Pherekydes’ Daktyloi

Classical studies of the Idaian Daktyloi rely on evolutionary and survivalist models which assume prehistoric smiths as the locus of their meaning. More recent anthropologies of technology evaluate technological symbols for their integration of technology into the intellectual, ritual, historical and economic structures of the subject culture. A fragmenta incerta of Pherekydes affords a testing-ground for this approach to the Daktyloi. The investigation reveals adaptability and integration into Pythagorean tradition, magical practice, and Cretan history. This offers more cogent reasons for the daimones’ longevity than previous models, and corrects the assumption that a fragmentary record reflects cultural insignificance.Les études classiques sur les Dactyles idéens se fondent sur des modèles évolutionnistes qui donnent sens à ces figures en les associant à des forgerons préhistoriques. Des approches anthropologiques récentes évaluent les symboles technologiques en fonction de l’intégration de la technologie qu’ils opèrent dans les structures intellectuelles, rituelles, historiques et économiques de la culture étudiée. Un fragment incertain de Phérécyde offre une possibilité de tester cette approche des Dactyles. L’étude révèle une adaptabilité et une intégration dans la tradition pythagoricienne, dans la pratique magique et l’histoire crétoise. Cela permet d’expliquer la longévité de ces daimones de manière plus convaincante que ne le faisaient les modèles précédents, et cela corrige l’affirmation qu’un témoignage fragmentaire n’a pas de signification culturelle

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Sailing with the Gods: serious games in an ancient sea

Maritime safety in the ancient Greek world was created through symbols and social practice as well as the science of seafaring. The human connections forged through ritual, myth and image enabled communication and granted authority to the civic institutions that offered legal and economic benefits. A gaming application offers a route to modelling the triangulation of seascapes, civic institutions, and narratives through which people and goods moved around the ancient Mediterranean. The game was inspired by the promise of maritime safety given to initiates into the mystery cult of the Great Gods of Samothrace, where grants of proxenia and theoria represent the civic counterparts of mystic promises and tales of supernatural intervention. The flexibility that characterizes ancient proxenia recommends the framework of a game; the bridge between imagination and strategic outcomes that characterizes serious games maps onto the ancient realities of the maritime success enabled through ritua

Social Mobility: Mithraism and Cosmography in the 2nd-5th Centuries CE

Pragmatic cognitive science, rooted in Dewey's epistemology and models of distributed cognition, offers new hypotheses for the emergence and decline of the Mithraic rites. These models foreground the responsiveness of the rites to their economic and social environment, generating new form-meaning pairs through multimodal engagements inside the Mithraic caves. These moments of cognitive blending answered the needs of the early social catchment of the rites, which was predominantly freedmen and soldiers benefitting from the upward mobility of the thriving second century CE. Within the caves, multimodal engagements with the triumph of light over dark physical movement, imagery, gesture, role playing, and interaction with cult equipment - aligned the experience of the initiate with Mithras' cosmological triumph. The caves are also a confluence of mechanisms for social mobility that were broadly familiar in the imperial period, including patronage, symposia, engagement with exotic cultural forms and philosophical speculation. The decline of the rites was coincident with the dissolution of the economic opportunities that enabled the rise of the Roman middle class and of the social currency of these practices. The language of euergetism yielded to the language of service to the poor, and the cosmological imagery that characterized the caves shifted into the restricted spheres of exchange among competing princes. This model of the rites suggests dynamics with Christianity focused less on theology than on responsiveness to the economic and social transformations. On cover:Monks singing the Office and decorated initial A[sperges me.]. Gradual Olivetan Master (Use of the Olivetan Benedictines), illuminated manuscript on parchment ca. 1430-1439. Italy, Monastero di Santa Maria di Baggio near Milan, Ca 1400-1775.Beinecke Ms1184: The olivetan Gradual. Gradual. General Collection, Beinecke Rare Book and Manuscript Library, Yale University

Integrating Social Determinants of Health in Health Care Education: Using Simulation Based Learning to Prepare Nurse Practitioner Students

Background/Purpose: Social determinants of Health (SDH) are conditions in which people are born, work, live, and age, and the policies, agendas, norms, and political systems that impact conditions of daily life. SDH should be an integral component of health professional education. Providers need the knowledge, skills, and motivations to address and act on these factors. The study purpose was to test the impact of a simulation intervention on improving Adult-Gerontology Primary Care Nurse Practitioner (AGPCNP) and Family Nurse Practitioner (FNP) student knowledge and confidence of enacting SDH in their clinical practices. Methods: A quasi-experimental pretest-posttest design was used. Students participating in Objective Structured Clinical Examinations (OSCE) were assigned to the control or experimental group based on their OSCE itinerary. Before the OSCE, subjects read an article on SDH. At the simulation center, subjects completed a 3-item confidence and a 10-item knowledge pre-test, developed by the research team and assessed for content validity by three experts. The experimental group then received a SDH-centered simulation, while the control group received a non-SDH simulation. Both groups then completed the confidence and knowledge post-tests. Results: Subjects (N = 118: Control n = 57, Experimental n = 61) were predominantly female (87%), age 20-50 (92%), Non-Hispanic/white (74%), and had practiced on average seven years. After the intervention, the control group statistically significantly improved on confidence (p = .03) but not on knowledge, while the experimental group improved on both (p = .02, p = .00),. For both groups, confidence was correlated with overall years in practice (r = .20, p = .05) and practice in a health professions shortage area (r = .21, p = .05). Implications: SDH-centered simulation based learning is an effective way to increase students’ knowledge and confidence in using tenets of SDH in assessing, developing and implementing plans of care for patients. Further testing of the instruments is needed to establish validity and reliability before larger studies are conducted. Future research is needed to examine the sustained use of SDH after graduates enter practice

Social Work’s Historical Legacy of Racism and White Supremacy (Part 1/Day 1)

Social work has a complex history of upholding White supremacy alongside a goal to achieve racial justice. Moreover, our profession simultaneously practices within racist systems and works to dismantle them. In the wake of a fervent #BlackLivesMatter movement and persistent racial disparities in key social welfare institutions, these paradoxes have come to the forefront of discussion in academic and practice circles. This unique moment presents an opportunity to interrogate our profession’s relationship to White supremacy and racial justice in order to reimagine an anti-racist future. We hope you’ll join us for a four-part series of virtual symposia that will address these themes. Symposium events will occur throughout the academic year and will address different aspects of our past, present, and future. This portion of the symposium features: 1. Welcome to the Symposium: Laura S. Abrams, Sandra Crewe, Alan Dettlaff, James Herbert Williams 2. Race-Making Through The Child Welfare And Juvenile Courts: Jenny Jones, Christin D. Haynes; Joan Blakely, Marva Lewis, & Rae Stevenson; Tanya Smith Brice 3. Social Work, Immigration and Displacement: Yoosun Park; Benjamin Roth; Alicia Chatterje

Single-Quantum-Dot Tracking Reveals Altered Membrane Dynamics of an Attention-Deficit/Hyperactivity-Disorder-Derived Dopamine Transporter Coding Variant

The presynaptic, cocaine- and amphetamine-sensitive dopamine (DA) transporter (DAT, <i>SLC6A3</i>) controls the intensity and duration of synaptic dopamine signals by rapid clearance of DA back into presynaptic nerve terminals. Abnormalities in DAT-mediated DA clearance have been linked to a variety of neuropsychiatric disorders, including addiction, autism, and attention deficit/hyperactivity disorder (ADHD). Membrane trafficking of DAT appears to be an important, albeit incompletely understood, post-translational regulatory mechanism; its dysregulation has been recently proposed as a potential risk determinant of these disorders. In this study, we demonstrate a link between an ADHD-associated DAT mutation (Arg615Cys, R615C) and variation on DAT transporter cell surface dynamics, a combination only previously studied with ensemble biochemical and optical approaches that featured limited spatiotemporal resolution. Here, we utilize high-affinity, DAT-specific antagonist-conjugated quantum dot (QD) probes to establish the dynamic mobility of wild-type and mutant DATs at the plasma membrane of living cells. Single DAT-QD complex trajectory analysis revealed that the DAT 615C variant exhibited increased membrane mobility relative to DAT 615R, with diffusion rates comparable to those observed after lipid raft disruption. This phenomenon was accompanied by a loss of transporter mobilization triggered by amphetamine, a common component of ADHD medications. Together, our data provides the first dynamic imaging of single DAT proteins, providing new insights into the relationship between surface dynamics and trafficking of both wild-type and disease-associated transporters. Our approach should be generalizable to future studies that explore the possibilities of perturbed surface DAT dynamics that may arise as a consequence of genetic alterations, regulatory changes, and drug use that contribute to the etiology or treatment of neuropsychiatric disorders