Identification of key residues that confer Rhodobacter sphaeroides LPS activity at horse TLR4/MD-2.

The molecular determinants underpinning how hexaacylated lipid A and tetraacylated precursor lipid IVa activate Toll-like receptor 4 (TLR4) are well understood, but how activation is induced by other lipid A species is less clear. Species specificity studies have clarified how TLR4/MD-2 recognises different lipid A structures, for example tetraacylated lipid IVa requires direct electrostatic interactions for agonism. In this study, we examine how pentaacylated lipopolysaccharide from Rhodobacter sphaeroides (RSLPS) antagonises human TLR4/MD-2 and activates the horse receptor complex using a computational approach and cross-species mutagenesis. At a functional level, we show that RSLPS is a partial agonist at horse TLR4/MD-2 with greater efficacy than lipid IVa. These data suggest the importance of the additional acyl chain in RSLPS signalling. Based on docking analysis, we propose a model for positioning of the RSLPS lipid A moiety (RSLA) within the MD-2 cavity at the TLR4 dimer interface, which allows activity at the horse receptor complex. As for lipid IVa, RSLPS agonism requires species-specific contacts with MD-2 and TLR4, but the R2 chain of RSLA protrudes from the MD-2 pocket to contact the TLR4 dimer in the vicinity of proline 442. Our model explains why RSLPS is only partially dependent on horse TLR4 residue R385, unlike lipid IVa. Mutagenesis of proline 442 into a serine residue, as found in human TLR4, uncovers the importance of this site in RSLPS signalling; horse TLR4 R385G/P442S double mutation completely abolishes RSLPS activity without its counterpart, human TLR4 G384R/S441P, being able to restore it. Our data highlight the importance of subtle changes in ligand positioning, and suggest that TLR4 and MD-2 residues that may not participate directly in ligand binding can determine the signalling outcome of a given ligand. This indicates a cooperative binding mechanism within the receptor complex, which is becoming increasingly important in TLR signalling.This work was supported by a project grant from the Horserace Betting Levy Board to CEB and a Horserace Betting Levy Board Veterinary Research Training Scholarship to KLI. This work was also supported by a Wellcome Trust program grant to NJG and CEB. CEB is a BBSRC Research Development Fellow.This is the final version of the article. It first appeared from PLOS at http://dx.doi.org/10.1371/journal.pone.0098776

NASA-UVA Light Aerospace Alloy and Structures Technology Program: LA(2)ST

The NASA-UVA Light Aerospace Alloy and Structures Technology (LA(2)ST) Program continues a high level of activity, with projects being conducted by graduate students and faculty advisors in the Departments of Materials Science and Engineering, Civil Engineering and Applied Mechanics, and Mechanical and Aerospace Engineering at the University of Virginia. This work is funded by the NASA-Langley Research Center under Grant NAG-1-745. We report on progress achieved between July 1 and December 31, 1992. The objective of the LA(2)ST Program is to conduct interdisciplinary graduate student research on the performance of next generation, light weight aerospace alloys, composites and thermal gradient structures in collaboration with NASA-Langley researchers. Specific technical objectives are presented for each research project. We generally aim to produce relevant data and basic understanding of material mechanical response, corrosion behavior, and microstructure; new monolithic and composite alloys; advanced processing methods; new solid and fluid mechanics analyses; measurement advances; and critically, a pool of educated graduate students for aerospace technologies

Multidimensional cluster states using a single spin-photon interface coupled strongly to an intrinsic nuclear register

Photonic cluster states are a powerful resource for measurement-based quantum computing and loss-tolerant quantum communication. Proposals to generate multi-dimensional lattice cluster states have identified coupled spin-photon interfaces, spin-ancilla systems, and optical feedback mechanisms as potential schemes. Following these, we propose the generation of multi-dimensional lattice cluster states using a single, efficient spin-photon interface coupled strongly to a nuclear register. Our scheme makes use of the contact hyperfine interaction to enable universal quantum gates between the interface spin and a local nuclear register and funnels the resulting entanglement to photons via the spin-photon interface. Among several quantum emitters, we identify the silicon-29 vacancy centre in diamond, coupled to a nanophotonic structure, as possessing the right combination of optical quality and spin coherence for this scheme. We show numerically that using this system a 2x5-sized cluster state with a lower-bound fidelity of 0.5 and repetition rate of 65 kHz is achievable under currently realised experimental performances and with feasible technical overhead. Realistic gate improvements put 100-photon cluster states within experimental reach

Time-crystalline behavior in central-spin models with Heisenberg interactions

Time-crystalline behavior has been predicted and observed in quantum central-spin systems with periodic driving and Ising interactions. Here, we theoretically show that it can also arise in central-spin systems with Heisenberg interactions. We present two methods to achieve this: application of a sufficiently large Zeeman splitting on the central spin compared to the satellite spins, or else by applying additional pulses to the central spin every Floquet period. In both cases, we show that the system exhibits a subharmonic response in spin magnetizations in the presence of disorder for both pure Heisenberg and XXZ interactions. Our results pertain to any XXZ central-spin system, including hyperfine-coupled electron-nuclear systems in quantum dots or color centers

Reconstruction microchirurgicale et prise en charge globale des patients porteurs de cancer ORL : l’importance d’une approche qualité et d’un circuit protocolisé [Microsurgical reconstruction and full management of patients with head and neck cancer: Importance of a quality approach and a circuit protocolisation]

Main of study: Management and surgical reconstruction of head and neck cancers remain a challenge. From the first consultation to surgery and radiotherapy, it is necessary to save time to ensure optimum treatment and better survival rates. Objectif: To establish a kind of quality approach to the management of patients with head and neck cancers. 54 patients who had microsurgical reconstruction after head and neck cancer were included in this study between 1997 and 2006. Results : Multiple data were considered: body mass index (BMI), ASA stage, age, existence of a pre-or postoperative radiotherapy, the surgeon's experience and the number of veins drainage. The success rate is superior when more than one draining vein is sutured to the flap for patients with a BMI > 20. Radiotherapy does not seem to affect the survival of the flap. Conclusion: According to current literature, the survival rate of these patients is better when the overall time care is less than 100 days. That period is possible with a perfect organization of the medical and paramedical team. Therefore, we propose to include these patients in a circuit protocolisation care, which saves time, to better inform patients and improve survival rates. Buts: la prise en charge et la reconstruction chirurgicale des cancers ORL restent un challenge. De la première consultation à la chirurgie et la radiothérapie, il est nécessaire de gagner du temps afin d’assurer une traitement optimum et un meilleur taux de survie. Objectif : établir une sorte d’approche qualité de la prise en charge des patients porteurs de cancers ORL. 54 patients qui ont bénéficié d’une reconstruction microchirurgicale suite à un cancer ORL ont été inclus dans cette étude entre 1997 et 2006. Résultats : plusieurs données ont été étudiées : l’index de masse corporelle (IMC), le stade ASA, l’âge, l’existence d’une radiothérapie pré ou post opératoire, l’expérience du chirurgien ainsi que le nombre de veines de drainage. Le taux de succès se révèle supérieur lorsque plus d’une veine de drainage est suturée au lambeau, pour des patients ayant un IMC > 20. La radiothérapie ne semble pas avoir de répercussion sur la survie du lambeau. Conclusion : conformément à la littérature actuelle, le taux de survie de ces patients est meilleur lorsque le temps global de prise en charge est inférieur à 100 jours. Ce délai court n’est possible qu’avec une parfaite organisation de l’équipe médicale et paramédicale. De ce fait, nous proposons d’inclure ces patients dans un circuit de prise en charge protocolisé, ce qui permet de gagner du temps, de mieux informer le patient et d’améliorer le taux de survie

A many-body singlet prepared by a central spin qubit

Controllable quantum many-body systems are platforms for fundamental investigations into the nature of entanglement and promise to deliver computational speed-up for a broad class of algorithms and simulations. In particular, engineering entanglement within a dense spin ensemble can turn it into a robust quantum memory or a computational platform. Recent experimental progress in dense central spin systems motivates the design of algorithms that use a central-spin qubit as a convenient proxy for the ensemble. Here we propose a protocol that uses a central spin to initialize two dense spin ensembles into a pure anti-polarized state and from there creates a many-body entangled state -- a singlet -- from the combined ensemble. We quantify the protocol performance for multiple material platforms and show that it can be implemented even in the presence of realistic levels of decoherence. Our protocol introduces an algorithmic approach to preparation of a known many-body state and to entanglement engineering in a dense spin ensemble, which can be extended towards a broad class of collective quantum states.Comment: 11 pages, 6 figures, and supplementary material

NASA-UVA Light Aerospace Alloy and Structures Technology Program (LA2ST)

Since 1986, the NASA-Langley Research Center has sponsored the NASA-UVa Light Alloy and Structures Technology (LA2ST) Program at the University of Virginia (UVa). The fundamental objective of the LA2ST program is to conduct interdisciplinary graduate student research on the performance of next generation, light-weight aerospace alloys, composites and thermal gradient structures. The LA2ST program has aimed to product relevant data and basic understanding of material mechanical response, environmental/corrosion behavior, and microstructure; new monolithic and composite alloys; advanced processing methods; measurement and modeling advances; and a pool of educated graduate students for aerospace technologies. The scope of the LA2ST Program is broad. Research areas include: (1) Mechanical and Environmental Degradation Mechanisms in Advanced Light Metals and Composites, (2) Aerospace Materials Science, (3) Mechanics of materials for Aerospace Structures, and (4) Thermal Gradient Structures. A substantial series of semi-annual progress reports issued since 1987 documents the technical objectives, experimental or analytical procedures, and detailed results of graduate student research in these topical areas

NASA-UVA Light Aerospace Alloy and Structures Technology Program (LA2ST)

The NASA-UVA Light Aerospace Alloy and Structures Technology (LA2ST) Program continues a high level of activity. Progress achieved between 1 Jan. and 30 Jun. 1993 is reported. The objective of the LA2ST Program is to conduct interdisciplinary graduate student research on the performance of next generation, light weight aerospace alloys, composites, and thermal gradient structures in collaboration with NASA-Langley researchers. The following projects are addressed: environmental fatigue of Al-Li-Cu alloys; mechanisms of localized corrosion and environmental fracture in Al-Cu-Li-Mg-Ag alloy X2095 and compositional variations; the effect of zinc additions on the precipitation and stress corrosion cracking behavior of alloy 8090; hydrogen interactions with Al-Li-Cu alloy 2090 and model alloys; metastable pitting of aluminum alloys; cryogenic fracture toughness of Al-Cu-Li + In alloys; the fracture toughness of Weldalite (TM); elevated temperature cracking of advanced I/M aluminum alloys; response of Ti-1100/SCS-6 composites to thermal exposure; superplastic forming of Weldalite (TM); research to incorporate environmental effects into fracture mechanics fatigue life prediction codes such as NASA FLAGRO; and thermoviscoplastic behavior

NASA-UVA light aerospace alloy and structures technology program (LA2ST)

The NASA-UVa Light Aerospace Alloy and Structures Technology (LA2ST) Program was initiated in 1986 and continues with a high level of activity. Projects are being conducted by graduate students and faculty advisors in the Department of Materials Science and Engineering, as well as in the Department of Civil Engineering and Applied Mechanics, at the University of Virginia. Here, we report on progress achieved between July 1 and December 31, 1994. The objective of the LA2ST Program is to conduct interdisciplinary graduate student research on the performance of next generation, light-weight aerospace alloys, composites and thermal gradient structures in collaboration with NASA-Langley researchers. Specific technical objectives are presented for each research project. We generally aim to produce relevant data and basic understanding of material mechanical response, environmental/corrosion behavior, and microstructure; new monolithic and composite alloys; advanced processing methods; new solid and fluid mechanics analyses; measurement and modeling advances; and a pool of educated graduate students for aerospace technologies

NASA-UVA Light Aerospace Alloy and Structures Technology Program (LA2ST)

The NASA-UVA Light Aerospace Alloy and Structures Technology (LA2ST) Program was initiated in 1986 and continues with a high level of activity. Here, we report on progress achieved between July I and December 31, 1996. The objective of the LA2ST Program is to conduct interdisciplinary graduate student research on the performance of next generation, light-weight aerospace alloys, composites and thermal gradient structures in collaboration with NASA-Langley researchers. Specific technical objectives are presented for each research project. We generally aim to produce relevant data and basic understanding of material mechanical response, environmental/corrosion behavior, and microstructure; new monolithic and composite alloys; advanced processing methods; new solid and fluid mechanics analyses; measurement and modeling advances; and a pool of educated graduate students for aerospace technologies. The accomplishments presented in this report are summarized as follows. Three research areas are being actively investigated, including: (1) Mechanical and Environmental Degradation Mechanisms in Advanced Light Metals, (2) Aerospace Materials Science, and (3) Mechanics of Materials for Light Aerospace Structures