Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types

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

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Emergent s-Wave Interactions between Identical Fermions in Quasi-One-Dimensional Geometries

Orbital degrees of freedom play an essential role in metals, semiconductors, and strongly confined electronic systems. Experiments with ultracold atoms have used highly anisotropic confinement to explore low-dimensional physics, but they typically eliminate orbital degrees of freedom by preparing atoms in the motional ground states of the strongly confined directions. Here, we prepare multiband systems of spin-polarized fermionic potassium (^{40}K) in the quasi-one-dimensional (q1D) regime and quantify the strength of atom-atom correlations using radio-frequency spectroscopy. The activation of orbital degrees of freedom leads to a new phenomenon: a low-energy scattering channel that has even particle-exchange parity along the q1D axis, as if the underlying interactions were s-wave. This emergent exchange symmetry is enabled by orbital singlet wave functions in the strongly confined directions, which also confer high-momentum components to low-energy q1D collisions. We measure both the q1D odd-wave and even-wave “contact” parameters for the first time and compare them to theoretical predictions of one-dimensional many-body models. The strength and spatial symmetry of interactions are tuned by a p-wave Feshbach resonance and by transverse confinement strength. Near resonance, the even-wave contact approaches its theoretical unitary value, whereas the maximum observed odd-wave contact remains several orders of magnitude below its unitary limit. Low-energy scattering channels of multi-orbital systems, such as those found here, may provide new routes for the exploration of universal many-body phenomena

P-wave interactions in a spin-polarized Fermi gas with and without confinement

Spin-polarized Fermi gases can only interact with exchange anti-symmetric pair wave functions. The resulting p-wave interactions are less well studied than the s-wave case. We improve our understanding and measure Feshbach resonance-enhanced p-wave interactions in fermionic Potassium (40K) with and without low-dimensional confinement. We first parameterize the three-dimensional (3D) resonance through a combination of coupled-channels calculations, a two-channel model, and dimer binding energies measured through resonant and spin-flip association. This benchmarks 3D interactions, which underlie lower-dimensional scattering. We attain confinement by loading atoms into two orthogonal standing waves to produce an ensemble of quasi-one-dimensional (q1D) tubes. We measure correlation strength through a connection between the power-law tail of radio-frequency transfer spectra and the 1D p-wave contact. Tuning of the magnetic field from the 3D resonance shows not only a confinement-induced resonance shift, but also additional features in a broader regime that arise due to collisions in transverse excited bands. Our studies build a foundation for further exploration of few- and many- body states in spin-polarized Fermi gases. AFOSR FA9550-19-1-0365, NSERC

Implications of SENSE MR in routine clinical practice

Sensitivity encoding (SENSE) uses multiple MRI receive coil elements to encode spatial information in addition to traditional gradient encoding. Requiring less gradient encodings translates into shorter scan times, which is extremely beneficial in many clinical applications. SENSE is available to routine diagnostic imaging for the past 2 years. This paper highlights the use of SENSE with scan time reduction factors up to 6 in contrast-enhanced MRA, routine abdominal imaging, mammography, cardiac and neuro imaging. It is shown that SENSE has opened new horizons in both routine and advanced MR imaging. © 2002 Elsevier Science Ireland Ltd. All rights reserved.SCOPUS: re.jinfo:eu-repo/semantics/publishe