Players, Characters, and the Gamer's Dilemma

Is there any difference between playing video games in which the player's character commits murder and video games in which the player's character commits pedophilic acts? Morgan Luck's “Gamer's Dilemma” has established this question as a puzzle concerning notions of permissibility and harm. We propose that a fruitful alternative way to approach the question is through an account of aesthetic engagement. We develop an alternative to the dominant account of the relationship between players and the actions of their characters, and argue that the ethical difference between so-called “virtual murder” and “virtual pedophilia” is to be understood in terms of the fiction-making resources available to players. We propose that the relevant considerations for potential players to navigate concern (1) attempting to make certain characters intelligible, and (2) using aspects of oneself as resources for homomorphic representation.Peer reviewe

Epigenetic silencing of CREB3L1 by DNA methylation is associated with high-grade metastatic breast cancers with poor prognosis and is prevalent in triple negative breast cancers

Methylation within specific CpG regions of the CREB3L1 gene in different breast tumor subtypes. The relative methylation was plotted for each tumor subtype. Methylation in regions 2 and 3 show an inverse correlation with CREB3L1 mRNA expression (found in Fig. 6b), whereas methylation in regions 16, 19 and 20 show a direct correlation with CREB3L1 mRNA expression. For all panels: normal (n = 97), luminal (n = 357), human epidermal growth factor receptor 2 (HER2) amplified (n = 19), triple negative breast cancer (TNBC) (n = 113). Statistical differences were analyzed using post-hoc pairwise comparison: *p <0.05; **p <0.01; ***p <0.001. (PDF 97 kb

The Vehicle, Spring 1997

Vol. 38, No. 2 Table of Contents Poetry: Don QuixotePatrick Scanlanpage 1 Last SupperChristine Starrpage 1 Marriage VowsKristopher Clausingpage 2 The LibraryPatrick Lairpage 4 GuruJohn Dylan McNeilpage 5 Tripping in OzKim Evanspage 5 TranceStephanie Kavanaughpage 6 The CleftEmilie Roypage 7 FlannelAmanda Watsonpage 8 Strip PokerEbben Moorepage 8 IceJohn Dylan McNeilpage 9 ChloeMichael Kawapage 11 OrchardCarmella Cosenzapage 12 Jenn & Cookie MonsterJacob Tolbertpage 13 Barry ManilowKatie Wrightpage 14 GoodbyesShannon Goodallpage 15 Prose: Alice (A Short, Short Story)Carmella Cosenzapage 17 UntitledJoe Robesonpage 17 A New World AloneKendall W. Baumanpage 22 Biographiespage 35https://thekeep.eiu.edu/vehicle/1069/thumbnail.jp

EndNote training for academic staff and students: the experience of the Manchester Metropolitan University Library

This article describes how the Manchester Metropolitan University Library delivers EndNote training to its academic staff and students through hands-on workshops and online tutorials. As the demand is user-led and the response extremely positive, the Library considers the provision of EndNote training as analogous to a 'Trojan horse' that allows the Library welcomed and unchallenged into the camp of the user. The Library has used the opportunity strategically and, consequently, has benefited in a number of ways, including improved communication with academic staff and increased awareness of library resources on the part of users. A short literature review is provided

Omnibus Sequences, Coupon Collection, and Missing Word Counts

An {\it Omnibus Sequence} of length $n$ is one that has each possible "message" of length $k$ embedded in it as a subsequence. We study various properties of Omnibus Sequences in this paper, making connections, whenever possible, to the classical coupon collector problem.Comment: 26 page

Acireductone Dioxygenase 1 (ARD1) Is an Effector of the Heterotrimeric G Protein Subunit in Arabidopsis

Heterotrimeric G protein complexes are conserved from plants to mammals, but the complexity of each system varies. Arabidopsis thaliana contains one Gα, one Gβ (AGB1), and at least three Gγ subunits, allowing it to form three versions of the heterotrimer. This plant model is ideal for genetic studies because mammalian systems contain hundreds of unique heterotrimers. The activation of these complexes promotes interactions between both the Gα subunit and the Gβγ dimer with enzymes and scaffolds to propagate signaling to the cytoplasm. However, although effectors of Gα and Gβ are known in mammals, no Gβ effectors were previously known in plants. Toward identifying AGB1 effectors, we genetically screened for dominant mutations that suppress Gβ-null mutant (agb1-2) phenotypes. We found that overexpression of acireductone dioxygenase 1 (ARD1) suppresses the 2-day-old etiolated phenotype of agb1-2. ARD1 is homologous to prokaryotic and eukaryotic ARD proteins; one function of ARDs is to operate in the methionine salvage pathway. We show here that ARD1 is an active metalloenzyme, and AGB1 and ARD1 both control embryonic hypocotyl length by modulating cell division; they also may contribute to the production of ethylene, a product of the methionine salvage pathway. ARD1 physically interacts with AGB1, and ARD enzymatic activity is stimulated by AGB1 in vitro. The binding interface on AGB1 was deduced using a comparative evolutionary approach and tested using recombinant AGB1 mutants. A possible mechanism for AGB1 activation of ARD1 activity was tested using directed mutations in a loop near the substrate-binding site

Suppression of Lung Adenocarcinoma Progression by Nkx2-1

Despite the high prevalence and poor outcome of patients with metastatic lung cancer the mechanisms of tumour progression and metastasis remain largely uncharacterized. Here we modelled human lung adenocarcinoma, which frequently harbours activating point mutations in KRAS and inactivation of the p53 pathway, using conditional alleles in mice. Lentiviral-mediated somatic activation of oncogenic Kras and deletion of p53 in the lung epithelial cells of Kras[superscript LSL-G12D/+];p53[superscript flox/flox] mice initiates lung adenocarcinoma development4. Although tumours are initiated synchronously by defined genetic alterations, only a subset becomes malignant, indicating that disease progression requires additional alterations. Identification of the lentiviral integration sites allowed us to distinguish metastatic from non-metastatic tumours and determine the gene expression alterations that distinguish these tumour types. Cross-species analysis identified the NK2-related homeobox transcription factor Nkx2-1 (also called Ttf-1 or Titf1) as a candidate suppressor of malignant progression. In this mouse model, Nkx2-1 negativity is pathognomonic of high-grade poorly differentiated tumours. Gain- and loss-of-function experiments in cells derived from metastatic and non-metastatic tumours demonstrated that Nkx2-1 controls tumour differentiation and limitsmetastatic potential in vivo. Interrogation of Nkx2-1-regulated genes, analysis of tumours at defined developmental stages, and functional complementation experiments indicate that Nkx2-1 constrains tumours in part by repressing the embryonically restricted chromatin regulator Hmga2. Whereas focal amplification of NKX2-1 in a fraction of human lung adenocarcinomas has focused attention on its oncogenic function, our data specifically link Nkx2-1 downregulation to loss of differentiation, enhanced tumour seeding ability and increased metastatic proclivity. Thus, the oncogenic and suppressive functions ofNkx2-1 in the sametumourNational Institutes of Health (U.S.) (grant U01-CA84306 )National Institutes of Health (U.S.) (grant K99-CA151968)Howard Hughes Medical InstituteLudwig Center for Molecular OncologyNational Cancer Institute (U.S.) (Cancer Center Support (core) grant P30-CA14051

A Policy-into-Practice Intervention to Increase the Uptake of Evidence-Based Management of Low Back Pain in Primary Care: A Prospective Cohort Study

BACKGROUND: Persistent non-specific low back pain (nsLBP) is poorly understood by the general community, by educators, researchers and health professionals, making effective care problematic. This study evaluated the effectiveness of a policy-into-practice intervention developed for primary care physicians (PCPs). METHODS: To encourage PCPs to adopt practical evidence-based approaches and facilitate time-efficient, integrated management of patients with nsLBP, we developed an interdisciplinary evidence-based, practical pain education program (gPEP) based on a contemporary biopsychosocial framework. One hundred and twenty six PCPs from primary care settings in Western Australia were recruited. PCPs participated in a 6.5-hour gPEP. Self-report measures recorded at baseline and at 2 months post-intervention included PCPs' attitudes, beliefs (modified Health Care Providers Pain and Impairment Relationship Scale (HC-PAIRS), evidence-based clinical practices (knowledge and skills regarding nsLBP management: 5-point Likert scale with 1  =  nil and 5  =  excellent) and practice behaviours (recommendations based on a patient vignette; 5-point Likert scale). RESULTS: Ninety one PCPs participated (attendance rate of 72%; post-intervention response rate 88%). PCP-responders adopted more positive, guideline-consistent beliefs, evidenced by clinically significant HC-PAIRS score differences (mean change  =  -5.6±8.2, p<0.0001; 95% confidence interval: -7.6 to -3.6) and significant positive shifts on all measures of clinical knowledge and skills (p<0.0001 for all questions). Self management strategies were recommended more frequently post-intervention. The majority of responders who were guideline-inconsistent for work and bed rest recommendations (82% and 62% respectively) at pre-intervention, gave guideline-consistent responses at post-intervention. CONCLUSION: An interprofessional pain education program set within a framework that aligns health policy and practice, encourages PCPs to adopt more self-reported evidence-based attitudes, beliefs and clinical behaviours in their management of patients with nsLBP. However, further research is required to determine cost effectiveness of this approach when compared with other modes of educational delivery and to examine PCP behaviours in actual clinical practice