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An updated and expanded data set that consists of 214 plagioclase-liquid equilibrium pairs from 40 experimental studies in the literature is used to recalibrate the thermodynamic model for the plagioclase-liquid hygrometer of Lange et al. (2009); the updated model is applicable to metaluminous and alkaline magmas. The model is based on the crystal-liquid exchange reaction between the anorthite (CaAl2Si2O8) and albite (NaAlSi3O8) components, and all available volumetric and calorimetric data for the pure end-member components are used in the revised model. The activities of the crystalline plagioclase components are taken from Holland and Powell (1992). Of the 214 experiments, 107 are hydrous and 107 are anhydrous. Four criteria were applied for inclusion of experiments in the final data set: (1) crystallinities <30%; (2) pure-H2O fluid saturated; (3) compositional totals (including H2O component) of 97-101% for hydrous quenched glasses and 98.5-101 for anhydrous quenched glasses; and (4) melt viscosities ≤5.2 log10 Pa·s. The final data set spans a wide range in liquid composition (45-80 wt% SiO2; 1-10 wt% Na2O+K2O), plagioclase composition (An17-95), temperature (750-1244°C), pressure (0-350 MPa), and H2O content (0-8.3 wt%). The water solubility model of Zhang et al. (2007) was applied to all hydrous experiments. The standard error estimate on the hygrometer model is 0.35 wt% H2O, and all liquid compositions are fitted equally well. Application of the model as a thermometer recovers temperatures to within ±12°, on average. Tests of the hygrometer on anhydrous piston-cylinder experiments in the literature, not included in the regression, show that the model is accurate at all pressures where plagioclase is stable. Applications of the hygrometer are made to natural rhyolites (Bishop Tuff, Katmai, and TobaTuff) with reported H2O analyses in quartz-hosted melt inclusions from the literature; the results show agreement. Applications of the hygrometer/thermometer are additionally made to natural rhyolites from Iceland and Glass Mountain, California. The updated model can be downloaded either as a program in Excel format or as a MatLab script from the Data Repository.

A cure for HIV-1 remains unattainable as only one case has been reported, a decade ago 1 , 2 . The individual—who is known as the ‘Berlin patient’—underwent two allogeneic haematopoietic stem-cell transplantation (HSCT) procedures using a donor with a homozygous mutation in the HIV coreceptor CCR5 (CCR5Δ32/Δ32) to treat his acute myeloid leukaemia. Total body irradiation was given with each HSCT. Notably, it is unclear which treatment or patient parameters contributed to this case of long-term HIV remission. Here we show that HIV-1 remission may be possible with a less aggressive and toxic approach. An adult infected with HIV-1 underwent allogeneic HSCT for Hodgkin’s lymphoma using cells from a CCR5Δ32/Δ32 donor. He experienced mild gut graft-versus-host disease. Antiretroviral therapy was interrupted 16 months after transplantation. HIV-1 remission has been maintained over a further 18 months. Plasma HIV-1 RNA has been undetectable at less than one copy per millilitre along with undetectable HIV-1 DNA in peripheral CD4 T lymphocytes. Quantitative viral outgrowth assays from peripheral CD4 T lymphocytes show no reactivatable virus using a total of 24 million resting CD4 T cells. CCR5-tropic, but not CXCR4-tropic, viruses were identified in HIV-1 DNA from CD4 T cells of the patient before the transplant. CD4 T cells isolated from peripheral blood after transplantation did not express CCR5 and were susceptible only to CXCR4-tropic virus ex vivo. HIV-1 Gag-specific CD4 and CD8 T cell responses were lost after transplantation, whereas cytomegalovirus-specific responses were detectable. Similarly, HIV-1-specific antibodies and avidities fell to levels comparable to those in the Berlin patient following transplantation. Although at 18 months after the interruption of treatment it is premature to conclude that this patient has been cured, these data suggest that a single allogeneic HSCT with homozygous CCR5Δ32 donor cells may be sufficient to achieve HIV-1 remission with reduced intensity conditioning and no irradiation, and the findings provide further support for the development of HIV-1 remission strategies based on preventing CCR5 expression. An adult infected with HIV-1 who underwent allogeneic haematopoietic stem-cell transplantation for Hodgkin’s lymphoma using cells from a CCR5Δ32/Δ32 donor achieved full remission of HIV-1 for 18 months after transplantation and 16 months after cessation of antiretroviral therapy.

There is an urgent need to understand the nature of immune responses against SARS-CoV-2, to inform risk-mitigation strategies for people living with HIV (PLWH). Here we show that the majority of PLWH with ART suppressed HIV viral load, mount a detectable adaptive immune response to SARS-CoV-2. Humoral and SARS-CoV-2-specific T cell responses are comparable between HIV-positive and negative subjects and persist 5-7 months following predominately mild COVID-19 disease. T cell responses against Spike, Membrane and Nucleoprotein are the most prominent, with SARS-CoV-2-specific CD4 T cells outnumbering CD8 T cells. We further show that the overall magnitude of SARS-CoV-2-specific T cell responses relates to the size of the naive CD4 T cell pool and the CD4:CD8 ratio in PLWH. These findings suggest that inadequate immune reconstitution on ART, could hinder immune responses to SARS-CoV-2 with implications for the individual management and vaccine effectiveness in PLWH. Understanding the pathology and immunological response to SARS CoV2 infection in specific patient groups is essential for informing the scientific and clinical handling of infections within these patient populations. Here the authors characterise the adaptive immune response to SARS-CoV2 infection in people living with HIV.

Developing stable biopharmaceutical formulations is of paramount importance and is typically achieved by incorporating surfactants as stabilising agents, such as polysorbate 20 and 80. However, little is known about the effect surfactant grade has on formulation stability. This study evaluates the effect of regular grade and Super-refined™ polysorbates 20 and 80 and their interaction with model proteins, namely β-lactoglobulin (β-Ig), human serum albumin (HSA) and immunoglobulin gamma (IgG), using isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC). ITC results indicated that all four polysorbates underwent binding interactions with β-Ig and HSA, yet no interaction was observed with IgG this is postulated to be a consequence of differences in secondary structure composition. Surfactant binding to β-Ig occurred at ratios of ~ 3:2 regardless of the surfactant used with dissociation constants ranging from 284 to 388 µM, whereas HSA bound at ratios of ~ 3:1 and dissociation constants ranging from 429 to 653 µM. Changes in enthalpy were larger for the surfactant interactions with HSA compared with β-Ig implying the former produced a greater binding interaction than the latter. DSC facilitated measurement of the temperature of unfolding of each protein with the presence of each polysorbate where results further confirmed interactions had occurred for β-Ig and HSA with an increased unfolding temperature between 4 and 6 K implying improved protein stability, yet again, no interaction was observed with IgG. This study thermodynamically characterised the role of polysorbates in protein stabilisation for biopharmaceutical formulations.

A freely accessible database has recently been released that provides measurements available in the literature on human skin permeation data, known as the ‘Human Skin Database – HuskinDB’. Although this database is extremely useful for sourcing permeation data to help with toxicity and efficacy determination, it cannot be beneficial when wishing to consider unlisted, or novel compounds. This study undertakes analysis of the data from within HuskinDB to create a model that predicts permeation for any compound (within the range of properties used to create the model). Using permeability coefficient ( K p ) data from within this resource, several models were established for K p values for compounds of interest by varying the experimental parameters chosen and using standard physicochemical data. Multiple regression analysis facilitated creation of one particularly successful model to predict K p through human skin based only on three chemical properties. The model transforms the dataset from simply a resource of information to a more beneficial model that can be used to replace permeation testing for a wide range of compounds.

Estimates of magmatic storage are typically made using mineral assemblages in natural samples, experiments and thermodynamic models (e.g., MELTS), where each method has limitations. Here, we compare each of these methods to assess their utility in estimating storage conditions for post‐collapse, two‐feldspar high‐silica rhyolites (HSRs) sourced from Valles Caldera, NM (USA). We focus on the Valle Grande HSRs, which have known whole rock, glass compositions, crystallinities and storage conditions (∼750–770°C; ∼130–165 MPa). Equilibrium experiments that overlap with magmatic storage conditions determined from sample petrology have glass and mineral compositions that match those in the natural samples, suggesting that the phenocryst assemblage is accurately recording pre‐eruptive conditions. RMELTS reproduces differing aspects of the natural samples and experiments, but generally confirm storage conditions (751–758°C; 179–215 MPa) recorded by the petrology of the post‐collapse high‐silica rhyolites. RMELTS reproduces the experimentally determined phase‐in curves within ±5°C, at pressures >125 MPa. Below 125 MPa, RMELTS overpredicts the stability of the experimental quartz, sanidine and anorthoclase. We apply the RMELTS geothermobarometer to the Glass Mountain obsidians (two‐feldspar HSRs) to evaluate possible reasons for the agreement between RMELTS, experiments, and Valle Grande HSRs. The RMELTS geothermobarometer overpredicts the Glass Mountain obsidians' temperatures by 50–77°C, and likely underpredicts pressures. RMELTS predicts a common co‐saturation temperature of ∼750°C for these two HSRS. We find that RMELTS recovers the storage temperature and pressures for Valle Grande HSRS because they have temperatures of ∼750°C, contain <30% total crystallinity, are near equilibrium and are stored at >125 MPa.

Health systems have improved their abilities to identify, diagnose, treat and, increasingly, achieve viral suppression among people living with HIV (PLHIV). Despite these advances, a higher burden of multimorbidity and poorer health-related quality of life are reported by many PLHIV in comparison to people without HIV. Stigma and discrimination further exacerbate these poor outcomes. A global multidisciplinary group of HIV experts developed a consensus statement identifying key issues that health systems must address in order to move beyond the HIV field’s longtime emphasis on viral suppression to instead deliver integrated, person-centered healthcare for PLHIV throughout their lives.

Mathematical models to predict skin permeation tend to be based on animal derived experimental data as well as knowing physicochemical properties of the compound under investigation, such as molecular volume, polarity and lipophilicity. This paper presents a strikingly contrasting model to predict permeability, formed entirely from simple chemical fragment (functional group) data and a recently released, freely accessible human (i.e. non-animal) skin permeation database, known as the ‘Human Skin Database – HuskinDB’. Data from within the database allowed development of several fragment-based models, each including a calculable effect for all of the most commonly encountered functional groups present in compounds within the database. The developed models can be applied to predict human skin permeability (log K p ) for any compound containing one or more of the functional groups analysed from the dataset with no need to know any other physicochemical properties, solely the type and number of each functional group within the chemical structure itself. This approach simplifies mathematical prediction of permeability for compounds with similar properties to those used in this study.

Natural killer (NK) cell subsets with adaptive properties are emerging as regulators of vaccine-induced T and B cell responses and are specialized towards antibody-dependent functions contributing to SARS-CoV-2 control. Although HIV-1 infection is known to affect the NK cell pool, the additional impact of SARS-CoV-2 infection and/or vaccination on NK cell responses in people living with HIV (PLWH) has remained unexplored. Our data show that SARS-CoV-2 infection skews NK cells towards a more differentiated/adaptive CD57 + FcεRIγ − phenotype in PLWH. A similar subset was induced following vaccination in SARS-CoV-2 naïve PLWH in addition to a CD56 bright population with cytotoxic potential. Antibody-dependent NK cell function showed robust and durable responses to Spike up to 148 days post-infection, with responses enriched in adaptive NK cells. NK cell responses were further boosted by the first vaccine dose in SARS-CoV-2 exposed individuals and peaked after the second dose in SARS-CoV-2 naïve PLWH. The presence of adaptive NK cells associated with the magnitude of cellular and humoral responses. These data suggest that features of adaptive NK cells can be effectively engaged to complement and boost vaccine-induced adaptive immunity in potentially more vulnerable groups such as PLWH.