Seeing Numbers

In 1890 William James listed several “elementary mental categories” that he postulated as having a natural origin. Among them, alongside the ideas of time and space, he also listed the idea of number. A symptomatic feature of Informatics as well as Cognitive Science today is the tendency not to talk so much about ideas as about their representations, either in the computer or in the brain. Taking up somewhat different perspective I will discuss the way natural numbers, viewed as counts of real or imagined objects, may be experienced phenomenally. I put forth even some speculative ideas about mental number processing by numerical savants

Sixty years of cybernetics: cybernetics still alive

summary:This informal essay, written on the occasion of 60th anniversary of Wienerian cybernetics, presents a series of themes and ideas that has emerged during last several decades and which have direct or indirect relationships to the principal concepts of cybernetics. Moreover, they share with original cybernetics the same transdisciplinary character

Strict deterministic grammars

A grammatical definition of a family of deterministic context free languages is presented. It is very easy to decide if a context free grammar is strict deterministic. A characterization theorem involving pushdown automata is proved, and it follows that the strict deterministic languages are coextensive with the family of prefix free deterministic languages. It is possible to obtain an infinite hierarchy of strict deterministic languages as defined by their degree

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

Uniqueness of episodic experience

In the paper a question is explored whether human person possess something that may be called “a sense of uniqueness” (uniqueness in numerical sense). Uniqueness may be primarily related to individual experience of an episodic situation in an actual context. Only from such an experience one could derive an objective (or intersubjective) notion of uniqueness of concrete things and events. The sense of uniqueness is connected to the sense of spatiotemporal presence, sense of Self, and sense of sameness of episodes really lived through and their recollections. A question is posed of the nature of such connections

Cybernetics Still Alive

This informal essay, written on the occasion of 60th anniversary of Wienerian cybernetics, presents a series of themes and ideas that has emerged during last several decades and which have direct or indirect relationships to the principal concepts of cybernetics. Moreover, they share with original cybernetics the same transdisciplinary character