Work-Based Antipoverty Programs for Parents Can Enhance the School Performance and Social Behavior of Children

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65246/1/1467-8624.00281.pd

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

Presenter First: Organizing Complex GUI Applications for Test-Driven Development

Presenter First (PF) is a technique for organizing source code and development activities to produce fully tested GUI applications from customer stories using test-driven development. The three elements of Presenter First are a strategy for how applications are developed and tested, a variant on the Model View Presenter (MVP) design pattern, and a particular means of composing MVP triads. Presenter tests provide an economical alternative to automated GUI system tests. We have used Presenter First on projects ranging in size from several to a hundred MVP triads. This paper describes MVP creation, composition, scaling, and the tools and process we use. An example C # application illustrate

Characterization of instream hydraulic and riparian habitat conditions and stream temperatures of the upper White River Basin, Washington, using multispectral imaging systems /

Includes bibliographical references (p. 67-68).Mode of access: Internet

Theorising international environmental law

From The Oxford Handbook of International Legal Theory (Florian Hoffmann and Anne Orford, eds, Oxford UP, forthcoming 2014). --- This paper, part of a larger work on international law theory, sketches some early lines of inquiry towards a theoretical understanding of international environmental law. As the body of international law regulating human interaction with the natural world, one might expect this branch of law to be a cornerstone of the international system. Yet in practice, international environmental law's reach is strikingly circumscribed. Little of the governance of natural resources, for example, is 'environmental'. Subsisting at the periphery, environmental law focuses on conserving particular (rare, exotic) species and 'ecosystems', and curbing certain kinds of pollution. Its principles are vague, peppering the margins of rulings within other judicial fora: it is quintessential soft law. In this paper, we suggest that international environmental law's dilemmas are due to two competing heritages. On one hand, this law enshrines the peculiar pantheism of the European romantic period, positing the 'natural world' as sacred, inviolable, redemptive. On the other, its main antecedents are found in colonial era practices, which provided the data for the earliest environmental science and a laboratory for prototypical attempts at conservation and sustainable development. Caught between irreconcilable demands, international environmental law struggles today to avoid utopian irrelevance or nugatory paralysis