27 research outputs found

    Evidence for Novel Hepaciviruses in Rodents

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    Hepatitis C virus (HCV) is among the most relevant causes of liver cirrhosis and hepatocellular carcinoma. Research is complicated by a lack of accessible small animal models. The systematic investigation of viruses of small mammals could guide efforts to establish such models, while providing insight into viral evolutionary biology. We have assembled the so-far largest collection of small-mammal samples from around the world, qualified to be screened for bloodborne viruses, including sera and organs from 4,770 roden

    Organometallic Single-Molecule Electronics: Tuning Electron Transport through X(diphosphine)2_2FeC4_4Fe(diphosphine)2_2X Building Blocks by Varying the Fe–X–Au Anchoring Scheme from Coordinative to Covalent

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    A series of X(depe)2FeC≡C–C≡CFe(depe)2X complexes (depe =1,2-bis(diethylphosphino)ethane; X = I 1, NCMe 2, N2 3, C2H 4, C2SnMe3 5, C4SnMe3 6, NCSe 7, NCS 8, CN 9, SH 10, and NO2 11) was designed to study the influence of the anchor group on organometallic molecular transport junctions to achieve high-conductive molecular wires. The FeC4Fe core is electronically functional due to the redox-active Fe centers and sp-bridging ligands allowing a strong electronic delocalization. 1–11 were characterized by elemental analyses, X-ray diffraction, cyclic voltammetry, NMR, IR, and Raman spectroscopy. DFT calculations on model compounds gave the HOMO/LUMO energies. 5–9 were investigated in mechanically controllable break-junctions. For 9, unincisive features at 8.1 × 10–7 G0 indicate that sterical reasons prevent stable junctions to form or that the coordinative binding motif prohibits electron injection. 7 and 8 with the hitherto unexploited coordinatively binding end groups NCSe and NCS yielded currents of 1.3 × 10–9 A (7) and 1.8 × 10–10 A (8) at ±1.0 V. The SnMe3 in 5 and 6 splits off, yielding junctions with covalent C–Au bonds and currents of 6.5 × 10–7 A (Au–5′–Au) or 2.1 × 10–7 A (Au–6′–Au). Despite of a length of almost 2 nm, the Au–5′–Au junction reaches 1% of the maximum current assuming one conductance channel in quantum point contacts. Additionally, the current noise in the transport data is considerably reduced for the covalent C–Au coupling compared to the coordinative anchoring of 7–9, endorsing C–Au coupled organometallic complexes as excellent candidates for low-ohmic molecular wires

    Blockchain-based traceability of inter-organisational business processes

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    Blockchain technology opens up new opportunities for Business Process Management. This is mainly due to its unprecedented capability to let transactions be automatically executed and recorded by Smart Contracts in multi-peer environments, in a decentralised fashion and without central authoritative players to govern the workflow. In this way, blockchains also provide traceability. Traceability of information plays a pivotal role particularly in those supply chains where multiple parties are involved and rigorous criteria must be fulfilled to lead to a successful outcome. In this paper, we investigate how to run a business process in the context of a supply chain on a blockchain infrastructure so as to provide full traceability of its run-time enactment. Our approach retrieves information to trace process instances execution solely from the transactions written on-chain. To do so, hash-codes are reverse-engineered based on the Solidity Smart Contract encoding of the generating process. We show the results of our investigation by means of an implemented software prototype, with a case study on the reportedly challenging context of the pharmaceutical supply chain

    Etude d'un generateur electrique a grande vitesse de rotation

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    SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : T 82818 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

    Organometallic Single-Molecule Electronics: Tuning Electron Transport through X(diphosphine)<sub>2</sub>FeC<sub>4</sub>Fe(diphosphine)<sub>2</sub>X Building Blocks by Varying the Fe–X–Au Anchoring Scheme from Coordinative to Covalent

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    A series of X­(depe)<sub>2</sub>FeCC–CCFe­(depe)<sub>2</sub>X complexes (depe =1,2-bis­(diethylphosphino)­ethane; X = I <b>1</b>, NCMe <b>2</b>, N<sub>2</sub> <b>3,</b> C<sub>2</sub>H <b>4</b>, C<sub>2</sub>SnMe<sub>3</sub> <b>5</b>, C<sub>4</sub>SnMe<sub>3</sub> <b>6</b>, NCSe <b>7</b>, NCS <b>8</b>, CN <b>9</b>, SH <b>10</b>, and NO<sub>2</sub> <b>11</b>) was designed to study the influence of the anchor group on organometallic molecular transport junctions to achieve high-conductive molecular wires. The FeC<sub>4</sub>Fe core is electronically functional due to the redox-active Fe centers and sp-bridging ligands allowing a strong electronic delocalization. <b>1</b>–<b>11</b> were characterized by elemental analyses, X-ray diffraction, cyclic voltammetry, NMR, IR, and Raman spectroscopy. DFT calculations on model compounds gave the HOMO/LUMO energies. <b>5</b>–<b>9</b> were investigated in mechanically controllable break-junctions. For <b>9</b>, unincisive features at 8.1 × 10<sup>–7</sup> G<sub>0</sub> indicate that sterical reasons prevent stable junctions to form or that the coordinative binding motif prohibits electron injection. <b>7</b> and <b>8</b> with the hitherto unexploited coordinatively binding end groups NCSe and NCS yielded currents of 1.3 × 10<sup>–9</sup> A (<b>7</b>) and 1.8 × 10<sup>–10</sup> A (<b>8</b>) at ±1.0 V. The SnMe<sub>3</sub> in <b>5</b> and <b>6</b> splits off, yielding junctions with covalent C–Au bonds and currents of 6.5 × 10<sup>–7</sup> A (<b>Au</b>–<b>5</b>′–<b>Au</b>) or 2.1 × 10<sup>–7</sup> A (<b>Au</b>–<b>6</b>′–<b>Au</b>). Despite of a length of almost 2 nm, the <b>Au</b>–<b>5</b>′–<b>Au</b> junction reaches 1% of the maximum current assuming one conductance channel in quantum point contacts. Additionally, the current noise in the transport data is considerably reduced for the covalent C–Au coupling compared to the coordinative anchoring of <b>7</b>–<b>9</b>, endorsing C–Au coupled organometallic complexes as excellent candidates for low-ohmic molecular wires

    Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells

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    When a T cell and an antigen-presenting cell form an immunological synapse, rapid dynein-driven translocation of the centrosome toward the contact site leads to reorganization of microtubules and associated organelles. Currently, little is known about how the regulation of microtubule dynamics contributes to this process. Here, we show that the knockout of KIF21B, a kinesin-4 linked to autoimmune disorders, causes microtubule overgrowth and perturbs centrosome translocation. KIF21B restricts microtubule length by inducing microtubule pausing typically followed by catastrophe. Catastrophe induction with vinblastine prevented microtubule overgrowth and was sufficient to rescue centrosome polarization in KIF21B-knockout cells. Biophysical simulations showed that a relatively small number of KIF21B molecules can restrict mirotubule length and promote an imbalance of dynein-mediated pulling forces that allows the centrosome to translocate past the nucleus. We conclude that proper control of microtubule length is important for allowing rapid remodeling of the cytoskeleton and efficient T cell polarization

    Kinesin-4 kif21b limits microtubule growth to allow rapid centrosome polarization in t cells

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    When a T cell and an antigen-presenting cell form an immunological synapse, rapid dynein-driven translocation of the centrosome towards the contact site leads to reorganization of microtubules and associated organelles. Currently, little is known about how the regulation of microtubule dynamics contributes to this process. Here, we show that the knockout of KIF21B, a kinesin-4 linked to autoimmune disorders, causes microtubule overgrowth and perturbs centrosome translocation. KIF21B restricts microtubule length by inducing microtubule pausing typically followed by catastrophe. Catastrophe induction with vinblastine prevented microtubule overgrowth and was sufficient to rescue centrosome polarization in KIF21B-knockout cells. Biophysical simulations showed that a relatively small number of KIF21B molecules can restrict microtubule length and promote an imbalance of dynein-mediated pulling forces that allows the centrosome to translocate past the nucleus. We conclude that proper control of microtubule length is important for allowing rapid remodeling of the cytoskeleton and efficient T cell polarization.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

    Application of transfer learning to predict drug-induced human in vivo gene expression changes using rat in vitro and in vivo data.

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    The liver is the primary site for the metabolism and detoxification of many compounds, including pharmaceuticals. Consequently, it is also the primary location for many adverse reactions. As the liver is not readily accessible for sampling in humans; rodent or cell line models are often used to evaluate potential toxic effects of a novel compound or candidate drug. However, relating the results of animal and in vitro studies to relevant clinical outcomes for the human in vivo situation still proves challenging. In this study, we incorporate principles of transfer learning within a deep artificial neural network allowing us to leverage the relative abundance of rat in vitro and in vivo exposure data from the Open TG-GATEs data set to train a model to predict the expected pattern of human in vivo gene expression following an exposure given measured human in vitro gene expression. We show that domain adaptation has been successfully achieved, with the rat and human in vitro data no longer being separable in the common latent space generated by the network. The network produces physiologically plausible predictions of human in vivo gene expression pattern following an exposure to a previously unseen compound. Moreover, we show the integration of the human in vitro data in the training of the domain adaptation network significantly improves the temporal accuracy of the predicted rat in vivo gene expression pattern following an exposure to a previously unseen compound. In this way, we demonstrate the improvements in prediction accuracy that can be achieved by combining data from distinct domains
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