Linezolid and Rifampicin Combination to Combat cfr-Positive Multidrug-Resistant MRSA in Murine Models of Bacteremia and Skin and Skin Structure Infection.

Linezolid resistance mediated by the cfr gene in MRSA represents a global concern. We investigated relevant phenotype differences between cfr-positive and -negative MRSA that contribute to pathogenesis, and the efficacy of linezolid-based combination therapies in murine models of bacteremia and skin and skin structure infection (SSSI). As a group, cfr-positive MRSA exhibited significantly reduced susceptibilities to the host defense peptides tPMPs, human neutrophil peptide-1 (hNP-1), and cathelicidin LL-37 (P < 0.01). In addition, increased binding to fibronectin (FN) and endothelial cells paralleled robust biofilm formation in cfr-positive vs. -negative MRSA. In vitro phenotypes of cfr-positive MRSA translated into poor outcomes of linezolid monotherapy in vivo in murine bacteremia and SSSI models. Importantly, rifampicin showed synergistic activity as a combinatorial partner with linezolid, and the EC50 of linezolid decreased 6-fold in the presence of rifampicin. Furthermore, this combination therapy displayed efficacy against cfr-positive MRSA at clinically relevant doses. Altogether, these data suggest that the use of linezolid in combination with rifampicin poses a viable therapeutic alternative for bacteremia and SSSI caused by cfr-positive multidrug resistant MRSA

Generation of 3-Dimensional graph state with Josephson charge qubits

On the basis of generations of 1-dimensional and 2-dimensional graph states, we generate a 3-dimensional N3-qubit graph state based on the Josephson charge qubits. Since any two charge qubits can be selectively and effectively coupled by a common inductance, the controlled phase transform between any two-qubit can be performed. Accordingly, we can generate arbitrary multi-qubit graph states corresponding to arbitrary shape graph, which meet the expectations of various quantum information processing schemes. All the devices in the scheme are well within the current technology. It is a simple, scalable and feasible scheme for the generation of various graph states based on the Josephson charge qubits.Comment: 4 pages, 4 figure

Disturbance Rejection Control for Autonomous Trolley Collection Robots with Prescribed Performance

Trajectory tracking control of autonomous trolley collection robots (ATCR) is an ambitious work due to the complex environment, serious noise and external disturbances. This work investigates a control scheme for ATCR subjecting to severe environmental interference. A kinematics model based adaptive sliding mode disturbance observer with fast convergence is first proposed to estimate the lumped disturbances. On this basis, a robust controller with prescribed performance is proposed using a backstepping technique, which improves the transient performance and guarantees fast convergence. Simulation outcomes have been provided to illustrate the effectiveness of the proposed control scheme

A possible role of HMGB1 in DNA demethylation in CD4+ T Cells from patients with systemic lupus erythematosus

The aberrant activity of CD4(+) T cells in patients with systemic lupus erythematosus (SLE) is associated with DNA hypomethylation of the regulatory regions in CD11a and CD70 genes. Our previous studies demonstrated that Gadd45a contributes to the development of SLE by promoting DNA demethylation in CD4(+) T cells. In this study, we identified proteins that bind to Gadd45a in CD4(+) T cells during SLE flare by using the method of co-immunoprecipitation and mass spectrometry, High mobility group box protein 1 (HMGB1) is one of identified proteins. Furthermore, gene and protein expression of HMGB1 was significantly increased in SLE CD4(+) T cells compared to controls, and HMGB1 mRNA was correlated with CD11a and CD70 mRNA. A significant, positive correlation was found between HMGB1 mRNA and SLEDAI for SLE patients. Our data demonstrate that HMGB1 binds to Gadd45a and may be involved in DNA demethylation in CD4(+) T cells during lupus flare.published_or_final_versio

Estimation of potential gains from bank mergers:a novel two-stage cost efficiency DEA model

This paper develops a novel two-stage cost efficiency model to estimate and decompose the potential gains from Mergers and Acquisitions (M&As). In this model, a merged DMU is defined as a combination of two or more candidate DMUs. The merged DMU would surpass the traditional Production Possibility Set (PPS). In order to solve the problem, a Merger Production Possibility Set (PPSM) is constructed. The model minimizes the total cost of the merged DMU while maintaining its outputs at the current level, estimates the overall merger efficiency by comparing its minimal total cost with its actual cost. Moreover, the overall merger efficiency could be decomposed into technical efficiency, harmony efficiency and scale efficiency. We show that the model can be extended to a two-stage structure and these efficiencies can be decomposed to both sub-systems. To show the usefulness of the proposed approach, we applied it to a real dataset of top 20 most competitive Chinese City Commercial Banks (CCBs). We concluded that (1) There exist considerably potential gains for the proposed merged banks. (2) It is also shown that the main impact on potential merger gains are from technical and harmony efficiency. (3) As an interesting result we found that the scale effect works against the merger, indicating that it is not favorable for a full-scale merger

A major reorganization of Asian climate by the early Miocene

The global climate system experienced a series of drastic changes during the Cenozoic. In Asia, these include the climate transformation from a zonal pattern to a <i>monsoon-dominated pattern</i>, the disappearance of typical subtropical aridity, and the onset of <i>inland deserts</i>. Despite major advances in the last two decades in characterizing and understanding these climate phenomena, disagreements persist relative to the timing, behaviors and underlying causes. <br><br> This paper addresses these issues mainly based on two lines of evidence. First, we compiled newly collected data from geological indicators of the Cenozoic environment in China as paleoenvironmental maps of ten intervals. In confirming the earlier observation that a zonal climate pattern was transformed into a monsoonal one, the maps within the Miocene indicate that this change was achieved by the early Miocene, roughly consistent with the onset of loess deposition in China. Although a monsoon-like regime would have existed in the Eocene, it was restricted to tropical-subtropical regions. The latitudinal oscillations of the climate zones during the Paleogene are likely attributable to the imbalance in evolution of polar ice-sheets between the two hemispheres. <br><br> Secondly, we examine the relevant depositional and soil forming processes of the Miocene loess-soil sequences to determine the circulation characteristics with emphasis on the early Miocene. Continuous eolian deposition in the middle reaches of the Yellow River since the early Miocene firmly indicates the formation of inland deserts, which have been constantly maintained during the past 22 Ma. Grain-size gradients between loess sections indicate northerly dust-carrying winds from northern sources, a clear indication of an Asian winter monsoon system. Meanwhile, well-developed Luvisols show evidence that moisture from the oceans reached northern China. This evidence shows the coexistence of two kinds of circulations, one from the ocean carrying moisture and another from the inland deserts transporting dust. The formation of the early Miocene paleosols resulted from interactive soil forming and dust deposition processes in these two seasonally alternating monsoonal circulations. The much stronger development of the early Miocene soils compared to those in the Quaternary loess indicates that summer monsoons were either significantly stronger, more persistent through the year, or both. <br><br> These lines of evidence indicate a joint change in circulation and inland aridity by the early Miocene and suggest a dynamic linkage of them. Our recent sensitivity tests with a general circulation model, along with relevant geological data, suggest that the onset of these contrasting wet/dry responses, as well as the change from the "planetary" subtropical aridity pattern to the "inland" aridity pattern, resulted from the combined effects of Tibetan uplift and withdrawal of the Paratethys seaway in central Asia, as suggested by earlier experiments. The spreading of South China Sea also helped to enhance the south-north contrast of humidity. The Miocene loess record provides a vital insight that these tectonic factors had evolved by the early Miocene to a threshold sufficient to cause this major climate reorganization in Asia

Phylogeographic patterns and conservation implications of the endangered Chinese giant salamander

Understanding genetic diversity patterns of endangered species is an important premise for biodiversity conservation. The critically endangered salamander Andrias davidianus, endemic to central and southern mainland in China, has suffered from sharp range and population size declines over the past three decades. However, the levels and patterns of genetic diversity of A. davidianus populations in wild remain poorly understood. Herein, we explore the levels and phylogeographic patterns of genetic diversity of wild-caught A. davidianus using larvae and adult collection with the aid of sequence variation in (a) the mitochondrial DNA (mtDNA) fragments (n = 320 individuals; 33 localities), (b) 19 whole mtDNA genomes, and (c) nuclear recombinase activating gene 2 (RAG2; n = 88 individuals; 19 localities). Phylogenetic analyses based on mtDNA datasets uncovered seven divergent mitochondrial clades (A-G), which likely originated in association with the uplifting of mountains during the Late Miocene, specific habitat requirements, barriers including mountains and drainages and lower dispersal ability. The distributions of clades were geographic partitioned and confined in neighboring regions. Furthermore, we discovered some mountains, rivers, and provinces harbored more than one clades. RAG2 analyses revealed no obvious geographic patterns among the five alleles detected. Our study depicts a relatively intact distribution map of A. davidianus clades in natural species range and provides important knowledge that can be used to improve monitoring programs and develop a conservation strategy for this critically endangered organism.Peer reviewe

Highly sensitive and selective Love mode surface acoustic wave ammonia sensor based on graphene oxides operated at room temperature

It is crucial to develop highly sensitive and selective sensors for ammonia, one of the most common toxic gases which have been widely used in pharmaceutical, chemical and manufacturing industries. In this study, graphene oxide (GO) film was spin-coated onto surfaces of ST-cut quartz surface acoustic wave (SAW) devices with a resonant frequency of 200 MHz for ammonia sensing. The oxygen-containing functional groups (such as hydroxyl and epoxy ones) on the surface of GO film strongly absorb ammonia molecules and thus increase the film stiffness. This is attributed to the main ammonia sensing mechanism of the Love mode SAW devices, which show not only a positive frequency shift of 620 Hz for 500 ppb ammonia gas, but also an excellent selectivity (as compared to other gases such as H2, H2S, CO and NO2) and a good reproducibility, operated at room temperature of 22 oC

Orthogonal methods based ant colony search for solving continuous optimization problems

Research into ant colony algorithms for solving continuous optimization problems forms one of the most significant and promising areas in swarm computation. Although traditional ant algorithms are designed for combinatorial optimization, they have shown great potential in solving a wide range of optimization problems, including continuous optimization. Aimed at solving continuous problems effectively, this paper develops a novel ant algorithm termed "continuous orthogonal ant colony" (COAC), whose pheromone deposit mechanisms would enable ants to search for solutions collaboratively and effectively. By using the orthogonal design method, ants in the feasible domain can explore their chosen regions rapidly and e±ciently. By implementing an "adaptive regional radius" method, the proposed algorithm can reduce the probability of being trapped in local optima and therefore enhance the global search capability and accuracy. An elitist strategy is also employed to reserve the most valuable points. The performance of the COAC is compared with two other ant algorithms for continuous optimization of API and CACO by testing seventeen functions in the continuous domain. The results demonstrate that the proposed COAC algorithm outperforms the others

Development of an Aryloxazole Class of Hepatitis C Virus Inhibitors Targeting the Entry Stage of the Viral Replication Cycle

Reliance on hepatitis C virus (HCV) replicon systems and protein-based screening assays has led to treatments that target HCV viral replication proteins. The model does not encompass other viral replication cycle steps such as entry, processing, assembly and secretion, or viral host factors. We previously applied a phenotypic high-throughput screening platform based on an infectious HCV system and discovered an aryloxazole-based anti-HCV hit. Structure– activity relationship studies revealed several compounds exhibiting EC50 values below 100 nM. Lead compounds showed inhibition of the HCV pseudoparticle entry, suggesting a different mode of action from existing HCV drugs. Hit 7a and lead 7ii both showed synergistic effects in combination with existing HCV drugs. In vivo pharmacokinetics studies of 7ii showed high liver distribution and long half-life without obvious hepatotoxicity. The lead compounds are promising as preclinical candidates for the treatment of HCV infection and as molecular probes to study HCV pathogenesis