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The importance of ATP in the immune system of molluscs
VE Coyne
Invertebrate Survival Journal , 2011,
Abstract: Molluscs rely on an innate immune system for defence against infection. Invading organisms are phagocytosed by circulating hemocytes and neutralised by a combination of hydrolytic enzymes and the production of reactive oxygen species. Phagocytosis, the central feature of the molluscan innate immune system, is an energy-demanding process as a consequence of actin polymerisation which requires a constant supply of ATP. Adenylate kinase, shown to couple local ATP supply and actomyosin assembly in macrophage cell lines, may play a similar role in molluscan hemocytes. Hemocyte conformational changes and chemotaxis are regulated via protein kinase C which is phosphorylated in response to bacterial lipopolysaccharide. ATP utilisation in protein kinase cascades is thought to be quite significant. The vast majority of the ATP required to support cellular functions in animal cells is generated via the mitochondrial electron transport chain. Disruption of this process with antimycin A resulted in a 50 % decrease in ATP levels in Haliotis midae hemocytes which also exhibited reduced phagocytic activity. Phosphoarginine and arginine kinase are thought to play a role in invertebrates that is similar to phosphocreatine and creatine kinase in vertebrates, by supplying additional ATP during periods of high energy demand. The energetically-expensive processes associated with the molluscan innate immune system, such as chemotaxis, phagocytosis, formation and acidification of the phagolysosome, are severely compromised by abiotic stresses such as elevated water temperature and pollutants, reflecting the fine balance that must be maintained to ensure sufficient ATP is available for both general metabolism and the immune response.
Diagnostic CT: Are Patients Adequately Informed?  [PDF]
John Coyne, Angela Brent, Ewan O’Farrell
Advances in Computed Tomography (ACT) , 2012, DOI: 10.4236/act.2012.11001
Abstract: AIM: CT scanning is a widely utilised effective diagnostic tool. We aimed to establish whether patients are adequately informed prior to undergoing CT investigations. Methods: All adult patients with mental capacity attending the department for a CT study over a week period were invited to fill out a brief questionnaire prior to their scan. Results: 57 patients returned completed questionnaires. Overall 23% of patients were unsure or incorrect about the type of scan scheduled. Of patients attending with a new condition, 46% of them did not know their provisional diagnosis. Only 32 % of patients had insight into how a CT scan worked. This was taken to mean that the patient had included some reference to either x-rays, radiation or cross sectional imaging. Only 23% of patients were aware of potential complications of CT scans. Conclusion: Although written consent prior to CT scan is probably a step too far in providing patients with relevant risks/benefits of their investigation, we propose all patients undergoing CT have prior access to a written information sheet should they wish to be further informed regarding their procedure.
Synthesis of Gemcitabine-(C4-amide)-[anti-HER2/neu] Utilizing a UV-Photoactivated Gemcitabine Intermediate: Cytotoxic Anti-Neoplastic Activity against Chemotherapeutic-Resistant Mammary Adenocarcinoma SKBr-3  [PDF]
Cody P. Coyne, Toni Jones, Ryan Bear
Journal of Cancer Therapy (JCT) , 2012, DOI: 10.4236/jct.2012.325089
Abstract: Gemcitabine is a pyrimidine nucleoside analog that becomes triphosphorylated intracellularly where it competitively inhibits cytidine incorporation into DNA strands. Another mechanism-of-action of gemcitabine (diphosphorylated form) involves irreversible inhibition of the enzyme ribonucleotide reductase thereby preventing deoxyribonucleotide synthesis. Functioning as a potent chemotherapeutic gemcitabine promote decreases in neoplastic cell proliferation and apoptosis which is frequently found to be effective for the treatment of several leukemias and a wide spectrum of carcinomas. A brief plasma half-life in part due to rapid deamination and chemotherapeutic-resistance restricts the utility of gemcitabine in clinical oncology. Selective “targeted” delivery of gemcitabine represents a potential molecular strategy for simultaneously prolonging its plasma half-life and minimizing innocient tissues and organ systems exposure to chemotherapy. The molecular design and an organic chemistry based synthesis reaction is described that initially generates a UV-photoactivated gemcitabine intermediate. In a subsequent phase of the synthesis method the UV-photoactivated gemcitabine intermediate is covalently bonded to a monoclonal immunoglobulin yielding an end-product in the form of gemcitabine-(C4-amide)-[anti-HER2/neu]. Analysis by SDS-PAGE/chemiluminescent auto-radiography did not detect evidence of gemcitabine-(C4-amide)-[anti-HER2/neu] polymerization or degradative fragmentation while cell-ELISA demonstrated retained binding-avidity for HER2/neu trophic membrane receptor complexes highly over-expressed by chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3). Compared to chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3), the covalent immunochemotherapeutic, gemcitabine-(C4-amide)-[anti-HER2/neu] is anticipated to exert greater levels of cytotoxic anti-neoplastic potency against other neoplastic cell types like pancreatic carcinoma, small-cell lung carcinoma, neuroblastoma, glioblastoma, oral squamous cell carcinoma, cervical epitheliod carcinoma, or leukemia/lymphoid neoplastic cell types based on their reported sensitivity to gemcitabine and gemcitabine covalent conjugates.
Simultaneous Dual Selective Targeted Delivery of Two Covalent Gemcitabine Immunochemotherapeutics and Complementary Anti-Neoplastic Potency of [Se]-Methylselenocysteine  [PDF]
C. P. Coyne, Toni Jones, Ryan Bear
Journal of Cancer Therapy (JCT) , 2015, DOI: 10.4236/jct.2015.61009

The anti-metabolite chemotherapeutic, gemcitabine is relatively effective for a spectrum of neoplastic conditions that include various forms of leukemia and adenocarcinoma/carcinoma. Rapid systemic deamination of gemcitabine accounts for a brief plasma half-life but its sustained administration is often curtailed by sequelae and chemotherapeutic-resistance. A molecular strategy that diminishes these limitations is the molecular design and synthetic production of covalent gemcitabine immunoche-motherapeutics that possess properties of selective “targeted” delivery. The simultaneous dual selective “targeted” delivery of gemcitabine at two separate sites on the external surface membrane of a single cancer cell types represents a therapeutic approach that can increase cytosol chemotherapeutic deposition; prolong chemotherapeutic plasma half-life (reduces administration frequency); minimize innocent exposure of normal tissues and healthy organ systems; and ultimately enhance more rapid and thorough resolution of neoplastic cell populations. Materials and Methods: A light-reactive gemcitabine intermediate synthesized utilizing succinimidyl 4,4-azipentanoate was covalently bound to anti-EGFR or anti-HER2/neu IgG by exposure to UV light (354-nm) resulting in the synthesis of covalent immunoche-motherapeutics, gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu]. Cytotoxic anti-neoplastic potency of gemcitabine-(C4-amide)-[anti-EGFR] and gemcitabine-(C4-amide)-[anti-HER2/neu] between gemcitabine-equivalent concentrations of 10-12 M and 10-6 M was determined utilizing chemotherapeutic-resistant mammary adenocarcinoma (SKRr-3). The organoselenium compound, [Se]-methylselenocysteine was evaluated to determine if it complemented the anti-neoplastic potency of the covalent gemcitabine immunoche-motherapeutics. Results: Gemcitabine-(C4-

A Scenario for Strong Gravity without Extra Dimensions
D. G. Coyne
Physics , 2006,
Abstract: A different reason for the apparent weakness of the gravitational interaction is advanced, and its consequences for Hawking evaporation of a Schwarzschild black hole are investigated. A simple analytical formulation predicts that evaporating black holes will undergo a type of phase transition resulting in variously long-lived objects of reasonable sizes, with normal thermodynamic properties and inherent duality characteristics. Speculations on the implications for particle physics and for some recently-advanced new paradigms are explored.
Singular chains on topological stacks
Thomas Coyne,Behrang Noohi
Mathematics , 2015,
Abstract: We extend the functor Sing of singular chains to the category of topological stacks and establish its main properties. We prove that Sing respects weak equivalences and takes a morphism of topological stacks that is both a Serre and a Reedy fibration to a Kan fibration of simplicial sets. When restricted to the category of topological spaces Sing coincides with the usual singular functor.
Les arts communautaires : des pratiques de résistance artistique interpellées par la souffrance sociale
ève Lamoureux
Amnis , 2010, DOI: 10.4000/amnis.314
Abstract: De plus en plus d’artistes nord-américains choisissent d’investir certaines communautés ou collectivités stigmatisées et marginalisées afin de créer, en collaboration étroite avec les membres de celle-ci, des uvres collectives. Ces pratiques artistiques, appelées arts communautaires, poursuivent un double objectif : explorer, par le biais de la création, la souffrance individuelle et collective engendrée par les rapports sociaux de domination (afin de favoriser un processus de subjectivation qui peut devenir politique) et contester ces rapports de domination au moyen d’ uvres à teneur critique. Ce type de résistance contrevient au principe moderne de l’espace public et de l’action politique puisqu’il conteste la stricte séparation entre le privé et le public, qu’il met de l’avant des expériences singulières et qu’il propose d’autres formes de délibération politique. C’est pourquoi l’auteure caractérisera les arts communautaires, réfléchira à la création artistique collective comme outil de subjectivation et discutera de certains enjeux politiques soulevés par ces pratiques artisticosociales originales. More and more North-American artists create collective works in collaboration with members of stigmatized and marginalized communities or collectivities. These artistic practices, called community arts , pursue a double objective: (1) to explore through creation the individual and collective suffering brought about by social relations of domination (in order to favour a process of subjectivization that may become political), and (2) to contest these relations of domination through critical works. This type of resistance violates the modern principle linking public space with political action because it contests the strict separation between private and public, it foregrounds particular experiences, and it proposes alternative forms of political deliberation. It is with this in mind that the author characterizes community arts, reflects on collective artistic creation as a tool of subjectivization, and discusses some of the political stakes raised by these original artistico-social practices. Cada vez más artistas norteamericanos optan por un compromiso con ciertas comunidades o colectividades estigmatizadas y marginadas, con el fin de crear obras colectivas en estrecha colaboración con sus miembros. Tales prácticas artísticas, son llamadas artes comunitarias y persiguen un doble objetivo. Por un lado, el de explorar –por medio de la creación– el sufrimiento individual y colectivo generado por las relaciones sociales de dominación (para dar pie a u
Quelques pistes de réflexion sur la restauration perceptible des vases céramiques antiques
ève Bouyer
CeROArt : Conservation, Exposition, Restauration d'Objets d'Art , 2010,
Abstract: En restauration de céramique, il existe un grand nombre de procédés permettant de rendre une restauration perceptible. Le choix de l'un ou l'autre de ces procédés dépend beaucoup du restaurateur : la formation, l'entourage professionnel, les go ts et les intentions de celui-ci le porteront vers certains procédés plut t que d'autres. The restoration of ceramics provides a wide variety of ways enabling to make a restoration perceptible. The choice of one of this ways relies much on the conservator: his/her training and education, the people he/she works with, his/her taste and preferences will lead him/her towards some process instead of others.
Playing through the Pain: A University-Based Study of Sports Injury  [PDF]
Geneviève Jessiman-Perreault, Jenny Godley
Advances in Physical Education (APE) , 2016, DOI: 10.4236/ape.2016.63020
Abstract: This paper presents findings from a survey that assessed university students’ opinions about sports injury. Specifically, the paper seeks to understand whether university students who participate in sports at different levels would choose to participate while injured, and who or what influences these decisions. An online survey was administered to 275 university students. Results indicate that the concept of the “sports ethic” was a major determinant in respondents’ reported willingness to play through injuries. The sports ethic influenced participants at all levels of sport (casual, amateur, and professional). We suggest that once the sports ethic is internalized, it may counter the potential buffering capacity of injury prevention programs. The implications of these findings for injury prevention education are assessed.
Designing a Training Programme to Promote the Exercise of Self-Determination and Civic Engagement in Individuals Having an Intellectual Disability: Feedback on Collaborative Research  [PDF]
Barbara Fontana-Lana, Geneviève Petitpierre
Creative Education (CE) , 2017, DOI: 10.4236/ce.2017.86071
Abstract: Individual self-determination and civic engagement are key resources in the life of every individual. All the more so in the case of individuals with an intellectual disability (ID), who are frequently prevented, voluntarily or passively (for example through the failure to promote favourable conditions for learning), from implementing the resources that are required for acquiring and developing these skills. The importance of being able to apply these skills in everyday life is however acknowledged and encouraged by the UN Convention on the Rights of Persons with Disabilities (2006). This article presents and analyses the conditions for vertical and horizontal collaboration (Greenhalgh et al., 2004), which have contributed to the successful introduction of an educational approach to self-determination and active citizenship in a social care establishment for individuals having a mild to moderate ID. The research was conducted over two years (2014-2016) within the framework of a partnership between the establishment concerned and academic researchers. The principal stakeholders involved in the research, including 16 individuals with an ID, 13 educational care professionals, 4members of the managerial staff and 4 research workers, worked together to promote the adoption of principles of self-determination and civic engagement within the establishment, and designed a training programme aimed at individuals with an ID and professional support staff. The effectiveness of the intervention mechanism applied by this team has been verified and validated using a pre- and post-test evaluation, the results of which have appeared in a separate publication. A qualitative analysis of the collaboration conditions indicates, and on first sight this may appear paradoxical, that individual self-determination and its implementation are most successful when supported by a close-knit community, based on meaningful interdependence and mutually dependent relationships.
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