Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with prognosis of estrogen receptor-negative breast cancer after chemotherapy

Introduction: Tumor lymphocyte infiltration is associated with clinical response to chemotherapy in estrogen receptor (ER) negative breast cancer. To identify variants in immunosuppressive pathway genes associated with prognosis after adjuvant chemotherapy for ER-negative patients, we studied stage I-III invasive breast cancer patients of European ancestry, including 9,334 ER-positive (3,151 treated with chemotherapy) and 2,334 ER-negative patients (1,499 treated with chemotherapy). Methods: We pooled data from sixteen studies from the Breast Cancer Association Consortium (BCAC), and employed two independent studies for replications. Overall 3,610 single nucleotide polymorphisms (SNPs) in 133 genes were genotyped as part of the Collaborative Oncological Gene-environment Study, in which phenotype and clinical data were collected and harmonized. Multivariable Cox proportional hazard regression was used to assess genetic associations with overall survival (OS) and breast

In vivo differentiated cytokine-producing CD4+ T cells express functional CCR7

Chemokines and their receptors fulfill specialized roles in inflammation and under homeostatic conditions. CCR7 and its ligands, CCL19 and CCL21, are involved in lymphocyte recirculation through secondary lymphoid organs and additionally navigate lymphocytes into distinct tissue compartments. The role of CCR7 in the migration of polarized T effector/memory cell subsets in vivo is still poorly understood. We therefore analyzed murine and human CD4+ cytokine-producing cells developed in vivo for their chemotactic reactivity to CCR7 ligands. The responses of cells producing cytokines, such as IFN-{gamma}, IL-4, and IL-10, as well as of subsets defined by memory or activation markers were comparable to that of naive CD4+ cells, with slightly lower reactivity in cells expressing IL-10 or CD69. This indicates that CCR7 ligands are able to attract naive as well as the vast majority of activated and effector/memory T cell stages. Chemotactic reactivity of these cells toward CCL21 was absent in CCR7-deficient cells, proving that effector cells do not use alternative receptors for this chemokine. Th1 cells generated from CCR7−/− mice failed to enter lymph nodes and Peyer’s patches, but did enter a site of inflammation. These findings indicate that CD4+ cells producing effector cytokines upon stimulation retain the capacity to recirculate through lymphoid tissues via CCR7

Interface control procedures for university satellite programmes

Now that more and more universities have joined the CubeSat community and have their own satellite in Earth orbit, it is expected that the planned successors will be of higher complexity. These successors within a university satellite programme will often house more technically ad-vanced subsystems as well as more challenging technology demonstrations for external partners. Also, the number of these third-party experiments is expected to increase throughout the programme. In order to have successful projects, these developments ask for a robust and well-defined inter-face control approach. Interface control ensures the proper mutual development of satellite systems and coordination of simultaneously operating design teams. Well-defined and properly implemented interface control procedures prevent engineers from designing non-complying components that are unable to be correctly incorporated into the satellite. Redesigns are thereby less likely. The characteristics of university satellite projects ask for a different approach to systems engi-neering techniques than what is common within industry. This is attributable to a scarcity of resources, most notably manpower and budget. Considering these limitations, above all, inter-face control procedures have to be practically implementable. This paper proposes a set of interface control tools and procedures which are based on common industry practice, but scaled down for university satellite programmes. By elaborating on the proposed tools for interface control one should be able to set up an own set of tools, customized to its own project. Imple-mentation of the interface control tools and procedures is illustrated based on the Delfi-n3Xt satellite development of the Delft University of Technology where the procedures are currently in place.Space EngineeringAerospace Engineerin