56 research outputs found

    A bounded degree SOS hierarchy for polynomial optimization

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    We consider a new hierarchy of semidefinite relaxations for the general polynomial optimization problem (P): f∗=min⁡{ f(x):x∈K }(P):\:f^{\ast}=\min \{\,f(x):x\in K\,\} on a compact basic semi-algebraic set K⊂RnK\subset\R^n. This hierarchy combines some advantages of the standard LP-relaxations associated with Krivine's positivity certificate and some advantages of the standard SOS-hierarchy. In particular it has the following attractive features: (a) In contrast to the standard SOS-hierarchy, for each relaxation in the hierarchy, the size of the matrix associated with the semidefinite constraint is the same and fixed in advance by the user. (b) In contrast to the LP-hierarchy, finite convergence occurs at the first step of the hierarchy for an important class of convex problems. Finally (c) some important techniques related to the use of point evaluations for declaring a polynomial to be zero and to the use of rank-one matrices make an efficient implementation possible. Preliminary results on a sample of non convex problems are encouraging

    A Systematic Survey of Mini-Proteins in Bacteria and Archaea

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    BACKGROUND: Mini-proteins, defined as polypeptides containing no more than 100 amino acids, are ubiquitous in prokaryotes and eukaryotes. They play significant roles in various biological processes, and their regulatory functions gradually attract the attentions of scientists. However, the functions of the majority of mini-proteins are still largely unknown due to the constraints of experimental methods and bioinformatic analysis. METHODOLOGY/PRINCIPAL FINDINGS: In this article, we extracted a total of 180,879 mini-proteins from the annotations of 532 sequenced genomes, including 491 strains of Bacteria and 41 strains of Archaea. The average proportion of mini-proteins among all genomic proteins is approximately 10.99%, but different strains exhibit remarkable fluctuations. These mini-proteins display two notable characteristics. First, the majority are species-specific proteins with an average proportion of 58.79% among six representative phyla. Second, an even larger proportion (70.03% among all strains) is hypothetical proteins. However, a fraction of highly conserved hypothetical proteins potentially play crucial roles in organisms. Among mini-proteins with known functions, it seems that regulatory and metabolic proteins are more abundant than essential structural proteins. Furthermore, domains in mini-proteins seem to have greater distributions in Bacteria than Eukarya. Analysis of the evolutionary progression of these domains reveals that they have diverged to new patterns from a single ancestor. CONCLUSIONS/SIGNIFICANCE: Mini-proteins are ubiquitous in bacterial and archaeal species and play significant roles in various functions. The number of mini-proteins in each genome displays remarkable fluctuation, likely resulting from the differential selective pressures that reflect the respective life-styles of the organisms. The answers to many questions surrounding mini-proteins remain elusive and need to be resolved experimentally

    Bacterial Delivery of Nuclear Proteins into Pluripotent and Differentiated Cells

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    Numerous Gram negative pathogens possess a type III secretion system (T3SS) which allows them to inject virulent proteins directly into the eukaryotic cell cytoplasm. Injection of these proteins is dependent on a variable secretion signal sequence. In this study, we utilized the N-terminal secretion signal sequence of Pseudomonas aeruginosa exotoxin ExoS to translocate Cre recombinase containing a nuclear localization sequence (Cre-NLS). Transient exposure of human sarcoma cell line, containing Cre-dependent lacZ reporter, resulted in efficient recombination in the host chromosome, indicating that the bacterially delivered protein was not only efficiently localized to the nucleus but also retained its biological function. Using this system, we also illustrate the ability of P. aeruginosa to infect mouse embryonic stem cells (mESC) and the susceptibility of these cells to bacterially delivered Cre-NLS. A single two-hour infection caused as high as 30% of the mESC reporter cells to undergo loxP mediated chromosomal DNA recombination. A simple antibiotic treatment completely eliminated the bacterial cells following the delivery, while the use of an engineered mutant strain greatly reduced cytotoxicity. Utility of the system was demonstrated by delivery of the Cre-NLS to induced pluripotent stem cells to excise the floxed oncogenic nuclear reprogramming cassette. These results validate the use of T3SS for the delivery of transcription factors for the purpose of cellular reprogramming

    Load Characteristics and Fatigue Damage Assessment of High Speed Train Bogie Frame

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    A bounded degree SOS hierarchy for polynomial optimization

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    International audienceWe consider a new hierarchy of semidefinite relaxations for the general polynomial optimization problem (P): f∗=min⁡{ f(x):x∈K }(P):\:f^{\ast}=\min \{\,f(x):x\in K\,\} on a compact basic semi-algebraic set K⊂RnK\subset\R^n. This hierarchy combines some advantages of the standard LP-relaxations associated with Krivine's positivity certificate and some advantages of the standard SOS-hierarchy. In particular it has the following attractive features: (a) In contrast to the standard SOS-hierarchy, for each relaxation in the hierarchy, the size of the matrix associated with the semidefinite constraint is the same and fixed in advance by the user. (b) In contrast to the LP-hierarchy, finite convergence occurs at the first step of the hierarchy for an important class of convex problems. Finally (c) some important techniques related to the use of point evaluations for declaring a polynomial to be zero and to the use of rank-one matrices make an efficient implementation possible. Preliminary results on a sample of non convex problems are encouraging

    Design and optimization of LNG-powered ship cold energy and waste heat integrated utilization system based on novel intermediate fluid vaporizer

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    Based on a novel integrated intermediate fluid vaporizer with liquefied natural gas (LNG) cold energy utilization proposed by the author's team, a full-power generation integrated system is constructed in this study. It is a two-stage cascade Rankine cycle with two-stage condensation and coupled with a trans-critical CO2 Rankine cycle. This study regards a river–sea direct transportation type of 25,000-ton LNG fuel-powered chemical ship as the application object and considers combined utilization of the medium-temperature waste heat of flue gas from the exhaust turbine power generation cycle outlet and the vaporization cold energy of LNG. Through the simulation and analysis of the scheme, circulating working fluid optimization and operation parameter optimization based on a genetic algorithm are conducted. The overall exergy efficiency of the optimized system reaches 45.1%, while the power generation of the system reaches 72.66 kW. Furthermore, economic analysis shows that the net annual income of the optimized system can reach 280,700 yuan, and the recovery cycle of initial investment cost is expected to be 6.11 years

    MexT Regulates the Type III Secretion System through MexS and PtrC in Pseudomonas aeruginosa▿

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    The type III secretion system (T3SS) is the most important virulence factor in Pseudomonas aeruginosa, and its expression level varies in different isolates. We studied the molecular basis for such differences in two laboratory strains, PAK and PAO1. A chromosomal clone library from the high-T3SS-producer strain PAK was introduced into the low-producer strain PAO1, and we found that a mexS gene from PAK confers high T3SS expression in the PAO1 background. Further tests demonstrated that both mexS and its neighboring mexT gene are required for the repression of the T3SS in PAO1, while the PAK genome encodes a defective MexS, accounting for the derepression of the T3SS in PAK and the dominant negative effect when it is introduced into PAO1. MexS is a probable oxidoreductase whose expression is dependent on MexT, a LysR-type transcriptional regulator. Various genetic data support the idea that MexS modulates the transcriptional regulator function of MexT. In searching for the MexT-dependent repressor of the T3SS, a small gene product of PA2486 (ptrC) was found effective in suppressing the T3SS upon overexpression. However, deletion of ptrC in the PAO1 background did not result in derepression of the T3SS, indicating the presence of another repressor for the T3SS. Interestingly, overexpression of functional mexS alone was sufficient to repress T3SS even in the absence of MexT, suggesting that MexS is another mediator of MexT-dependent T3SS repression. Overexpression of mexS alone had no effect on the well-known MexT-dependent genes, including those encoding MexEF efflux pump, elastase, and pyocyanin, indicating alternative regulatory mechanisms. A model has been proposed for the MexS/MexT-mediated regulation of the T3SS, the MexEF efflux pump, and the production of elastase and pyocyanin

    HigB of Pseudomonas aeruginosa enhances killing of phagocytes by up-regulating the type III secretion system in ciprofloxacin induced persister cells

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    Bacterial persister cells are dormant and highly tolerant to lethal antibiotics, which are believed to be the major cause of recurring and chronic infections. Activation of toxins of bacterial toxin-antitoxin systems inhibits bacterial growth and plays an important role in persister formation. However, little is known about the overall gene expression profile upon toxin activation. More importantly, how the dormant bacterial persisters evade host immune clearance remains poorly understood. Here we demonstrate that a Pseudomonas aeruginosa toxin-antitoxin system HigB-HigA is required for the ciprofloxacin induced persister formation. Transcriptome analysis of a higA::Tn mutant revealed up regulation of type III secretion systems (T3SS) genes. Overexpression of HigB increased the expression of T3SS genes as well as bacterial cytotoxicity. We further demonstrate that wild type bacteria that survived ciprofloxacin treatment contain higher levels of T3SS proteins and display increased cytotoxicity to macrophage compared to vegetative bacterial cells. These results suggest that P. aeruginosa accumulates T3SS proteins during persister formation, which can protect the persister cells from host clearance by efficiently killing host immune cells
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