Safety and Pharmacokinetics of a Four Monoclonal Antibody Combination Against Botulinum C and D Neurotoxins.

Botulism is caused by botulinum neurotoxin (BoNT), the most poisonous substance known. BoNTs are also classified as Tier 1 biothreat agents due to their high potency and lethality. The existence of seven BoNT serotypes (A-G), which differ between 35% to 68% in amino acid sequence, necessitates the development of serotype specific countermeasures. We present results of a Phase 1 clinical study of an anti-toxin to BoNT serotypes C and D, NTM-1634, which consists of an equimolar mixture of four fully human IgG1 monoclonal antibodies (mAbs), each binding to non-overlapping epitopes on BoNT serotypes C and D resulting in potent toxin neutralization in rodents. This first-in-human study evaluated the safety and pharmacokinetics of escalating doses of NTM-1634 administered intravenously to healthy adults (NCT03046550). Three cohorts of eight healthy subjects received a single intravenous dose of NTM-1634 or placebo at 0.33 mg/kg, 0.66 mg/kg or 1 mg/kg. Follow-up examinations and pharmacokinetic evaluations were continued up to 121 days post-infusion. Subjects were monitored using physical examinations, hematology and chemistry blood tests, and electrocardiograms. Pharmacokinetic parameters were estimated using noncompartmental methods. The results demonstrated that the materials were safe and well-tolerated with the expected half-lives for human mAbs and with minimal anti-drug antibodies detected over the dose ranges and duration of the study

Propagation dynamics of spin excitations along skyrmion strings

Magnetic skyrmions, topological solitons characterized by a two-dimensional swirling spin texture, have recently attracted attention as stable particle-like objects. In a three-dimensional system, a skyrmion can extend in the third dimension forming a robust and flexible string structure, whose unique topology and symmetry are anticipated to host nontrivial functional responses. Here we experimentally demonstrate the coherent propagation of spin excitations along skyrmion strings for the chiral-lattice magnet Cu$_{2}$OSeO$_{3}$. We find that this propagation is directionally non-reciprocal and the degree of non-reciprocity, as well as group velocity and decay length, are strongly dependent on the character of the excitation modes. These spin excitations can propagate over a distance exceeding 50 μm, demonstrating the excellent long-range ordered nature of the skyrmion-string structure. Our combined experimental and theoretical analyses offer a comprehensive account of the propagation dynamics of skyrmion-string excitations and suggest the possibility of unidirectional information transfer along such topologically protected strings

Quantum oscillations in a centrosymmetric skyrmion-hosting magnet GdRu2Si2

We have performed magnetic torque and resistivity measurements on a centrosymmetric skyrmion-host GdRu2Si2, in which the dominant magnetic interaction leading to skyrmion formation is under debate. We observe both the de Haas-van Alphen and Shubnikov-de Haas oscillations in the forced ferromagnetic phase. The angular dependence of the quantum oscillation frequencies can be reproduced by the ab-initio calculation. The de Haas-van Alphen oscillation is also observed in the double-Q phase with a different frequency to that in the forced ferromagnetic phase, indicating a Fermi surface reconstruction due to the coupling between localized spins and conduction electrons. Based on these experimental findings, the magnetic interactions in this system are discussed.Comment: 11 pages, 8 figure

Genome-wide association mapping for root traits in a panel of rice accessions from Vietnam

Background: Despite recent sequencing efforts, local genetic resources remain underexploited, even though they carry alleles that can bring agronomic benefits. Taking advantage of the recent genotyping with 22,000 single-nucleotide polymorphism markers of a core collection of 180 Vietnamese rice varieties originating from provinces from North to South Vietnam and from different agrosystems characterized by contrasted water regimes, we have performed a genome-wide association study for different root parameters. Roots contribute to water stress avoidance and are a still underexploited target for breeding purpose due to the difficulty to observe them. Results: The panel of 180 rice varieties was phenotyped under greenhouse conditions for several root traits in an experimental design with 3 replicates. The phenotyping system consisted of long plastic bags that were filled with sand and supplemented with fertilizer. Root length, root mass in different layers, root thickness, and the number of crown roots, as well as several derived root parameters and shoot traits, were recorded. The results were submitted to association mapping using a mixed model involving structure and kinship to enable the identification of significant associations. The analyses were conducted successively on the whole panel and on its indica (115 accessions) and japonica (64 accessions) subcomponents. The two associations with the highest significance were for root thickness on chromosome 2 and for crown root number on chromosome 11. No common associations were detected between the indica and japonica subpanels, probably because of the polymorphism repartition between the subspecies. Based on orthology with Arabidopsis, the possible candidate genes underlying the quantitative trait loci are reviewed. Conclusions: Some of the major quantitative trait loci we detected through this genome-wide association study contain promising candidate genes encoding regulatory elements of known key regulators of root formation and development

On quantum teleportation with beam-splitter-generated entanglement

Following the lead of Cochrane, Milburn, and Munro [Phys. Rev. A {\bf 62}, 062307 (2000)], we investigate theoretically quantum teleportation by means of the number-sum and phase-difference variables. We study Fock-state entanglement generated by a beam splitter and show that two-mode Fock-state inputs can be entangled by a beam splitter into close approximations of maximally entangled eigenstates of the phase difference and the photon-number sum (Einstein-Podolsky-Rosen -- EPR -- states). Such states could be experimentally feasible with on-demand single-photon sources. We show that the teleportation fidelity can reach near unity when such ``quasi-EPR'' states are used as the quantum channel.Comment: 7 pages (two-column), 7 figures, submitted to Phys. Rev. A. Text unmodified, postscript error correcte