7,874 research outputs found

    Analysis of feedback mechanisms with unknown delay using sparse multivariate autoregressive method

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    This paper discusses the study of two interacting processes in which a feedback mechanism exists between the processes. The study was motivated by problems such as the circadian oscillation of gene expression where two interacting protein transcriptions form both negative and positive feedback loops with long delays to equilibrium. Traditionally, data of this type could be examined using autoregressive analysis. However, in circadian oscillation the order of an autoregressive model cannot be determined a priori. We propose a sparse multivariate autoregressive method that incorporates mixed linear effects into regression analysis, and uses a forward-backward greedy search algorithm to select nonzero entries in the regression coefficients, the number of which is constrained not to exceed a pre-specified number. A small simulation study provides preliminary evidence of the validity of the method. Besides the circadian oscillation example, an additional example of blood pressure variations using data from an intervention study is used to illustrate the method and the interpretation of the results obtained from the sparse matrix method. These applications demonstrate how sparse representation can be used for handling high dimensional variables that feature dynamic, reciprocal relationships

    Pre-expression of a sulfhydryl oxidase significantly increases the yields of eukaryotic disulfide bond containing proteins expressed in the cytoplasm of E.coli

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    <p>Abstract</p> <p>Background</p> <p>Disulfide bonds are one of the most common post-translational modifications found in proteins. The production of proteins that contain native disulfide bonds is challenging, especially on a large scale. Either the protein needs to be targeted to the endoplasmic reticulum in eukaryotes or to the prokaryotic periplasm. These compartments that are specialised for disulfide bond formation have an active catalyst for their formation, along with catalysts for isomerization to the native state. We have recently shown that it is possible to produce large amounts of prokaryotic disulfide bond containing proteins in the cytoplasm of wild-type bacteria such as <it>E. coli </it>by the introduction of catalysts for both of these processes.</p> <p>Results</p> <p>Here we show that the introduction of Erv1p, a sulfhydryl oxidase and a disulfide isomerase allows the efficient formation of natively folded eukaryotic proteins with multiple disulfide bonds in the cytoplasm of <it>E. coli</it>. The production of disulfide bonded proteins was also aided by the use of an appropriate fusion protein to keep the folding intermediates soluble and by choice of media. By combining the pre-expression of a sulfhydryl oxidase and a disulfide isomerase with these other factors, high level expression of even complex disulfide bonded eukaryotic proteins is possible</p> <p>Conclusions</p> <p>Our results show that the production of eukaryotic proteins with multiple disulfide bonds in the cytoplasm of <it>E. coli </it>is possible. The required exogenous components can be put onto a single plasmid vector allowing facile transfer between different prokaryotic strains. These results open up new avenues for the use of <it>E. coli </it>as a microbial cell factory.</p

    Sulfur-Modulated Tin Sites Enable Highly Selective Electrochemical Reduction of CO2 to Formate

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    Electrochemical reduction of carbon dioxide (CO2RR) to formate provides an avenue to the synthesis of value-added carbon-based fuels and feedstocks powered using renewable electricity. Here, we hypothesized that the presence of sulfur atoms in the catalyst surface could promote undercoordinated sites, and thereby improve the electrochemical reduction of CO2 to formate. We explored, using density functional theory, how the incorporation of sulfur into tin may favor formate generation. We used atomic layer deposition of SnSx followed by a reduction process to synthesize sulfur-modulated tin (Sn(S)) catalysts. X-ray absorption near-edge structure (XANES) studies reveal higher oxidation states in Sn(S) compared with that of tin in Sn nanoparticles. Sn(S)/Au accelerates CO2RR at geometric current densities of 55 mA cm−2 at −0.75 V versus reversible hydrogen electrode with a Faradaic efficiency of 93%. Furthermore, Sn(S) catalysts show excellent stability without deactivation (&lt;2% productivity change) following more than 40 hours of operation. With rapid advances in the efficient and cost-effective conversion of sunlight to electrical power, the development of storage technologies for renewable energy is even more urgent. Using renewable electricity to convert CO2 into formate simultaneously addresses the need for storage of intermittent renewable energy sources and the need to reduce greenhouse gas emissions. We report an increase of greater than 4-fold in the current density (hence the rate of reaction) in formate electrosynthesis compared with relevant controls. Our catalysts also show excellent stability without deactivation (&lt;2% productivity change) following more than 40 hours of operation. The electrochemical reduction of carbon dioxide (CO2RR) offers a compelling route to energy storage and high-value chemical manufacture. The presence of sulfur atoms in catalyst surfaces promotes undercoordinated sites, thereby improving the electrochemical reduction of CO2 to formate. The resulting sulfur-modulated tin catalysts accelerate CO2RR at geometric current densities of 55 mA cm−2 at −0.75 V versus RHE with a Faradaic efficiency of 93%

    Feature pyramid transformer

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    Feature interactions across space and scales underpin modern visual recognition systems because they introduce beneficial visual contexts. Conventionally, spatial contexts are passively hidden in the CNN's increasing receptive fields or actively encoded by non-local convolution. Yet, the non-local spatial interactions are not across scales, and thus they fail to capture the non-local contexts of objects (or parts) residing in different scales. To this end, we propose a fully active feature interaction across both space and scales, called Feature Pyramid Transformer (FPT). It transforms any feature pyramid into another feature pyramid of the same size but with richer contexts, by using three specially designed transformers in self-level, top-down, and bottom-up interaction fashion. FPT serves as a generic visual backbone with fair computational overhead. We conduct extensive experiments in both instance-level (i.e., object detection and instance segmentation) and pixel-level segmentation tasks, using various backbones and head networks, and observe consistent improvement over all the baselines and the state-of-the-art methods.Comment: Published at the European Conference on Computer Vision, 202

    Pauli's Principle in Probe Microscopy

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    Exceptionally clear images of intramolecular structure can be attained in dynamic force microscopy through the combination of a passivated tip apex and operation in what has become known as the "Pauli exclusion regime" of the tip-sample interaction. We discuss, from an experimentalist's perspective, a number of aspects of the exclusion principle which underpin this ability to achieve submolecular resolution. Our particular focus is on the origins, history, and interpretation of Pauli's principle in the context of interatomic and intermolecular interactions.Comment: This is a chapter from "Imaging and Manipulation of Adsorbates using Dynamic Force Microscopy", a book which is part of the "Advances in Atom and Single Molecule Machines" series published by Springer [http://www.springer.com/series/10425]. To be published late 201

    Monolithic semiconductor lasers with dynamically tunable linear-to-circular polarization

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    The ability to control the polarization state of emission from semiconductor lasers is essential for many applications in spectroscopy, imaging, and communications, inter alia, with monolithic integration approaches being extremely beneficial. Although manipulating the output polarization of radiation from a laser can be achieved through a number of approaches, obtaining continuous dynamic control, e.g., from linear to circular, remains extremely challenging. In this paper, we demonstrate that the polarization of terahertz (THz) frequency radiation can be continuously tuned electronically from linear to circular polarization by monolithically integrating in-plane metasurfaces with two phase-locked semiconductor-based THz quantum cascade lasers. Moreover, the metasurfaces—metal antenna arrays in this case—also act as efficient beam collimators, yielding a collimated beam divergence of ∼10° × 10°. Our results, however, have broad applicability to a wide range of semiconductor lasers operating from the visible to THz regions of the electromagnetic spectrum

    Attrition among Human Immunodeficiency Virus (HIV)- Infected Patients Initiating Antiretroviral Therapy in China, 2003–2010

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    BACKGROUND: Mortality and morbidity from HIV have dramatically decreased in both high- and low-income countries. However, some patients may not benefit from combination antiretroviral therapy (cART) because of inadequate access to HIV care, including attrition after care initiation. METHODOLOGY/PRINCIPAL FINDINGS: The study population included all HIV-infected patients receiving cART through the Chinese National Free Antiretroviral Treatment Program from 1 January 2003 to 31 December 2010 (n = 106,542). We evaluated retention in HIV care and used multivariable Cox proportional hazard models to identify independent factors predictive of attrition. The cumulative probability of attrition from cART initiation was 9% at 12 months, 13% at 18 months, 16% at 24 months and 24% at 60 months. A number of factors were associated with attrition, including younger age, male gender, and being single or divorced. Patients with higher CD4 cell counts at cART initiation were more likely to drop out of HIV care. The proportion of patients remaining in HIV care increased in more recent calendar years and among patients who initiated modern cART regimens. CONCLUSIONS/SIGNIFICANCE: Retention in HIV care is essential for optimizing individual and public health outcomes. Attrition, even the degree observed in our study, can lead to premature morbidity and mortality, and possibly affect further transmission of HIV and HIV resistant drug variants. Effective strategies to promote retention in HIV care programs are needed. In China these strategies may include focusing particularly on younger male patients and those with higher CD4 cell counts at therapy initiation
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