To bnAb or Not to bnAb: Defining Broadly Neutralising Antibodies Against HIV-1

Since their discovery, antibodies capable of broad neutralisation have been at the forefront of HIV-1 research and are of particular interest due to in vivo passive transfer studies demonstrating their potential to provide protection. Currently an exact definition of what is required for a monoclonal antibody to be classed as a broadly neutralising antibody (bnAb) has not yet been established. This has led to hundreds of antibodies with varying neutralisation breadth being studied and has given insight into antibody maturation pathways and epitopes targeted. However, even with this knowledge, immunisation studies and vaccination trials to date have had limited success in eliciting antibodies with neutralisation breadth. For this reason there is a growing need to identify factors specifically associated with bnAb development, yet to do this a set of criteria is necessary to distinguish bnAbs from non-bnAbs. This review aims to define what it means to be a HIV-1 bnAb by comparing neutralisation breadth, genetic features and epitopes of bnAbs, and in the process highlights the challenges of comparing the array of antibodies that have been isolated over the years

Lessons learned from humoral responses of HIV patients

L.E.M. receives support from an FP7 Marie Curie International Outgoing Fellowship for Career Development number 623038

Finite-size scaling properties of random transverse-field Ising chains : Comparison between canonical and microcanonical ensembles for the disorder

The Random Transverse Field Ising Chain is the simplest disordered model presenting a quantum phase transition at T=0. We compare analytically its finite-size scaling properties in two different ensembles for the disorder (i) the canonical ensemble, where the disorder variables are independent (ii) the microcanonical ensemble, where there exists a global constraint on the disorder variables. The observables under study are the surface magnetization, the correlation of the two surface magnetizations, the gap and the end-to-end spin-spin correlation $C(L)$ for a chain of length $L$. At criticality, each observable decays typically as $e^{- w \sqrt{L}}$ in both ensembles, but the probability distributions of the rescaled variable $w$ are different in the two ensembles, in particular in their asymptotic behaviors. As a consequence, the dependence in $L$ of averaged observables differ in the two ensembles. For instance, the correlation $C(L)$ decays algebraically as 1/L in the canonical ensemble, but sub-exponentially as $e^{-c L^{1/3}}$ in the microcanonical ensemble. Off criticality, probability distributions of rescaled variables are governed by the critical exponent $\nu=2$ in both ensembles, but the following observables are governed by the exponent $\tilde \nu=1$ in the microcanonical ensemble, instead of the exponent $\nu=2$ in the canonical ensemble (a) in the disordered phase : the averaged surface magnetization, the averaged correlation of the two surface magnetizations and the averaged end-to-end spin-spin correlation (b) in the ordered phase : the averaged gap. In conclusion, the measure of the rare events that dominate various averaged observables can be very sensitive to the microcanonical constraint.Comment: 24 page

Convalescent plasma for COVID-19: a meta-analysis, trial sequential analysis, and meta-regression

Background: SARS-CoV-2-specific antibodies, particularly those preventing interaction between the viral spike receptor-binding domain and the host angiotensin-converting enzyme 2 receptor, may prevent viral entry into host cells and disease progression. / Objective: We performed a systematic review, meta-analysis, trials sequential analysis (TSA) and meta-regression of randomized control trials (RCTs) to evaluate the benefit of convalescent plasma for COVID-19. The primary outcome was 28-30-day mortality. Secondary outcomes included need for mechanical ventilation and intensive care (ICU) admission. / Data sources: PubMed, Embase, MedRxiv, and the Cochrane library on 2nd July 2021. / Results: Seventeen RCTs were identified recruiting 15,587 patients with 8027 (51.5%) allocated to receive convalescent plasma. Convalescent plasma use was not associated with a mortality benefit (24.7% vs. 25.5%; OR 0.94 (0.85 – 1.04); p = 0.23; I2 = 4%; TSA adjusted CI 0.84 – 1.05), or reduction in need for mechanical ventilation (15.7% vs. 15.4%; OR 1.01 [0.92 – 1.11]; p = 0.82; I2 = 0%; TSA adjusted CI 0.91 – 1.13), or ICU admission (22.4% vs. 16.7%; OR 0.80 (0.21 – 3.09); p = 0.75; I2 = 63%; TSA adjusted CI 0.0 – 196.05). Meta-regression did not reveal any association with titre of convalescent plasma, timing of administration, nor risk of death and treatment effect (p>0.05). Risk of bias was high in most studies. / Conclusions: In patients with COVID-19, there was no clear mortality benefit associated with convalescent plasma. In patients with mild disease, convalescent plasma did not prevent either the need for mechanical ventilation or ICU admission. PROSPERO registration CRD42021234201

Unitary representations of the Galilean line group: Quantum mechanical principle of equivalence

We present a formalism of Galilean quantum mechanics in non-inertial reference frames and discuss its implications for the equivalence principle. This extension of quantum mechanics rests on the Galilean line group, the semidirect product of the real line and the group of analytic functions from the real line to the Euclidean group in three dimensions. This group provides transformations between all inertial and non-inertial reference frames and contains the Galilei group as a subgroup. We construct a certain class of unitary representations of the Galilean line group and show that these representations determine the structure of quantum mechanics in non-inertial reference frames. Our representations of the Galilean line group contain the usual unitary projective representations of the Galilei group, but have a more intricate cocycle structure. The transformation formula for the Hamiltonian under the Galilean line group shows that in a non-inertial reference frame it acquires a fictitious potential energy term that is proportional to the inertial mass, suggesting the equivalence of inertial mass and gravitational mass in quantum mechanics

The Two-Dimensional Disordered Boson Hubbard Model: Evidence for a Direct Mott Insulator-to-Superfluid Transition and Localization in the Bose Glass Phase

We investigate the Bose glass phase and the insulator-to-superfluid transition in the two-dimensional disordered boson Hubbard model in the Villain representation via Monte Carlo simulations. In the Bose glass phase the probability distribution of the local susceptibility is found to have a $1/ \chi^2$ tail and the imaginary time Green's function decays algebraically $C(\tau) \sim \tau^{-1}$, giving rise to a divergent global susceptibility. By considering the participation ratio it is shown that the excitations in the Bose glass phase are fully localized and a scaling law is established. For commensurate boson densities we find a direct Mott insulator to superfluid transition without an intervening Bose glass phase for weak disorder. For this transition we obtain the critical exponents $z=1, \nu=0.7\pm 0.1$ and $\eta = 0.1 \pm 0.1$, which agree with those for the classical three-dimensional XY model without disorder. This indicates that disorder is irrelevant at the tip of the Mott-lobes and that here the inequality $\nu\ge2/d$ is violated.Comment: 15 pages RevTeX, 18 postscript-figures include

The Intrinsic Coupling in Integrable Quantum Field Theories

The intrinsic 4-point coupling, defined in terms of a truncated 4-point function at zero momentum, provides a well-established measure for the interaction strength of a QFT. We show that this coupling can be computed non-perturbatively and to high accuracy from the form factors of an (integrable) QFT. The technique is illustrated and tested with the Ising model, the XY-model and the O(3) nonlinear sigma-model. The results are compared to those from high precision lattice simulations.Comment: 69 pages, Late