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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.

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.

A detailed petrological study is presented for six phenocryst-poor obsidian samples (73–75 wt% SiO 2 ) erupted as small volume, monogenetic domes in the Mexican and Cascade arcs. Despite low phenocryst (+microphenocryst) abundances (2–6 %), these rhyolites are each multiply saturated with five to eight mineral phases (plagioclase + orthopyroxene + titanomagnetite + ilmenite + apatite ± zircon ± hornblende ± clinopyroxene ± sanidine ± pyrrhotite). Plagioclase and orthopyroxene phenocrysts (identified using phase-equilibrium constraints) span ≤30 mol % An and ≤15 % Mg#, respectively. Eruptive temperatures (±1 σ ), on the basis of Fe–Ti two oxide thermometry, range from 779 (±25) to 940 (±18) °C. Oxygen fugacities (±1 σ ) range from −0.4 to 1.4 (±0.1) log units relative to those along the Ni–NiO buffer. With temperature known, the plagioclase-liquid hygrometer was applied; maximum water concentrations calculated for the most calcic plagioclase phenocryst in each sample range from 2.6 to 6.5 wt%. This requires that the rhyolites were fluid-saturated at depths ≥2–7 km. It is proposed that the wide compositional range in plagioclase and orthopyroxene phenocrysts, despite their low abundance, can be attributed to changing melt water concentrations owing to degassing during magma ascent. Phase-equilibrium experiments from the literature show that higher dissolved water concentrations lead to more Fe-rich orthopyroxene, as well as more calcic plagioclase. Loss of dissolved water leads to a progressive increase in melt viscosity, and phenocrysts often display diffusion-limited growth textures (e.g., dendritic and vermiform), consistent with large undercoolings caused by degassing. A kinetic barrier to microlite crystallization occurred at viscosities from 4.5 to 5.0 log 10 Pa s for these rhyolites, presumably because the rate at which melt viscosity changed was high owing to rapid loss of dissolved water during magma ascent.

The Glass Mountain obsidians (Long Valley, CA) are crystal poor (<8 vol%) and highly evolved (high SiO 2 , low Sr), and therefore, their formation required extremely efficient separation of melts from a crystal-rich source. A petrologic and experimental investigation of the mineral phases in Glass Mountain lavas identifies conditions under which phenocrysts grew and the driving mechanism for crystallization, which places constraints on the possible processes that generated the obsidians. The obsidian in this study (GM-11) is saturated in nine phases (sanidine + quartz + plagioclase + titanomagnetite + ilmenite + zircon + apatite + allanite + biotite), and results of high-resolution SEM compositional mapping and electron microprobe analysis reveal that individual sanidine crystals are normally zoned and span a range of compositions (Or 40–78 ). Sanidines have a “granophyric” texture, characterized by intergrowths of quartz and sanidine. Mineral phases in the natural sample are compared to H 2 O-saturated phase equilibrium experiments conducted in cold-seal pressure vessels, over a range of conditions (700–850 °C; 75–225 MPa), and all are found to be plausible phenocrysts. Comparison of sanidine compositions from the natural sample with those grown in phase equilibrium experiments demonstrates that sanidine in the natural sample occurs in a reduced abundance. Further comparison with phase equilibrium experiments suggests that sanidine compositions track progressive loss of dissolved melt water (±cooling), suggesting that crystallization in the natural obsidian was driven predominantly by degassing resulting from decompression. It is paradoxical that an effusively (slowly) erupted lava should contain multiple phenocryst phases, including sanidine crystals that span a range of compositions with granophyric textures, and yet remain so crystal poor. To resolve this paradox, it is necessary that the solidification mechanism (degassing or cooling) that produced the sanidine crystals (and other mineral phases) must have an associated kinetic effect(s) that efficiently hinders crystal nucleation and growth. Decompression experiments conducted in this study and from the literature collectively demonstrate that the simplest way to inhibit nucleation during degassing-induced crystallization is to initiate degassing ± cooling from superliquidus conditions, and therefore, the Glass Mountain obsidians were superheated prior to crystallization.

The effect of temperature, pressure, and dissolved H 2 O in the melt on the Fe 2+ –Mg exchange coefficient between orthopyroxene and rhyolite melt was investigated with a series of H 2 O fluid-saturated phase-equilibrium experiments. Experiments were conducted in a rapid-quench cold-seal pressure vessel over a temperature and pressure range of 785–850 °C and 80–185 MPa, respectively. Oxygen fugacity was buffered with the solid Ni–NiO assemblage in a double-capsule assembly. These experiments, when combined with H 2 O-undersaturated experiments in the literature, show that Fe 2 + - Mg K D between orthopyroxene and rhyolite liquid increases strongly (from 0.23 to 0.54) as a function of dissolved water in the melt (from 2.7 to 5.6 wt%). There is no detectable effect of temperature or pressure over an interval of 65 °C and 100 MPa, respectively, on the Fe 2+ –Mg exchange coefficient values. The data show that Fe-rich orthopyroxene is favored at high water contents, whereas Mg-rich orthopyroxene crystallizes at low water contents. It is proposed that the effect of dissolved water in the melt on the composition of orthopyroxene is analogous to its effect on the composition of plagioclase. In the latter case, dissolved hydroxyl groups preferentially complex with Na + relative to Ca 2+ , which reduces the activity of the albite component, leading to a more anorthite-rich (calcic) plagioclase. Similarly, it is proposed that dissolved hydroxyl groups preferentially complex with Mg 2+ relative to Fe 2+ , thus lowering the activity of the enstatite component, leading to a more Fe-rich orthopyroxene at high water contents in the melt. The experimental results presented in this study show that reversely zoned pyroxene (i.e., Mg-rich rims) in silicic magmas may be a result of H 2 O degassing and not necessarily the result of mixing with a more mafic magma.

(ProQuest: ... denotes formulae and/or non-USASCII text omitted; see image) The effect of temperature, pressure, and dissolved H2O in the melt on the Fe2+–Mg exchange coefficient between orthopyroxene and rhyolite melt was investigated with a series of H2O fluid-saturated phase-equilibrium experiments. Experiments were conducted in a rapid-quench cold-seal pressure vessel over a temperature and pressure range of 785–850 °C and 80–185 MPa, respectively. Oxygen fugacity was buffered with the solid Ni–NiO assemblage in a double-capsule assembly. These experiments, when combined with H2O-undersaturated experiments in the literature, show that ... between orthopyroxene and rhyolite liquid increases strongly (from 0.23 to 0.54) as a function of dissolved water in the melt (from 2.7 to 5.6 wt%). There is no detectable effect of temperature or pressure over an interval of 65 °C and 100 MPa, respectively, on the Fe2+–Mg exchange coefficient values. The data show that Fe-rich orthopyroxene is favored at high water contents, whereas Mg-rich orthopyroxene crystallizes at low water contents. It is proposed that the effect of dissolved water in the melt on the composition of orthopyroxene is analogous to its effect on the composition of plagioclase. In the latter case, dissolved hydroxyl groups preferentially complex with Na+ relative to Ca2+, which reduces the activity of the albite component, leading to a more anorthite-rich (calcic) plagioclase. Similarly, it is proposed that dissolved hydroxyl groups preferentially complex with Mg2+ relative to Fe2+, thus lowering the activity of the enstatite component, leading to a more Fe-rich orthopyroxene at high water contents in the melt. The experimental results presented in this study show that reversely zoned pyroxene (i.e., Mg-rich rims) in silicic magmas may be a result of H2O degassing and not necessarily the result of mixing with a more mafic magma.

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.

The autosomal dominant spinocerebellar ataxias (SCAs) are a diverse group of neurological disorders anchored by the phenotypes of motor incoordination and cerebellar atrophy. Disease heterogeneity is appreciated through varying comorbidities: dysarthria, dysphagia, oculomotor and/or retinal abnormalities, motor neuron pathology, epilepsy, cognitive impairment, autonomic dysfunction, and psychiatric manifestations. Our study focuses on SCA13, which is caused by several allelic variants in the voltage-gated potassium channel KCNC3 (Kv3.3). We detail the clinical phenotype of four SCA13 kindreds that confirm causation of the KCNC3R423H allele. The heralding features demonstrate congenital onset with non-progressive, neurodevelopmental cerebellar hypoplasia and lifetime improvement in motor and cognitive function that implicate compensatory neural mechanisms. Targeted expression of human KCNC3R423H in Drosophila triggers aberrant wing veins, maldeveloped eyes, and fused ommatidia consistent with the neurodevelopmental presentation of patients. Furthermore, human KCNC3R423H expression in mammalian cells results in altered glycosylation and aberrant retention of the channel in anterograde and/or endosomal vesicles. Confirmation of the absence of plasma membrane targeting was based on the loss of current conductance in cells expressing the mutant channel. Mechanistically, genetic studies in Drosophila, along with cellular and biophysical studies in mammalian systems, demonstrate the dominant negative effect exerted by the mutant on the wild-type (WT) protein, which explains dominant inheritance. We demonstrate that ocular co-expression of KCNC3R423H with Drosophila epidermal growth factor receptor (dEgfr) results in striking rescue of the eye phenotype, whereas KCNC3R423H expression in mammalian cells results in aberrant intracellular retention of human epidermal growth factor receptor (EGFR). Together, these results indicate that the neurodevelopmental consequences of KCNC3R423H may be mediated through indirect effects on EGFR signaling in the developing cerebellum. Our results therefore confirm the KCNC3R423H allele as causative for SCA13, through a dominant negative effect on KCNC3WT and links with EGFR that account for dominant inheritance, congenital onset, and disease pathology.