31 research outputs found

    Differential Evolution for Many-Particle Adaptive Quantum Metrology

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    We devise powerful algorithms based on differential evolution for adaptive many-particle quantum metrology. Our new approach delivers adaptive quantum metrology policies for feedback control that are orders-of-magnitude more efficient and surpass the few-dozen-particle limitation arising in methods based on particle-swarm optimization. We apply our method to the binary-decision-tree model for quantum-enhanced phase estimation as well as to a new problem: a decision tree for adaptive estimation of the unknown bias of a quantum coin in a quantum walk and show how this latter case can be realized experimentally.Comment: Fig. 2(a) is the cover of Physical Review Letters Vol. 110 Issue 2

    A rapid and scalable method for selecting recombinant mouse monoclonal antibodies

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    <p>Abstract</p> <p>Background</p> <p>Monoclonal antibodies with high affinity and selectivity that work on wholemount fixed tissues are valuable reagents to the cell and developmental biologist, and yet isolating them remains a long and unpredictable process. Here we report a rapid and scalable method to select and express recombinant mouse monoclonal antibodies that are essentially equivalent to those secreted by parental IgG-isotype hybridomas.</p> <p>Results</p> <p>Increased throughput was achieved by immunizing mice with pools of antigens and cloning - from small numbers of hybridoma cells - the functionally rearranged light and heavy chains into a single expression plasmid. By immunizing with the ectodomains of zebrafish cell surface receptor proteins expressed in mammalian cells and screening for formalin-resistant epitopes, we selected antibodies that gave expected staining patterns on wholemount fixed zebrafish embryos.</p> <p>Conclusions</p> <p>This method can be used to quickly select several high quality monoclonal antibodies from a single immunized mouse and facilitates their distribution using plasmids.</p

    Screening of a library of recombinant Schistosoma mansoni proteins with sera from murine and human controlled infections identifies early serological markers.

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    Schistosomiasis is a major global health problem caused by blood-dwelling parasitic worms, which is currently tackled primarily by mass administration of the drug praziquantel. Appropriate drug treatment strategies are informed by diagnostics that establish the prevalence and intensity of infection, which, in regions of low transmission, should be highly sensitive. To identify sensitive new serological markers of Schistosoma mansoni infections, we have compiled a recombinant protein library of parasite cell-surface and secreted proteins expressed in mammalian cells. Together with a time series of sera samples from volunteers experimentally infected with a defined number of male parasites, we probed this protein library to identify several markers that can detect primary infections with as low as ten parasites and as early as five weeks post infection. These new markers could be further explored as valuable tools to detect ongoing and previous S. mansoni infections, including in endemic regions where transmission is low. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America

    Complement receptor 1 is the human erythrocyte receptor for Plasmodium vivax erythrocyte binding protein

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    The discovery that Africans were resistant to infection by Plasmodium vivax ( P. vivax) led to the conclusion that P. vivax invasion relied on the P. vivax Duffy Binding Protein (PvDBP) interacting with the Duffy Antigen Receptor for Chemokines (DARC) expressed on erythrocytes. However, the recent reporting of P. vivax infections in DARC-negative Africans suggests that the parasite might use an alternate invasion pathway to infect DARC-negative reticulocytes. To identify the parasite ligands and erythrocyte receptors that enable P. vivax invasion of both DARC-positive and -negative erythrocytes, we expressed region II containing the Duffy Binding-Like (DBL) domain of P. vivax erythrocyte binding protein (PvEBP-RII) and verified that the DBL domain binds to both DARC-positive and -negative erythrocytes. Furthermore, an AVidity-based EXtracelluar Interaction Screening (AVEXIS) was used to identify the receptor for PvEBP among over 750 human cell surface receptor proteins, and this approach identified only Complement Receptor 1 (CR1, CD35, or C3b/C4b receptor) as a PvEBP receptor. CR1 is a well-known receptor for P. falciparum Reticulocyte binding protein Homology 4 (PfRh4) and is present on the surfaces of both reticulocytes and normocytes, but its expression decreases as erythrocytes age. Indeed, PvEBP-RII bound to a subpopulation of both reticulocytes and normocytes, and this binding was blocked by the addition of soluble CR1 recombinant protein, indicating that CR1 is the receptor of PvEBP. In addition, we found that the Long Homology Repeat A (LHR-A) subdomain of CR1 is the only subdomain responsible for mediating the interaction with PvEBP-RII

    A PfRH5-Based Vaccine Is Efficacious against Heterologous Strain Blood-Stage Plasmodium falciparum Infection in Aotus Monkeys

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    SummaryAntigenic diversity has posed a critical barrier to vaccine development against the pathogenic blood-stage infection of the human malaria parasite Plasmodium falciparum. To date, only strain-specific protection has been reported by trials of such vaccines in nonhuman primates. We recently showed that P. falciparum reticulocyte binding protein homolog 5 (PfRH5), a merozoite adhesin required for erythrocyte invasion, is highly susceptible to vaccine-inducible strain-transcending parasite-neutralizing antibody. In vivo efficacy of PfRH5-based vaccines has not previously been evaluated. Here, we demonstrate that PfRH5-based vaccines can protect Aotus monkeys against a virulent vaccine-heterologous P. falciparum challenge and show that such protection can be achieved by a human-compatible vaccine formulation. Protection was associated with anti-PfRH5 antibody concentration and in vitro parasite-neutralizing activity, supporting the use of this in vitro assay to predict the in vivo efficacy of future vaccine candidates. These data suggest that PfRH5-based vaccines have potential to achieve strain-transcending efficacy in humans

    Natural malaria infection elicits rare but potent neutralizing antibodies to the blood-stage antigen RH5

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    Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is the most advanced blood-stage malaria vaccine candidate and is being evaluated for efficacy in endemic regions, emphasizing the need to study the underlying antibody response to RH5 during natural infection, which could augment or counteract responses to vaccination. Here, we found that RH5-reactive B cells were rare, and circulating immunoglobulin G (IgG) responses to RH5 were short-lived in malaria-exposed Malian individuals, despite repeated infections over multiple years. RH5-specific monoclonal antibodies isolated from eight malaria-exposed individuals mostly targeted non-neutralizing epitopes, in contrast to antibodies isolated from five RH5-vaccinated, malaria-naive UK individuals. However, MAD8-151 and MAD8-502, isolated from two malaria-exposed Malian individuals, were among the most potent neutralizers out of 186 antibodies from both cohorts and targeted the same epitopes as the most potent vaccine-induced antibodies. These results suggest that natural malaria infection may boost RH5-vaccine-induced responses and provide a clear strategy for the development of next-generation RH5 vaccines

    Conductance et étalement d'une onde quantique dans un guide unidimensionnel : effet d'une force.

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    A wave can be exponentially localized in a disordered medium, due to interference effects. This Anderson localization phenomenon leads to a cancellation of the conductance of a quantum fluid in 1D. However, theoretical works pointed out that an electric field may reduce or cancel this localization. We study here the effect of a force on the localization of a 1D quantum matter wave. Since both Anderson localization of an expanding wave packet and the effect of disorder on the transport between two reservoirs have been studied in ultracold atom experiments, we focus on two systems, namely the diffusion, or the transmission, of a particle.In order to calculate the transmission, we generalize a transfer matrix formalism to the presence of a, possibly inhomogeneous, force. The case of a speckle disorder as used in ultracold atom experiments is dealt with using two other analytical approaches. Our main is result is that the force can be entirely taken into account by renormalising the length with a local mean free path of the particle. For white-noise disorder, the force leads to a weaker, algebraic localization, whereas full delocalization appears for a correlated disorder. We then focus on the diffusion of a particle, using a numerical approach. A transition of delocalization of the particle for strong forces is shed into light through a power law increase of its position, whose exponent increases with the force. Moreover, we show that localization is systematically destroyed in a correlated disorder.Dans un milieu désordonné, une onde peut être localisée exponentiellement par des effets d'interférence. Ce phénomène de localisation d'Anderson conduit notamment à une annulation de la conductance d'un fluide quantique unidimensionnel. Des travaux théoriques ont cependant montré que l'application d'un champ électrique pouvait réduire, voire supprimer, cette localisation. Nous étudions ici l'effet d'une force sur la localisation d'une onde quantique de matière dans un système unidimensionnel. En lien direct avec les expériences d'atomes ultrafroids, qui permettent d'observer la localisation d'Anderson d'un paquet d'onde en étalement, ou bien l'effet du désordre sur le transport entre deux réservoirs, nous nous intéressons à deux systèmes : la diffusion et la transmission d'une particule. Afin d'étudier la transmission à travers un guide, nous étendons un formalisme de matrices de transfert à la présence d'une force, éventuellement inhomogène. Deux approches analytiques complémentaires nous permettent d'étendre les résultats au cas d'un désordre de tavelures tel que celui utilisé dans les expériences d'atomes ultrafroids. Nous montrons que la force peut être entièrement prise en compte à l'aide d'une renormalisation de la longueur du guide par un libre parcours moyen local de la particule. Pour un désordre blanc, la force conduit alors une localisation plus faible, algébrique, tandis qu'une délocalisation apparaît pour un désordre corrélé. Nous nous intéressons ensuite à la diffusion d'une particule, à l'aide d'une approche numérique. Nous mettons en évidence une délocalisation de la position à grande force sous la forme d'une croissance temporelle algébrique, dont l'exposant augmente avec la force. Nous montrons de plus que la localisation est systématiquement détruite dans un désordre corrélé

    Conductance and expansion of a quantum wave in a one-dimensional guide : effect of a force.

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    Dans un milieu désordonné, une onde peut être localisée exponentiellement par des effets d'interférence. Ce phénomène de localisation d'Anderson conduit notamment à une annulation de la conductance d'un fluide quantique unidimensionnel. Des travaux théoriques ont cependant montré que l'application d'un champ électrique pouvait réduire, voire supprimer, cette localisation. Nous étudions ici l'effet d'une force sur la localisation d'une onde quantique de matière dans un système unidimensionnel. En lien direct avec les expériences d'atomes ultrafroids, qui permettent d'observer la localisation d'Anderson d'un paquet d'onde en étalement, ou bien l'effet du désordre sur le transport entre deux réservoirs, nous nous intéressons à deux systèmes : la diffusion et la transmission d'une particule. Afin d'étudier la transmission à travers un guide, nous étendons un formalisme de matrices de transfert à la présence d'une force, éventuellement inhomogène. Deux approches analytiques complémentaires nous permettent d'étendre les résultats au cas d'un désordre de tavelures tel que celui utilisé dans les expériences d'atomes ultrafroids. Nous montrons que la force peut être entièrement prise en compte à l'aide d'une renormalisation de la longueur du guide par un libre parcours moyen local de la particule. Pour un désordre blanc, la force conduit alors une localisation plus faible, algébrique, tandis qu'une délocalisation apparaît pour un désordre corrélé. Nous nous intéressons ensuite à la diffusion d'une particule, à l'aide d'une approche numérique. Nous mettons en évidence une délocalisation de la position à grande force sous la forme d'une croissance temporelle algébrique, dont l'exposant augmente avec la force. Nous montrons de plus que la localisation est systématiquement détruite dans un désordre corrélé.A wave can be exponentially localized in a disordered medium, due to interference effects. This Anderson localization phenomenon leads to a cancellation of the conductance of a quantum fluid in 1D. However, theoretical works pointed out that an electric field may reduce or cancel this localization. We study here the effect of a force on the localization of a 1D quantum matter wave. Since both Anderson localization of an expanding wave packet and the effect of disorder on the transport between two reservoirs have been studied in ultracold atom experiments, we focus on two systems, namely the diffusion, or the transmission, of a particle.In order to calculate the transmission, we generalize a transfer matrix formalism to the presence of a, possibly inhomogeneous, force. The case of a speckle disorder as used in ultracold atom experiments is dealt with using two other analytical approaches. Our main is result is that the force can be entirely taken into account by renormalising the length with a local mean free path of the particle. For white-noise disorder, the force leads to a weaker, algebraic localization, whereas full delocalization appears for a correlated disorder. We then focus on the diffusion of a particle, using a numerical approach. A transition of delocalization of the particle for strong forces is shed into light through a power law increase of its position, whose exponent increases with the force. Moreover, we show that localization is systematically destroyed in a correlated disorder

    Basigin opens the door to malaria

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