4,383 research outputs found
Linear Toric Fibrations
These notes are based on three lectures given at the 2013 CIME/CIRM summer
school. The purpose of this series of lectures is to introduce the notion of a
toric fibration and to give its geometrical and combinatorial
characterizations. Polarized toric varieties which are birationally equivalent
to projective toric bundles are associated to a class of polytopes called
Cayley polytopes. Their geometry and combinatorics have a fruitful interplay
leading to fundamental insight in both directions. These notes will illustrate
geometrical phenomena, in algebraic geometry and neighboring fields, which are
characterized by a Cayley structure. Examples are projective duality of toric
varieties and polyhedral adjunction theory
Cyclin D1 Restrains Oncogene-Induced Autophagy by Regulating the AMPK-LKB1 Signaling Axis.
Autophagy activated after DNA damage or other stresses mitigates cellular damage by removing damaged proteins, lipids, and organelles. Activation of the master metabolic kinase AMPK enhances autophagy. Here we report that cyclin D1 restrains autophagy by modulating the activation of AMPK. In cell models of human breast cancer or in a cyclin D1-deficient model, we observed a cyclin D1-mediated reduction in AMPK activation. Mechanistic investigations showed that cyclin D1 inhibited mitochondrial function, promoted glycolysis, and reduced activation of AMPK (pT172), possibly through a mechanism that involves cyclin D1-Cdk4/Cdk6 phosphorylation of LKB1. Our findings suggest how AMPK activation by cyclin D1 may couple cell proliferation to energy homeostasis
The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia
CD56 is expressed in 15–20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56+ monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML
Novel P53 mutations detected by FAMA in colorectal cancers
Background: The aim of the study was to identify p53 gene mutations by FAMA (fluorescence-assisted mismatch
analysis) in colorectal cancers.
Patients and methods: Analytical scanning of the p53 gene (exons 5\u20139) was performed in colon cancer samples
from 44 consecutive patients by FAMA. FAMA is a semiautomatic scanning approach based on the chemical cleavage
of the mismatch in fluorescently labeled heteroduplex DNA, obtained from the combination of a normal and a mutated
allele. FAMA has already shown optimal levels of diagnostic accuracy and sensitivity in detecting gene mutations
(nucleotide substitutions, insertions/deletions) both at the germline and somatic level. The peculiar feature of FAMA is
its ability to detect and localize mutations, by a redundant pattern of signals due to fluorescent DNA fragments
generated by chemical cleavage. Moreover, previous data have demonstrated that normal contaminating DNA from
stromal cells in the sample does not affect the sensitivity of the procedure, leading to the identification of the mutation
even when the ratio mutant/normal allele is 10%.
Results: Eighteen mutations (12 missense, one nonsense, two deletions, three nucleotide substitutions at the level of
the splice-junctions) and two polymorphisms were detected by FAMA in 17 patients (39%) and then confirmed by
automated sequence analysis. Six of 18 mutations (33%) were not previously reported for colon cancer samples and
two of 18 lesions (11%) were identified as novel p53 mutations.
Conclusions: Analytical scanning of the p53 gene by FAMA in DNA from colon cancer samples provides a sensitive,
accurate and specific diagnostic procedure for routine clinical application
Robotic ubiquitous cognitive ecology for smart homes
Robotic ecologies are networks of heterogeneous robotic devices pervasively embedded in everyday environments, where they cooperate to perform complex tasks. While their potential makes them increasingly popular, one fundamental problem is how to make them both autonomous and adaptive, so as to reduce the amount of preparation, pre-programming and human supervision that they require in real world applications. The project RUBICON develops learning solutions which yield cheaper, adaptive and efficient coordination of robotic ecologies. The approach we pursue builds upon a unique combination of methods from cognitive robotics, machine learning, planning and agent- based control, and wireless sensor networks. This paper illustrates the innovations advanced by RUBICON in each of these fronts before describing how the resulting techniques have been integrated and applied to a smart home scenario. The resulting system is able to provide useful services and pro-actively assist the users in their activities. RUBICON learns through an incremental and progressive approach driven by the feed- back received from its own activities and from the user, while also self-organizing the manner in which it uses available sensors, actuators and other functional components in the process. This paper summarises some of the lessons learned by adopting such an approach and outlines promising directions for future work
Measurement of the cross-section and charge asymmetry of bosons produced in proton-proton collisions at TeV with the ATLAS detector
This paper presents measurements of the and cross-sections and the associated charge asymmetry as a
function of the absolute pseudorapidity of the decay muon. The data were
collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with
the ATLAS experiment at the LHC and correspond to a total integrated luminosity
of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements
varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the
1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured
with an uncertainty between 0.002 and 0.003. The results are compared with
predictions based on next-to-next-to-leading-order calculations with various
parton distribution functions and have the sensitivity to discriminate between
them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables,
submitted to EPJC. All figures including auxiliary figures are available at
https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13
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