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| 1 | Three-dimensional FDEM numerical simulation of failure processes observed in Opalinus Clay laboratory samples显示文摘This study presents the first step of a research project that aims at using a three-dimensional(3D) hybrid finite-discrete element method(FDEM) to investigate the development of an excavation damaged zone(EDZ) around tunnels in a clay shale formation known as Opalinus Clay. The 3D FDEM was first calibrated against standard laboratory experiments, including Brazilian disc test and uniaxial compression test. The effect of increasing confining pressure on the mechanical response and fracture propagation of the rock was quantified under triaxial compression tests. Polyaxial(or true triaxial) simulations highlighted the effect of the intermediate principal stress(s2) on fracture directions in the model: as the intermediate principal stress increased, fractures tended to align in the direction parallel to the plane defined by the major and intermediate principal stresses. The peak strength was also shown to vary with changing σ2. | Omid Mahabadi Patrick Kaifosh Paul Marschall Tim Vietor | 2014 | Journal of Rock Mechanics and Geotechnical Engineering2014，6，6： | 10 |
| 2 | Efficacy and Safety of the Farnesoid X Receptor Agonist Obeticholic Acid in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease显示文摘 | Sunder Mudaliar Robert R. Henry Arun J. Sanyal Linda Morrow Hanns-Ulrich Marschall Mark Kipnes Luciano Adorini Cathi I. Sciacca Paul Clopton Erin Castelloe Paul Dillon Mark Pruzanski David Shapiro | 2013 | Gastroenterology2013，，： | 7 |
| 3 | Analysis of ileal sodium/bile acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic bile acid malabsorption显示文摘The etiology of most cases of idiopathic bile acid malabsorption (IBAM) is unknown. In this study, a Swedish family with bile acid malabsorption in three consecutive generations was screened for mutations in the ileal apical sodium-bile acid cotransporter gene (ASBT; gene symbol, SLC10A2) and in the genes for several of the nuclear receptors known to be important for ASBT expression: the farnesoid X receptor (FXR) and peroxisome proliferator activated receptor alpha (PPARa). The patients presented with a clinical history of idiopathic chronic watery diarrhea, which was responsive to cholestyramine treatment and consistent with IBAM. Bile acid absorption was determined using 75Se-homocholic acid taurine (SeHCAT); bile acid synthesis was estimated by measuring the plasma levels of 7a-hydroxy-4-cholesten-3-one (C4). The ASBT, FXR, and PPARa genes in the affected and unaffected family members were analyzed using single stranded conformation polymorphism (SSCP), denaturing HPLC, and direct sequencing. No ASBT mutations were identified and the ASBT gene did not segregate withthe bile acid malabsorption phenotype. Similarly, no mutations or polymorphisms were identified in the FXR or PPARa genes associated with the bile acid malabsorption phenotype. These studies indicate that the intestinal bile acid malabsorption in these patients cannot be attributed to defects in ASBT. In the absence of apparent ileal disease, alternative explanations such as accelerated transit through the small intestine may be responsible for the IBAM. | Marco Montagnani Anna Abrahamsson Cecilia Glman Gsta Eggertsen Hanns-Ulrich Marschall Elisa Ravaioli Curt Einarsson Paul A Dawson | 2006 | World Journal of Gastroenterology2006，12，47： | 1 |
| 4 | Analysis of flow path around the sealing section HG-A experiment in the Mont Terri Rock Laboratory显示文摘 | Wenjie Xu Hua Shao Paul Marschall Jürgen Hesser Olaf Kolditz | 2013 | Environmental Earth Sciences2013，，7： | 1 |
| 5 | K_(2P)18.1 translates T cell receptor signals into thymic regulatory T cell development显示文摘It remains largely unclear how thymocytes translate relative differences in T cell receptor(TCR)signal strength into distinct developmental programs that drive the cell fate decisions towards conventional(Tconv)or regulatory T cells(Treg).Following TCR activation,intracellular calcium(Ca^(2+))is the most important second messenger,for which the potassium channel K_(2P)18.1 is a relevant regulator.Here,we identify K_(2P)18.1 as a central translator of the TCR signal into the thymus-derived Treg(tTreg)selection process.TCR signal was coupled to NF-κB-mediated K_(2P)18.1 upregulation in tTreg progenitors.K_(2P)18.1 provided the driving force for sustained Ca^(2+) influx that facilitated NF-κB-and NFAT-dependent expression of FoxP3,the master transcription factor for Treg development and function.Loss of K_(2P)18.1 ion-current function induced a mild lymphoproliferative phenotype in mice,with reduced Treg numbers that led to aggravated experimental autoimmune encephalomyelitis,while a gain-of-function mutation in K_(2P)18.1 resulted in increased Treg numbers in mice.Our findings in human thymus,recent thymic emigrants and multiple sclerosis patients with a dominant-negative missense K_(2P)18.1 variant that is associated with poor clinical outcomes indicate that K_(2P)18.1 also plays a role in human Treg development.Pharmacological modulation of K_(2P)18.1 specifically modulated Treg numbers in vitro and in vivo.Finally,we identified nitroxoline as a K_(2P)18.1 activator that led to rapid and reversible Treg increase in patients with urinary tract infections.Conclusively,our findings reveal how K_(2P)18.1 translates TCR signals into thymic T cell fate decisions and Treg development,and provide a basis for the therapeutic utilization of Treg in several human disorders. | Tobias Ruck Stefanie Bock Steffen Pfeuffer Christina B.Schroeter Derya Cengiz Paul Marciniak Maren Lindner Alexander Herrmann Marie Liebmann Stjepana Kovac Lukas Gola Leoni Rolfes Marc Pawlitzki Nils Opel Tim Hahn Udo Dannlowski Thomas Pap Felix Luessi Julian A.Schreiber Bernhard Wunsch Tanja Kuhlmann Guiscard Seebohm Bjorn Tackenberg Patricia Seja Frank Doring Erhard Wischmeyer Achmet Imam Chasan Johannes Roth Luisa Klotz Gerd Meyer zu Hörste Heinz Wiendl Tobias Marschall Stefan Floess Jochen Huehn Thomas Budde Tobias Bopp Stefan Bittner Sven G.Meuth | 2022 | Cell Research2022，32，1： | 1 |
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