Th1 and Th2 cytokine profile in patients with early onset periodontitis and their healthy siblings.

Early onset periodontitis (EOP) is a chronic inflammatory periodontal disease with a strong genetic link affecting individuals aged 17 to 25. In the familial studies we tested the hypothesis about the role of Th1 and Th2 cytokines in the pathogenesis of EOP disease. The study involved 6 individuals with EOP disease and their 6 siblings with healthy periodontium. Actinobacillus actinomycetemcomitans (A. a), a bacterium typical for EOP, was detected in all people studied. Th1 and Th2 cytokine production was measured after in vitro stimulation. Peripheral blood mononuclear cells (PBMC) were isolated and cultivated for 24 h and 7 days with PWM, A. a. or Escherichia coli. The levels of IL-4, IFN-gamma, IgA, IgG and IgM were measured by ELISA methods. After in vitro stimulation of PBMC, a significantly higher production of IL-4 and significantly lower production of IFN-gamma were found in the group of patients compared with their healthy siblings. The increased level of IL-4 in patients was in good agreement with an increased level of IgM after stimulation of lymphocytes with E. coli. These results support Seymour's hypothesis according to which patients with progressive disease primarily activate Th2 lymphocytes while non-susceptible individuals activate Th1 lymphocytes

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

Longitudinal and lateral slip control of autonomous wheeled mobile robot for trajectory tracking

This research formulates a path-following control problem subjected to wheel slippage and skid and solves it using a logic-based control scheme for a wheeled mobile robot (WMR). The novelty of the proposed scheme lies in its methodology that considers both longitudinal and lateral slip components. Based on the derived slip model, the controller for longitudinal motion slip has been synthesized. Various control parameters have been studied to investigate their effects on the performance of the controller resulting in selection of their optimum values. The designed controller for lateral slip or skid is based on the proposed side friction model and skid check condition. Considering a car-like WMR, simulation results demonstrate the effectiveness of the proposed control scheme. The robot successfully followed the desired circular trajectory in the presence of wheel slippage and skid. This research finds its potential in various applications involving WMR navigation and control

Architecture and functional morphology of the skeletal apparatus of ozarkodinid conodonts

Ozarkodinid conodonts were one of the most successful groups of agnathan vertebrates. Only the oropharyngeal feeding apparatus of conodonts was mineralized, and the skeletal elements were generally disarticulated on the death and decay of the body. Occasionally, however, they were preserved in association as 'natural assemblages', fossilized in situ after post-mortem collapse of the apparatus. From analysis of element arrangement in natural assemblages of Idiognathodus from the Pennsylvanian of Illinois we have produced a precise scale model of the feeding apparatus of ozarkodinid conodonts. At the front lay an axial Sa element, flanked by two groups of four close-set elongate Sb and Sc elements which were inclined obliquely inwards and forwards; above these elements lay a pair of arched and inward pointing M elements. Behind the S-M array lay transversely oriented and bilaterally opposed Pb and Pa elements. Our model sheds new light on food acquisition in conodonts. We propose that the anterior S and M elements of ozarkodinid conodonts were attached to cartilaginous plates. In order for the animal to feed, these plates were first everted, and then drawn back and upward over the anterior edge of an underlying cartilage. These movements produced a highly effective grasping action, the cusps and denticles of the elements converging to grab and impale any food item that lay anterior to the open array. According to this hypothesis, the anterior part of the conodont apparatus is comparable to, and possibly homologous with, the lingual apparatus of extant agnathans; the elements themselves, however, have no direct homologues. <br