Competition and forgetting during context-based episodic memory retrieval

Recent memory models highlight the importance of contextual information for remembering episodic events. A consequence of binding event memories with their context is that contextually related memories can interfere with the retrieval of targeted memories, leading to retrieval induced forgetting (RIF) of the competing memories (Anderson et al., 2000). A model built to explain this effect describes a nonmonotonic “U shaped” relationship between memory activation and changes in memory strength (Norman et al., 2007). Specifically, competing memories that activate to a moderate degree (vs. low or high activation) are more likely to be weakened and forgotten. However, the factors governing whether and how memories will activate and compete during retrieval are not well understood. Here, we test the hypothesis that events experienced closer in time will be more likely to compete during memory retrieval, leading to RIF.Psycholog

3D printed relief valve analysis and validation

Additive Manufacturing allows for faster, lower cost product development including customization, print at point of use, and low cost per volume produced. This research uses Stereolithography produced prototypes to develop an improvement to an existing product, the internal pressure relief valve of a positive displacement pump. Four 3D printed prototype assemblies were developed and tested in this research. The relief valve assemblies consisted of additive manufacturing produced pressure vessel components, post processed, and installed on the positive displacement pump with no additional machining. Prototype designs were analyzed with Computational Fluid Dynamic simulation to increase flow through the valve. The simulation was validated with performance testing to reduce the cracking to full bypass pressure range of the valve. By reducing this operational range of the valve, the power requirement of the pump drive system could be reduced allowing for increased energy efficiency in pump drive systems. Performance testing of the 3D printed relief valves measured pump flow, poppet movement within the valve, and discharge pressure at operational conditions similar to existing applications. The Stereolithography prototype assemblies performed very well, demonstrating a 56% reduction in the pressure differential of the cracking to full bypass stage of the valve. This research has demonstrated the short term ability of additive manufactured produced components to replace existing metal components in pressure vessel applications. Keywords: Additive Manufacturing, Stereolithography, Prototype, Internal Pressure Relief Valve, Positive Displacement Pum

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

The emergence of event organization during development

Everyday, adults organize our continuous experience into discrete episodic events, which allows us to not only recall events in the near and distant past but also to use previous experiences to generate expectations for the future. Children, on the other hand, often struggle to efficiently organize temporal experience into discrete events, leading to worse memory for event detail and order. The refinement in temporal organization that occurs during development has been attributed to a number of factors; including the accumulation of existing knowledge to draw upon and the developmental emergence of integration and differentiation mechanisms of the hippocampal and prefrontal cortex (PFC) memory network. As experience unfolds, a mature memory system relies on hippocampal processes to integrate predictable event elements of ongoing experience into a shared representation and to differentiate event elements into separate representations under conditions of uncertainty. To generate predictions, a mature memory system relies on abstract generalizable event representation when encountering new or related experiences. This aids in the efficient organization of ongoing experience, and facilitates event memory. Several open questions remain when and how integration and differentiation processes emerge in a developing memory system to organize the perceptual complexity of continuous experience into discrete event memories. In this proposal, I will probe the developmental trajectory of the capacity to efficiently organize our continuous experience by (1) understanding the features of experience that both facilitate and worsen event memories during development and (2) understanding the change in neural representations underlying the refinement of temporal organization during development. By focusing on a period of middle childhood (7-12 years of age), I can tie refinements in temporal organization to key developmental changes in the hippocampal—PFC network. I will demonstrate that as the anterior hippocampus and medial PFC (mPFC) matures – including the connections between these regions – children’s capacity to efficiently organize temporal experience becomes more adult-like. This work provides important theoretical contributions to the role of the hippocampus— mPFC memory network in organizing continuous temporal experience into discrete events.Neuroscienc

On the Habits and Behavior of the Herring Gull, Larus Argentatus Pont

Volume: 31Start Page: 22End Page: 4

Parameter Interpretation and Reduction for a Unified Statistical Mechanical Surface Tension Model.

Surface properties of aqueous solutions are important for environments as diverse as atmospheric aerosols and biocellular membranes. Previously, we developed a surface tension model for both electrolyte and nonelectrolyte aqueous solutions across the entire solute concentration range (Wexler and Dutcher, J. Phys. Chem. Lett. 2013, 4, 1723-1726). The model differentiated between adsorption of solute molecules in the bulk and surface of solution using the statistical mechanics of multilayer sorption solution model of Dutcher et al. (J. Phys. Chem. A 2013, 117, 3198-3213). The parameters in the model had physicochemical interpretations, but remained largely empirical. In the current work, these parameters are related to solute molecular properties in aqueous solutions. For nonelectrolytes, sorption tendencies suggest a strong relation with molecular size and functional group spacing. For electrolytes, surface adsorption of ions follows ion surface-bulk partitioning calculations by Pegram and Record (J. Phys. Chem. B 2007, 111, 5411-5417)

Surface tensions of inorganic multicomponent aqueous electrolyte solutions and melts

A semiempirical model is presented that predicts surface tensions (s) of aqueous electrolyte solutions and their mixtures, for concentrations ranging from infinitely dilute solution to molten salt. The model requires, at most, only two temperature-dependent terms to represent surface tensions of either pure aqueous solutions, or aqueous or molten mixtures, over the entire composition range. A relationship was found for the coefficients of the equation s = c1 + c2T (where T (K) is temperature) for molten salts in terms of ion valency and radius, melting temperature, and salt molar volume. Hypothetical liquid surface tensions can thus be estimated for electrolytes for which there are no data, or which do not exist in molten form. Surface tensions of molten (single) salts, when extrapolated to normal temperatures, were found to be consistent with data for aqueous solutions. This allowed surface tensions of very concentrated, supersaturated, aqueous solutions to be estimated. The model has been applied to the following single electrolytes over the entire concentration range, using data for aqueous solutions over the temperature range 233-523 K, and extrapolated surface tensions of molten salts and pure liquid electrolytes: HCl, HNO3, H2SO4, NaCl, NaNO3, Na2SO 4, NaHSO4, Na2CO3, NaHCO 3, NaOH, NH4Cl, NH4NO3, (NH 4)2SO4, NH4HCO3, NH 4OH, KCl, KNO3, K2SO4, K 2CO3, KHCO3, KOH, CaCl2, Ca(NO 3)2, MgCl2, Mg(NO3)2, and MgSO4. The average absolute percentage error between calculated and experimental surface tensions is 0.80% (for 2389 data points). The model extrapolates smoothly to temperatures as low as 150 K. Also, the model successfully predicts surface tensions of ternary aqueous mixtures; the effect of salt-salt interactions in these calculations was explored