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  • Geological Society of America (GSA)  (1)
  • Nature Publishing Group (NPG)  (1)
  • Cambridge University Press
  • Periodicals Archive Online (PAO)
  • 2010-2014  (2)
  • 1
    Publication Date: 2014-04-19
    Description: Chemically zoned minerals are useful records of temporal variations in ambient conditions and bulk chemical composition of the fluid from which the minerals precipitate. In fluid-buffered systems, zoning of mineral compositions is expected to reflect directly the evolution of fluid composition. Here we show that during rapid fluid-rock reactions, ultra-local equilibrium can form complex mineral zoning patterns, even when the overall system is highly fluid buffered. We reacted cleaved calcite single crystals with aqueous arsenate-phosphate solutions with molar ratios of As/(As + P) between 0.01 and 0.15 at 250 °C and water-saturated pressure. We find that complex zoning patterns and solid solution between hydroxylapatite- and arsenate-bearing hydroxylapatite that pseudomorphically replaced calcite formed within hours, and these zoning patterns were destroyed within days during secondary reactions. We propose a two-stage reaction process in the formation of the final reaction product. (1) On an hour time scale, calcite is dissolved and replaced by compositionally heterogeneous apatite. The thin reaction-interface fluid layer becomes extremely enriched in arsenic at an ultra-local scale as the reaction removes phosphate faster than the interface fluid can re-equilibrate with the bulk fluid. (2) The heterogeneous apatite is replaced by homogeneous apatite that reflects the bulk fluid composition over a longer (days) time scale through interface-coupled dissolution-precipitation. This paper highlights the complexity that can arise from ultra-local fluid composition variations due to rapid fluid-rock interaction in a short-lived fluid flow event, for example during a seismic cycle. Subsequent interpretation of complex zoning patterns as reflecting the evolution of bulk fluid would be erroneous.
    Print ISSN: 0091-7613
    Electronic ISSN: 1943-2682
    Topics: Geosciences
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  • 2
    Publication Date: 2014-06-12
    Description: Inhibitors against the p110delta isoform of phosphoinositide-3-OH kinase (PI(3)K) have shown remarkable therapeutic efficacy in some human leukaemias. As p110delta is primarily expressed in leukocytes, drugs against p110delta have not been considered for the treatment of solid tumours. Here we report that p110delta inactivation in mice protects against a broad range of cancers, including non-haematological solid tumours. We demonstrate that p110delta inactivation in regulatory T cells unleashes CD8(+) cytotoxic T cells and induces tumour regression. Thus, p110delta inhibitors can break tumour-induced immune tolerance and should be considered for wider use in oncology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501086/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501086/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ali, Khaled -- Soond, Dalya R -- Pineiro, Roberto -- Hagemann, Thorsten -- Pearce, Wayne -- Lim, Ee Lyn -- Bouabe, Hicham -- Scudamore, Cheryl L -- Hancox, Timothy -- Maecker, Heather -- Friedman, Lori -- Turner, Martin -- Okkenhaug, Klaus -- Vanhaesebroeck, Bart -- 095691/Wellcome Trust/United Kingdom -- 095691/Z/11/Z/Wellcome Trust/United Kingdom -- 12888/Cancer Research UK/United Kingdom -- 14355/Cancer Research UK/United Kingdom -- A10200/Cancer Research UK/United Kingdom -- A12888/Cancer Research UK/United Kingdom -- A15965/Cancer Research UK/United Kingdom -- BB/E009867/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- C18270/A12888/Cancer Research UK/United Kingdom -- C23338/A10200/Cancer Research UK/United Kingdom -- C23338/A15965/Cancer Research UK/United Kingdom -- England -- Nature. 2014 Jun 19;510(7505):407-11. doi: 10.1038/nature13444. Epub 2014 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street London WC1E 6DD, UK [2]. ; 1] Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK [2] [3]. ; Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. ; UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street London WC1E 6DD, UK. ; Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK. ; Mary Lyon Centre, MRC Harwell, Harwell Science and Innovation Campus, Harwell OX11 0RD, UK. ; Piramed Pharma, 957 Buckingham Avenue, Slough, Berkshire SL1 4NL, UK. ; Cancer Signaling and Translational Oncology, Genentech Inc, 1 DNA Way, South San Francisco, California 94080-4990, USA. ; 1] Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24919154" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/pharmacology ; Enzyme Activation/drug effects ; Enzyme Inhibitors/*pharmacology ; Immune Tolerance/*drug effects/immunology ; Mice ; Neoplasms/*enzymology/*immunology ; Phosphatidylinositol 3-Kinases/*metabolism ; T-Lymphocytes, Regulatory/*drug effects/enzymology/immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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