Clinical relevance of molecular characteristics in Burkitt lymphoma differs according to age

While survival has improved for Burkitt lymphoma patients, potential differences in outcome between pediatric and adult patients remain unclear. In both age groups, survival remains poor at relapse. Therefore, we conducted a comparative study in a large pediatric cohort, including 191 cases and 97 samples from adults. While TP53 and CCND3 mutation frequencies are not age related, samples from pediatric patients showed a higher frequency of mutations in ID3, DDX3X, ARID1A and SMARCA4, while several genes such as BCL2 and YY1AP1 are almost exclusively mutated in adult patients. An unbiased analysis reveals a transition of the mutational profile between 25 and 40 years of age. Survival analysis in the pediatric cohort confirms that TP53 mutations are significantly associated with higher incidence of relapse (25 ± 4% versus 6 ± 2%, p-value 0.0002). This identifies a promising molecular marker for relapse incidence in pediatric BL which will be used in future clinical trials

Symposion

Das Politische drängt sich gegenwärtig in den gesellschaftlichen Vordergrund wie schon lange nicht mehr. Das Symposion nimmt diese Situation zum Anlass, um das Verhältnis von Politik und Soziologie grundsätzlich auf den Prüfstand zu stellen: Aus unterschiedlichen Blickwinkeln wird die Frage beleuchtet, wie wir das Politische heute soziologisch denken müssen, um den gesellschaftlichen Phänomenen unserer Zeit wissenschaftlich gerecht werden zu können. Die Beiträge des Symposions loten dazu das Potential Politischer Soziologie theoretisch und methodisch aus. Gemeinsam führen sie vor Augen, dass es Grund gibt, die Stellung des Politischen in der Gesellschaft innerhalb der Soziologie viel offensiver und grundsätzlicher zu diskutieren, als dies derzeit der Fall ist. Politics and the political system have become topics of intense public debates we have not witnessed in a long time. The symposium takes stock of these debates by systematically scrutinizing the relation between politics and sociology. More specifically, it explores how we might think about politics sociologically, in a way that does justice to current social developments. The contributions to the symposium address this question from different theoretical and epistemological perspectives, thereby unpacking the conceptual and methodological potentials of political sociology. Together, they draw attention to the importance of understanding political processes in order to get a better grip on current workings of society

Modern meat: the next generation of meat from cells

Modern Meat is the first textbook on cultivated meat, with contributions from over 100 experts within the cultivated meat community. The Sections of Modern Meat comprise 5 broad categories of cultivated meat: Context, Impact, Science, Society, and World. The 19 chapters of Modern Meat, spread across these 5 sections, provide detailed entries on cultivated meat. They extensively tour a range of topics including the impact of cultivated meat on humans and animals, the bioprocess of cultivated meat production, how cultivated meat may become a food option in Space and on Mars, and how cultivated meat may impact the economy, culture, and tradition of Asia

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

The art of manipulation : gender inequity and the picture study movement

textThis study locates and examines the relationship between societal gendered expectations in nineteenth century United States and the content of a picture study manual published at the turn of the century: Lucy Langdon Williams Wilson’s Picture Study in Elementary Schools: A Manual for Teachers (1909). Critical analysis of the images, artists, and content of the picture study manual provides insight into the relationship between curricular materials and the social climate during which they were produced. Recognition of this connection will enable art educators and curriculum developers to produce materials and textbooks conscious of the potential bias and marginalization of students.Art Educatio

Synthesis of Zwitterionic, Hydrophobic, and Amphiphilic Polymers: Via RAFT Polymerization Induced Self-Assembly (PISA) in Acetic Acid

Polymerization induced self-assembly (PISA) in acetic acid was employed to polymerize the hydrophilic sulfobetaine monomer 2-(N-3-sulfopropyl-N,N-dimethyl ammonium)ethyl methacrylate (DMAPS) and the hydrophobic monomer lauryl methacrylate (LMA). Polymerizations were conducted from a macro chain transfer agent (macro-CTA) consisting of 66% 2-hydroxyethyl methacrylate (HEMA) and 33% poly(ethylene glycol) methyl ether methacrylate FW ~ 300 Da (O300). A degree of polymerization (DP) of 50 was targeted for the macro-CTA in order to yield diblock copolymers with significantly larger 2nd blocks. From the poly(HEMA-co-O300) macro-CTA, diblock copolymers of poly[(HEMA-co-O300)-b-(DMAPS)] and poly[(HEMA-co-O300)-b-(LMA)] were grown via PISA in acetic acid. In order to maintain colloidal stability, it was necessary to conduct PISA of DMAPS at 10 wt% monomer, while LMA polymerizations maintained stability at 20 wt% monomer. Mnvs. conversion plots for both DMAPS and LMA show linear increases in molecular weight over the course of the polymerizations. Analysis of the molecular weight distributions revealed a progressive narrowing throughout the polymerization from an initial bimodal state. Copolymers of DMAPS and LMA were also synthesized over a large range of comonomer feed ratios. These materials show composition-dependent sizes in buffered solutions between 11 nm for the copolymer containing 80% by mol DMAPS to 75 nm for the copolymer containing 40 mol% DMAPS. PISA in acetic acid was then used to prepare copolymers of DMAPS with a range of hydrophobic polymerizable prodrug monomers as well as a polymerizable peptide macromonomer. The resultant copolymers had narrow molecular weight distributions and were readily soluble in saline solutions