Designing Auteurs: Video Games, Authorship, and MoMA

This article uses The Museum of Modern Art’s 2012 foray into video game collection as an occasion to consider several key issues related to video game authorship and critical comprehension. By relating video games to film, it demonstrates the importance of avoiding medium-specific generalizations regarding how to critically apprehend video games

Accountability and legitimacy in transboundary networked forest governance: a case study of the Roundtable on the Crown of the Continent

2015 Spring.Includes bibliographical references.Using a social constructivist ontology to examine key debates and areas of inquiry vis-à-vis the democratic nature of transboundary forest governance, this research examines the case of the Roundtable on the Crown of the Continent, an instance of networked governance. Part I builds up to an examination of the movement toward conceptualizing transboundary networked governance, exploring the claim that government has given way to governance, blurring the lines between public and private, and moving beyond its antecedent models--systems theory and complexity, corporatism, state-in-society, new public management and privatization, inter alia--to reflect a more complicated and inherently collaborative relationship between state, society, and market-based actors. The dissertation project, then, investigates several key questions. At a basic level, it asks, what does networked governance look like, and in the case of the Crown Roundtable, how might these arrangements be adaptive given the absence of an overarching forests treaty? Looking deeper into the implications of networked governance, the project then moves to an investigation of the ways that these processes become legitimate modes of governing and how they allow actors to hold each other accountable. Evidence in the Crown Roundtable suggests that the state is simply one actor among many. In this sea of various players, without the traditional forms of accountability, how do we ensure that governance retains its democratic qualities? The second part (chapters 4, 5, 6, 7) builds from the initial observations in the first part (chapters 1, 2, and 3) that state boundaries in the Crown of the Continent are transected by landscape identities and norms. It examines the implications for maintaining democracy in governance. Given the lack of institutions (such as the juridical, legal, and electoral channels) available at the domestic level, how can actors be held accountable? What do shifts toward a flattened and fragmented forest governance landscape represent in terms of both the ability of diverse actors to relate to one another and also for the participants to see NG as a worthwhile process to engage? In answering these questions, Part II examines whether NG architectures are able to incorporate channels for accountability while simultaneously drawing upon a broad base of participation and maintaining social legitimacy. Finally, the dissertation concludes with thoughts on institutional design. In so doing, it hopefully contributes to an understanding of how to build collaborative networked arrangements that are better able to address transboundary environmental problems

Predicting the targeting of tail-anchored proteins to subcellular compartments in mammalian cells

This is the author accepted manuscript. The final version is available from Company of Biologists via the DOI in this record.Tail-anchored (TA) proteins contain a single transmembrane domain (TMD) at the Cterminus, anchoring them to organelle membranes where they mediate a variety of critical cellular processes. Mutations in individual TA proteins cause a number of severe inherited disorders. However, the molecular mechanisms and signals facilitating proper TA protein targeting are not fully understood, in particular in mammals. Here, we identify additional TA proteins at peroxisomes or shared by multiple organelles in mammals and reveal that a combination of TMD hydrophobicity and tail charge determines targeting to distinct organelles. Specifically, an increase in tail charge can override a hydrophobic TMD signal and re-direct a protein from the ER to peroxisomes or mitochondria and vice versa. We demonstrate that subtle alterations in those physicochemical parameters can shift TA protein targeting between organelles, explaining why peroxisomes and mitochondria share many TA proteins. Our analyses enabled us to allocate characteristic physicochemical parameters to different organelle groups. This classification allows for the first time, successful prediction of the location of uncharacterized TA proteins.We thank colleagues who provided materials (see Tables S1-S4) and acknowledge support from A. C. Magalhães, M. Almeida, D. Tuerker, S. Kuehl and C. Davies. This work was supported by the Biotechnology and Biological Sciences Research Council (BB/K006231/1 to M.S.), a Wellcome Trust Institutional Strategic Support Award (WT097835MF, WT105618MA to M.S.), the Portuguese Foundation for Science and Technology and FEDER/COMPETE (PTDC/BIA-BCM/118605/2010 to M.S.; SFRH/BD/37647/2007 to N.B.; SFRH/BPD/77619/2011 and UID/BIM/04501/2013 to D.R.). M.W., E.A.G., and M.S. are supported by Marie Curie Initial Training Network (ITN) action PerFuMe (316723)

Monohydroxamic acids and bridging dihydroxamic acids as chelators to ruthenium(III) and as nitric oxide donors: syntheses, speciation studies and nitric oxide releasing investigations.

The synthesis and spectroscopic characterisation of novel mononuclear Ru(III)(edta)(hydroxamato) complexes of general formula [Ru(H2edta)(monoha)] (where monoha = 3- or 4-NH2, 2-, 3- or 4-C1 and 3-Me-phenylhydroxamato), as well as the first example of a Ru(III)-N-aryl aromatic hydroxamate, [Ru(H2edta)(N-Me-bha)].H2O (N-Me-bha = N-methylbenzohydroxamato) are reported. Three dinuclear Ru(III) complexes with bridging dihydroxamato ligands of general formula [{Ru(H2edta)}2(mu-diha)] where diha = 2,6-pyridinedihydroxamato and 1,3- or 1,4-benzodihydroxamato, the first of their kind with Ru(III), are also described. The speciation of all of these systems (with the exception of the Ru-1,4-benzodihydroxamic acid and Ru-N-methylbenzohydroxamic systems) in aqueous solution was investigated. We previously proposed that nitrosyl abstraction from hydroxamic acids by Ru(III) involves initial formation of Ru(III)-hydroxamates. Yet, until now, no data on the rate of nitric oxide (NO) release from hydroxamic acids has been published. We now describe a UV-VIS spectroscopic study, where we monitored the decrease in the ligand-to-metal charge-transfer band of a series of Ru(III)-monohydroxamates with time, with a view to gaining an insight into the NO-releasing properties of hydroxamic acids

40 YEARS ON THE INTERNATIONAL FLATHEAD: AN ASSESSMENT OF TRANSBOUNDARY RIVER GOVERNANCE

Global population growth, climate change, and industrialization, are putting extreme pressures on worldwide freshwater supplies (Cosens 2010). Of the global freshwater supplies, transboundary water sources play a crucial role in sustaining populations. Over 40% of humans on Earth rely on a transboundary river or lake for access to water, and 90% of the world’s population lives in countries that share bodies of water with at least one other country (UN 2008). Taken together, the motivations for improving governance of transboundary water systems have never been stronger. To meet the challenges associated with transboundary water governance, researchers working at multiple scales and across international, state and sub-state levels, have been applying the concepts of adaptive governance to analyze complex water contexts (Cosens 2010, Akamani and Wilson 2011, and Chaffin et al. 2016). To contribute to this body of work and extend transboundary water governance literature, this study applies the lens of adaptive governance (AG) to an historic analysis of the environmental governance of the pristine and wild international Flathead River that cuts across the border between Canada and the United States. Proposed coal mines in the upper basin located in the western Canadian province of British Columbia (BC) threatened this diverse river environment from 1974 to 2014. Fortunately, dual mining bans passed by BC and the US in 2011 and 2014, respectively, removed this industrial threat from the entire basin. To better understand how these bans emerged this study identifies and examines four key historic events that were crucial to collaboration across borders and communities and to preventing coal mining. This study uses a conceptual framework for AG, which describes the criteria necessary for AG to emerge and the governance conditions that functional AG enables. This analytical framework helps to shed light on the extent to which AG emerged during the 40 year timespan and the ways in which the key events constituted adaptations. Results showed that an adaptive outcome was reached but that the complexities of transboundary environmental governance prevented adaptations in most instances. Examining the recent history of the international Flathead River advances our understanding of the unique sequence of events that resulted in preserving, at least for the present, a unique transboundary ecosystem. This understanding also contributes to the need for creative strategies to improve transboundary water governance outcomes globally

Immunologic responses to xenogeneic tyrosinase DNA vaccine administered by electroporation in patients with malignant melanoma

BACKGROUND: Prior studies show that intramuscular injection and particle-mediated epidermal delivery of xenogeneic melanosomal antigens (tyrosinase or Tyr, gp100) induce CD8(+) T cell responses to the syngeneic protein. To further define the optimal vaccination strategy, we conducted a phase I study of in vivo electroporation (EP) of a murine Tyr DNA vaccine (pINGmuTyr) in malignant melanoma patients. METHODS: Human leukocyte antigen (HLA)-A1, A2, A24 or B35 stage IIb-IV melanoma patients received up to five doses of the mouse tyrosinase DNA vaccine by EP every three weeks at dose levels of 0.2 mg, 0.5 mg, or 1.5 mg per injection. Peripheral blood mononuclear cells (PBMC) were collected, cultured with a peptide pool containing eight HLA class I-restricted Tyr-specific T-cell epitopes, and analyzed by HLA-A*0101-restricted tetramers and intracellular cytokine staining (ICS). RESULTS: Twenty-four patients received ≥1 dose of the pINGmuTyr vaccine; PBMCs from 21 patients who completed all five doses were available for Tyr immune assays. The only common toxicity was grade 1 injection site reaction. Six of 15 patients (40%) in the 1.5 mg dose cohort developed Tyr-reactive CD8(+) T cell responses following stimulation, defined as a ≥3 standard deviation increase in baseline reactivity by tetramer or ICS assays. No Tyr-reactive CD8(+) T cell response was detected in the 0.2 mg and 0.5 mg dose cohort patients. Epitope spreading of CD8(+) T cell response to NY-ESO-1 was observed in one patient with vitiligo. One patient subsequently received ipilimumab and developed an enhanced Tyr-reactive response with polyfunctional cytokine profile. After a median follow-up of 40.9 months, median survival has not been reached. CONCLUSIONS: A regimen of five immunizations with pINGmuTyr administered by EP was found to be safe and resulted in Tyr-reactive immune responses in six of 15 patients at 1.5 mg dose cohort. TRIAL REGISTRATION: ClinicalTrials.gov NCT0047113

An improved plasmid for transformation of Neurospora crassa using the pan-2 gene as a selectable marker

The pOKE103 plasmid can be used to transform Neurospora crassa using the pan-2 gene (NCU10048.3) as a selective marker. We mapped the pan-2 fragment to the right arm of LG VI, contig 4, and found that it carries a pan-2 linked gene, atg-12 (NCU10049.3). We report the removal of atg-12 to produce an improved plasmid, pOKE104