales (UNLP-CONICET); Argentina.

De la prensa al libro : Radical libre de Manuel Vicent: El proceso compositivo de una antología

Fil: Macciuci, Raquel. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales (UNLP-CONICET); Argentina.