Release of mineral-bound water prior to subduction tied to shallow seismogenic slip off Sumatra

Plate-boundary fault rupture during the 2004 Sumatra-Andaman subduction earthquake extended closer to the trench than expected, increasing earthquake and tsunami size. International Ocean Discovery Program Expedition 362 sampled incoming sediments offshore northern Sumatra, revealing recent release of fresh water within the deep sediments. Thermal modeling links this freshening to amorphous silica dehydration driven by rapid burial-induced temperature increases in the past 9 million years. Complete dehydration of silicates is expected before plate subduction, contrasting with prevailing models for subduction seismogenesis calling for fluid production during subduction. Shallow slip offshore Sumatra appears driven by diagenetic strengthening of deeply buried fault-forming sediments, contrasting with weakening proposed for the shallow Tohoku-Oki 2011 rupture, but our results are applicable to other thickly sedimented subduction zones including those with limited earthquake records

Voice to Vision VI: Tsitsernakaberd

University of Minnesota Center for Holocaust and Genocide Studies. University of Minnesota Department of Art.University of Minnesota: Grant-in-Aid of Research and The Imagine Fund; Armenian Cultural Organization of Minnesota; Rimon: The Minnesota Jewish Arts Council; The Howard B. Brin Jewish Arts Endowmen

Voice to Vision VI: Children of Survivors: A Strong New Branch

University of Minnesota Center for Holocaust and Genocide Studies. University of Minnesota Department of Art.University of Minnesota: Undergraduate Research Opportunities Program (UROP), CLA Freshman Research and Creative Awards Program, Imagine Gran

Identification of Highly Promising Antioxidants/Neuroprotectants Based on Nucleoside 5′-Phosphorothioate Scaffold. Synthesis, Activity, and Mechanisms of Action

With a view to identify novel and biocompatible neuroprotectants, we designed nucleoside 5′-thiophosphate analogues, <b>6</b>–<b>11</b>. We identified 2-SMe-ADP­(α-S), <b>7A</b>, as a most promising neuroprotectant. <b>7A</b> reduced ROS production in PC12 cells under oxidizing conditions, IC₅₀ of 0.08 vs 21 μM for ADP. Furthermore, <b>7A</b> rescued primary neurons subjected to oxidation, EC₅₀ of 0.04 vs 19 μM for ADP. <b>7A</b> is a most potent P2Y₁-R agonist, EC₅₀ of 0.0026 μM. Activity of <b>7A</b> in cells involved P2Y_1/12-R as indicated by blocking P2Y₁₂-R or P2Y₁-R. Compound <b>7A</b> inhibited Fenton reaction better than EDTA, IC₅₀ of 37 vs 54 μM, due to radical scavenging, IC₅₀ of 12.5 vs 30 μM for ADP, and Fe­(II)-chelation, IC₅₀ of 80 vs >200 μM for ADP (ferrozine assay). In addition, <b>7A</b> was stable in human blood serum, <i>t</i>_1/2 of 15 vs 1.5 h for ADP, and resisted hydrolysis by NPP1/3, 2-fold vs ADP. Hence, we propose <b>7A</b> as a highly promising neuroprotectant

Highly Potent and Selective Ectonucleotide Pyrophosphatase/Phosphodiesterase I Inhibitors Based on an Adenosine 5′-(α or γ)-Thio-(α,β- or β,γ)-methylenetriphosphate Scaffold

Aberrant nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) activity is associated with chondrocalcinosis, osteoarthritis, and type 2 diabetes. The potential of NPP1 inhibitors as therapeutic agents, and the scarceness of their structure–activity relationship, encouraged us to develop new NPP1 inhibitors. Specifically, we synthesized ATP-α-thio-β,γ-CH₂ (<b>1</b>), ATP-α-thio-β,γ-CCl₂ (<b>2</b>), ATP-α-CH₂-γ-thio (<b>3</b>), and 8-SH-ATP (<b>4</b>) and established their resistance to hydrolysis by NPP1,3 and NTPDase1,2,3,8 (<5% hydrolysis) (NTPDase = ectonucleoside triphosphate diphosphohydrolase). Analogues <b>1</b>–<b>3</b> at 100 μM inhibited thymidine 5′-monophosphate <i>p</i>-nitrophenyl ester hydrolysis by NPP1 and NPP3 by >90% and 23–43%, respectively, and only slightly affected (0–40%) hydrolysis of ATP by NTPDase1,2,3,8. Analogue <b>3</b> is the most potent NPP1 inhibitor currently known, <i>K</i>_i = 20 nM and IC₅₀ = 0.39 μM. Analogue <b>2a</b> is a selective NPP1 inhibitor with <i>K</i>_i = 685 nM and IC₅₀ = 0.57 μM. Analogues <b>1</b>–<b>3</b> were found mostly to be nonagonists of P2Y₁/P2Y₂/P2Y₁₁ receptors. Docking analogues <b>1</b>–<b>3</b> into the NPP1 model suggested that activity correlates with the number of H-bonds with binding site residues. In conclusion, we propose analogues <b>2a</b> and <b>3</b> as highly promising NPP1 inhibitors

The role of input materials in shallow seismogenic slip and forearc plateau development

Drilling the input materials of the north Sumatran subduction zone, part of the 5000 km long Sunda subduction zone system and the origin of the Mw ∼9.2 earthquake and tsunami that devastated coastal communities around the Indian Ocean in 2004, was designed to groundtruth the material properties causing unexpectedly shallow seismogenic slip and a distinctive forearc prism structure. The intriguing seismogenic behavior and forearc structure are not well explained by existing models or by relationships observed at margins where seismogenic slip typically occurs farther landward. The input materials of the north Sumatran subduction zone are a distinctively thick (as thick as 4-5 km) succession of primarily Bengal-Nicobar Fan-related sediments. The correspondence between the 2004 rupture location and the overlying prism plateau, as well as evidence for a strengthened input section, suggest the input materials are key to driving the distinctive slip behavior and long-term forearc structure. During Expedition 362, two sites on the Indian oceanic plate ∼250 km southwest of the subduction zone, Sites U1480 and U1481, were drilled, cored, and logged to a maximum depth of 1500 meters below seafloor. The succession of sediment/rocks that will develop into the plate boundary detachment and will drive growth of the forearc were sampled, and their progressive mechanical, frictional, and hydrogeological property evolution will be analyzed through postcruise experimental and modeling studies. Large penetration depths with good core recovery and successful wireline logging in the challenging submarine fan materials will enable evaluation of the role of thick sedimentar y subduction zone input sections in driving shallow slip and amplifying earthquake and tsunami magnitudes, at the Sunda subduction zone and globally at other subduction zones where submarine fan-influenced sections are being subducted