“Untiring Labor Overcomes All!” The History of the Dutch Mathematical Society in Comparison to Its Various Counterparts in Europe

AbstractThe Netherlands, like some other European countries, witnessed the emergence of several amateur mathematical societies in a “philomathy” atmosphere during the 18th and early 19th century. One of them, the Amsterdam Mathematical Society “Untiring Labor Overcomes All” (nowadays known as the Wiskundig Genootschap), during the early 19th century became a national institution which embodied almost the entire Dutch mathematical community. It would fulfil its role as a national mathematical Society even before the 1860s, when pure mathematics became the subject of professional research and mathematical Societies of “professionals” were founded all over Europe. This article points out the Dutch social climate (the gap between the social classes was not as enormous as elsewhere in Europe, and engineering courses were part of the mathematics curriculum at the university) and changes within the Society itself, thus describing how it was possible for the Wiskundig Genootschap to become a link between two kinds of societies (“amateurs” vs “professionals”) which should be clearly distinguished. Copyright 2001 Academic Press.Zoals in vele Europese landen ontstonden er ook in Nederland gedurende de 18de en vroege 19de eeuw wiskundige genootschappen van “liefhebbers.” Een van deze amateurgezelschappen, het Amsterdams Wiskundig Genootschap onder de zinspreuk “onvermoeide arbeid komt alles te boven,” groeide gedurende de eerste decennia van de 19de eeuw uit tot een nationaal genootschap dat de Nederlandse wiskundige gemeenschap vertegenwoordigde. Het genootschap vervulde haar rol van nationaal genootschap zodoende reeds lang voordat in de jaren 1860 onder invloed van professionalisering van (wiskundig) onderzoek dergelijke genootschappen van “professionals” in de andere Europese landen opkwamen. In dit artikel wordt gewezen op het sociale klimaat (er was nauwelijks sprake van een kloof tussen de sociale klassen zoals elders in Europa, en ingenieurswiskunde maakte deel uit van het universitair curriculum) en veranderingen binnen het genootschap zelf, waarmee beschreven wordt hoe het Wiskundig Genootschap een verband vormt tussen twee soorten van genootschappen (“amateurs” vs “professionals”) die nadrukkelijk van elkaar onderscheiden dienen te worden. Copyright 2001 Academic Press.MSC 1991 subject classifications: 01A50, 01A55

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

Jacob de Gelder en de wiskundige ideologie in Nederland (1800-1840)

Jacob de Gelder and the mathematic ideology in The Netherlands (1800-1840) During the period which is commonly called the Enlightenment, changes occurred in the social perception of mathematics. The teaching of mathematics used to be almost strictly academic and was considered to be an important part of knowledge to those who had a scientific career in view. In The Netherlands, during the first part of the nineteenth century, people began to think that mathematics was indispensable to everyone: even to the craftsmen who until then were educated within the guilds on a purely practical basis. Because of their character these views will here be called the 'mathematical ideology'. In The Netherlands, the reception of this mathematical ideology may be illustrated by the biography of the Dutch mathematician Jacob de Gelder (1765-1848). This man started off as an unimportant schoolteacher during the late eighties of the eighteenth century. He took an interest in mathematics and educated himself and his pupils in this science. In his teaching as well as in his writings he would proclaim the mathematical ideology. He made a remarkable career and was appointed professor of mathematics at Leiden University in 1819. The following three aspects constituted De Gelder's views: 1. Mathematics became more and more the basis of reasoning. The argument was even reversed: every good argument was called a mathematical one and if an argument was considered not convincingly enough, a mathematical formula was added, a phenomenon easily illustrated by several of De Gelder's manuscripts. 2. Mathematics became a necessary prerequisite for the study of all other sciences. Therefore, it actually became a standard part of the curriculum of all Dutch schools preparing students for the university. 3. Mathematics even became a necessity for craftsmen. De Gelder was convinced, and the Government agreed with him, that the teaching of mathematics to labourers would result in a better and faster development of industry in The Netherlands, which in this respect lagged behind England and Germany. Engineering schools with a strong propaedeutic mathematics course would largely solve this problem. The Dutch Government supported De Gelder in proclaiming the mathematical ideology. De Gelder himself had quite some influence in Dutch mathematical circles, and he was regarded an authority on the subject of the teaching of mathematics. We may therefore assume that his views, in particular the mathematical ideology, were not solely his, but found support within large circles in Dutch society during the first half of the nineteenth century