Off-diagonal matrix elements of local operators in many-body quantum systems

In the time evolution of isolated quantum systems out of equilibrium, local observables generally relax to a long-time asymptotic value, governed by the expectation values (diagonal matrix elements) of the corresponding operator in the eigenstates of the system. The temporal fluctuations around this value, response to further perturbations, and the relaxation toward this asymptotic value, are all determined by the off-diagonal matrix elements. Motivated by this non-equilibrium role, we present generic statistical properties of off-diagonal matrix elements of local observables in two families of interacting many-body systems with local interactions. Since integrability (or lack thereof) is an important ingredient in the relaxation process, we analyze models that can be continuously tuned to integrability. We show that, for generic non-integrable systems, the distribution of off-diagonal matrix elements is a gaussian centered at zero. As one approaches integrability, the peak around zero becomes sharper, so that the distribution is approximately a combination of two gaussians. We characterize the proximity to integrability through the deviation of this distribution from a gaussian shape. We also determine the scaling dependence on system size of the average magnitude of off-diagonal matrix elements.Comment: 10 pages, 6 figure

Natural and bioinspired excipients for dry powder inhalation formulations

Pulmonary drug delivery can have several advantages over other administration routes, in particular when using dry powder formulations. Such dry powder inhalation formulations generally include natural and bio-inspired excipients, which, among other purposes, are used to improve dosing reproducibility and aerosolization performance. Amino acids can enhance powder dispersibility and provide protection against moisture uptake. Sugars are used as drug-carrying diluents, stabilizers for biopharmaceuticals, and surface enrichers. Lipids and lipid-like excipients can reduce interparticle adhesive forces and are also used as constituents of liposomal drug delivery systems. Finally, biodegradable polymers are used to facilitate sustained release and targeted drug delivery. Despite their promise, pulmonary toxicity of many of the discussed excipients remains largely unknown and requires attention in future research

Development of a Stable Respiratory Syncytial Virus Pre-Fusion Protein Powder Suitable for a Core-Shell Implant with a Delayed Release in Mice:A Proof of Concept Study

Currently, there is an increasing interest to apply pre-fusion (pre-F) protein of respiratory syncytial virus (RSV) as antigen for the development of a subunit vaccine. A pre-F-containing powder would increase the flexibility regarding the route of administration. For instance, a pre-F-containing powder could be incorporated into a single-injection system releasing a primer, and after a lag time, a booster. The most challenging aspect, obtaining the booster after a lag time, may be achieved by incorporating the powder into a core encapsulated by a nonporous poly(dl-lactic-co-glycolic acid) (PLGA) shell. We intended to develop a stable freeze-dried pre-F-containing powder. Furthermore, we investigated whether incorporation of this powder into the core-shell implant was feasible and whether this system would induce a delayed RSV virus-neutralizing antibody (VNA) response in mice. The developed pre-F-containing powder, consisting of pre-F in a matrix of inulin, HEPES, sodium chloride, and Tween 80, was stable during freeze-drying and storage for at least 28 days at 60 degrees C. Incorporation of this powder into the core-shell implant was feasible and the core-shell production process did not affect the stability of pre-F. An in vitro release study showed that pre-F was incompletely released from the core-shell implant after a lag time of 4 weeks. The incomplete release may be the result of pre-F instability within the core-shell implant during the lag time and requires further research. Mice subcutaneously immunized with a pre-F-containing core-shell implant showed a delayed RSV VNA response that corresponded with pre-F release from the core-shell implant after a lag time of approximately 4 weeks. Moreover, pre-F-containing core-shell implants were able to boost RSV VNA titers of primed mice after a lag time of 4 weeks. These findings could contribute to the development of a single-injection pre-F-based vaccine containing a primer and a booster

Counterpropagating topological and quantum Hall edge channels

The survival of the quantum spin Hall edge channels in presence of an external magnetic field has been a subject of experimental and theoretical research. The inversion of Landau levels that accommodates the quantum spin Hall effect is destroyed at a critical magnetic field, and a trivial insulating gap appears in the spectrum for stronger fields. In this work, we report the absence of this transport gap in disordered two dimensional topological insulators in perpendicular magnetic fields of up to 16 T. Instead, we observe that a topological edge channel (from band inversion) coexists with a counterpropagating quantum Hall edge channel for magnetic fields at which the transition to the insulating regime is expected. For larger fields, we observe only the quantum Hall edge channel with transverse resistance close to $h/e^2$. By tuning the disorder using different fabrication processes, we find evidence that this unexpected $\nu=1$ plateau originates from extended quantum Hall edge channels along a continuous network of charge puddles at the edges of the device.Comment: 8+3 pages, 5+2 figure

Respiratory syncytial virus subunit vaccines based on the viral envelope glycoproteins intended for pregnant women and the elderly

Introduction: Respiratory syncytial virus (RSV) causes high morbidity and mortality rates among infants, young children, and the elderly worldwide. Unfortunately, a safe and effective vaccine is still unavailable. In 1966, a formalin-inactivated RSV vaccine failed and resulted in the death of two young children. This failure shifted research toward the development of subunit-based vaccines for pregnant women (to passively vaccinate infants) and the elderly. Among these subunit-based vaccines, the viral envelope glycoproteins show great potential as antigens. Areas covered: In this review, progress in the development of safe and effective subunit RSV vaccines based on the viral envelope glycoproteins and intended for pregnant women and the elderly, are reviewed and discussed. Studies published in the period 2012-2018 were included. Expert opinion: Researchers are close to bringing safe and effective subunit-based RSV vaccines to the market using the viral envelope glycoproteins as antigens. However, it remains a major challenge to elicit protective immunity, with a formulation that has sufficient (storage) stability. These issues may be overcome by using the RSV fusion protein in its pre-fusion conformation, and by formulating this protein as a dry powder. It may further be convenient to administer this powder via the pulmonary route

Topological band inversion in HgTe(001): surface and bulk signatures from photoemission

HgTe is a versatile topological material and has enabled the realization of a variety of topological states, including two- and three-dimensional (3D) topological insulators and topological semimetals. Nevertheless, a quantitative understanding of its electronic structure remains challenging, in particular due to coupling of the Te 5p-derived valence electrons to Hg 5d core states at shallow binding energy. We present a joint experimental and theoretical study of the electronic structure in strained HgTe(001) films in the 3D topological-insulator regime, based on angle-resolved photoelectron spectroscopy and density functional theory. The results establish detailed agreement in terms of (i) electronic band dispersions and orbital symmetries, (ii) surface and bulk contributions to the electronic structure, and (iii) the importance of Hg 5d states in the valence-band formation. Supported by theory, our experiments directly image the paradigmatic band inversion in HgTe, underlying its non-trivial band topology

Ovalbumin-containing core-shell implants suitable to obtain a delayed IgG1 antibody response in support of a biphasic pulsatile release profile in mice

A single-injection vaccine formulation that provides for both a prime and a boost immunization would have various advantages over a multiple-injection regime. For such a vaccine formulation, it is essential that the booster dose is released after a certain, preferably adjustable, lag time. In this study we investigated whether a core-shell based implant, containing ovalbumin as core material and poly(DL-lactic-co-glycolic acid) of various monomer ratios as shell material can be used to obtain such a booster release. An in vitro release study showed that the lag time after which the ovalbumin was released from the core-shell implant increased with increasing lactic to glycolic acid ratio of the polymer and ranged from 3-6 weeks. Fluorescence spectroscopy showed minimal differences between native ovalbumin and ovalbumin from core-shell implants that were incubated until just before the observed in vitro release. In addition, mice immunized with a subcutaneous inserted core-shell implant containing ovalbumin showed an ovalbumin-specific IgG1 antibody response after a lag time of 4 or 6-8 weeks. Moreover, delayed release of ovalbumin caused higher IgG1 antibody titers than conventional subcutaneous vaccination with ovalbumin dissolved in PBS. Collectively, these findings could contribute to the further development of a single-injection vaccine, making multiple injections of the vaccine superfluous

The mechanism behind the biphasic pulsatile drug release from physically mixed poly(DL-lactic(-co-glycolic) acid)-based compacts

Successful immunization often requires a primer, and after a certain lag time, a booster administration of the antigen. To improve the vaccinees' comfort and compliance, a single-injection vaccine formulation with a biphasic pulsatile release would be preferable. Previous work has shown that such a release profile can be obtained with compacts prepared from physical mixtures of various poly(DL-lactic(-co-glycolic) acid) types (Murakami et al., 2000). However, the mechanism behind this release profile is not fully understood. In the present study, the mechanism that leads to this biphasic pulsatile release was investigated by studying the effect of the glass transition temperature (Tg) of the polymer, the temperature of compaction, the compression force, the temperature of the release medium, and the molecular weight of the incorporated drug on the release behavior. Compaction resulted in a porous compact. Once immersed into release medium with a temperature above the Tg of the polymer, the drug was released by diffusion through the pores. Simultaneously, the polymer underwent a transition from the glassy state into the rubbery state. The pores were gradually closed by viscous flow of the polymer and further release was inhibited. After a certain period of time, the polymer matrix ruptured, possibly due to a build-up in osmotic pressure, resulting in a pulsatile release of the remaining amount of drug. The compression force and the molecular weight of the incorporated drug did not influence the release profile. Understanding this mechanism could contribute to further develop single-injection vaccines

Statistical properties of eigenstate amplitudes in complex quantum systems

We study the eigenstates of quantum systems with large Hilbert spaces, via their distribution of wave-function amplitudes in a real-space basis. For single-particle “quantum billiards,” these real-space amplitudes are known to have Gaussian distribution for chaotic systems. In this work, we formulate and address the corresponding question for many-body lattice quantum systems. For integrable many-body systems, we examine the deviation from Gaussianity and provide evidence that the distribution generically tends toward power-law behavior in the limit of large sizes. We relate the deviation from Gaussianity to the entanglement content of many-body eigenstates. For integrable billiards, we find several cases where the distribution has power-law tails