Rough Sets and Three Valued Connectives Extended Abstract

<正>1 Introduction In[5]we investigated the significance of some truth-functional three valued logics of ill-known sets described by pairs of disjoint(or pairs of nested) subsets.In particular,we referred to the case of rough sets showing that if from a mathematical standpoint we obtain sound results,the interpretation with respect to     

Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR

Inhibition of the BRAF(V600E) oncoprotein by the small-molecule drug PLX4032 (vemurafenib) is highly effective in the treatment of melanoma. However, colon cancer patients harbouring the same BRAF(V600E) oncogenic lesion have poor prognosis and show only a very limited response to this drug. To investigate the cause of the limited therapeutic effect of PLX4032 in BRAF(V600E) mutant colon tumours, here we performed an RNA-interference-based genetic screen in human cells to search for kinases whose knockdown synergizes with BRAF(V600E) inhibition. We report that blockade of the epidermal growth factor receptor (EGFR) shows strong synergy with BRAF(V600E) inhibition. We find in multiple BRAF(V600E) mutant colon cancers that inhibition of EGFR by the antibody drug cetuximab or the small-molecule drugs gefitinib or erlotinib is strongly synergistic with BRAF(V600E) inhibition, both in vitro and in vivo. Mechanistically, we find that BRAF(V600E) inhibition causes a rapid feedback activation of EGFR, which supports continued proliferation in the presence of BRAF(V600E) inhibition. Melanoma cells express low levels of EGFR and are therefore not subject to this feedback activation. Consistent with this, we find that ectopic expression of EGFR in melanoma cells is sufficient to cause resistance to PLX4032. Our data suggest that BRAF(V600E) mutant colon cancers (approximately 8-10% of all colon cancers), for which there are currently no targeted treatment options available, might benefit from combination therapy consisting of BRAF and EGFR inhibitors.     

Solving the Giant Stars Problem: Theories of Stellar Evolution from The 1930s to The 1950s

Historiography has pointed out that the time between the mid 1910s and the early 1930s can be considered a pivotal period in the history of stellar astrophysics. In those years, scholars like Saha and Eddington first applied atomic physics to astrophysics. Theoretical astrophysics was born. This led to the development of the first physically sound models for stellar interiors and atmospheres. These landmark achievements spurred scholars to elaborate theories for stellar evolutions, and in the following decades several astrophysicists focused on this problem. The evolutionary role of red giants turned out to be the main issue. Those stars were initially assumed to be young ones going through the formation stage, but astrophysicists gradually realized that they were rather to be considered old, evolved stars. The solution of the giant stars issue required a couple of decades: it was not until the mid 1950s that a satisfactory explanation was obtained. This provides a detailed picture of the theories of stellar evolution from the 1930s to the 1950s and of the solution to the red giants problem, with special emphasis on how such a solution was made possible by a series of subsequent steps: the identification of changing chemical composition as a main evolutionary feature of a star, the inclusion of nuclear physics within the theoretical framework of stellar astrophysics, the recognition of the importance of inhomogeneities that settle within stars as nuclear processes go on.     

Analysis of the coding genome of diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common form of human lymphoma. Although a number of structural alterations have been associated with the pathogenesis of this malignancy, the full spectrum of genetic lesions that are present in the DLBCL genome, and therefore the identity of dysregulated cellular pathways, remains unknown. By combining next-generation sequencing and copy number analysis, we show that the DLBCL coding genome contains, on average, more than 30 clonally represented gene alterations per case. This analysis also revealed mutations in genes not previously implicated in DLBCL pathogenesis, including those regulating chromatin methylation (MLL2; 24% of samples) and immune recognition by T cells. These results provide initial data on the complexity of the DLBCL coding genome and identify novel dysregulated pathways underlying its pathogenesis.