Dehydration of subducting slow-spread oceanic lithosphere in the Lesser Antilles

Subducting slabs carry water into the mantle and are a major gateway in the global geochemical water cycle. Fluid transport and release can be constrained with seismological data. Here we use joint active-source/local-earthquake seismic tomography to derive unprecedented constraints on multi-stage fluid release from subducting slow-spread oceanic lithosphere. We image the low P-wave velocity crustal layer on the slab top and show that it disappears beneath 60–100 km depth, marking the depth of dehydration metamorphism and eclogitization. Clustering of seismicity at 120–160 km depth suggests that the slab’s mantle dehydrates beneath the volcanic arc, and may be the main source of fluids triggering arc magma generation. Lateral variations in seismic properties on the slab surface suggest that serpentinized peridotite exhumed in tectonized slow-spread crust near fracture zones may increase water transport to sub-arc depths. This results in heterogeneous water release and directly impacts earthquakes generation and mantle wedge dynamics

ICAR: endoscopic skull‐base surgery

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Targeting the Biophysical Properties of the Myeloma Initiating Cell Niches: A Pharmaceutical Synergism Analysis Using Multi-Scale Agent-Based Modeling

<div><p>Multiple myeloma, the second most common hematological cancer, is currently incurable due to refractory disease relapse and development of multiple drug resistance. We and others recently established the biophysical model that myeloma initiating (stem) cells (MICs) trigger the stiffening of their niches <i>via</i> SDF-1/CXCR4 paracrine; The stiffened niches then promote the colonogenesis of MICs and protect them from drug treatment. In this work we examined <i>in silico</i> the pharmaceutical potential of targeting MIC niche stiffness to facilitate cytotoxic chemotherapies. We first established a multi-scale agent-based model using the Markov Chain Monte Carlo approach to recapitulate the niche stiffness centric, pro-oncogenetic positive feedback loop between MICs and myeloma-associated bone marrow stromal cells (MBMSCs), and investigated the effects of such intercellular chemo-physical communications on myeloma development. Then we used AMD3100 (to interrupt the interactions between MICs and their stroma) and Bortezomib (a recently developed novel therapeutic agent) as representative drugs to examine if the biophysical properties of myeloma niches are drugable. Results showed that our model recaptured the key experimental observation that the MBMSCs were more sensitive to SDF-1 secreted by MICs, and provided stiffer niches for these initiating cells and promoted their proliferation and drug resistance. Drug synergism analysis suggested that AMD3100 treatment undermined the capability of MICs to modulate the bone marrow microenvironment, and thus re-sensitized myeloma to Bortezomib treatments. This work is also the first attempt to virtually visualize in 3D the dynamics of the bone marrow stiffness during myeloma development. In summary, we established a multi-scale model to facilitate the translation of the niche-stiffness centric myeloma model as well as experimental observations to possible clinical applications. We concluded that targeting the biophysical properties of stem cell niches is of high clinical potential since it may re-sensitize tumor initiating cells to chemotherapies and reduce risks of cancer relapse.</p></div

The SCUBA-2 Cosmology Legacy Survey: 850um maps, catalogues and number counts

We present a catalogue of ∼3,000 submillimetre sources detected (≥3.5σ) at 850μm over ∼5 deg2 surveyed as part of the James Clerk Maxwell Telescope (JCMT) SCUBA-2 Cosmology Legacy Survey (S2CLS). This is the largest survey of its kind at 850μm, increasing the sample size of 850-μm-selected submillimetre galaxies by an order of magnitude. The wide 850μm survey component of S2CLS covers the extragalactic fields: UKIDSS-UDS, COSMOS, Akari-NEP, Extended Groth Strip, Lockman Hole North, SSA22 and GOODS-North. The average 1σ depth of S2CLS is 1.2 mJy beam−1, approaching the SCUBA-2 850μm confusion limit, which we determine to be σc ≈ 0.8 mJy beam−1. We measure the 850μm number counts, reducing the Poisson errors on the differential counts to approximately 4% at S850 ≈ 3 mJy. With several independent fields, we investigate field-to-field variance, finding that the number counts on 0.5–1° scales are generally within 50% of the S2CLS mean for S850 &gt; 3 mJy, with scatter consistent with the Poisson and estimated cosmic variance uncertainties, although there is a marginal (2σ) density enhancement in GOODS-North. The observed counts are in reasonable agreement with recent phenomenological and semi-analytic models, although determining the shape of the faint end slope (S850 &lt; 3 mJy) remains a key test. The large solid angle of S2CLS allows us to measure the bright-end counts: at S850 &gt; 10 mJy there are approximately ten sources per square degree, and we detect the distinctive up-turn in the number counts indicative of the detection of local sources of 850μm emission, and strongly lensed high-redshift galaxies. All calibrated maps and the catalogue are made publicly available