Time scales of magma transport and mixing at Kīlauea Volcano, Hawai'i

Modelling of volcanic processes is strongly limited by a poor knowledge of the timescales of storage, mixing and final ascent of magmas into the shallowest portions of volcanic 'plumbing' systems immediately prior to eruption. It is impossible to measure these timescales directly; however, micro-analytical techniques provide indirect estimates based on the extent of diffusion of species through melts and crystals. Here, diffusion in olivine phenocrysts from the 1959 Kīlauea Iki eruption is used to constrain the timing of mixing events in the crustal plumbing system on timescales of months to years before eruption. The timescales derived from zonation of Fe-Mg in olivines, combined with contemporaneous geophysical data suggests mixing occurred on 3 timescales: (1) up to 2 years prior to eruption in the deep storage system, (2), in a shallow reservoir, between incoming hot melts and cooler, resident melt for several weeks to months prior to eruption, and (3), in the conduit and summit reservoir, between the resident magma and cooled surface lava, draining back into the vent on timescales of hours to several days during pauses between episodes. Synchronous inflation of the shallow reservoir with deep earthquake swarms and mixing suggests a fitfully open transcrustal magmatic system prior to and during eruption.We acknowledge NERC studentship funds (I. Sides) and a United States Geological Survey Jack Kleinman grant, which allowed samples for this study to be collected.This is the final version of the article. It first appeared from the Geological Society of America via https://doi.org/10.1130/G37800.

Analysis of the Ex Vivo and In Vivo Antiretroviral Activity of Gemcitabine

Replication of retroviral and host genomes requires ribonucleotide reductase to convert rNTPs to dNTPs, which are then used as substrates for DNA synthesis. Inhibition of ribonucleotide reductase by hydroxyurea (HU) has been previously used to treat cancers as well as HIV. However, the use of HU as an antiretroviral is limited by its associated toxicities such as myelosuppression and hepatotoxicity. In this study, we examined the ribonucleotide reductase inhibitor, gemcitabine, both in cell culture and in C57Bl/6 mice infected with LP-BM5 murine leukemia virus (LP-BM5 MuLV, a murine AIDS model). Gemcitabine decreased infectivity of MuLV in cell culture with an EC50 in the low nanomolar range with no detectable cytotoxicity. Similarly, gemcitabine significantly decreased disease progression in mice infected with LP-BM5. Specifically, gemcitabine treatment decreased spleen size, plasma IgM, and provirus levels compared to LP-BM5 MuLV infected, untreated mice. Gemcitabine efficacy was observed at doses as low as 1 mg/kg/day in the absence of toxicity. Higher doses of gemcitabine (3 mg/kg/day and higher) were associated with toxicity as determined by a loss in body mass. In summary, our findings demonstrate that gemcitabine has antiretroviral activity ex vivo and in vivo in the LP-BM5 MuLV model. These observations together with a recent ex vivo study with HIV-1[1], suggest that gemcitabine has broad antiretroviral activity and could be particularly useful in vivo when used in combination drug therapy