43,088 research outputs found

    Optimization of deliveries from distribution points

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    We solve an optimization problem involving the assignment of transport routes to a delivery point. The general and particular cases of the optimization problem are described. An algorithm for the simplified case and ideas for the general case is presented

    AKT activation controls cell survival in response to HDAC6 inhibition.

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    HDAC6 is emerging as an important therapeutic target for cancer. We investigated mechanisms responsible for survival of tumor cells treated with a HDAC6 inhibitor. Expression of the 20 000 genes examined did not change following HDAC6 treatment in vivo. We found that HDAC6 inhibition led to an increase of AKT activation (P-AKT) in vitro, and genetic knockdown of HDAC6 phenocopied drug-induced AKT activation. The activation of AKT was not observed in PTEN null cells; otherwise, PTEN/PIK3CA expression per se did not predict HDAC6 inhibitor sensitivity. Interestingly, HDAC6 inhibitor treatment led to inactivating phosphorylation of PTEN (P-PTEN Ser380), which likely led to the increased P-AKT in cells that express PTEN. Synergy was observed with phosphatidylinositol 3-kinases (PI3K) inhibitor treatment in vitro, accompanied by increased caspase 3/7 activity. Furthermore, combination of HDAC6 inhibitor with a PI3K inhibitor caused substantial tumor growth inhibition in vivo compared with either treatment alone, also detectable by Ki-67 immunostaining and (18)F-FLT positron emission tomography (PET). In aggregate AKT activation appears to be a key survival mechanism for HDAC6 inhibitor treatment. Our findings indicate that dual inhibition of HDAC6 and P-AKT may be necessary to substantially inhibit growth of solid tumors

    Positive Quantization in the Presence of a Variable Magnetic Field

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    Starting with a previously constructed family of coherent states, we introduce the Berezin quantization for a particle in a variable magnetic field and we show that it constitutes a strict quantization of a natural Poisson algebra. The phase-space reinterpretation involves a magnetic version of the Bargmann space and leads naturally to Berezin-Toeplitz operators.Comment: 15 page
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