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  • 1
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    Myofibrillar instability exacerbated by acute exercise in filaminopathy (2015)
    Oxford University Press
    Details
    Publication Date: 2015-12-01
    Description: Filamin C ( FLNC ) mutations in humans cause myofibrillar myopathy (MFM) and cardiomyopathy, characterized by protein aggregation and myofibrillar degeneration. We generated the first patient-mimicking knock-in mouse harbouring the most common disease-causing filamin C mutation (p.W2710X). These heterozygous mice developed muscle weakness and myofibrillar instability, with formation of filamin C- and Xin-positive lesions streaming between Z-discs. These lesions, which are distinct from the classical MFM protein aggregates by their morphology and filamentous appearance, were greatly increased in number upon acute physical exercise in the mice. This pathology suggests that mutant filamin influences the mechanical stability of myofibrillar Z-discs, explaining the muscle weakness in mice and humans. Re-evaluation of biopsies from MFM-filaminopathy patients with different FLNC mutations revealed a similar, previously unreported lesion pathology, in addition to the classical protein aggregates, and suggested that structures previously interpreted as aggregates may be in part sarcomeric lesions. We postulate that these lesions define preclinical disease stages, preceding the formation of protein aggregates.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 2
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    Preparation, hydrothermal stability and thermal adsorption storage properties of binderless zeolite beads (2012)
    Oxford University Press
    Details
    Publication Date: 2012-11-09
    Description: Novel binderless zeolite beads of types A and X have been synthesized and characterized by scanning electron microscopy, mercury intrusion, nitrogen adsorption, thermogravimetry, water adsorption isotherm measurements, cyclic hydrothermal treatments and storage tests. The binderless molecular sieves show an improved adsorption capacity, sufficient hydrothermal stability, higher specific energies and the potential for a better performance density of the storage. Both open and closed storage tests have shown comparable adsorption capacities and specific energies for the binderless molecular sieves. A significantly higher discharging temperature, however, could be realized with the open storage system.
    Print ISSN: 1748-1317
    Electronic ISSN: 1748-1325
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Published by Oxford University Press
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  • 3
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    Benchmarking NAPL redirection and matrix entry at fracture intersections below the water table (2019)
    Wiley
    Details
    Publication Date: 2019
    Description: Abstract This paper examines a numerical modeling approach for two‐phase flow and considers the contribution of a simple network of fracture intersections to the whole discrete fracture‐matrix (DFM) flow system; it develops a benchmark problem for a non‐wetting, dense, nonaqueous phase liquid (DNAPL) invading a water‐saturated, discretely fractured, porous medium near a fracture intersection under cases of DNAPL redirection at the intersection, breakthrough to a constricted fracture branch, or breakthrough into the rock matrix using capillary entry pressures. Numerical simulation is performed with a multiphase, compositional, DFM software, using a finite difference discretization of the governing equations. In these simulation cases, the “star‐delta” method for eliminating line‐ and point‐control volumes at fracture intersections is contrasted to retaining all control volumes, the goal of which is to test the efficacy of the star‐delta simplification. Flux over the domain's boundaries and mass storage are comparison metrics. Results indicate that conduits (or lack thereof) have a strong effect on NAPL architecture with an accompanying change in efflux in the case of redirection; they have some early‐time effects on architecture and efflux in constricted fracture cases. The conceptual scenario presented herein leads to multiphase flow forecasts in intersection conduits which can serve as an experimentally testable hypothesis and as a benchmark for comparisons of simulator forecasts.
    Print ISSN: 0043-1397
    Electronic ISSN: 1944-7973
    Topics: Architecture, Civil Engineering, Surveying , Geography
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 4
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    Monolithic microfabricated valves and pumps by multilayer soft lithography (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-02-07
    Description: Soft lithography is an alternative to silicon-based micromachining that uses replica molding of nontraditional elastomeric materials to fabricate stamps and microfluidic channels. We describe here an extension to the soft lithography paradigm, multilayer soft lithography, with which devices consisting of multiple layers may be fabricated from soft materials. We used this technique to build active microfluidic systems containing on-off valves, switching valves, and pumps entirely out of elastomer. The softness of these materials allows the device areas to be reduced by more than two orders of magnitude compared with silicon-based devices. The other advantages of soft lithography, such as rapid prototyping, ease of fabrication, and biocompatibility, are retained.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Unger, M A -- Chou, H P -- Thorsen, T -- Scherer, A -- Quake, S R -- DA-9121/DA/NIDA NIH HHS/ -- NS-11756/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2000 Apr 7;288(5463):113-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10753110" target="_blank"〉PubMed〈/a〉
    Keywords: Adhesiveness ; *Biocompatible Materials ; Elasticity ; Materials Testing ; Pressure ; *Prostheses and Implants ; *Silicone Elastomers
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    Native GABA(B) receptors are heteromultimers with a family of auxiliary subunits (2010)
    Nature Publishing Group (NPG)
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    Publication Date: 2010-04-20
    Description: GABA(B) receptors are the G-protein-coupled receptors for gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain. They are expressed in almost all neurons of the brain, where they regulate synaptic transmission and signal propagation by controlling the activity of voltage-gated calcium (Ca(v)) and inward-rectifier potassium (K(ir)) channels. Molecular cloning revealed that functional GABA(B) receptors are formed by the heteromeric assembly of GABA(B1) with GABA(B2) subunits. However, cloned GABA(B(1,2)) receptors failed to reproduce the functional diversity observed with native GABA(B) receptors. Here we show by functional proteomics that GABA(B) receptors in the brain are high-molecular-mass complexes of GABA(B1), GABA(B2) and members of a subfamily of the KCTD (potassium channel tetramerization domain-containing) proteins. KCTD proteins 8, 12, 12b and 16 show distinct expression profiles in the brain and associate tightly with the carboxy terminus of GABA(B2) as tetramers. This co-assembly changes the properties of the GABA(B(1,2)) core receptor: the KCTD proteins increase agonist potency and markedly alter the G-protein signalling of the receptors by accelerating onset and promoting desensitization in a KCTD-subtype-specific manner. Taken together, our results establish the KCTD proteins as auxiliary subunits of GABA(B) receptors that determine the pharmacology and kinetics of the receptor response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schwenk, Jochen -- Metz, Michaela -- Zolles, Gerd -- Turecek, Rostislav -- Fritzius, Thorsten -- Bildl, Wolfgang -- Tarusawa, Etsuko -- Kulik, Akos -- Unger, Andreas -- Ivankova, Klara -- Seddik, Riad -- Tiao, Jim Y -- Rajalu, Mathieu -- Trojanova, Johana -- Rohde, Volker -- Gassmann, Martin -- Schulte, Uwe -- Fakler, Bernd -- Bettler, Bernhard -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 May 13;465(7295):231-5. doi: 10.1038/nature08964. Epub 2010 Apr 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Physiology II, University of Freiburg, Engesserstrasse 4, 79108 Freiburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20400944" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Electric Conductivity ; GABA-B Receptor Agonists ; Heterotrimeric GTP-Binding Proteins/metabolism ; Kinetics ; Mice ; Multiprotein Complexes/*chemistry/*metabolism ; Neurons/metabolism ; Oocytes/metabolism ; Potassium/metabolism ; Potassium Channels/metabolism ; *Protein Multimerization ; Protein Structure, Tertiary ; Protein Subunits/*chemistry/*metabolism ; Rats ; Rats, Wistar ; Receptors, GABA-B/*chemistry/*metabolism ; Signal Transduction ; Xenopus
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 6
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    The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-02-21
    Description: Tumour metastasis is the primary cause of mortality in cancer patients and remains the key challenge for cancer therapy. New therapeutic approaches to block inhibitory pathways of the immune system have renewed hopes for the utility of such therapies. Here we show that genetic deletion of the E3 ubiquitin ligase Cbl-b (casitas B-lineage lymphoma-b) or targeted inactivation of its E3 ligase activity licenses natural killer (NK) cells to spontaneously reject metastatic tumours. The TAM tyrosine kinase receptors Tyro3, Axl and Mer (also known as Mertk) were identified as ubiquitylation substrates for Cbl-b. Treatment of wild-type NK cells with a newly developed small molecule TAM kinase inhibitor conferred therapeutic potential, efficiently enhancing anti-metastatic NK cell activity in vivo. Oral or intraperitoneal administration using this TAM inhibitor markedly reduced murine mammary cancer and melanoma metastases dependent on NK cells. We further report that the anticoagulant warfarin exerts anti-metastatic activity in mice via Cbl-b/TAM receptors in NK cells, providing a molecular explanation for a 50-year-old puzzle in cancer biology. This novel TAM/Cbl-b inhibitory pathway shows that it might be possible to develop a 'pill' that awakens the innate immune system to kill cancer metastases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Paolino, Magdalena -- Choidas, Axel -- Wallner, Stephanie -- Pranjic, Blanka -- Uribesalgo, Iris -- Loeser, Stefanie -- Jamieson, Amanda M -- Langdon, Wallace Y -- Ikeda, Fumiyo -- Fededa, Juan Pablo -- Cronin, Shane J -- Nitsch, Roberto -- Schultz-Fademrecht, Carsten -- Eickhoff, Jan -- Menninger, Sascha -- Unger, Anke -- Torka, Robert -- Gruber, Thomas -- Hinterleitner, Reinhard -- Baier, Gottfried -- Wolf, Dominik -- Ullrich, Axel -- Klebl, Bert M -- Penninger, Josef M -- W 1101/Austrian Science Fund FWF/Austria -- England -- Nature. 2014 Mar 27;507(7493):508-12. doi: 10.1038/nature12998. Epub 2014 Feb 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria. ; Lead Discovery Center GmbH, D-44227 Dortmund, Germany. ; Medical University Innsbruck, 6020 Innsbruck, Austria. ; Department of Microbiology and Immunology, Brown University, Providence, Rhode Island 02912, USA. ; School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, Western Australia 6009, Perth, Australia. ; Max-Planck, Institute for Biochemistry, Department of Molecular Biology, D-82152 Martinsried, Germany. ; 1] Medical University Innsbruck, 6020 Innsbruck, Austria [2] Internal Medicine III, University Hospital Bonn, 53127 Bonn, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24553136" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/deficiency/genetics/*metabolism ; Animals ; Anticoagulants/pharmacology/therapeutic use ; Female ; Killer Cells, Natural/drug effects/*immunology/metabolism ; Male ; Mammary Neoplasms, Experimental/drug therapy/genetics/immunology/*pathology ; Melanoma, Experimental/drug therapy/genetics/immunology/*pathology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neoplasm Metastasis/drug therapy/*immunology/prevention & control ; Proto-Oncogene Proteins/antagonists & inhibitors/metabolism ; Proto-Oncogene Proteins c-cbl/deficiency/genetics/*metabolism ; Receptor Protein-Tyrosine Kinases/antagonists & inhibitors/*metabolism ; Ubiquitin-Protein Ligases/deficiency/genetics/*metabolism ; Ubiquitination ; Warfarin/pharmacology/therapeutic use
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 7
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    Impact of eliminating fracture intersection nodes in multiphase compositional flow simulation (2017)
    Wiley
    Details
    Publication Date: 2017-03-17
    Description: Algebraic elimination of nodes at discrete fracture intersections via the star-delta technique has proven to be a valuable tool for making multiphase numerical simulations more tractable and efficient. This study examines the assumptions of the star-delta technique and exposes its effects in a 3D, multiphase context for advective and dispersive/diffusive fluxes. Key issues of relative permeability-saturation-capillary pressure ( k r -S-P c ) and capillary barriers at fracture-fracture intersections are discussed. This study uses a multiphase compositional, finite difference numerical model in discrete fracture network (DFN) and discrete fracture-matrix (DFM) modes. It verifies that the numerical model replicates analytical solutions and performs adequately in convergence exercises (conservative and decaying tracer, one- and two-phase flow, DFM and DFN domains). The study culminates in simulations of a two-phase laboratory experiment in which a fluid invades a simple fracture intersection. The experiment and simulations evoke different invading fluid flow paths by varying fracture apertures as oil invades water-filled fractures and as water invades air-filled fractures. Results indicate that the node elimination technique as implemented in numerical model correctly reproduces the long-term flow path of the invading fluid, but that short-term temporal effects of the capillary traps and barriers arising from the intersection node are lost. This article is protected by copyright. All rights reserved.
    Print ISSN: 0043-1397
    Electronic ISSN: 1944-7973
    Topics: Architecture, Civil Engineering, Surveying , Geography
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 8
    Electronic Resource
    Electronic Resource
    Time for a career called full-time research?
    Amsterdam : Elsevier
    Trends in Biochemical Sciences 5 (1980), S. I-II 
    Details
    ISSN: 0968-0004
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/0968-0004(80)90244-3
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  • 9
    Electronic Resource
    Electronic Resource
    Reproduzierbare Gradientenchromatographie an Kolonnen mit schrumpfenden Austauschern
    Amsterdam : Elsevier
    Journal of Chromatography A 40 (1969), S. 318-321 
    Details
    ISSN: 0021-9673
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/S0021-9673(01)96670-1
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  • 10
    Electronic Resource
    Electronic Resource
    Reproduzierbare Gradientenchromatographie an Kolonnen mit schrumpfenden Austauschern
    Amsterdam : Elsevier
    Journal of Chromatography A 40 (1969), S. 318-321 
    Details
    ISSN: 0021-9673
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/S0021-9673(01)96670-1
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