Multidimensional Approach to Comparative Avian Visual Systems

Since the birth of visual ecology, comparative studies on how birds see their world have been limited to a small number of species and tended to focus on a single visual trait. This approach has constrained our ability to understand the diversity and evolution of the avian visual system. The goal of this dissertation was to characterize multiple visual dimensions on bird groups that are highly speciouse (e.g., Passeriformes), and test some hypotheses and predictions, using modern comparative tools, on the relationship between different visual traits and their association with visual information sampling behaviors. First, I developed a novel method for characterizing quantitatively the retinal topography (e.g., variation in cell density across the retina) of different bird species in a standardized manner. Second, using this method, I established that retinal configuration has converged particularly in terrestrial vertebrates into three types of retinal specializations: fovea, area, and visual streak, with the highest, intermediate, and lowest peak and peripheral ganglion cell densities, respectively. The implication is that foveate species may have more enhanced visual centers in the brain than non-foveate vertebrates. Third, forest passerines that form multi-species flocks and belong to an insectivore niche differ in their visual system configuration, which appeared associated to behavioral specializations to enhance foraging opportunities: species that searched for food at steep angles had relatively wide binocular fields with a high degree of eye movement right above their short bills, whereas species that searched for food at shallower angles had narrower binocular fields with a high degree of eye movement below their bills. Eye movement allows these species to move their fovea around to visually search for food in the complex forest environment. Fourth, I studied the visual system configuration of nine species of closely related emberizid sparrows, which appear to maximize binocular vision, even seeing their bill tips, to enhance food detection and handling. Additionally, species with more visual coverage had higher visual acuity, which may compensate for their larger blind spots above their foveae, enhancing predator detection. Overall, the visual configuration of these passive prey foragers is substantially different from previously studied avian groups (e.g., sit-and-wait and tactile foragers). Finally, I studied the visual system configuration and visual exploratory behavior of 29 North American bird species across 14 Families. I found that species with a wider blind spot in the visual field (pecten) tended to move their heads at a higher rate probably to compensate for the lack of visual information. Additionally, species with a more pronounced difference in cell density between the fovea and the retinal periphery tended to have a higher degree of eye movement likely to enhance their ability to move their fovea around to gather high quality information. Overall, the avian visual system seems to have specializations to enhance both foraging and anti-predator behaviors that differ greatly between species probably to adjust to specific environmental conditions

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

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