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.

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

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?

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.

Radical Ambition: A Portrait of the Toronto New Left, 1958-1985

This thesis examines the rise and decline of the New Left in Toronto from 1958 to 1985. It argues that New Leftism — whose three leading ideals were self-management, national liberation, and community — arose as much from the Old Left as it did from the peace movement. In contrast to earlier readings that interpret the New Left narrowly — essentially, as the combined forces of the white student and peace movements evident mainly on university campuses — this thesis documents the extent to which New Leftism, interpreted as a political formation, provided a framework for a diversity of radical social movements, especially feminism, Black Power, gay liberation, resistance to the capitalist redevelopment of the city, and transnational solidarity. It also questions a declensionist narrative that adopts a “decadal” approach to the radicalism of the sixties, according to which 1970 spelled the end of “60s” radicalism. Quite the contrary, this thesis argues: in Toronto, it would be truer to say that 1970s were “the sixties,” in that only in this later decade did many New Left movements attain their full maturity. New Leftists successfully challenged a host of institutions, sometimes with permanent effects. The educational system was transformed. Cultural institutions and practices were revolutionized. Questions of race and gender, once peripheral to the left, were made central to it. Democratic community institutions became far more powerful. A token of the strength and durability of the New Left in Toronto was the extent to which it remained the bête noir of a series of other radical groups upholding the model of the vanguard communist party — which challenged the New Leftists’ prominence but many members of which often wound up agreeing with their positions. It was only in the early 1980s, with the ascent of a new right, that Toronto’s New Left unmistakably entered a period of decline. Yet, even then, many of its key themes were picked up by fast-growing anarchist and socialist feminist currents. Far from constituting a minor phenomenon, Toronto’s New Left, one of the largest movements for social justice in Canadian history, bequeathed to its progressive successors an imposing legacy of struggle and cultural achievements. It is the purpose of this thesis to evaluate, both critically and sympathetically, the extent to which the New Left attained its radical ambition.

Agonism Reloaded: Potentia, Renewal and Radical Democracy

This article focuses on the agonistic account of renewal and discusses its place within the broader horizon of radical democracy. It suggests that while the emphasis which agonistic theorists place on difference and popular struggles (particularly social movement politics) ensures some common ground with other theories of radical democracy, their account of renewal also displays some marked differences. The article explores these differences and discusses whether agonism is sufficient to address the limits of the current neoliberal order.

Guerrilla Networks: An Anarcheology of 1970s Radical Media Ecologies

A monograph based on my sabbatical research on radical media ecologies in the 1970s in film, video, radio, television and music. This project aims to develop the paradgims of media archaeology and ecologies in a political way via the concepts of media anarchaeology and guerrilla networks

Doreen Massey: geógrafa radical, feminista, pensadora y activista

Doreen Massey: geógrafa radical, feminista, pensadora y activista