An analytical model of layered continuous beams with partial interaction

Schnabl, Simon,Planinc, Igor,Saje, Miran,Cas, Bojan,Turk, Goran Techno-Press 2006 Structural Engineering and Mechanics, An Int'l Jou Vol.22 No.3

Starting with the geometrically non-linear formulation and the subsequent linearization, this paper presents a consistent formulation of the exact mechanical analysis of geometrically and materially linear three-layer continuous planar beams. Each layer of the beam is described by the geometrically linear beam theory. Constitutive laws of layer materials and relationships between interlayer slips and shear stresses at the interface are assumed to be linear elastic. The formulation is first applied in the analysis of a three-layer simply supported beam. The results are compared to those of Goodman and Popov (1968) and to those obtained from the formulation of the European code for timber structures, Eurocode 5 (1993). Comparisons show that the present and the Goodman and Popov (1968) results agree completely, while the Eurocode 5 (1993) results differ to a certain degree. Next, the analytical solution is used in formulating a general procedure for the analysis of layered continuous beams. The applications show the qualitative and quantitative effects of the layer and the interlayer slip stiffnesses on internal forces, stresses and deflections of composite continuous beams.

Interactive Interface between Gut Microbiome and Immunome in Alcohol- Related Liver Disease

( Bernd Schnabl ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Alcohol-associated intestinal dysbiosis and bacterial overgrowth can lead to a dysregulation of tryptophan metabolism and lower production of indoles. Several of these indole derivatives are aryl hydrocarbon receptor ligands that, in turn, are involved in antimicrobial defense via induction of interleukin-22 (IL-22). IL-22 increases the expression of intestinal Reg3 lectins, which maintain low bacterial colonization of the inner mucus layer and reduce bacterial translocation to the liver. Chronic alcohol consumption is associated with reduced intestinal expression of the Reg3b and Reg3g, increased numbers of mucosa-associated bacteria and bacterial translocation. Translocated microbial products and viable bacteria reach the liver and activate the innate immune system. Release of inflammatory molecules promotes inflammation, contributes to hepatocyte death and results in a fibrotic response. This talk summarizes the mechanisms by which chronic alcohol intake changes the gut microbiota and contributes to alcohol-associated liver disease by changing microbial-derived metabolites.

An analytical model of layered continuous beams with partial interaction

Simon Schnabl,Igor Planinc,Miran Saje,Bojan Cas,Goran Turk 국제구조공학회 2006 Structural Engineering and Mechanics, An Int'l Jou Vol.22 No.3

Analytical modelling of multilayer beams with compliant interfaces

Skec, L.,Schnabl, S.,Planinc, I.,Jelenic, G. Techno-Press 2012 Structural Engineering and Mechanics, An Int'l Jou Vol.44 No.4

Different mathematical models are proposed and their analytical solutions derived for the analysis of linear elastic Reissner's multilayer beams. The models take into account different combinations of contact plane conditions, different material properties of individual layers, different transverse shear deformations of each layer, and different boundary conditions of the layers. The analytical studies are carried out to evaluate the influence of different contact conditions on the static and kinematic quantities. A considerable difference of the results between the models is obtained.

Degradation of buckling capacity of slender concrete-filled double skin steel tubular columns due to interface compliance

Bojan Čas,Simon Schnabl 국제구조공학회 2022 Structural Engineering and Mechanics, An Int'l Jou Vol.82 No.5

In this paper a novel mathematical model and its analytical solution of global buckling behaviour of slender elastic concrete-filled double-skin tubular (CFDST) columns with finite compliance between the steel tubes and a sandwiched concrete core is derived for the first time. The model is capable of investigating the influence of various basic parameters on critical buckling loads of CFDST columns. It is shown that the elastic buckling load of circular and slender CFDST columns is independent on longitudinal contact stiffness, but, on the other hand, it can be considerably dependent on circumferential contact stiffness. The increasing of the circumferential contact stiffness increases the critical buckling load. Furthermore, it is shown that analytical results can agree well with the experimental and numerical results if the calibrated values of circumferential contact stiffness are used in the calculations. Moreover, it is shown that the contact between the steel tubes and a sandwiched concrete core of tested large-scale CFDST columns used in the comparison is relatively weak. Finally, the proposed analytical results can be used as a benchmark solution.

Analytical modelling of multilayer beams with compliant interfaces

L. Škec,S. Schnabl,I. Planinc,G. Jelenic 국제구조공학회 2012 Structural Engineering and Mechanics, An Int'l Jou Vol.44 No.4

Different mathematical models are proposed and their analytical solutions derived for the analysis of linear elastic Reissner’s multilayer beams. The models take into account different combinations of contact plane conditions, different material properties of individual layers, different transverse shear deformations of each layer, and different boundary conditions of the layers. The analytical studies are carried out to evaluate the influence of different contact conditions on the static and kinematic quantities. A considerable difference of the results between the models is obtained.

Host-Microbiome Interactions in Alcoholic Liver Disease

( Peng Chen ),( Bernd Schnabl ) 대한소화기학회 2014 Gut and Liver Vol.8 No.3

Alcoholic liver disease is a leading cause of morbidity and liver-related death worldwide. Intestinal bacterial overgrowth and dysbiosis induced by ethanol ingestion play an important role in the pathogenesis of alcoholic liver disease. After exposure to alcohol in the lumen, enteric bacteria alter their metabolism and thereby disturb intestinal homeostasis. Disruption of the mucosal barrier results in the translocation of microbial products that contribute to liver disease by inducing hepatic inflammation. In this review, we will discuss the effects of alcohol on the intestinal microbiome, and in particular, its effects on bacterial metabolism, bacterial translocation and ecological balance. A better understanding of the interactions among alcohol, the host and the microbiome will reveal new targets for therapy and lead to new treatments.

From intestinal dysbiosis to alcohol-associated liver disease

Beatriz Garcia Mendes,Bernd Schnabl 대한간학회 2020 Clinical and Molecular Hepatology(대한간학회지) Vol.26 No.4

Alcohol-associated intestinal dysbiosis and bacterial overgrowth can lead to a dysregulation of tryptophan metabolism and lower production of indoles. Several of these indole derivatives are aryl hydrocarbon receptor ligands that, in turn, are involved in antimicrobial defense via induction of interleukin-22 (IL-22). IL-22 increases the expression of intestinal regenerating islet-derived 3 (Reg3) lectins, which maintain low bacterial colonization of the inner mucus layer and reduce bacterial translocation to the liver. Chronic alcohol consumption is associated with reduced intestinal expression of Reg3β and Reg3γ, increased numbers of mucosa-associated bacteria and bacterial translocation. Translocated microbial products and viable bacteria reach the liver and activate the innate immune system. Release of inflammatory molecules promotes inflammation, contributes to hepatocyte death and results in a fibrotic response. This review summarizes the mechanisms by which chronic alcohol intake changes the gut microbiota and contributes to alcohol-associated liver disease by changing microbial-derived metabolites.

Gliotoxin-mediated apoptosis of activated human hepatic stellate cells

Kweon, Young-Oh,Paik, Yong-Han,Schnabl, Bernd,Qian, Ting,Lemasters, John J.,Brenner, David A. 경북대학교 병원 2003 경북대학교병원의학연구소논문집 Vol.7 No.1

Background: Activated hepatic stellate cells(HSCs) play a central role in liver fibrogenesis, and apoptosis of activated HSCs might be essential to clear HSCs from injured liver. Gliotoxin induces apoptosis of activated human and rat HSCs by an unknown mechanism. Aim: This study investigated the role of reactive oxygen species(ROS) and membrane permeability transition(MPT) in gliotoxin-induced apoptosis of activated human HSCs. Methods: Primary and immortalized human HSCs were analyzed using confocal microscopy for ROS with dichlorodihdrofluorescence diacetate(DCFH-DA) fluorophore and for the mitochoudrial membrane potential(MMP) using tetramethylrhodamine methylester(TMRM). Results: Gliotoxin at higher concentrations(≥7.5μM) markedly increased ROS formation, and ROS production was also evident at concentrations of gliotoxin causing necrotic cell death(≥32.5μM). Gliotoxin rapidly(begins about 20min at 1.5μM and 10min at 7.5μM) disrupts MMP at a concentration as low as 300nM. MMP disruption was followed by cytochrome c release and caspase-3 activation. The MPT inhibitors, cyclosporine A(5μM) plus trifluoperazine(12.5μM), blocked depolarization of the mitochondrial membrane and release of cytochrome c, but did not block apoptosis in HSCs. Conclusions: Gliotoxin(0.3-7.5μM) induces apoptosis of activated human HSCs with induction of MPT, cytochrome c release and caspase-3 activation, whereas at higher doses(>325.μM), it induces necrosis. However, gliotoxin also activates a mitochondrial independent pathway.

The nicotinamide adenine dinucleotide phosphate oxidase (NOX) homologues NOX1 and NOX2/gp91^phox mediate hepatic fibrosis in mice

Paik, Yong‐,Han,Iwaisako, Keiko,Seki, Ekihiro,Inokuchi, Sayaka,Schnabl, Bernd,Ö,sterreicher, Christoph H.,Kisseleva, Tatiana,Brenner, David A. Wiley Subscription Services, Inc., A Wiley Company 2011 Hepatology Vol.53 No.5

<P><B>Abstract</B></P><P>Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is a multicomponent enzyme that mediates electron transfer from nicotinamide adenine dinucleotide phosphate to molecular oxygen, which leads to the production of superoxide. NOX2/gp91<SUP>phox</SUP> is a catalytic subunit of NOX expressed in phagocytic cells. Several homologues of NOX2, including NOX1, have been identified in nonphagocytic cells. We investigated the contributory role of NOX1 and NOX2 in hepatic fibrosis. Hepatic fibrosis was induced in wild‐type (WT) mice, NOX1 knockout (NOX1KO) mice, and NOX2 knockout (NOX2KO) mice by way of either carbon tetrachloride (CCl<SUB>4</SUB>) injection or bile duct ligation (BDL). The functional contribution of NOX1 and NOX2 in endogenous liver cells, including hepatic stellate cells (HSCs), and bone marrow (BM)‐derived cells, including Kupffer cells (KCs), to hepatic reactive oxygen species (ROS) generation and hepatic fibrosis was assessed <I>in vitro</I> and <I>in vivo</I> using NOX1 or NOX2 BM chimeric mice. Hepatic NOX1 and NOX2 messenger RNA expression was increased in the two experimental mouse models of hepatic fibrosis. Whereas NOX1 was expressed in HSCs but not in KCs, NOX2 was expressed in both HSCs and KCs. Hepatic fibrosis and ROS generation were attenuated in both NOX1KO and NOX2KO mice after CCl<SUB>4</SUB> or BDL. Liver fibrosis in chimeric mice indicated that NOX1 mediates the profibrogenic effects in endogenous liver cells, whereas NOX2 mediates the profibrogenic effects in both endogenous liver cells and BM‐derived cells. Multiple NOX1 and NOX2 components were up‐regulated in activated HSCs. Both NOX1‐ and NOX2‐deficient HSCs had decreased ROS generation and failed to up‐regulate collagen α1(I) and transforming growth factor β in response to angiotensin II. <I>Conclusion:</I> Both NOX1 and NOX2 have an important role in hepatic fibrosis in endogenous liver cells, including HSCs, whereas NOX2 has a lesser role in BM‐derived cells. (H<SMALL>EPATOLOGY</SMALL> 2011;)</P>