4,171 research outputs found

    Assessment of the anticancer mechanisms of the c-MET inhibitor tivantinib in the therapy of gastrointestinal tumors

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    CHARACTERIZATION OF THE COHESIN ACETYLTRANSFERASE ECO1 AND ITS ROLE IN NUCLEAR FUNCTIONS

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    Sister-chromatid cohesion plays a vital role in precise chromosome segregation and genome stability. This process is carried out by the cohesin complex and its associated proteins. In addition, a growing body of evidence suggests that the cohesin complex affects other processes, including gene transcription, DNA damage repair, and DNA replication. One piece of evidence for cohesin's role in other processes is that individuals with mutations in the cohesin complex can survive, albeit with congenital abnormalities. For example, mutations in ESCO2 cause Roberts syndrome. ESCO2 is the human homolog of Eco1 in budding yeast. Eco1 is a critical acetyltransferase for establishing cohesion during S phase and also re-establishing cohesion in G2/M phase in response to DNA damage. To identify the roles of the cohesin complex beyond chromosome segregation, we have constructed mutations in Eco1 which do not cause gross chromosome separation defect. We have shown that DNA damage repair is strongly affected in the eco1 mutants and that a specific DNA recombination pathway is affected. Further investigation of eco1 mutants showed transcription and DNA replication defects genome-wide. Interestingly, deletion of Fob1, a nucleolar protein required for replication fork blocking in rDNA region, corrects the genome-wide replication defects, nucleolar structure and chromosome segregation in an eco1 mutant by allowing bidirectional replication of the rDNA. This highlights cohesin's central role at the rDNA for global control of DNA replication and gene expression. Our results demonstrate the diversity of cohesin functions and have direct implications for the etiology of human cohesinopathies

    Advanced Control and Analysis of Cascaded Multilevel Converters Based on P-Q Compensation

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    This paper introduces new controls for the cascaded multilevel power converter. This converter is also sometimes referred to as a ldquohybrid converterrdquo since it splits high-voltage/low-frequency and low-voltage/pulsewidth-modulation (PWM)-frequency power production between ldquobulkrdquo and ldquoconditioningrdquo converters respectively. Cascaded multilevel converters achieve higher power quality with a given switch count when compared to traditional multilevel converters. This is a particularly favorable option for high power and high performance applications such as naval ship propulsion. This paper first presents a new control method for the topology using three-level bulk and conditioning inverters connected in series through a three-phase load. This control avoids PWM frequency switching in the bulk inverter. The conditioning inverter uses a capacitor source and its control is based on compensating the real and reactive (P-Q) power difference between the bulk inverter and the load. The new control explicitly commands power into the conditioning inverter so that its capacitor voltage remains constant. A unique space vector analysis of hybrid converter modulation is introduced to quantitatively determine operating limitations. The conclusion is then generalized for all types of controls of the hybrid multilevel converters (involving three-level converter cells). The proposed control methods and analytical conclusions are verified by simulation and laboratory measurements

    Direct Torque Control of Five-Phase Induction Motor Using Space Vector Modulation with Harmonics Elimination and Optimal Switching Sequence

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    In this paper an effective direct torque control (DTC) for a 5-phase induction motor with sinusoidally distributed windings is developed. First by coordinate transformation, the converter/motor models are represented by two independent equivalent d-q circuit models; and the 5-phase VSI input are decoupled into the torque producing and non-torque producing harmonics sets. Then with the torque production component of the induction motor model, the space vector modulation (SVM) can be applied to the five-phase induction motor DTC control, resulting in considerable torque ripple reduction over the lookup table method. Based on the decoupled system model, the current distortion issue due to lack of back EMF for certain harmonics is analyzed. Two equally effective SVM schemes with the harmonic cancellation effect are introduced to solve this problem. To analyze the DTC control torque ripple, an insightful perspective (also applicable to 3-phase analysis) is introduced to predict the torque ripple pattern evolution with changing motor speed and stator flux angular position. Therefore the switching sequence for lowest torque ripple can be determined and re-arranged online. Finally, with the overall optimal switching scheme adopted, detailed simulations verify the effectiveness of the new control

    Heuristic parameter selection based on functional minimization: Optimality and model function approach

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    We analyze some parameter choice strategies in regularization of inverse problems, in particular the (modified) L-curve method and a variant of the Hanke-Raus rule. These are heuristic rules, free of the noise level, and they are based on minimization of some functional. We analyze these functionals, and we prove some optimality results under general smoothness conditions. We also devise some numerical approach for finding the minimizers, which uses model functions. Numerical experiments indicate that this is an efficient numerical procedure
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