Quantum Interference in Superconducting Wire Networks and Josephson Junction Arrays: Analytical Approach based on Multiple-Loop Aharonov-Bohm Feynman Path-Integrals

We investigate analytically and numerically the mean-field superconducting-normal phase boundaries of two-dimensional superconducting wire networks and Josephson junction arrays immersed in a transverse magnetic field. The geometries we consider include square, honeycomb, triangular, and kagome' lattices. Our approach is based on an analytical study of multiple-loop Aharonov-Bohm effects: the quantum interference between different electron closed paths where each one of them encloses a net magnetic flux. Specifically, we compute exactly the sums of magnetic phase factors, i.e., the lattice path integrals, on all closed lattice paths of different lengths. A very large number, e.g., up to $10^{81}$ for the square lattice, exact lattice path integrals are obtained. Analytic results of these lattice path integrals then enable us to obtain the resistive transition temperature as a continuous function of the field. In particular, we can analyze measurable effects on the superconducting transition temperature, $T_c(B)$, as a function of the magnetic filed $B$, originating from electron trajectories over loops of various lengths. In addition to systematically deriving previously observed features, and understanding the physical origin of the dips in $T_c(B)$ as a result of multiple-loop quantum interference effects, we also find novel results. In particular, we explicitly derive the self-similarity in the phase diagram of square networks. Our approach allows us to analyze the complex structure present in the phase boundaries from the viewpoint of quantum interference effects due to the electron motion on the underlying lattices.Comment: 18 PRB-type pages, plus 8 large figure

Inflammasome-independent role for NLRP3 in controlling innate antihelminth immunity and tissue repair in the lung

Alternatively activated macrophages are essential effector cells during type 2 immunity and tissue repair following helminth infections. We previously showed that Ym1, an alternative activation marker, can drive innate IL-1R-dependent neutrophil recruitment during infection with the lung-migrating nematode, Nippostrongylus brasiliensis, suggesting a potential role for the inflammasome in the IL-1-mediated innate response to infection. Although inflammasome proteins such as NLRP3 have important proinflammatory functions in macrophages, their role during type 2 responses and repair are less defined. We therefore infected Nlrp3-/- mice with N. brasiliensis Unexpectedly, compared with wild-type (WT) mice, infected Nlrp3 -/- mice had increased neutrophilia and eosinophilia, correlating with enhanced worm killing but at the expense of increased tissue damage and delayed lung repair. Transcriptional profiling showed that infected Nlrp3 -/- mice exhibited elevated type 2 gene expression compared with WT mice. Notably, inflammasome activation was not evident early postinfection with N. brasiliensis, and in contrast to Nlrp3 -/- mice, antihelminth responses were unaffected in caspase-1/11-deficient or WT mice treated with the NLRP3-specific inhibitor MCC950. Together these data suggest that NLRP3 has a role in constraining lung neutrophilia, helminth killing, and type 2 immune responses in an inflammasome-independent manner.Alistair L. Chenery, Rafid Alhallaf, Zainab Agha, Jesuthas Ajendra, James E. Parkinson, Martha M. Cooper, Brian H.K. Chan, Ramon M. Eichenberger, Lindsay A. Dent, Avril A.B. Robertson, Andreas Kupz, David Brough, Alex Loukas, Tara E. Sutherland, Judith E. Allen, and Paul R. Giacomi

A trial platform to assess approved SARS-CoV-2 vaccines in immunocompromised patients: first sub-protocol for a pilot trial comparing the mRNA vaccines Comirnaty® and COVID-19 mRNA Vaccine Moderna®.

Late 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to assess the efficacy and safety of interventions in a timely manner. The two existing Swiss cohorts of immunocompromised patients (i.e., Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS)) are an ideal foundation to set-up a trial platform in Switzerland leveraging routinely collected data. Within a newly founded trial platform, we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland in the frame of a pilot randomized controlled trial (RCT) while at the same time assessing the functionality of the trial platform. We will conduct a multicenter randomized controlled, open-label, 2-arm sub-study pilot trial of a platform trial nested into two Swiss cohorts. Patients included in the SHCS or the STCS will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the COVID-19 mRNA Vaccine Moderna®. The primary clinical outcome will be change in pan-lg antibody response (pan-Ig anti-S1-RBD; baseline vs. 3 months after first vaccination; binary outcome, considering ≥ 0.8 units/ml as a positive antibody response). The pilot study will also enable us to assess endpoints related to trial conduct feasibility (i.e., duration of RCT set-up; time of patient recruitment; patient consent rate; proportion of missing data). Assuming vaccine reactivity of 90% in both vaccine groups, we power our trial, using a non-inferiority margin such that a 95% two-sided confidence interval excludes a difference in favor of the reference group of more than 10%. A sample size of 380 (190 in each treatment arm) is required for a statistical power of 90% and a type I error of 0.025. The study is funded by the Swiss National Science Foundation (National Research Program NRP 78, "COVID-19"). This study will provide crucial information about the efficacy and safety of the mRNA SARS-CoV-2 vaccines in HIV patients and organ transplant recipients. Furthermore, this project has the potential to pave the way for further platform trials in Switzerland. ClinicalTrials.gov NCT04805125 . Registered on March 18, 2021