Generation, Translocation, and Action of Nitric Oxide in Living Systems

Nitric oxide (NO) is a gaseous diatomic radical that is involved in a wide range of physiological and pathological functions in biology. Conceptually, the biochemistry of NO can be separated into three stages: generation (stage 1), translocation (stage 2), and action (stage 3). In stage 1 the oxygenase domain of NO synthase converts L-arginine to L-citrulline and NO (g). Owing to its short-lived nature, this molecule is converted into a different nitrogen oxide such as NO[subscript 2], an organonitrosyl such as a nitrosothiol, or a metal nitrosyl such as a heme-nitrosyl, for transportation in stage 2. Each of these derivatives features unique physical characteristics, chemical reactivity, and biological activity. Upon delivery in stage 3, NO exerts its physiological or pathological function by reaction with biomolecules containing redox-active metals or other residues.National Science Foundation (U.S.) (Grant CHE-0907905

Constellations of identity: place-ma(r)king beyond heritage

This paper will critically consider the different ways in which history and belonging have been treated in artworks situated in the Citadel development in Ayr on the West coast of Scotland. It will focus upon one artwork, Constellation by Stephen Hurrel, as an alternative to the more conventional landscapes of heritage which are adjacent, to examine the relationship between personal history and place history and argue the primacy of participatory process in the creation of place and any artwork therein. Through his artwork, Hurrel has attempted to adopt a material process through which place can be created performatively but, in part due to its non-representational form, proves problematic, aesthetically and longitudinally, in wholly engaging the community. The paper will suggest that through variants of ‘new genre public art’ such as this, personal and place histories can be actively re-created through the redevelopment of contemporary urban landscapes but also highlight the complexities and indeterminacies involved in the relationship between artwork, people and place

Bodily relations and reciprocity in the art of Sonia Khurana

This article explores the significance of the ‘somatic’ and ‘ontological turn’ in locating the radical politics articulated in the contemporary performance, installation, video and digital art practices of New Delhi-based artist, Sonia Khurana (b. 1968). Since the late 1990s Khurana has fashioned a range of artworks that require new sorts of reciprocal and embodied relations with their viewers. While this line of art practice suggests the need for a primarily philosophical mode of inquiry into an art of the body, such affective relations need to be historicised also in relation to a discursive field of ‘difference’ and public expectations about the artist’s ethnic, gendered and national identity. Thus, this intimate, visceral and emotional field of inter- and intra-action is a novel contribution to recent transdisciplinary perspectives on the gendered, social and sentient body, that in turn prompts a wider debate on the ethics of cultural commentary and art historiography

"The Collecting Itself Feels Good": Towards Collection Interfaces for Digital Game Objects

© Lennart Nacke, 2016. This is the author’s version of the work. It is posted here for your personal use. Not for redistribution. The definitive version was published in CHI PLAY Companion '16 Proceedings of the 2016 Annual Symposium on Computer-Human Interaction in Play Companion Extended Abstracts, https://doi.org/10.1145/2967934.2968088Digital games offer a variety of collectible objects. We investigate players' collecting behaviors in digital games to determine what digital game objects players enjoyed collecting and why they valued these objects. Using this information, we seek to inform the design of future digital game object collection interfaces. We discuss the types of objects that players prefer, the reasons that players value digital game objects, and how collection behaviors may guide play. Through our findings, we identify design implications for digital game object collection interfaces: enable object curation, preserve rules and mechanics, preserve context of play, and allow players to share their collections with others. Digital game object collection interfaces are applicable to the design of digital games, gamified applications, and educational software.Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada Social Sciences and Humanities Research Council of CanadaPeer-reviewe

Lifeworld Inc. : and what to do about it

Can we detect changes in the way that the world turns up as they turn up? This paper makes such an attempt. The first part of the paper argues that a wide-ranging change is occurring in the ontological preconditions of Euro-American cultures, based in reworking what and how an event is produced. Driven by the security – entertainment complex, the aim is to mass produce phenomenological encounter: Lifeworld Inc as I call it. Swimming in a sea of data, such an aim requires the construction of just enough authenticity over and over again. In the second part of the paper, I go on to argue that this new world requires a different kind of social science, one that is experimental in its orientation—just as Lifeworld Inc is—but with a mission to provoke awareness in untoward ways in order to produce new means of association. Only thus, or so I argue, can social science add to the world we are now beginning to live in

Component Interactions and Electron Transfer in Toluene/o-Xylene Monooxygenase

The multicomponent protein toluene/o-xylene monooxygenase (ToMO) activates molecular oxygen to oxidize aromatic hydrocarbons. Prior to dioxygen activation, two electrons are injected into each of two diiron(III) units of the hydroxylase, a process that involves three redox active proteins: the ToMO hydroxylase (ToMOH), Rieske protein (ToMOC), and an NADH oxidoreductase (ToMOF). In addition to these three proteins, a small regulatory protein is essential for catalysis (ToMOD). Through steady state and pre-steady state kinetics studies, we show that ToMOD attenuates electron transfer from ToMOC to ToMOH in a concentration-dependent manner. At substoichiometric concentrations, ToMOD increases the rate of turnover, which we interpret to be a consequence of opening a pathway for oxygen transport to the catalytic diiron center in ToMOH. Excess ToMOD inhibits steady state catalysis in a manner that depends on ToMOC concentration. Through rapid kinetic assays, we demonstrate that ToMOD attenuates formation of the ToMOC–ToMOH complex. These data, coupled with protein docking studies, support a competitive model in which ToMOD and ToMOC compete for the same binding site on the hydroxylase. These results are discussed in the context of other studies of additional proteins in the superfamily of bacterial multicomponent monooxygenases.National Institute of General Medical Sciences (U.S.) (5-R01-GM032134)United States. National Institutes of Health (T32GM008334

Increase of Direct C-C Coupling Reaction Yield by Identifying Structural and Electronic Properties of High-Spin Iron Tetra-azamacrocyclic Complexes

Macrocyclic ligands have been explored extensively as scaffolds for transition metal catalysts for oxygen and hydrogen atom transfer reactions. C–C reactions facilitated using earth abundant metals bound to macrocyclic ligands have not been well-understood but could be a green alternative to replacing the current expensive and toxic precious metal systems most commonly used for these processes. Therefore, the yields from direct Suzuki–Miyaura C–C coupling of phenylboronic acid and pyrrole to produce 2-phenylpyrrole facilitated by eight high-spin iron complexes ([Fe3+L1(Cl)2]+, [Fe3+L4(Cl)2]+, [Fe2+L5(Cl)]+, [Fe2+L6(Cl)2], [Fe3+L7(Cl)2]+, [Fe3+L8(Cl)2]+, [Fe2+L9(Cl)]+, and [Fe2+L10(Cl)]+) were compared to identify the effect of structural and electronic properties on catalytic efficiency. Specifically, catalyst complexes were compared to evaluate the effect of five properties on catalyst reaction yields: (1) the coordination requirements of the catalyst, (2) redox half-potential of each complex, (3) topological constraint/rigidity, (4) N atom modification(s) increasing oxidative stability of the complex, and (5) geometric parameters. The need for two labile cis-coordination sites was confirmed based on a 42% decrease in catalytic reaction yield observed when complexes containing pentadentate ligands were used in place of complexes with tetradentate ligands. A strong correlation between iron(III/II) redox potential and catalytic reaction yields was also observed, with [Fe2+L6(Cl)2] providing the highest yield (81%, −405 mV). A Lorentzian fitting of redox potential versus yields predicts that these catalysts can undergo more fine-tuning to further increase yields. Interestingly, the remaining properties explored did not show a direct, strong relationship to catalytic reaction yields. Altogether, these results show that modifications to the ligand scaffold using fundamental concepts of inorganic coordination chemistry can be used to control the catalytic activity of macrocyclic iron complexes by controlling redox chemistry of the iron center. Furthermore, the data provide direction for the design of improved catalysts for this reaction and strategies to understand the impact of a ligand scaffold on catalytic activity of other reactions

Chronic cisplatin treatment promotes enhanced damage repair and tumor progression in a mouse model of lung cancer

Chemotherapy resistance is a major obstacle in cancer treatment, yet the mechanisms of response to specific therapies have been largely unexplored in vivo. Employing genetic, genomic, and imaging approaches, we examined the dynamics of response to a mainstay chemotherapeutic, cisplatin, in multiple mouse models of human non-small-cell lung cancer (NSCLC). We show that lung tumors initially respond to cisplatin by sensing DNA damage, undergoing cell cycle arrest, and inducing apoptosis—leading to a significant reduction in tumor burden. Importantly, we demonstrate that this response does not depend on the tumor suppressor p53 or its transcriptional target, p21. Prolonged cisplatin treatment promotes the emergence of resistant tumors with enhanced repair capacity that are cross-resistant to platinum analogs, exhibit advanced histopathology, and possess an increased frequency of genomic alterations. Cisplatin-resistant tumors express elevated levels of multiple DNA damage repair and cell cycle arrest-related genes, including p53-inducible protein with a death domain (Pidd). We demonstrate a novel role for PIDD as a regulator of chemotherapy response in human lung tumor cells.National Institutes of Health (U.S.) (grant 5-UO1-CA84306)National Cancer Institute (U.S.) (CA034992