NMR quality control of fragment libraries for screening

Fragment-based screening has evolved as a remarkable approach within the drug discovery process both in the industry and academia. Fragment screening has become a more structure-based approach to inhibitor development, but also towards development of pathway-specific clinical probes. However, it is often witnessed that the availability, immediate and long-term, of a high quality fragment-screening library is still beyond the reach of most academic laboratories. Within iNEXT (Infrastructure for NMR, EM and X-rays for Translational research), a EU-funded Horizon 2020 program, a collection of 782 fragments were assembled utilizing the concept of "poised fragments" with the aim to facilitate downstream synthesis of ligands with high affinity by fragment ligation. Herein, we describe the analytical procedure to assess the quality of this purchased and assembled fragment library by NMR spectroscopy. This quality assessment requires buffer solubility screening, comparison with LC/MS quality control and is supported by state-of-the-art software for high throughput data acquisition and on-the-fly data analysis. Results from the analysis of the library are presented as a prototype of fragment progression through the quality control process

The <i>Castalia</i> mission to Main Belt Comet 133P/Elst-Pizarro

We describe Castalia, a proposed mission to rendezvous with a Main Belt Comet (MBC), 133P/Elst-Pizarro. MBCs are a recently discovered population of apparently icy bodies within the main asteroid belt between Mars and Jupiter, which may represent the remnants of the population which supplied the early Earth with water. Castalia will perform the first exploration of this population by characterising 133P in detail, solving the puzzle of the MBC’s activity, and making the first in situ measurements of water in the asteroid belt. In many ways a successor to ESA’s highly successful Rosetta mission, Castalia will allow direct comparison between very different classes of comet, including measuring critical isotope ratios, plasma and dust properties. It will also feature the first radar system to visit a minor body, mapping the ice in the interior. Castalia was proposed, in slightly different versions, to the ESA M4 and M5 calls within the Cosmic Vision programme. We describe the science motivation for the mission, the measurements required to achieve the scientific goals, and the proposed instrument payload and spacecraft to achieve these

Synergies between interstellar dust and heliospheric science with an interstellar probe

We discuss the synergies between heliospheric and dust science, the open science questions, the technological endeavours, and programmatic aspects that are important to maintain or develop in the decade to come. In particular, we illustrate how we can use interstellar dust in the solar system as a tracer for the (dynamic) heliosphere properties, and emphasize the fairly unexplored, but potentially important science question of the role of cosmic dust in heliospheric and astrospheric physics. We show that an interstellar probe mission with a dedicated dust suite would bring unprecedented advances to interstellar dust research, and can also contribute – through measuring dust – to heliospheric science. This can, in particular, be done well if we work in synergy with other missions inside the solar system, thereby using multiple vantage points in space to measure the dust as it ‘rolls’ into the heliosphere. Such synergies between missions inside the solar system and far out are crucial for disentangling the spatially and temporally varying dust flow. Finally, we highlight the relevant instrumentation and its suitability for contributing to finding answers to the research questions

Sierra Gorda 009: A New Member of the Metal-Rich G Chondrites Grouplet

We investigated the metal-rich chondrite Sierra Gorda (SG) 009, a member of the new G chondrite grouplet (also including NWA 5492, GRO 95551). G chondrites contain 23% metal, very reduced silicates, and rare oxidized mineral phases (Mg-chromite, FeO-rich pyroxene). G chondrites are not related to CH-CB chondrites, based on bulk O, C, and N isotopic compositions, mineralogy, and geochemistry. G chondrites have no fine-grained matrix or matrix lumps enclosing hydrated material typical for CH-CB chondrites. G chondrites’ average metal compositions are similar to H chondrites. Siderophile and lithophile geochemistry indicates sulfidization and fractionation of the SG 009 metal and silicates, unlike NWA 5492 and GRO 95551. The G chondrites have average O isotopic compositions Δ17O'0‰ ranging between bulk enstatite (E) and ordinary (O) chondrites. An Al-rich chondrule from SG 009 has Δ17O'0‰ indicating some heterogeneity in oxygen isotopic composition of G chondrite components. SG 009’s bulk carbon and nitrogen isotopic compositions correspond to E and O chondrites. Neon isotopic composition reflects a mixture of cosmogenic and solar components, and cosmic ray exposure age of SG 009 is typical for O, E, and R chondrites. G chondrites are closely related to O, E, and R chondrites and may represent a unique metal-rich parent asteroid containing primitive and fractionated material from the inner solar system. Oxidizing and reducing conditions during SG 009 formation may be connected with a chemical microenvironment and possibly could indicate that G chondrites may have formed by a planetesimal collision resulting in the lack of matrix. © The Meteoritical Society, 2020.We thank M. Weisberg, H. Downes, an anonymous reviewer, and Associate Editor C. Goodrich, for their thoughtful reviews which helped to improve this paper. The authors thank Sasha Krot for very fruitful discussions. This work was supported by the Russian Fond of Basic Research no. 20-05-00117A, by Klaus Tschira Stiftung gGmbH, by the NASA Emerging Worlds program (80NSSC18K0595, MH), and we thank the National High Magnetic Field Laboratory, which is supported by National Science Foundation Cooperative Agreement No. DMR-1644779* and the State of Florida. This work was also supported?by the Project No. FEUZ-2020-0059 of the Ministry of Science and Higher Education of the Russian Federation. This study was a partial contribution to research theme no. 0137-2019-0002

Geology, geochemistry and earthquake history of Lō`ihi Seamount, Hawai`i

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Chemie der Erde - Geochemistry 66 (2006): 81-108, doi:10.1016/j.chemer.2005.09.002.A half century of investigations are summarized here on the youngest Hawaiian volcano, Lō`ihi Seamount. It was discovered in 1952 following an earthquake swarm. Surveying in 1954 determined it has an elongate shape, which is the meaning of its Hawaiian name. Lō`ihi was mostly forgotten until two earthquake swarms in the 1970’s led to a dredging expedition in 1978, which recovered young lavas. This led to numerous expeditions to investigate the geology, geophysics, and geochemistry of this active volcano. Geophysical monitoring, including a realtime submarine observatory that continuously monitored Lō`ihi’s seismic activity for three months, captured some of the volcano’s earthquake swarms. The 1996 swarm, the largest recorded in Hawai`i, was preceded by at least one eruption and accompanied by the formation of a ~300-m deep pit crater, renewing interest in this submarine volcano. Seismic and petrologic data indicate that magma was stored in a ~8-9 km deep reservoir prior to the 1996 eruption. Studies on Lō`ihi have altered conceptual models for the growth of Hawaiian and other oceanic island volcanoes and led to a refined understanding of mantle plumes. Petrologic and geochemical studies of Lō`ihi lavas showed that the volcano taps a relatively primitive part of the Hawaiian plume, producing a wide range of magma compositions. These compositions have become progressively more silica-saturated with time reflecting higher degrees of partial melting as the volcano drifts towards the center of the hotspot. Seismic and bathymetric data have highlighted the importance of landsliding in the early formation of an ocean island volcano. Lō`ihi’s internal structure and eruptive behavior, however, cannot be fully understood without installing monitoring equipment directly on the volcano. The presence of hydrothermal activity at Lō`ihi was initially proposed based on nontronite deposits on dredged samples that indicated elevated temperatures (31oC), and on the detection of water temperature, methane and 3He anomalies, and clumps of benthic micro-organisms in the water column over the volcano in 1982. Submersible observations in 1987 confirmed a low temperature system (15-30oC) prior to the 1996 formation of Pele’s Pit. The sulfide mineral assemblage (wurtzite, pyrrhotite, and chalcopyrite) deposited after the pit crater collapsed are consistent with hydrothermal fluids >250oC. Vent temperatures have decreased to ~60oC during the 2004 dive season indicating the current phase of hydrothermal activity may be waning.This work was supported by a NSF grant to M. Garcia (OCE 97-29894)

The Castalia mission to Main Belt Comet 133P/Elst-Pizarro

We describe Castalia, a proposed mission to rendezvous with a Main Belt Comet (MBC), 133P/Elst-Pizarro. MBCs are a recently discovered population of apparently icy bodies within the main asteroid belt between Mars and Jupiter, which may represent the remnants of the population which supplied the early Earth with water. Castalia will perform the first exploration of this population by characterising 133P in detail, solving the puzzle of the MBC's activity, and making the first in situ measurements of water in the asteroid belt. In many ways a successor to ESA's highly successful Rosetta mission, Castalia will allow direct comparison between very different classes of comet, including measuring critical isotope ratios, plasma and dust properties. It will also feature the first radar system to visit a minor body, mapping the ice in the interior. Castalia was proposed, in slightly different versions, to the ESA M4 and M5 calls within the Cosmic Vision programme. We describe the science motivation for the mission, the measurements required to achieve the scientific goals, and the proposed instrument payload and spacecraft to achieve these

Late accretion of Ceres-like asteroids and their implantation into the outer main belt

International audienc

Noble gas composition, cosmic-ray exposure age, ³⁹Ar-⁴⁰Ar, and I-Xe analyses of ungrouped achondrite NWA 7325

Northwest Africa (NWA) 7325 is an anomalous achondrite that experienced episodes of large‐degree melt extraction and interaction with melt under reducing conditions. Its composition led to speculations about a Mercurian origin and provoked a series of studies of this meteorite. We present the noble gas composition, and results of 40Ar/39Ar and 129I‐129Xe studies of whole rock splits of NWA 7325. The light noble gases are dominated by cosmogenic isotopes. 21Ne and 38Ar cosmic‐ray exposure ages are 25.6 and 18.9 Ma, respectively, when calculated with a nominal whole rock composition. This 38Ar age is in reasonable agreement with a cosmic‐ray exposure age of 17.5 Ma derived in our 40Ar/39Ar dating study. Due to the low K‐content of 19 ± 1 ppm and high Ca‐content of approximately 12.40 ± 0.15 wt%, no reliable 40Ar/39Ar age could be determined. The integrated age strongly depends on the choice of an initial 40Ar/36Ar ratio. An air‐like component is dominant in lower temperature extractions and assuming air 40Ar/36Ar for the trapped component results in a calculated integrated age of 3200 ± 260 (1σ) Ma. This may represent the upper age limit for a major reheating event affecting the K‐Ar system. Results of 129I‐129Xe dating give no useful chronological information, i.e., no isochron is observed. Considering the highest 129Xe*/128XeI ratio as equivalent to a lower age limit, we calculate an I‐Xe age of about 4536 Ma. In addition, elevated 129Xe/132Xe ratios of up to 1.65 ± 0.18 in higher temperature extractions indicate an early formation of NWA 7325, with subsequent disturbance of the I‐Xe system

He–Ne–Ar–N₂–CO₂ Systematics of Fernando de Noronha Mantle Xenoliths: Confirmation of Mantle Plume Origin

The Fernando de Noronha archipelago (southwest Atlantic, 345 km from the coast of Brazil) is considered as the result of mantle plume activity. However, data on the isotopic composition of helium and neon, which are, perhaps, the only unambiguous geochemical criterion for deep mantle plumes have not been published yet for the region. In this paper, we present the first data on the isotopic composition of helium, neon, argon, and nitrogen, obtained by stepwise crushing of mantle xenoliths from the basanites of the San José Formation. The results obtained may indicate that fluid inclusions contain the very first portions of the exsolved gases—they are ultra-depleted in helium in relation to neon and especially argon. This conclusion is also supported by He–Ar–CO2 systematics. The isotopic composition of helium (4He/3He = 31 879 ± 6796) and neon (21Ne/22Ne(mantle) = 0.0453 ± 0.0012) indicates that it was indeed a mantle plume, identical in noble gas composition to the Kerguelen plume. According to the Ar–Ne isotope systematics 40Ar/36Ar (mantle) = 7455 ± 2290. Nitrogen is characterized by a heavy isotopic composition (δ15N = +5.4 ± 0.2‰), which corresponds to the hypothesis of the subduction nature of nitrogen in deep mantle plumes