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Sample records for nash korrespondent tatjana

  1. Gidon Kremer ja Tatjana Grindenko : vana arm ei roosteta! / Tatjana Grindenko ; interv. Aleksandra Moorast

    Index Scriptorium Estoniae

    Grindenko, Tatjana

    2007-01-01

    Viiuldajatest Gidon Kremerist ja Tatjana Grindenkost. Kontserdist Tallinna Polütehnilise Instituudi aulas 30 aasta eest. Kontserdist "Jubilate: Gidon Kremer 60 ja Kremerata Baltica 10" 11. veebr. Estonia kontserdisaalis

  2. Empaatiline helilooja Tatjana Kozlova / Mirje Mändla

    Index Scriptorium Estoniae

    Mändla, Mirje

    2011-01-01

    26. veebruaril Eesti muusika päevade ja programmi "Tallinn - Euroopa kultuuripealinn 2011" raames Salme kultuurikeskuses toimunud Tatjana Kozlova autorikontserdist, kus kaasa tegid Annamaria Morini (flööt, Itaalia), Enzo Porta (viiul, Itaalia) ja ansambel Resonabilis

  3. Molecular Pathogenesis of NASH

    Directory of Open Access Journals (Sweden)

    Alessandra Caligiuri

    2016-09-01

    Full Text Available Nonalcoholic steatohepatitis (NASH is the main cause of chronic liver disease in the Western world and a major health problem, owing to its close association with obesity, diabetes, and the metabolic syndrome. NASH progression results from numerous events originating within the liver, as well as from signals derived from the adipose tissue and the gastrointestinal tract. In a fraction of NASH patients, disease may progress, eventually leading to advanced fibrosis, cirrhosis and hepatocellular carcinoma. Understanding the mechanisms leading to NASH and its evolution to cirrhosis is critical to identifying effective approaches for the treatment of this condition. In this review, we focus on some of the most recent data reported on the pathogenesis of NASH and its fibrogenic progression, highlighting potential targets for treatment or identification of biomarkers of disease progression.

  4. Non-commutative Nash inequalities

    International Nuclear Information System (INIS)

    Kastoryano, Michael; Temme, Kristan

    2016-01-01

    A set of functional inequalities—called Nash inequalities—are introduced and analyzed in the context of quantum Markov process mixing. The basic theory of Nash inequalities is extended to the setting of non-commutative L p spaces, where their relationship to Poincaré and log-Sobolev inequalities is fleshed out. We prove Nash inequalities for a number of unital reversible semigroups

  5. "Hello!" from Crosby and Nash

    CERN Multimedia

    CERN Bulletin

    2015-01-01

    On Tuesday, 29 September, American musicians David Crosby and Graham Nash visited CERN. They also recorded a video message, commenting on their visit and sending their greetings and thanks to CERN's people.   (Video: Christoph M. Madsen/CERN.) David Crosby, Graham Nash, and Stephen Stills have played together for over 30 years in the Crosby, Stills and Nash folk rock band. Originally, together with Neil Young, they were all members of the Crosby, Stills, Nash and Young band, having played at the iconic Woodstock Festival and produced many legendary songs such as Teach Your Children, Judy Blue Eyes, Our House and Marrakech Express. ​

  6. Nonalcoholic Fatty Liver Disease & NASH

    Science.gov (United States)

    ... Eating, Diet, & Nutrition Clinical Trials Wilson Disease Nonalcoholic Fatty Liver Disease & NASH View or Print All Sections Definition & Facts Nonalcoholic fatty liver disease (NAFLD) is a condition in which fat ...

  7. Tallinna ajalugu Rootsi aja teisel poolel / Otto Liiv ; koost. Tatjana Shor

    Index Scriptorium Estoniae

    Liiv, Otto, 1905-1942

    1996-01-01

    Tallinna halduslikust korraldusest. Sisepoliitiline areng ja välispilt, majanduslik olukord Karl X ja Karl XII valitsemise ajal, usu-, haridus- ja kombeelu, eestlus Tallinnas hilisel Rootsi ajal ning Tallinna vallutamine Põhjasõja ajal venelaste poolt. Lisaks ka Otto Liivi bibliograafia lk. 63-78, koost. Shori, Tatjana

  8. Miks tulite e-õppe konverentsile? / Tia Vene, Tatjana Guž, Eha Kaukveer...[jt.

    Index Scriptorium Estoniae

    2009-01-01

    Konverentsist " Õppijalt õppijale". Küsimusele vastavad: Kallavere Keskkooli algklassiõpetaja Tia Vene, Lasnamäe Põhikooli inglise keele õpetaja Tatjana Guž, Tallinna Päikesejänku lasteaia õpetaja Eha Kaukveer, Pelgulinna Gümnaasiumi IT-arendusjuht, arvutiõpetaja Birgit Lorenz ja Haapsalu Sanatoorse Internaatkooli õpetaja Villu Baumann

  9. The Creative Genius: John Nash

    Indian Academy of Sciences (India)

    IAS Admin

    the Nobel Prize in Economic Sciences in 2007 and whose textbook on game theory is a classic. The celebrated journalist ... in electrical engineering from Texas A&M University, served in France during World War I and .... In 2015, the Norwegian Academy of Sciences and Letters awarded the Abel Prize to Nash and Louis.

  10. Game Theory-Nash Equilibrium

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 3; Issue 7. Game Theory - Nash Equilibrium. P G Babu. General Article Volume 3 Issue 7 July 1998 pp 53- ... Author Affiliations. P G Babu1. Indira Gandhi Institute of Development Research Gen. A K Vaidya Marg Goregaon(East) Mumbai 400 065, India.

  11. The Creative Genius: John Nash

    Indian Academy of Sciences (India)

    IAS Admin

    longer because Nash equilibrium is standard vocabulary; every mathematician knows what it means. While he published ... University) in Pittsburg, on a George Westinghouse Scholarship, and started his BS in chemical engineering. He soon switched to chemistry and subsequently, to mathematics major. Because of his.

  12. Nash equilibrium with lower probabilities

    DEFF Research Database (Denmark)

    Groes, Ebbe; Jacobsen, Hans Jørgen; Sloth, Birgitte

    1998-01-01

    We generalize the concept of Nash equilibrium in mixed strategies for strategic form games to allow for ambiguity in the players' expectations. In contrast to other contributions, we model ambiguity by means of so-called lower probability measures or belief functions, which makes it possible...... to distinguish between a player's assessment of ambiguity and his attitude towards ambiguity. We also generalize the concept of trembling hand perfect equilibrium. Finally, we demonstrate that for certain attitudes towards ambiguity it is possible to explain cooperation in the one-shot Prisoner's Dilemma...

  13. Nash Social Welfare in Multiagent Resource Allocation

    NARCIS (Netherlands)

    S. Ramezani (Sara); U. Endriss; E. David; E.H. Gerding (Enrico); D. Sarne; O. Shehory (Onn)

    2010-01-01

    htmlabstractWe study different aspects of the multiagent resource allocation problem when the objective is to find an allocation that maximizes Nash social welfare, the product of the utilities of the individual agents. The Nash solution is an important welfare criterion that combines efficiency and

  14. On the Nash Bargaining Solution with Noise

    NARCIS (Netherlands)

    Güth, W.; Ritzberger, K.; van Damme, E.E.C.

    2002-01-01

    Suppose two parties have to share a surplus of random size.Each of the two can either commit to a demand prior to the realization of the surplus - as in the Nash demand game with noise - or remain silent and wait until the surplus was publicly observed.Adding the strategy to wait to the noisy Nash

  15. [Tatjana Niemsch. Reval im 16. Jahrhundert : erfahrungsräumliche Deutungsmuster städtischer Konflikte] / Robert Riemer

    Index Scriptorium Estoniae

    Riemer, Robert

    2015-01-01

    Arvustus: Niemsch, Tatjana. Reval im 16. Jahrhundert : erfahrungsräumliche Deutungsmuster städtischer Konflikte. Frankfurt am Main [etc.] : Lang, 2013. (Kieler Werkstücke. Reihe G, Beiträge zur Frühen Neuzeit ; Bd. 6)

  16. Mida teeb Narva kutseõppekeskus teie arvates Narva linna heaks? / Burkina, Irina; Patlep, Kaarel; Kaalik, Ljubov; Dolgovskaja, Tatjana; Ibragimov, Muret; Vorobjova, Anna

    Index Scriptorium Estoniae

    2007-01-01

    Vastavad Narva Kutseõppekeskuse kutseõpetajad Irina Burkina, Tatjana Dolgovskaja ja Murat Ibragimov ning autovaldkonna juht Kaarel Patlep, projektijuht Ljubov Kaalik ja PR-spetsialist Anna Vorobjova

  17. Nash Equilibria in Fisher Market

    Science.gov (United States)

    Adsul, Bharat; Babu, Ch. Sobhan; Garg, Jugal; Mehta, Ruta; Sohoni, Milind

    Much work has been done on the computation of market equilibria. However due to strategic play by buyers, it is not clear whether these are actually observed in the market. Motivated by the observation that a buyer may derive a better payoff by feigning a different utility function and thereby manipulating the Fisher market equilibrium, we formulate the Fisher market game in which buyers strategize by posing different utility functions. We show that existence of a conflict-free allocation is a necessary condition for the Nash equilibria (NE) and also sufficient for the symmetric NE in this game. There are many NE with very different payoffs, and the Fisher equilibrium payoff is captured at a symmetric NE. We provide a complete polyhedral characterization of all the NE for the two-buyer market game. Surprisingly, all the NE of this game turn out to be symmetric and the corresponding payoffs constitute a piecewise linear concave curve. We also study the correlated equilibria of this game and show that third-party mediation does not help to achieve a better payoff than NE payoffs.

  18. Local Nash equilibrium in social networks.

    Science.gov (United States)

    Zhang, Yichao; Aziz-Alaoui, M A; Bertelle, Cyrille; Guan, Jihong

    2014-08-29

    Nash equilibrium is widely present in various social disputes. As of now, in structured static populations, such as social networks, regular, and random graphs, the discussions on Nash equilibrium are quite limited. In a relatively stable static gaming network, a rational individual has to comprehensively consider all his/her opponents' strategies before they adopt a unified strategy. In this scenario, a new strategy equilibrium emerges in the system. We define this equilibrium as a local Nash equilibrium. In this paper, we present an explicit definition of the local Nash equilibrium for the two-strategy games in structured populations. Based on the definition, we investigate the condition that a system reaches the evolutionary stable state when the individuals play the Prisoner's dilemma and snow-drift game. The local Nash equilibrium provides a way to judge whether a gaming structured population reaches the evolutionary stable state on one hand. On the other hand, it can be used to predict whether cooperators can survive in a system long before the system reaches its evolutionary stable state for the Prisoner's dilemma game. Our work therefore provides a theoretical framework for understanding the evolutionary stable state in the gaming populations with static structures.

  19. Quantum gambling based on Nash-equilibrium

    Science.gov (United States)

    Zhang, Pei; Zhou, Xiao-Qi; Wang, Yun-Long; Liu, Bi-Heng; Shadbolt, Pete; Zhang, Yong-Sheng; Gao, Hong; Li, Fu-Li; O'Brien, Jeremy L.

    2017-06-01

    The problem of establishing a fair bet between spatially separated gambler and casino can only be solved in the classical regime by relying on a trusted third party. By combining Nash-equilibrium theory with quantum game theory, we show that a secure, remote, two-party game can be played using a quantum gambling machine which has no classical counterpart. Specifically, by modifying the Nash-equilibrium point we can construct games with arbitrary amount of bias, including a game that is demonstrably fair to both parties. We also report a proof-of-principle experimental demonstration using linear optics.

  20. The Embedding Theorems of Whitney and Nash

    Indian Academy of Sciences (India)

    IAS Admin

    We begin by briefly motivating the idea of a manifold and then discuss the embedding the- orems of Whitney and Nash that allow us to view these objects inside appropriately large Eu- clidean spaces. 1. Introduction. Let us begin by motivating the concept of a manifold. Start with the unit circle C in the plane given by x2.

  1. The Embedding Theorems of Whitney and Nash

    Indian Academy of Sciences (India)

    We begin by briefly motivating the idea of amanifold and then discuss the embedding theorems of Whitney and Nash that allow us toview these objects inside appropriately large Euclidean spaces. Resonance – Journal of Science Education. Current Issue : Vol. 23, Issue 2. Current Issue Volume 23 | Issue 2. February 2018.

  2. Nash-Williams’ cycle-decomposition theorem

    DEFF Research Database (Denmark)

    Thomassen, Carsten

    2016-01-01

    We give an elementary proof of the theorem of Nash-Williams that a graph has an edge-decomposition into cycles if and only if it does not contain an odd cut. We also prove that every bridgeless graph has a collection of cycles covering each edge at least once and at most 7 times. The two results...

  3. The Embedding Theorems of Whitney and Nash

    Indian Academy of Sciences (India)

    We begin by briefly motivating the idea of amanifold and then discuss the embedding theorems of Whitney and Nash that allow us toview these objects inside appropriately large Euclidean spaces. Resonance – Journal of Science Education. Current Issue : Vol. 23, Issue 4. Current Issue Volume 23 | Issue 4. April 2018.

  4. Data completion problems solved as Nash games

    International Nuclear Information System (INIS)

    Habbal, A; Kallel, M

    2012-01-01

    The Cauchy problem for an elliptic operator is formulated as a two-player Nash game. Player (1) is given the known Dirichlet data, and uses as strategy variable the Neumann condition prescribed over the inaccessible part of the boundary. Player (2) is given the known Neumann data, and plays with the Dirichlet condition prescribed over the inaccessible boundary. The two players solve in parallel the associated Boundary Value Problems. Their respective objectives involve the gap between the non used Neumann/Dirichlet known data and the traces of the BVP's solutions over the accessible boundary, and are coupled through a difference term. We prove the existence of a unique Nash equilibrium, which turns out to be the reconstructed data when the Cauchy problem has a solution. We also prove that the completion algorithm is stable with respect to noise, and present two 3D experiments which illustrate the efficiency and stability of our algorithm.

  5. Nash equilibrium and multi criterion aerodynamic optimization

    Science.gov (United States)

    Tang, Zhili; Zhang, Lianhe

    2016-06-01

    Game theory and its particular Nash Equilibrium (NE) are gaining importance in solving Multi Criterion Optimization (MCO) in engineering problems over the past decade. The solution of a MCO problem can be viewed as a NE under the concept of competitive games. This paper surveyed/proposed four efficient algorithms for calculating a NE of a MCO problem. Existence and equivalence of the solution are analyzed and proved in the paper based on fixed point theorem. Specific virtual symmetric Nash game is also presented to set up an optimization strategy for single objective optimization problems. Two numerical examples are presented to verify proposed algorithms. One is mathematical functions' optimization to illustrate detailed numerical procedures of algorithms, the other is aerodynamic drag reduction of civil transport wing fuselage configuration by using virtual game. The successful application validates efficiency of algorithms in solving complex aerodynamic optimization problem.

  6. Uncovering a Predictive Molecular Signature for the Onset of NASH-Related Fibrosis in a Translational NASH Mouse Model

    NARCIS (Netherlands)

    Koppen, A. van; Verschuren, L.; Hoek, A.M. van den; Verheij, J.; Morrison, M.C.; Li, K.; Nagabukuro, H.; Costessi, A.; Caspers, M.P.M.; Broek, T.J. van den; Sagartz, J.; Kluft, C.; Beysen, C.; Emson, C.; Gool, A.J. van; Goldschmeding, R.; Stoop, R.; Bobeldijk-Pastorova, I.; Turner, S.M.; Hanauer, G.; Hanemaaijer, R.

    2017-01-01

    Background & Aims: The incidence of nonalcoholic steatohepatitis (NASH) is increasing. The pathophysiological mechanisms of NASH and the sequence of events leading to hepatic fibrosis are incompletely understood. The aim of this study was to gain insight into the dynamics of key molecular processes

  7. Nash Equilibria in Theory of Reasoned Action

    Science.gov (United States)

    Almeida, Leando; Cruz, José; Ferreira, Helena; Pinto, Alberto Adrego

    2009-08-01

    Game theory and Decision Theory have been applied to many different areas such as Physics, Economics, Biology, etc. In its application to Psychology, we introduce, in the literature, a Game Theoretical Model of Planned Behavior or Reasoned Action by establishing an analogy between two specific theories. In this study we take in account that individual decision-making is an outcome of a process where group decisions can determine individual probabilistic behavior. Using Game Theory concepts, we describe how intentions can be transformed in behavior and according to the Nash Equilibrium, this process will correspond to the best individual decision/response taking in account the collective response. This analysis can be extended to several examples based in the Game Theoretical Model of Planned Behavior or Reasoned Action.

  8. Nash Stability in Additively Separable Hedonic Games and Community Structures

    DEFF Research Database (Denmark)

    Olsen, Martin

    2009-01-01

      We prove that the problem of deciding whether a Nash stable   partition exists in an Additively Separable Hedonic Game is   NP-complete. We also show that the problem of deciding whether a   non trivial Nash stable partition exists in an   Additively Separable Hedonic Game with   non......-negative and symmetric   preferences is NP-complete. We motivate our study of the   computational complexity by linking Nash stable partitions in   Additively Separable Hedonic Games to community structures in   networks. Our results formally justify that computing community   structures in general is hard....

  9. Uranium uptake of Vetiveria zizanioides (L.) Nash

    International Nuclear Information System (INIS)

    Luu Viet Hung; Maslov, O.D.; Trinh Thi Thu My; Phung Khac Nam Ho; Dang Duc Nhan

    2010-01-01

    Uranium uptake of vetiver grass (Vetiveria zizanioides (L.) Nash) from Eutric Fluvisols (AK), Albic Acrisols (BG), Dystric Fluvisols (HP) and Ferralic Acrisols (TC) in northern Vietnam is assessed. The soils were mixed with aqueous solution of uranyl nitrate to make soils contaminated with uranium at 0, 50, 100, 250 mg/kg before planting the grass. The efficiency of uranium uptake by the grass was assessed based on the soil-to-plant transfer factor (TF U , kg·kg -1 ). It was found that the TF U values are dependent upon the soils properties. CEC facilitates the uptake and the increased soil pH could reduce the uptake and translocation of uranium in the plant. Organic matter content, as well as iron and potassium, inhibits the uranium uptake of the grass. It was revealed that the lower fertile soil, the higher uranium uptake. The translocation of uranium in root for all the soil types studied is almost higher than that in its shoot. It seems that vetiver grass could potentially be used for the purpose of phytoremediation of soils contaminated with uranium

  10. Nash y von Neumann: mundos posibles y juegos de lenguaje

    Directory of Open Access Journals (Sweden)

    Salazar , Boris

    2004-06-01

    Full Text Available Este ensayo emplea las nociones de juego de lenguaje y de equivalencia entre juegos para examinar la decisión de John Nash de no jugar el juego coalicional que propuso John von Neumann. El argumento central es que Nash concibió una clase de mundos posibles incompatible con la de von Neumann, y que en el origen de esa divergencia estarían sus distintas nociones de racionalidad.

  11. Uncovering a Predictive Molecular Signature for the Onset of NASH-Related Fibrosis in a Translational NASH Mouse Model.

    Science.gov (United States)

    van Koppen, Arianne; Verschuren, Lars; van den Hoek, Anita M; Verheij, Joanne; Morrison, Martine C; Li, Kelvin; Nagabukuro, Hiroshi; Costessi, Adalberto; Caspers, Martien P M; van den Broek, Tim J; Sagartz, John; Kluft, Cornelis; Beysen, Carine; Emson, Claire; van Gool, Alain J; Goldschmeding, Roel; Stoop, Reinout; Bobeldijk-Pastorova, Ivana; Turner, Scott M; Hanauer, Guido; Hanemaaijer, Roeland

    2018-01-01

    The incidence of nonalcoholic steatohepatitis (NASH) is increasing. The pathophysiological mechanisms of NASH and the sequence of events leading to hepatic fibrosis are incompletely understood. The aim of this study was to gain insight into the dynamics of key molecular processes involved in NASH and to rank early markers for hepatic fibrosis. A time-course study in low-density lipoprotein-receptor knockout. Leiden mice on a high-fat diet was performed to identify the temporal dynamics of key processes contributing to NASH and fibrosis. An integrative systems biology approach was used to elucidate candidate markers linked to the active fibrosis process by combining transcriptomics, dynamic proteomics, and histopathology. The translational value of these findings were confirmed using human NASH data sets. High-fat-diet feeding resulted in obesity, hyperlipidemia, insulin resistance, and NASH with fibrosis in a time-dependent manner. Temporal dynamics of key molecular processes involved in the development of NASH were identified, including lipid metabolism, inflammation, oxidative stress, and fibrosis. A data-integrative approach enabled identification of the active fibrotic process preceding histopathologic detection using a novel molecular fibrosis signature. Human studies were used to identify overlap of genes and processes and to perform a network biology-based prioritization to rank top candidate markers representing the early manifestation of fibrosis. An early predictive molecular signature was identified that marked the active profibrotic process before histopathologic fibrosis becomes manifest. Early detection of the onset of NASH and fibrosis enables identification of novel blood-based biomarkers to stratify patients at risk, development of new therapeutics, and help shorten (pre)clinical experimental time frames.

  12. Current and future pharmacological therapies for NAFLD/NASH.

    Science.gov (United States)

    Sumida, Yoshio; Yoneda, Masashi

    2018-03-01

    Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and there is no approved pharmacotherapy. The efficacy of vitamin E and pioglitazone has been established in nonalcoholic steatohepatitis (NASH), a progressive form of NAFLD. GLP-1RA and SGLT2 inhibitors, which are currently approved for use in diabetes, have shown early efficacy in NASH, and also have beneficial cardiovascular or renal effects. Innovative NASH therapies include four main pathways. The first approach is targeting hepatic fat accumulation. Medications in this approach include modulation of peroxisome proliferator-activator receptors (e.g., pemafibrate, elafibranor), medications targeting farnesoid X receptor axis [obeticholic acid; OCA)], inhibitors of de novo lipogenesis (aramchol, ACC inhibitor), and fibroblast growth factor-21 analogues. A second target is oxidative stress, inflammation, and apoptosis. This class of drug includes apoptosis signaling kinase 1 (ASK1) inhibitor and emricasan (an irreversible caspase inhibitor). A third target is intestinal microbiomes and metabolic endotoxemia. Several agents are in ongoing trials, including IMMe124, TLR4 antagonist, and solithromycin (macrolide antibiotics). The final target is hepatic fibrosis, which is strongly associated with all-cause or liver-related mortality in NASH. Antifibrotic agents are a cysteine-cysteine motif chemokine receptor-2/5 antagonist (cenicriviroc; CVC) and galectin 3 antagonist. Among a variety of medications in development, four agents such as OCA, elafibranor, ASK1 inhibitor, and CVC are currently being evaluated in an international phase 3 trial for the treatment of NASH. Within the next few years, the availability of therapeutic options for NASH will hopefully curb the rising trend of NASH-related diseases.

  13. Therapy of experimental NASH and fibrosis with galectin inhibitors.

    Directory of Open Access Journals (Sweden)

    Peter G Traber

    Full Text Available Non-alcoholic steatohepatitis (NASH and resultant liver fibrosis is a major health problem without effective therapy. Some data suggest that galectin-3 null mice are resistant to the development of NASH with fibrosis. We examined the ability of two complex carbohydrate drugs that bind galectin-3, GM-CT-01 and GR-MD-02, to treat NASH with fibrosis in a murine model. GR-MD-02 treatment resulted in marked improvement in liver histology with significant reduction in NASH activity and collagen deposition. Treatments seemed also to improve both glomerulopathy and interstitial fibrosis observed in kidneys. The improvement in liver histology was evident when animals were treated early in disease or after establishment of liver fibrosis. In all measures, GM-CT-01 had an intermediate effect between vehicle and GR-MD-02. Galectin-3 protein expression was increased in NASH with highest expression in macrophages surrounding lipid laden hepatocytes, and reduced following treatment with GR-MD-02, while the number of macrophages was unchanged. Treatment with GR-MD-02 also reduced the expression of pathological indicators including iNOS, an important TH1 inflammatory mediator, CD36, a scavenger receptor for lipoproteins on macrophages, and α-smooth muscle actin, a marker for activated stellate cells which are the primary collagen producing cells in liver fibrosis. We conclude that treatment with these galectin-3 targeting drugs improved histopathological findings of NASH and markedly reduced fibrosis in a murine model of NASH. While the mechanisms require further investigation, the treatment effect is associated with a reduction of galectin-3 expressed by activated macrophages which was associated with regression of NASH, including hepatocellular fat accumulation, hepatocyte ballooning, intra-portal and intra-lobular inflammatory infiltrate, and deposition of collagen. Similar effects were found with GM-CT-01, but with approximately four-fold lower potency than

  14. Nash Equilibria in Symmetric Games with Partial Observation

    DEFF Research Database (Denmark)

    Bouyer, Patricia; Markey, Nicolas; Vester, Steen

    2014-01-01

    and symmetry constraints, which make the computation of Nash equilibria difficult. We show several undecidability results, and for bounded-memory strategies, we precisely characterize the complexity of computing pure Nash equilibria (for qualitative objectives) in this game model.......We investigate a model for representing large multiplayer games, which satisfy strong symmetry properties. This model is made of multiple copies of an arena; each player plays in his own arena, and can partially observe what the other players do. Therefore, this game has partial information...

  15. Nash Equilibria in Symmetric Graph Games with Partial Observation

    DEFF Research Database (Denmark)

    Bouyer, Patricia; Markey, Nicolas; Vester, Steen

    2017-01-01

    and symmetry constraints, which make the computation of Nash equilibria difficult. We show several undecidability results, and for bounded-memory strategies, we precisely characterize the complexity of computing pure Nash equilibria for qualitative objectives in this game model.......We investigate a model for representing large multiplayer games, which satisfy strong symmetry properties. This model is made of multiple copies of an arena; each player plays in his own arena, and can partially observe what the other players do. Therefore, this game has partial information...

  16. Muusika : Kaljuste Madalmaade kooriga USAs. Weekend Guitar Trio Lüneburgis. Petrovi koor Iirimaal ja Norras. Poola kvintett Tallinna Raekojas. Esineb Tatjana Smelova. "improvizz'01" Tartus. "Klassikaraadio" Wagnerit avastamas

    Index Scriptorium Estoniae

    2001-01-01

    Tõnu Kaljuste käis Madalmaade kammerkooriga USAs. Weekend Guitar Trio esineb Lüneburgis. Õigeusu Vaimuliku Muusika Kammerkoor Valeri Petrovi juhatusel käis Iirimaal ja Norras esinemas. Poola keelpillikvintett MultiCamerata esines Tallinna Raekojas. Eestis annab kontserte pianist Tatjana Smelova. 8.-10. nov. toimub Tartus "improvizz'01" . "Klassikaraadio" Wagnerit avastamas

  17. Model Checking Coalition Nash Equilibria in MAD Distributed Systems

    Science.gov (United States)

    Mari, Federico; Melatti, Igor; Salvo, Ivano; Tronci, Enrico; Alvisi, Lorenzo; Clement, Allen; Li, Harry

    We present two OBDD based model checking algorithms for the verification of Nash equilibria in finite state mechanisms modeling Multiple Administrative Domains (MAD) distributed systems with possibly colluding agents (coalitions) and with possibly faulty or malicious nodes (Byzantine agents). Given a finite state mechanism, a proposed protocol for each agent and the maximum sizes f for Byzantine agents and q for agents collusions, our model checkers return PASS if the proposed protocol is an ɛ-f-q-Nash equilibrium, i.e. no coalition of size up to q may have an interest greater than ɛ in deviating from the proposed protocol when up to f Byzantine agents are present, FAIL otherwise. We implemented our model checking algorithms within the NuSMV model checker: the first one explicitly checks equilibria for each coalition, while the second represents symbolically all coalitions. We present experimental results showing their effectiveness for moderate size mechanisms. For example, we can verify coalition Nash equilibria for mechanisms which corresponding normal form games would have more than 5 ×1021 entries. Moreover, we compare the two approaches, and the explicit algorithm turns out to outperform the symbolic one. To the best of our knowledge, no model checking algorithm for verification of Nash equilibria of mechanisms with coalitions has been previously published.

  18. On Nash equilibria for noncooperative games governed by Burgers equation

    Czech Academy of Sciences Publication Activity Database

    Roubíček, Tomáš

    2007-01-01

    Roč. 132, č. 1 (2007), s. 41-50 ISSN 0022-3239 Grant - others:GA ČR(CZ) GA201/03/0934 Institutional research plan: CEZ:AV0Z10750506 Keywords : Nash equilibria * noncooperative games * Burgers equation Subject RIV: BA - General Mathematics Impact factor: 0.688, year: 2007

  19. On the Sensitivity Matrix of the Nash Bargaining Solution

    NARCIS (Netherlands)

    Engwerda, J.C.

    2006-01-01

    In this note we provide a characterization of a subclass of bargaining problems for which the Nash solution has the property of disagreement point monotonicity.While the original d-monotonicity axiom and its stronger notion, strong d-monotonicity, were introduced and discussed by Thomson [15], this

  20. Existence and Policy Effectiveness in Feedback Nash LQ-Games

    Directory of Open Access Journals (Sweden)

    Nicola Acocella

    2008-12-01

    Full Text Available This paper illustrates how the classical theory of economic policy can profitably be used to verify some properties of the Linear Nash Feedback Equilibrium in difference LQ-games. In particular, we find that both a necessary condition for the equilibrium existence and a sufficient condition for policy ineffectiveness can be defined in the terms of the simple Tinbergen counting rule.

  1. Feedback Nash Equilibria for Linear Quadratic Descriptor Differential Games

    NARCIS (Netherlands)

    Engwerda, J.C.; Salmah, Y.

    2010-01-01

    In this note we consider the non-cooperative linear feedback Nash quadratic differential game with an infinite planning horizon for descriptor systems of index one. The performance function is assumed to be indefinite. We derive both necessary and sufficient conditions under which this game has a

  2. Feedback nash equilibria for linear quadratic descriptor differential games

    NARCIS (Netherlands)

    Engwerda, J.C.; Salmah, S.

    2012-01-01

    In this paper, we consider the non-cooperative linear feedback Nash quadratic differential game with an infinite planning horizon for descriptor systems of index one. The performance function is assumed to be indefinite. We derive both necessary and sufficient conditions under which this game has a

  3. On the Sensitivity Matrix of the Nash Bargaining Solution

    NARCIS (Netherlands)

    Engwerda, J.C.; Douven, R.C.M.H.

    2005-01-01

    In this note we derive the sensitivity matrix of the Nash bargaining solution w.r.t. the disagreement point d.This first order derivative is completely specified in terms of the Pareto frontier function.We show that whenever one player increases his threatpoint always at least one player will loose

  4. Quantum mechanics gives stability to a Nash equilibrium

    International Nuclear Information System (INIS)

    Iqbal, A.; Toor, A.H.

    2002-01-01

    We consider a slightly modified version of the rock-scissors-paper (RSP) game from the point of view of evolutionary stability. In its classical version the game has a mixed Nash equilibrium (NE) not stable against mutants appearing in small numbers. We find a quantized version of the RSP game for which the classical mixed NE becomes stable

  5. A Numerical Algorithm to find All Scalar Feedback Nash Equilibria

    NARCIS (Netherlands)

    Engwerda, J.C.

    2013-01-01

    Abstract: In this note we generalize a numerical algorithm presented in [9] to calculate all solutions of the scalar algebraic Riccati equations that play an important role in finding feedback Nash equilibria of the scalar N-player linear affine-quadratic differential game. The algorithm is based on

  6. Algorithms for Computing Nash Equilibria in Deterministic LQ Games

    NARCIS (Netherlands)

    Engwerda, J.C.

    2006-01-01

    In this paper we review a number of algorithms to compute Nash equilibria in deterministic linear quadratic differential games.We will review the open-loop and feedback information case.In both cases we address both the finite and the infinite-planning horizon.

  7. Computing Nash Equilibrium in Wireless Ad Hoc Networks

    DEFF Research Database (Denmark)

    Bulychev, Peter E.; David, Alexandre; Larsen, Kim G.

    2012-01-01

    This paper studies the problem of computing Nash equilibrium in wireless networks modeled by Weighted Timed Automata. Such formalism comes together with a logic that can be used to describe complex features such as timed energy constraints. Our contribution is a method for solving this problem us...

  8. Macrophage Stimulating Protein Enhances Hepatic Inflammation in a NASH Model

    NARCIS (Netherlands)

    Li, Jieyi; Chanda, Dipanjan; van Gorp, Patrick J.; Jeurissen, Mike L. J.; Houben, Tom; Walenbergh, Sofie M. A.; Debets, Jacques; Oligschlaeger, Yvonne; Gijbels, Marion J. J.; Neumann, Dietbert; Shiri-Sverdlov, Ronit

    2016-01-01

    Non-alcoholic steatohepatitis (NASH) is a common liver disease characterized by hepatic lipid accumulation (steatosis) and inflammation. Currently, therapeutic options are poor and the long-term burden to society is constantly increasing. Previously, macrophage stimulating protein (MSP)-a serum

  9. Ex post Nash consistent representation of effectivity functions

    NARCIS (Netherlands)

    Peters, H.J.M.; Schröder, M.J.W.; Vermeulen, A.J.

    2013-01-01

    We consider effectivity functions for finitely many players and alternatives. We assume that players have incomplete information with respect to the preferences of the other players. Our main result is the characterization of effectivity functions which have an ex post Nash consistent

  10. Critical Realism and Statistical Methods--A Response to Nash

    Science.gov (United States)

    Scott, David

    2007-01-01

    This article offers a defence of critical realism in the face of objections Nash (2005) makes to it in a recent edition of this journal. It is argued that critical and scientific realisms are closely related and that both are opposed to statistical positivism. However, the suggestion is made that scientific realism retains (from statistical…

  11. Metabolic pathway analysis using a nash equilibrium approach

    NARCIS (Netherlands)

    Lucia, Angelo; DiMaggio, Peter A.; Alonso-Martinez, Diego

    2018-01-01

    A novel approach to metabolic network analysis using a Nash Equilibrium (NE) formulation is proposed in which enzymes are considered players in a multi-player game. Each player has its own payoff function with the objective of minimizing the Gibbs free energy associated with the biochemical

  12. Uncovering a Predictive Molecular Signature for the Onset of NASH-Related Fibrosis in a Translational NASH Mouse Model

    Directory of Open Access Journals (Sweden)

    Arianne van Koppen

    2018-01-01

    Conclusions: An early predictive molecular signature was identified that marked the active profibrotic process before histopathologic fibrosis becomes manifest. Early detection of the onset of NASH and fibrosis enables identification of novel blood-based biomarkers to stratify patients at risk, development of new therapeutics, and help shorten (preclinical experimental time frames.

  13. Complex structures in the Nash-Moser category

    DEFF Research Database (Denmark)

    Gravesen, Jens

    1989-01-01

    Working in the Nash-Moser category, it is shown that the harmonic and holomorphic differentials and the Weierstrass points on a closed Riemann surface depend smoothly on the complex structure. It is also shown that the space of complex structures on any compact surface forms a principal bundle over...... the Teichmüller space and hence that the uniformization maps of the closed disk and the sphere depend smoothly on the complex structure....

  14. Long-term Nash equilibria in electricity markets

    Energy Technology Data Exchange (ETDEWEB)

    Pozo, David; Contreras, Javier [Department of Applied Mechanics and Project Engineering - Universidad de Castilla - La Mancha, Avda. Camilo Jose Cela s/n. 13071 Ciudad Real (Spain); Caballero, Angel; de Andres, Antonio [Gas Natural Fenosa, 28033 Madrid (Spain)

    2011-02-15

    In competitive electricity markets, companies simultaneously offer their productions to obtain the maximum profits on a daily basis. In the long run, the strategies utilized by the electric companies lead to various long-term equilibria that can be analyzed with the appropriate tools. We present a methodology to find plausible long-term Nash equilibria in pool-based electricity markets. The methodology is based on an iterative market Nash equilibrium model in which the companies can decide upon their offer strategies. An exponential smoothing of the bids submitted by the companies is applied to facilitate the convergence of the iterative procedure. In each iteration of the model the companies face residual demand curves that are accurately modeled by Hermite interpolating polynomials. We introduce the concept of meta-game equilibrium strategies to allow companies to have a range of offer strategies where several pure and mixed meta-game Nash equilibria are possible. With our model it is also possible to model uncertainty or to generate price scenarios for financial models that assess the value of a generating unit by real options analysis. The application of the proposed methodology is illustrated with several realistic case studies. (author)

  15. Long-term Nash equilibria in electricity markets

    International Nuclear Information System (INIS)

    Pozo, David; Contreras, Javier; Caballero, Angel; de Andres, Antonio

    2011-01-01

    In competitive electricity markets, companies simultaneously offer their productions to obtain the maximum profits on a daily basis. In the long run, the strategies utilized by the electric companies lead to various long-term equilibria that can be analyzed with the appropriate tools. We present a methodology to find plausible long-term Nash equilibria in pool-based electricity markets. The methodology is based on an iterative market Nash equilibrium model in which the companies can decide upon their offer strategies. An exponential smoothing of the bids submitted by the companies is applied to facilitate the convergence of the iterative procedure. In each iteration of the model the companies face residual demand curves that are accurately modeled by Hermite interpolating polynomials. We introduce the concept of meta-game equilibrium strategies to allow companies to have a range of offer strategies where several pure and mixed meta-game Nash equilibria are possible. With our model it is also possible to model uncertainty or to generate price scenarios for financial models that assess the value of a generating unit by real options analysis. The application of the proposed methodology is illustrated with several realistic case studies. (author)

  16. Equilibrio de Nash y resolución de conflictos

    Directory of Open Access Journals (Sweden)

    Maritza Vanegas de Medina

    2014-01-01

    Full Text Available En el presente artículo, se introduce la noción de juegos suma-cero construida a partir de las teorías de von Neumann y Morgenstern (1953 sus propiedades básicas y algunos ejemplos elaborados a partir del lenguaje matemático, para explicar a la luz de las teorías de Nash (1950 las estrategias usadas por los jugadores en el contexto económico, militar y social. También, se presenta la noción de juego suma no-cero, no cooperativos entre dos personas, asumiendo la continuidad diferenciable de la función de pago. Finalmente, se explica a través de ejemplos construidos por los autores, los métodos de determinación del equilibrio de Nash puro y una metodología elemental para la determinación del equilibrio de Nash mixto.

  17. Investigation of land use effects on Nash model parameters

    Science.gov (United States)

    Niazi, Faegheh; Fakheri Fard, Ahmad; Nourani, Vahid; Goodrich, David; Gupta, Hoshin

    2015-04-01

    Flood forecasting is of great importance in hydrologic planning, hydraulic structure design, water resources management and sustainable designs like flood control and management. Nash's instantaneous unit hydrograph is frequently used for simulating hydrological response in natural watersheds. Urban hydrology is gaining more attention due to population increases and associated construction escalation. Rapid development of urban areas affects the hydrologic processes of watersheds by decreasing soil permeability, flood base flow, lag time and increase in flood volume, peak runoff rates and flood frequency. In this study the influence of urbanization on the significant parameters of the Nash model have been investigated. These parameters were calculated using three popular methods (i.e. moment, root mean square error and random sampling data generation), in a small watershed consisting of one natural sub-watershed which drains into a residentially developed sub-watershed in the city of Sierra Vista, Arizona. The results indicated that for all three methods, the lag time, which is product of Nash parameters "K" and "n", in the natural sub-watershed is greater than the developed one. This logically implies more storage and/or attenuation in the natural sub-watershed. The median K and n parameters derived from the three methods using calibration events were tested via a set of verification events. The results indicated that all the three method have acceptable accuracy in hydrograph simulation. The CDF curves and histograms of the parameters clearly show the difference of the Nash parameter values between the natural and developed sub-watersheds. Some specific upper and lower percentile values of the median of the generated parameters (i.e. 10, 20 and 30 %) were analyzed to future investigates the derived parameters. The model was sensitive to variations in the value of the uncertain K and n parameter. Changes in n are smaller than K in both sub-watersheds indicating

  18. A corrigendum on paper: Effects of symmetry and familiarity on the attractiveness of human faces, Tatjana Mentus and Slobodan Marković, DOI: 10.2298/PSI1603301M published in Psihologija 49(3, 301-311

    Directory of Open Access Journals (Sweden)

    Editorial

    2017-01-01

    Full Text Available The authors informed us that the original publication contained an error that does not affect any of the findings. Tatjana Mentus and Slobodan Marković failed to include a footnote denoting that the research reported in the publication in question was presented at 38th European Conference on Visual Perception that took place in Liverpool, August 23.-27., 2015. The authors deeply regret this omission. Link to the corrected article 10.2298/PSI1603301M

  19. Generalizations of the Nash Equilibrium Theorem in the KKM Theory

    Directory of Open Access Journals (Sweden)

    Sehie Park

    2010-01-01

    Full Text Available The partial KKM principle for an abstract convex space is an abstract form of the classical KKM theorem. In this paper, we derive generalized forms of the Ky Fan minimax inequality, the von Neumann-Sion minimax theorem, the von Neumann-Fan intersection theorem, the Fan-type analytic alternative, and the Nash equilibrium theorem for abstract convex spaces satisfying the partial KKM principle. These results are compared with previously known cases for G-convex spaces. Consequently, our results unify and generalize most of previously known particular cases of the same nature. Finally, we add some detailed historical remarks on related topics.

  20. On Cournot-Nash-Walras Equilibria and Their Computation

    Czech Academy of Sciences Publication Activity Database

    Outrata, Jiří; Ferris, M.C.; Červinka, Michal; Outrata, M.

    2016-01-01

    Roč. 24, č. 3 (2016), s. 387-402 ISSN 1877-0533 R&D Projects: GA ČR GAP402/12/1309; GA ČR GA15-00735S Grant - others:GA UK(CZ) SFG 2567; Australian Research Council(AU) DP-110102011 Institutional support: RVO:67985556 Keywords : Cournot-Nash-Walras equilibrium * Existence * Stationarity conditions * Stability * MOPEC Subject RIV: BA - General Mathematics Impact factor: 0.886, year: 2016 http://library.utia.cas.cz/separaty/2016/MTR/outrata-0460895.pdf

  1. A novel role of astrocyte elevated gene-1 (AEG-1) in regulating nonalcoholic steatohepatitis (NASH).

    Science.gov (United States)

    Srivastava, Jyoti; Robertson, Chadia L; Ebeid, Kareem; Dozmorov, Mikhail; Rajasekaran, Devaraja; Mendoza, Rachel; Siddiq, Ayesha; Akiel, Maaged A; Jariwala, Nidhi; Shen, Xue-Ning; Windle, Jolene J; Subler, Mark A; Mukhopadhyay, Nitai D; Giashuddin, Shah; Ghosh, Shobha; Lai, Zhao; Chen, Yidong; Fisher, Paul B; Salem, Aliasger K; Sanyal, Arun J; Sarkar, Devanand

    2017-08-01

    Nonalcoholic steatohepatitis (NASH) is the most prevalent cause of chronic liver disease in the Western world. However, an optimum therapy for NASH is yet to be established, mandating more in-depth investigation into the molecular pathogenesis of NASH to identify novel regulatory molecules and develop targeted therapies. Here, we unravel a unique function of astrocyte elevated gene-1(AEG-1)/metadherin in NASH using a transgenic mouse with hepatocyte-specific overexpression of AEG-1 (Alb/AEG-1) and a conditional hepatocyte-specific AEG-1 knockout mouse (AEG-1 ΔHEP ). Alb/AEG-1 mice developed spontaneous NASH whereas AEG-1 ΔHEP mice were protected from high-fat diet (HFD)-induced NASH. Intriguingly, AEG-1 overexpression was observed in livers of NASH patients and wild-type (WT) mice that developed steatosis upon feeding HFD. In-depth molecular analysis unraveled that inhibition of peroxisome proliferator-activated receptor alpha activity resulting in decreased fatty acid β-oxidation, augmentation of translation of fatty acid synthase resulting in de novo lipogenesis, and increased nuclear factor kappa B-mediated inflammation act in concert to mediate AEG-1-induced NASH. Therapeutically, hepatocyte-specific nanoparticle-delivered AEG-1 small interfering RNA provided marked protection from HFD-induced NASH in WT mice. AEG-1 might be a key molecule regulating initiation and progression of NASH. AEG-1 inhibitory strategies might be developed as a potential therapeutic intervention in NASH patients. (Hepatology 2017;66:466-480). © 2017 by the American Association for the Study of Liver Diseases.

  2. Negotiating transfer pricing using the Nash bargaining solution

    Directory of Open Access Journals (Sweden)

    Clempner Julio B.

    2017-12-01

    Full Text Available This paper analyzes and proposes a solution to the transfer pricing problem from the point of view of the Nash bargaining game theory approach. We consider a firm consisting of several divisions with sequential transfers, in which central management provides a transfer price decision that enables maximization of operating profits. Price transferring between divisions is negotiable throughout the bargaining approach. Initially, we consider a disagreement point (status quo between the divisions of the firm, which plays the role of a deterrent. We propose a framework and a method based on the Nash equilibrium approach for computing the disagreement point. Then, we introduce a bargaining solution, which is a single-valued function that selects an outcome from the feasible pay-offs for each bargaining problem that is a result of cooperation of the divisions of the firm involved in the transfer pricing problem. The agreement reached by the divisions in the game is the most preferred alternative within the set of feasible outcomes, which produces a profit-maximizing allocation of the transfer price between divisions. For computing the bargaining solution, we propose an optimization method. An example illustrating the usefulness of the method is presented.

  3. Adam Nash: legally speaking, a happy ending or slippery slope?

    Science.gov (United States)

    Crockin, Susan

    2001-01-01

    The birth of Adam Nash, following IVF and then preimplantation genetic diagnosis (PGD) on the resulting 15 embryos to find which would be a potential bone marrow match for his older sibling, suffering from Fanconi's anaemia, is the first reported case of genetic selection of an embryo to save the life of an existing person. The case has stirred debates worldwide over the appropriateness and implications of using the technique for this and related purposes. Legally, it is suggested that embryos are indeed entitled to special respect because of their potential for life, but certain principles must not be overlooked, and the Nash case was wholly within acceptable legal principles. The legal perspective offered here concludes: (i) while embryos are entitled to certain protections, the mere fact that they are extracorporeal raises the danger that the rights and protections assigned to them will be wrongly elevated over the legally protected procreation rights of the adults who create them; (ii) divorce litigation involving "custody" of embryos is not a direct parallel and legal analogies must be distinguished; (iii) the status of embryos must be carefully defined; and (iv) a national or international, multi-disciplinary body should be created to grapple with the developing issues and uses that are sure to follow.

  4. Dragotsennaja osen / Tatjana Barmakova

    Index Scriptorium Estoniae

    Barmakova, Tatjana

    2004-01-01

    Moefirmade Dior, Yves Saint Laurent (jumestuskunstnik Linda Cantello), Guerlain (kunstnik Olivier Echaudemaison), Shiseido (kunstnik Tom Pecheux) meigikollektsioonidest. Diori, Kenzo ja Thierry Mugleri uutest parfüümidest. "Kenzoairi" parfüümipudeli disainis klaasikunstnik Laura de Santillana

  5. Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-κB translocation.

    Science.gov (United States)

    Afrin, Rejina; Arumugam, Somasundaram; Rahman, Azizur; Wahed, Mir Imam Ibne; Karuppagounder, Vengadeshprabhu; Harima, Meilei; Suzuki, Hiroshi; Miyashita, Shizuka; Suzuki, Kenji; Yoneyama, Hiroyuki; Ueno, Kazuyuki; Watanabe, Kenichi

    2017-03-01

    Curcumin, a phenolic compound, has a wide spectrum of therapeutic effects such as antitumor, anti-inflammatory, anti-cancer and so on. The study aimed to investigate the underlying mechanisms of curcumin to protect liver damage and progression of non-alcoholic steatohepatitis (NASH) in a novel NASH-hepatocellular carcinoma (HCC) mouse model. To induce this model neonatal C57BL/6J male mice were exposed to low-dose streptozotocin and were fed a high-fat diet (HFD) from the age of 4weeks to 14weeks. Curcumin was given at 100mg/kg dose daily by oral gavage started at the age of 10weeks and continued until 14weeks along with HFD feeding. We found that curcumin improved the histopathological changes of the NASH liver via reducing the level of steatosis, fibrosis associated with decreasing serum aminotransferases. In addition, curcumin treatment markedly reduced the hepatic protein expression of oxidative stress, pro-inflammatory cytokines, and chemokines including interferon (IFN) γ, interleukin-1β and IFNγ-inducible protein 10, in NASH mice. Furthermore, curcumin treatment significantly reduced the cytoplasmic translocation of high mobility group box 1 (HMGB1) and the protein expression of toll like receptor 4. Nuclear translocation of nuclear factor kappa B (NF-κB) was also dramatically attenuated by the curcumin in NASH liver. Curcumin treatment effectively reduced the progression of NASH to HCC by suppressing the protein expression of glypican-3, vascular endothelial growth factor, and prothrombin in the NASH liver. Our data suggest that curcumin reduces the progression of NASH and liver damage, which may act via inhibiting HMGB1-NF-κB translocation. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Existential-R-Complete Decision Problems about Symmetric Nash Equilibria in Symmetric Multi-Player Games

    OpenAIRE

    Bilò, Vittorio; Mavronicolas, Marios

    2017-01-01

    We study the complexity of decision problems about symmetric Nash equilibria for symmetric multi-player games. These decision problems concern the existence of a symmetric Nash equilibrium with certain natural properties. We show that a handful of such decision problems are Existential-R-complete; that is, they are exactly as hard as deciding the Existential Theory of the Reals.

  7. Exact Solutions of the Field Equations for Empty Space in the Nash Gravitational Theory

    Directory of Open Access Journals (Sweden)

    Matthew T. Aadne

    2017-02-01

    Full Text Available John Nash has proposed a new theory of gravity. We define a Nash-tensor equal to the curvature tensor appearing in the Nash field equations for empty space, and calculate its components for two cases: 1. A static, spherically symmetric space; and 2. The expanding, homogeneous and isotropic space of the Friedmann-Lemaitre-Robertson-Walker (FLRW universe models. We find the general, exact solution of Nash’s field equations for empty space in the static case. The line element turns out to represent the Schwarzschild-de Sitter spacetime. Also we find the simplest non-trivial solution of the field equations in the cosmological case, which gives the scale factor corresponding to the de Sitter spacetime. Hence empty space in the Nash theory corresponds to a space with Lorentz Invariant Vacuum Energy (LIVE in the Einstein theory. This suggests that dark energy may be superfluous according to the Nash theory. We also consider a radiation filled universe model in an effort to find out how energy and matter may be incorporated into the Nash theory. A tentative interpretation of the Nash theory as a unified theory of gravity and electromagnetism leads to a very simple form of the field equations in the presence of matter. It should be noted, however, that the Nash theory is still unfinished. A satisfying way of including energy momentum into the theory has yet to be found.

  8. 75 FR 41518 - Match-E-Be-Nash-She-Wish (Gun Lake) Tribe Liquor Control Ordinance

    Science.gov (United States)

    2010-07-16

    ... DEPARTMENT OF THE INTERIOR Bureau of Indian Affairs Match-E-Be-Nash-She-Wish (Gun Lake) Tribe... publishes the Secretary's certification of the Match-E-Be-Nash-She-Wish Band of Pottawatomi Indians (Gun.... The Tribal Council of the Gun Lake Tribe Liquor Control Ordinance adopted this Liquor Ordinance on...

  9. The Solution Set of the n-Player Scalar Feedback Nash Algebraic Riccati Equations

    NARCIS (Netherlands)

    Engwerda, J.C.

    1999-01-01

    In this paper we analyse the set of scalar algebraic Riccati equations (ARE) that play an important role in finding feedback Nash equilibria of the scalar N-player linear-quadratic differential game. We show that in general there exist maximal 2N - 1 solutions of the (ARE) that give rise to a Nash

  10. Necessary and Sufficient Conditions for Feedback Nash Equilibria for the Affine Quadratic Differential

    NARCIS (Netherlands)

    Engwerda, J.C.; Salmah, Y.

    2010-01-01

    In this note we consider the non-cooperative linear feedback Nash quadratic differential game with an infinite planning horizon. The performance function is assumed to be indefinite and the underlying system affine. We derive both necessary and sufficient conditions under which this game has a Nash

  11. Liver transplantation for NASH cirrhosis is not performed at the expense of major post-operative morbidity

    NARCIS (Netherlands)

    van den Berg, Eline H.; Douwes, Rianne M.; de Meijer, Vincent E.; Schreuder, Tim C. M. A.; Blokzijl, Hans

    Background: Non-alcoholic steatohepatitis (NASH) is an emerging indication for liver transplantation (LT) and coexists with multiple comorbidities. Obese and cirrhotic patients experience more perioperative complications. Limited data exist about short-term complications after LT for NASH cirrhosis.

  12. Generalized Nash equilibrium problems, bilevel programming and mpec

    CERN Document Server

    Lalitha, CS

    2017-01-01

    The book discusses three classes of problems: the generalized Nash equilibrium problems, the bilevel problems and the mathematical programming with equilibrium constraints (MPEC). These problems interact through their mathematical analysis as well as their applications. The primary aim of the book is to present the modern tool of variational analysis and optimization, which are used to analyze these three classes of problems. All contributing authors are respected academicians, scientists and researchers from around the globe. These contributions are based on the lectures delivered by experts at CIMPA School, held at the University of Delhi, India, from 25 November–6 December 2013, and peer-reviewed by international experts. The book contains five chapters. Chapter 1 deals with nonsmooth, nonconvex bilevel optimization problems whose feasible set is described by using the graph of the solution set mapping of a parametric optimization problem. Chapter 2 describes a constraint qualification to MPECs considere...

  13. Hepatic neuregulin 4 signaling defines an endocrine checkpoint for steatosis-to-NASH progression

    Science.gov (United States)

    Guo, Liang; Chen, Zhimin; Xia, Houjun; Li, Siming; Zhang, Yanqiao; Kobberup, Sune; Zou, Weiping; Lin, Jiandie D.

    2017-01-01

    Nonalcoholic steatohepatitis (NASH) is characterized by progressive liver injury, inflammation, and fibrosis; however, the mechanisms that govern the transition from hepatic steatosis, which is relatively benign, to NASH remain poorly defined. Neuregulin 4 (Nrg4) is an adipose tissue–enriched endocrine factor that elicits beneficial metabolic effects in obesity. Here, we show that Nrg4 is a key component of an endocrine checkpoint that preserves hepatocyte health and counters diet-induced NASH in mice. Nrg4 deficiency accelerated liver injury, fibrosis, inflammation, and cell death in a mouse model of NASH. In contrast, transgenic expression of Nrg4 in adipose tissue alleviated diet-induced NASH. Nrg4 attenuated hepatocyte death in a cell-autonomous manner by blocking ubiquitination and proteasomal degradation of c-FLIPL, a negative regulator of cell death. Adeno-associated virus–mediated (AAV-mediated) rescue of hepatic c-FLIPL expression in Nrg4-deficent mice functionally restored the brake for steatosis to NASH transition. Thus, hepatic Nrg4 signaling serves as an endocrine checkpoint for steatosis-to-NASH progression by activating a cytoprotective pathway to counter stress-induced liver injury. PMID:29106384

  14. Near-Nash equilibrium strategies for LQ differential games with inaccurate state information

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available ε -Nash equilibrium or “near equilibrium” for a linear quadratic cost game is considered. Due to inaccurate state information, the standard solution for feedback Nash equilibrium cannot be applied. Instead, an estimation of the players' states is substituted into the optimal control strategies equation obtained for perfect state information. The magnitude of the ε in the ε -Nash equilibrium will depend on the quality of the estimation process. To illustrate this approach, a Luenberger-type observer is used in the numerical example to generate the players' state estimates in a two-player non-zero-sum LQ differential game.

  15. Effects of dietary supplementation with betaine on a nonalcoholic steatohepatitis (NASH) mouse model.

    Science.gov (United States)

    Kawakami, Sakura; Han, Kyu-Ho; Nakamura, Yumi; Shimada, Ken-ichiro; Kitano, Tomoko; Aritsuka, Tsutomu; Nagura, Taizo; Ohba, Kiyoshi; Nakamura, Kimihide; Fukushima, Michihiro

    2012-01-01

    The effects of betaine supplementation on non-alcoholic steatohepatitis (NASH) model mice were examined by measuring the accumulation of fat in the livers of NASH model mice compared to a control. Betaine from sugar beets was provided to the model mice as a dietary supplement. After 3 wk of dietary supplementation, there were no significant differences in body weight or liver weight between the groups. However, the liver to body weight ratio in the high-fat diet with betaine (HFB) group was significantly (pNASH model mice.

  16. Welfare in the nash equilibrium in export taxes und Bertrand duopoly

    OpenAIRE

    Clarke, Roger; Collie, David R.

    2006-01-01

    In the Eaton and Grossman (1986) model of export taxes under Bertrand duopoly, it is shown that welfare in the Nash equilibrium in export taxes is always higher than welfare under free trade for both countries.

  17. Welfare in the Nash Equilibrium in Export Taxes under Bertrand Duopoly

    OpenAIRE

    Clarke, Roger; Collie, David R.

    2006-01-01

    In the Eaton and Grossman (1986) model of export taxes under Bertrand duopoly, it is shown that welfare in the Nash equilibrium in export taxes is always higher than welfare under free trade for both countries.

  18. A classification model for non-alcoholic steatohepatitis (NASH) using confocal Raman micro-spectroscopy

    Science.gov (United States)

    Yan, Jie; Yu, Yang; Kang, Jeon Woong; Tam, Zhi Yang; Xu, Shuoyu; Fong, Eliza Li Shan; Singh, Surya Pratap; Song, Ziwei; Tucker Kellogg, Lisa; So, Peter; Yu, Hanry

    2017-07-01

    We combined Raman micro-spectroscopy and machine learning techniques to develop a classification model based on a well-established non-alcoholic steatohepatitis (NASH) mouse model, using spectrum pre-processing, biochemical component analysis (BCA) and logistic regression.

  19. Cytokeratin 18 as a non invasive marker in diagnosis of NASH and ...

    African Journals Online (AJOL)

    Cytokeratin 18 as a non invasive marker in diagnosis of NASH and its usefulness in correlation with disease severity in Egyptian patients. MM Maher, WA Ibrahim, SA Saleh, L Shash, HA Gabal, M Tarif, M Gamal ...

  20. Spectrum Allocation for Decentralized Transmission Strategies: Properties of Nash Equilibria

    Directory of Open Access Journals (Sweden)

    Peter von Wrycza

    2009-01-01

    Full Text Available The interaction of two transmit-receive pairs coexisting in the same area and communicating using the same portion of the spectrum is analyzed from a game theoretic perspective. Each pair utilizes a decentralized iterative water-filling scheme to greedily maximize the individual rate. We study the dynamics of such a game and find properties of the resulting Nash equilibria. The region of achievable operating points is characterized for both low- and high-interference systems, and the dependence on the various system parameters is explicitly shown. We derive the region of possible signal space partitioning for the iterative water-filling scheme and show how the individual utility functions can be modified to alter its range. Utilizing global system knowledge, we design a modified game encouraging better operating points in terms of sum rate compared to those obtained using the iterative water-filling algorithm and show how such a game can be imitated in a decentralized noncooperative setting. Although we restrict the analysis to a two player game, analogous concepts can be used to design decentralized algorithms for scenarios with more players. The performance of the modified decentralized game is evaluated and compared to the iterative water-filling algorithm by numerical simulations.

  1. Greening Software Requirements Change Management Strategy Based on Nash Equilibrium

    Directory of Open Access Journals (Sweden)

    Zhixiang Tong

    2017-01-01

    Full Text Available Recently, green computing has become more and more important in software engineering (SE, which can be achieved by effectively recycling the software system and utilizing the computing resources. However, the requirement change may lead to unnecessary labor and time cost. Moreover, it may also result in the waste of hardware and computing resources once unreasonable requirements are realized. Thus, to perform green computing in SE, it is necessary to propose effective strategies to manage the requirement change. For this decision-making problem, game theoretical methods can be feasible solutions. In this paper, we propose a novel requirement change management approach based on game theory. Specifically, we model the problem as a game between the stakeholders and the developer and devise the payoff matrix between different strategies of the players. We then propose a Nash equilibrium-based game theoretical algorithm to manage requirement change. The evaluation results show that, compared to the exhaustive algorithm, our method not only can achieve almost the same optimal results but also can significantly reduce the computational time complexity. Thus, our method is feasible for a lot of requirement changes and can facilitate the green computing targets from the perspective of software engineering.

  2. Gender difference in NASH susceptibility: Roles of hepatocyte Ikkβ and Sult1e1.

    Science.gov (United States)

    Matsushita, Noriko; Hassanein, Mohamed T; Martinez-Clemente, Marcos; Lazaro, Raul; French, Samuel W; Xie, Wen; Lai, Keane; Karin, Michael; Tsukamoto, Hidekazu

    2017-01-01

    Myeloid cell and hepatocyte IKKβ may mediate the genesis of obesity and insulin resistance in mice fed high fat diet. However, their gender-specific roles in the pathogenesis of non-alcoholic steatohepatitis (NASH) are not known. Here we demonstrate myeloid IKKβ deficiency prevents Western diet-induced obesity and visceral adiposity in females but not in males, and attenuates hyperglycemia, global IR, and NASH in both genders. In contrast, all metabolic sequela including NASH are aggravated by hepatocyte IKKβ deficiency (IkbkbΔhep) in male but not female mice. Gene profiling identifies sulfotransferase family 1E (Sult1e1), which encodes a sulfotransferase E1 responsible for inactivation of estrogen, as a gene upregulated in NASH in both genders and most conspicuously in male IkbkbΔhep mice having worst NASH and lowest plasma estradiol levels. LXRα is enriched to LXRE on Sult1e1 promoter in male WT and IkbkbΔhep mice with NASH, and a Sult1e1 promoter activity is increased by LXRα and its ligand and augmented by expression of a S32A mutant of IκBα. These results demonstrate striking gender differences in regulation by IKKβ of high cholesterol saturated fat diet-induced metabolic changes including NASH and suggest hepatocyte IKKβ is protective in male due at least in part to its ability to repress LXR-induced Sult1e1. Our findings also raise a caution for systemic IKK inhibition for the treatment of NASH as it may exacerbate the disease in male patients.

  3. Computing the Pareto-Nash equilibrium set in finite multi-objective mixed-strategy games

    Directory of Open Access Journals (Sweden)

    Victoria Lozan

    2013-10-01

    Full Text Available The Pareto-Nash equilibrium set (PNES is described as intersection of graphs of efficient response mappings. The problem of PNES computing in finite multi-objective mixed-strategy games (Pareto-Nash games is considered. A method for PNES computing is studied. Mathematics Subject Classification 2010: 91A05, 91A06, 91A10, 91A43, 91A44.

  4. Proteomic and lipidomic signatures of lipid metabolism in NASH-associated hepatocellular carcinoma.

    Science.gov (United States)

    Muir, Kyle; Hazim, Antonious; He, Ying; Peyressatre, Marion; Kim, Do-Young; Song, Xiaoling; Beretta, Laura

    2013-08-01

    Nonalcoholic steatohepatitis (NASH) is a common preneoplastic condition of hepatocellular carcinoma (HCC). Mice with hepatocytic deletion of Pten develop NASH and HCC later in life. This model is highly valuable for studies aimed at identifying the molecular mechanism by which metabolic disorders contribute to tumor development. We applied proteomic and lipidomic profiling approaches to Pten-null NASH liver and tumors. Circulating fatty acid composition was also characterized in these mice. The relevance to human NASH and HCC was further validated. This integrative proteomic and lipidomic study from mouse to human and from liver to blood identified the following disease signatures: (i) an HCC signature: upregulated hepatic scd1/scd2, fads2, and acsl5:acsl1 ratio, elevated vaccenic and erucic acids, and reduced margaric and linoleic acids in both liver and plasma; (ii) a NASH signature that correlates with tumor burden: upregulated hepatic elovl6, elevated oleic, adrenic, and osbond acids, and reduced cervonic acid in liver and plasma; and (iii) a NASH signature: reduced hepatic and circulating lignoceric and eicosapentaenoic acids. Altogether, these results show the role of lipid-modifying enzymes converting saturated fatty acids (SFA) to monounsaturated fatty acids (MUFA) in HCC and the importance of an increased ratio of long chain n6-polyunsaturated fatty acids over n3-polyunsaturated fatty acids in NASH and HCC risk. They also highlight the relevance of the Pten-null model for studies related to NASH and HCC and show that circulating lipid metabolome provides a direct read of lipid changes in the liver. Most importantly, novel candidate targets for HCC diagnosis, therapy, risk assessment, and prevention were identified. ©2013 AACR.

  5. Study of Nash equilibrium by increasing game parameters in 3-player quantum game

    Directory of Open Access Journals (Sweden)

    H Goudarzi

    2013-03-01

    Full Text Available  Using the quantum game formalism in 3-player system, we calculate the Nash equilibrium in quantum Prisoners’ Dilemma by increasing parameters of unitary operator. Since, the entanglement plays an important role in quantum states of particles quantum game, actually its effect on the obtained results of Nash equilibrium is investigated. It is shown that increasing the parameters enhances the game payoff function.

  6. NASH Therapy: omega 3 supplementation, vitamin E, insulin sensitizers and statin drugs

    Directory of Open Access Journals (Sweden)

    Stephen Caldwell

    2017-06-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is the more aggressive form of non-alcoholic fatty liver disease (NAFLD. NASH can progress to hepatic fibrosis, cirrhosis, portal hypertension and primary liver cancer. Therapy is evolving with a substantial number of trials of promising new agents now in progress. In this article however, we will examine data for several older forms of therapy which have been fairly extensively studied over the years: Polyunsaturated Fatty Acid (PUFA supplements, vitamin E, insulin sensitizing agents with a focus on pioglitazone and statin agents. Early interest in PUFA derived from their potential benefit in cardio-metabolic disease and the close association of NAFLD/NASH with Metabolic Syndrome. Results have been variable although most studies show reduction of liver fat without other major effects and their effects are influenced by concomitant weight loss and underlying genetic factors. Vitamin E has had some efficacy in pediatric NASH but questionable efficacy in even mild NASH among adults. Pioglitazone has shown significant histological benefit in a number of trials but concern over side-effects (especially weight gain have dampened enthusiasm. A newer insulin sensitizer, liraglutide, has also shown promise in a small randomized, controlled trial. Very limited data exists regarding the histological effects of the statins in NASH and these agents appear to be fairly neutral with neither clear cut benefit nor detriment. Their use is best guided by cardiovascular risks rather than liver histology.

  7. A Noninvasive Score Model for Prediction of NASH in Patients with Chronic Hepatitis B and Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Jing Liang

    2017-01-01

    Full Text Available Aims. To develop a noninvasive score model to predict NASH in patients with combined CHB and NAFLD. Objective and Methods. 65 CHB patients with NAFLD were divided into NASH group (34 patients and non-NASH group (31 patients according to the NAS score. Biochemical indexes, liver stiffness, and Controlled Attenuation Parameter (CAP were determined. Data in the two groups were compared and subjected to multivariate analysis, to establish a score model for the prediction of NASH. Results. In the NASH group, ALT, TG, fasting blood glucose (FBG, M30 CK-18, CAP, and HBeAg positive ratio were significantly higher than in the non-NASH group (P<0.05. Multivariate analysis showed that CK-18 M30, CAP, FBG, and HBVDNA level were independent predictors of NASH. Therefore, a new model combining CK18 M30, CAP, FBG, and HBVDNA level was established using logistic regression. The AUROC curve predicting NASH was 0.961 (95% CI: 0.920–1.00, cutoff value is 0.218, with a sensitivity of 100% and specificity of 80.6%. Conclusion. A noninvasive score model might be considered for the prediction of NASH in patients with CHB combined with NAFLD.

  8. Overexpression of the Vitronectin V10 Subunit in Patients with Nonalcoholic Steatohepatitis: Implications for Noninvasive Diagnosis of NASH

    Directory of Open Access Journals (Sweden)

    Maria Del Ben

    2018-02-01

    Full Text Available Nonalcoholic steatohepatitis (NASH is the critical stage of nonalcoholic fatty liver disease (NAFLD. The persistence of necroinflammatory lesions and fibrogenesis in NASH is the leading cause of liver cirrhosis and, ultimately, hepatocellular carcinoma. To date, the histological examination of liver biopsies, albeit invasive, remains the means to distinguish NASH from simple steatosis (NAFL. Therefore, a noninvasive diagnosis by serum biomarkers is eagerly needed. Here, by a proteomic approach, we analysed the soluble low-molecular-weight protein fragments flushed out from the liver tissue of NAFL and NASH patients. On the basis of the assumption that steatohepatitis leads to the remodelling of the liver extracellular matrix (ECM, NASH-specific fragments were in silico analysed for their involvement in the ECM molecular composition. The 10 kDa C-terminal fragment of the ECM protein vitronectin (VTN was then selected as a promising circulating biomarker in discriminating NASH. The analysis of sera of patients provided these major findings: the circulating VTN fragment (i is overexpressed in NASH patients and positively correlates with the NASH activity score (NAS; (ii originates from the disulfide bond reduction between the V10 and the V65 subunits. In conclusion, V10 determination in the serum could represent a reliable tool for the noninvasive discrimination of NASH from simple steatosis.

  9. Molecular Mechanisms and New Treatment Strategies for Non-Alcoholic Steatohepatitis (NASH

    Directory of Open Access Journals (Sweden)

    Akinobu Takaki

    2014-04-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is a severe form of non-alcoholic fatty liver disease (NAFLD, in which most patients exhibit non-progressive, non-alcoholic fatty liver (NAFL attributable to simple steatosis. Multiple hits, including genetic differences, fat accumulation, insulin resistance and intestinal microbiota changes, account for the progression of NASH. NAFLD is strongly associated with obesity, which induces adipokine secretion, endoplasmic reticulum (ER and oxidative stress at the cellular level, which in turn induces hepatic steatosis, inflammation and fibrosis. Among these factors, gut microbiota are acknowledged as having an important role in initiating this multifactorial disease. Oxidative stress is considered to be a key contributor in the progression from NAFL to NASH. Macrophage infiltration is apparent in NAFL and NASH, while T-cell infiltration is apparent in NASH. Although several clinical trials have shown that antioxidative therapy with vitamin E can effectively control hepatitis pathology in the short term, the long-term effects remain obscure and have often proved to be ineffective in many other diseases. Several long-term antioxidant protocols have failed to reduce mortality. New treatment modalities that incorporate current understanding of NAFLD molecular pathogenesis must be considered.

  10. Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model

    Energy Technology Data Exchange (ETDEWEB)

    Stefano, J.T.; Pereira, I.V.A.; Torres, M.M.; Bida, P.M. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Coelho, A.M.M. [Disciplina de Transplante de Órgãos do Aparelho Digestivo (LIM-37), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Xerfan, M.P. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Cogliati, B. [Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil); Barbeiro, D.F. [Disciplina de Emergências Clínicas (LIM-51), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Mazo, D.F.C. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Kubrusly, M.S.; D' Albuquerque, L.A.C. [Disciplina de Transplante de Órgãos do Aparelho Digestivo (LIM-37), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Souza, H.P. [Disciplina de Emergências Clínicas (LIM-51), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Carrilho, F.J.; Oliveira, C.P. [Disciplina de Gastroenterologia Clínica (LIM-07), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2015-02-24

    Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg·kg{sup -1}·day{sup -1} by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1α) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1α and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1α expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.

  11. Hepatic cholesterol crystals and crown-like structures distinguish NASH from simple steatosis.

    Science.gov (United States)

    Ioannou, George N; Haigh, W Geoffrey; Thorning, David; Savard, Christopher

    2013-05-01

    We sought to determine whether hepatic cholesterol crystals are present in patients or mice with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH), and whether their presence or distribution correlates with the presence of NASH as compared with simple steatosis. We identified, by filipin staining, free cholesterol within hepatocyte lipid droplets in patients with NASH and in C57BL/6J mice that developed NASH following a high-fat high-cholesterol diet. Under polarized light these lipid droplets exhibited strong birefringence suggesting that some of the cholesterol was present in the form of crystals. Activated Kupffer cells aggregated around dead hepatocytes that included strongly birefringent cholesterol crystals, forming "crown-like structures" similar to those recently described in inflamed visceral adipose tissue. These Kupffer cells appeared to process the lipid of dead hepatocytes turning it into activated lipid-laden "foam cells" with numerous small cholesterol-containing droplets. In contrast, hepatocyte lipid droplets in patients and mice with simple steatosis did not exhibit cholesterol crystals and their Kupffer cells did not form crown-like structures or transform into foam cells. Our results suggest that cholesterol crystallization within hepatocyte lipid droplets and aggregation and activation of Kupffer cells in crown-like structures around such droplets represent an important, novel mechanism for progression of simple steatosis to NASH.

  12. On Nash Equilibrium and Evolutionarily Stable States That Are Not Characterised by the Folk Theorem

    Science.gov (United States)

    Li, Jiawei; Kendall, Graham

    2015-01-01

    In evolutionary game theory, evolutionarily stable states are characterised by the folk theorem because exact solutions to the replicator equation are difficult to obtain. It is generally assumed that the folk theorem, which is the fundamental theory for non-cooperative games, defines all Nash equilibria in infinitely repeated games. Here, we prove that Nash equilibria that are not characterised by the folk theorem do exist. By adopting specific reactive strategies, a group of players can be better off by coordinating their actions in repeated games. We call it a type-k equilibrium when a group of k players coordinate their actions and they have no incentive to deviate from their strategies simultaneously. The existence and stability of the type-k equilibrium in general games is discussed. This study shows that the sets of Nash equilibria and evolutionarily stable states have greater cardinality than classic game theory has predicted in many repeated games. PMID:26288088

  13. Non-Alcoholic Steatohepatitis (NASH): Risk Factors in Morbidly Obese Patients

    Science.gov (United States)

    Losekann, Alexandre; Weston, Antonio C.; de Mattos, Angelo A.; Tovo, Cristiane V.; de Carli, Luis A.; Espindola, Marilia B.; Pioner, Sergio R.; Coral, Gabriela P.

    2015-01-01

    The aim was to investigate the prevalence of non-alcoholic steatohepatitis (NASH) and risk factors for hepatic fibrosis in morbidly obese patients submitted to bariatric surgery. This retrospective study recruited all patients submitted to bariatric surgery from January 2007 to December 2012 at a reference attendance center of Southern Brazil. Clinical and biochemical data were studied as a function of the histological findings of liver biopsies done during the surgery. Steatosis was present in 226 (90.4%) and NASH in 176 (70.4%) cases. The diagnosis of cirrhosis was established in four cases (1.6%) and fibrosis in 108 (43.2%). Risk factors associated with NASH at multivariate analysis were alanine aminotransferase (ALT) >1.5 times the upper limit of normal (ULN); glucose ≥ 126 mg/dL and triglycerides ≥ 150 mg/dL. All patients with ALT ≥1.5 times the ULN had NASH. When the presence of fibrosis was analyzed, ALT > 1.5 times the ULN and triglycerides ≥ 150 mg/dL were risk factors, furthermore, there was an increase of 1% in the prevalence of fibrosis for each year of age increase. Not only steatosis, but NASH is a frequent finding in MO patients. In the present study, ALT ≥ 1.5 times the ULN identifies all patients with NASH, this finding needs to be further validated in other studies. Moreover, the presence of fibrosis was associated with ALT, triglycerides and age, identifying a subset of patients with more severe disease. PMID:26512661

  14. Non-Alcoholic Steatohepatitis (NASH: Risk Factors in Morbidly Obese Patients

    Directory of Open Access Journals (Sweden)

    Alexandre Losekann

    2015-10-01

    Full Text Available The aim was to investigate the prevalence of non-alcoholic steatohepatitis (NASH and risk factors for hepatic fibrosis in morbidly obese patients submitted to bariatric surgery. This retrospective study recruited all patients submitted to bariatric surgery from January 2007 to December 2012 at a reference attendance center of Southern Brazil. Clinical and biochemical data were studied as a function of the histological findings of liver biopsies done during the surgery. Steatosis was present in 226 (90.4% and NASH in 176 (70.4% cases. The diagnosis of cirrhosis was established in four cases (1.6% and fibrosis in 108 (43.2%. Risk factors associated with NASH at multivariate analysis were alanine aminotransferase (ALT >1.5 times the upper limit of normal (ULN; glucose ≥ 126 mg/dL and triglycerides ≥ 150 mg/dL. All patients with ALT ≥1.5 times the ULN had NASH. When the presence of fibrosis was analyzed, ALT > 1.5 times the ULN and triglycerides ≥ 150 mg/dL were risk factors, furthermore, there was an increase of 1% in the prevalence of fibrosis for each year of age increase. Not only steatosis, but NASH is a frequent finding in MO patients. In the present study, ALT ≥ 1.5 times the ULN identifies all patients with NASH, this finding needs to be further validated in other studies. Moreover, the presence of fibrosis was associated with ALT, triglycerides and age, identifying a subset of patients with more severe disease.

  15. Nash equilibria in quantum games with generalized two-parameter strategies

    International Nuclear Information System (INIS)

    Flitney, Adrian P.; Hollenberg, Lloyd C.L.

    2007-01-01

    In the Eisert protocol for 2x2 quantum games [J. Eisert, et al., Phys. Rev. Lett. 83 (1999) 3077], a number of authors have investigated the features arising from making the strategic space a two-parameter subset of single qubit unitary operators. We argue that the new Nash equilibria and the classical-quantum transitions that occur are simply an artifact of the particular strategy space chosen. By choosing a different, but equally plausible, two-parameter strategic space we show that different Nash equilibria with different classical-quantum transitions can arise. We generalize the two-parameter strategies and also consider these strategies in a multiplayer setting

  16. Metabolically induced liver inflammation leads to NASH and differs from LPS- or IL-1β-induced chronic inflammation.

    Science.gov (United States)

    Liang, Wen; Lindeman, Jan H; Menke, Aswin L; Koonen, Debby P; Morrison, Martine; Havekes, Louis M; van den Hoek, Anita M; Kleemann, Robert

    2014-05-01

    The nature of the chronic inflammatory component that drives the development of non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory triggers have not been investigated systematically. We examined the effect of non-metabolic triggers (lipopolysaccharide (LPS), interleukin-1β (IL-1β), administered by slow-release minipumps) and metabolic dietary triggers (carbohydrate, cholesterol) of inflammation on the progression of bland liver steatosis (BS) to NASH. Transgenic APOE3*Leiden.huCETP (APOE3L.CETP) mice fed a high-fat diet (HFD) developed BS after 10 weeks. Then, inflammatory triggers were superimposed or not (control) for six more weeks. Mouse livers were analyzed with particular emphasis on hallmarks of inflammation which were defined in human liver biopsies with and without NASH. Livers of HFD-treated control mice remained steatotic and did not progress to NASH. All four inflammatory triggers activated hepatic nuclear factor-κB (NF-κB) significantly and comparably (≥5-fold). However, HFD+LPS or HFD+IL-1β did not induce a NASH-like phenotype and caused intrahepatic accumulation of almost exclusively mononuclear cells. By contrast, mice treated with metabolic triggers developed NASH, characterized by enhanced steatosis, hepatocellular hypertrophy, and formation of mixed-type inflammatory foci containing myeloperoxidase-positive granulocytes (neutrophils) as well as mononuclear cells, essentially as observed in human NASH. Specific for the metabolic inducers was an activation of the proinflammatory transcription factor activator protein-1 (AP-1), neutrophil infiltration, and induction of risk factors associated with human NASH, that is, dyslipidemia (by cholesterol) and insulin resistance (by carbohydrate). In conclusion, HFD feeding followed by NF-κB activation per se (LPS, IL-1β) does not promote the transition from BS to NASH. HFD feeding followed by metabolically evoked inflammation induces additional inflammatory components

  17. Statins improve NASH via inhibition of RhoA and Ras

    DEFF Research Database (Denmark)

    Schierwagen, Robert; Maybüchen, Lara; Hittatiya, Kanishka

    2016-01-01

    in NASH. SMV blunted fibrosis due to inhibition of both RhoA/Rho kinase and Ras/ERK pathways. Interestingly, inhibition of RAC1 and Ras (by LT) failed to decrease fibrosis to the same extent. Inhibition of RAC1 (by NSC) showed no significant effect at all. Inhibition of RhoA and Ras downstream signaling...

  18. Evolving Concepts in the Pathogenesis of NASH: Beyond Steatosis and Inflammation

    Directory of Open Access Journals (Sweden)

    William Peverill

    2014-05-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is characterised by hepatic steatosis and inflammation and, in some patients, progressive fibrosis leading to cirrhosis. An understanding of the pathogenesis of NASH is still evolving but current evidence suggests multiple metabolic factors critically disrupt homeostasis and induce an inflammatory cascade and ensuing fibrosis. The mechanisms underlying these changes and the complex inter-cellular interactions that mediate fibrogenesis are yet to be fully elucidated. Lipotoxicity, in the setting of excess free fatty acids, obesity, and insulin resistance, appears to be the central driver of cellular injury via oxidative stress. Hepatocyte apoptosis and/or senescence contribute to activation of the inflammasome via a variety of intra- and inter-cellular signalling mechanisms leading to fibrosis. Current evidence suggests that periportal components, including the ductular reaction and expansion of the hepatic progenitor cell compartment, may be involved and that the Th17 response may mediate disease progression. This review aims to provide an overview of the pathogenesis of NASH and summarises the evidence pertaining to key mechanisms implicated in the transition from steatosis and inflammation to fibrosis. Currently there are limited treatments for NASH although an increasing understanding of its pathogenesis will likely improve the development and use of interventions in the future.

  19. Existence of nash equilibrium in competitive nonlinear pricing games with adverse selection

    OpenAIRE

    Monteiro, P. K.

    2003-01-01

    We show that for a large class of competitive nonlinear pricing games with adverse selection, the property of better-reply security is naturally satisfied - thus, resolving via a result due to Reny (1999) the issue of existence of Nash equilibrium for a large class of competitive nonlinear pricing games.

  20. A numerical algorithm to find all feedback Nash equilibria in scalar affine quadratic differential games

    NARCIS (Netherlands)

    Engwerda, Jacob

    2015-01-01

    This note deals with solving scalar coupled algebraic Riccati equations. These equations arise in finding linear feedback Nash equilibria of the scalar N-player affine quadratic differential game. A numerical procedure is provided to compute all the stabilizing solutions. The main idea is to

  1. On pure-strategy Nash equilibria in price-quantity games

    NARCIS (Netherlands)

    Bos, I.; Vermeulen, A.J.

    2015-01-01

    This paper examines the existence and characteristics of pure-strategy Nash equilibria in oligopoly models in which firms set both prices and quantities. Existence is proved for a broad and natural class of price-quantity games. With differentiated products, the equilibrium outcome is similar to

  2. Truth-telling and Nash equilibria in minimum cost spanning tree models

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Tvede, Mich

    2012-01-01

    to the rules of the game. We characterize ways of allocating costs such that true announcements constitute Nash equilibria both in case of full and incomplete information. In particular, we find that the Shapley rule based on the irreducible cost matrix is consistent with truthful announcements while a series...

  3. Computation of the Nash Equilibrium Selected by the Tracing Procedure in N-Person Games

    NARCIS (Netherlands)

    Herings, P.J.J.; van den Elzen, A.H.

    1998-01-01

    Harsanyi and Selten (1988) have proposed a theory of equilibrium selection that selects a unique Nash equilibrium for any non-cooperative N-person game. The heart of their theory is given by the tracing procedure, a mathematical construction that adjusts arbitrary prior beliefs into equilibrium

  4. Overmathematisation in game theory : pitting the Nash Equilibrium Refinement Programme against the Epistemic Programme

    NARCIS (Netherlands)

    de Bruin, Boudewijn

    The paper argues that the Nash Equilibrium Refinement Programme was less successful than its competitor, the Epistemic Programme (Interactive Epistemology). The prime criterion of success is the extent to which the programmes were able to reach the key objective guiding non-cooperative game theory

  5. Long term highly saturated fat diet does not induce NASH in Wistar rats

    Directory of Open Access Journals (Sweden)

    Filippi Céline

    2007-02-01

    Full Text Available Abstract Background Understanding of nonalcoholic steatohepatitis (NASH is hampered by the lack of a suitable model. Our aim was to investigate whether long term high saturated-fat feeding would induce NASH in rats. Methods 21 day-old rats fed high fat diets for 14 weeks, with either coconut oil or butter, and were compared with rats feeding a standard diet or a methionine choline-deficient (MCD diet, a non physiological model of NASH. Results MCDD fed rats rapidly lost weight and showed NASH features. Rats fed coconut (86% of saturated fatty acid or butter (51% of saturated fatty acid had an increased caloric intake (+143% and +30%. At the end of the study period, total lipid ingestion in term of percentage of energy intake was higher in both coconut (45% and butter (42% groups than in the standard (7% diet group. No change in body mass was observed as compared with standard rats at the end of the experiment. However, high fat fed rats were fattier with enlarged white and brown adipose tissue (BAT depots, but they showed no liver steatosis and no difference in triglyceride content in hepatocytes, as compared with standard rats. Absence of hepatic lipid accumulation with high fat diets was not related to a higher lipid oxidation by isolated hepatocytes (unchanged ketogenesis and oxygen consumption or hepatic mitochondrial respiration but was rather associated with a rise in BAT uncoupling protein UCP1 (+25–28% vs standard. Conclusion Long term high saturated fat feeding led to increased "peripheral" fat storage and BAT thermogenesis but did not induce hepatic steatosis and NASH.

  6. Dietary trans-Fatty Acid Induced NASH is Normalized Following Loss of trans-Fatty Acids from Hepatic Lipid Pools

    Science.gov (United States)

    Ford, David A.; Acharya, Sahaja; Gilkey, George; Basaranoglu, Metin; Tetri, Laura H.; Brunt, Elizabeth M.

    2012-01-01

    Previous experiments in mice showed that dietary trans-fats could play a role in non-alcoholic steatohepatitis (NASH) yet little is known about the accumulation trans-fats in hepatic lipid pools in relationship to liver injury. NASH is also associated with obesity yet improves with only modest weight loss. To distinguish the role of obesity versus sustained consumption of a trans-fat containing diet in causing NASH, mice with obesity and NASH induced by consuming a high trans-fat diet for 16 weeks were subsequently fed standard chow or maintained on trans-fat chow for another 8 weeks. The accumulation, partitioning and loss of trans-fats in the major hepatic lipid pools during and after trans-fat consumption were determined. Obese mice switched to standard chow remained obese but steatohepatitis improved. trans-fats were differentially incorporatedinto the majorhepatic lipid pools and the loss of trans-fats after crossover to control chow was greatest in the cholesteryl ester pool. In summary, dietary changes can improve the biochemical and histopathological changes of NASH despite persistent obesity in mice. Analysis of hepatic lipids confirmed that dietary trans-fats accumulate in the major lipid pools and are released differentially with diet normalization. The substantial loss of trans-fats from the cholesteryl ester pool in parallel with improvement in NASH suggests that this pool of trans-fats could play a role in the pathogenesis of NASH. PMID:22923371

  7. Otvlekajas na zhizn / Tatjana Poznjak

    Index Scriptorium Estoniae

    Poznjak, Tatjana

    2000-01-01

    Vene kirjaniku Ivan Bunini (1870-1953) elulõpu armastusloost tehtud filmis "Tema naise päevik" ("Dnevnik jego zhenõ") on Bunini rollis Andrei Smirnov. Näitleja räägib oma suhtest rolliga ning artikli autor avaldab mõtteid kirjaniku elu ja iseloomu üle. Ka ajalehes Vesti : Nedelja pljuss, 15. detsember, lk. 32-33

  8. Iskusstvo i dizain / Tatjana Pissareva

    Index Scriptorium Estoniae

    Pissareva, Tatjana

    2004-01-01

    Tallinna Viru Keskuse neljandal korrusel avatakse Baltimaade suurim galerii KUNST ja DISAIN. Ruumi kujundasid Pille ja Raivo Hein. Projektijuht on Ilme Rätsep. Galerii avanäitusel osalevad Erika Tammpere, Ene Pars, Sigrid Kuik, Kadi Pajupuu, Ilme Rätsep, Siiri Tammsalu ja teised

  9. "Rossiju spasjot pragmatizm" / Tatjana Poloskova

    Index Scriptorium Estoniae

    Poloskova, Tatjana

    2005-01-01

    Ambitsioonikas idee nn "vene maailma" konsolideerimiseks ei ole praegusele vene poliitilisele eliidile jõukohane, 2005. a. planeeritud välisriikides elavate kaasmaalaste kongressi toimumine on kahtluse all. Vastavalt avaliku arvamuse uuringutele oli 80% küsitletud venemaalastest vastu kaasmaalaste toetamiseks vahendite eraldamisele

  10. Muzei bez sten / Tatjana Pissareva

    Index Scriptorium Estoniae

    Pissareva, Tatjana

    2005-01-01

    Skulptori, graafiku ja maalikunstniku Rafael Arutjunjani loomingut kajastavast raamatust "Rafael Arutjunjan. Proizvedenija iskusstva" räägib raamatu väljaandja Areg Arutjunjan. Reprod ja fotod on Valeri Baretalt ja Sergei Didõkilt. Artiklite autorid on Boris Bernshtein, Aleksandr Sidorov ja Emma Darvis

  11. "Nu, pogodi!" vozvrashtshajetsja / Tatjana Rostova

    Index Scriptorium Estoniae

    Rostova, Tatjana

    2005-01-01

    Populaarsele vene animafilmile "Oota sa!" ("Nu, pogodi!") valmis stuudios Christmas Films uus, 19. osa, mis tuleb ekraanile novembris. Filmi stsenarist on Aleksandr Kurljandski ja režissöör vana multifilmi tegija režissöör Vjatsheslav Kotjonotshkini poeg Aleksei

  12. Probabilistic approach to the estimation of the Nash model scale parameter; Un enfoque probabilistica para la estimacion del parametro de escala del modelo de Nash

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, Patricia M. [Instituo Nacional del Agua y del ambiente (Argentina); Seoane, Rafael S. [Consejo Nacional de Investigaciones Cientificas y Tecnicas (Argentina)

    1999-08-01

    An indirect estimation method of the scale parameter in the Nash model considering basin climatic and geomorphologic characteristics is proposed. The proposal links the results of the dependence of instantaneous unit hydrograph model parameters with Horton's laws and basic expressions of the geomorphoclitina with different characteristics and the comparison between their simulated hydrographs with indirect estimation and with moment method estimation are presented. [Spanish] En este trabajo se propone una metodologia de estimacion indirecta del parametro de escala de modelo de Nash, que permite considerar las caracteristicas geomorfologicas y climaticas de la cuenca. El metodo de estimacion propuesto utiliza la tecnica de la funcion de densidad de probabilidad derivada para integrar resultados que muestran la dependencia de los parametros del modelo del hidrograma unitario instantaneo, con las leyes de Horton y con expresiones basicas de la teoria del geomorfoclimatico. La metodologia es aplicada a dos cuencas de la Republica Argentina con caracteristicas climaticas diferentes y sus resultados son comparados con los caudales estimados con el metodo directo de los momentos.

  13. Spike-based decision learning of Nash equilibria in two-player games.

    Directory of Open Access Journals (Sweden)

    Johannes Friedrich

    Full Text Available Humans and animals face decision tasks in an uncertain multi-agent environment where an agent's strategy may change in time due to the co-adaptation of others strategies. The neuronal substrate and the computational algorithms underlying such adaptive decision making, however, is largely unknown. We propose a population coding model of spiking neurons with a policy gradient procedure that successfully acquires optimal strategies for classical game-theoretical tasks. The suggested population reinforcement learning reproduces data from human behavioral experiments for the blackjack and the inspector game. It performs optimally according to a pure (deterministic and mixed (stochastic Nash equilibrium, respectively. In contrast, temporal-difference(TD-learning, covariance-learning, and basic reinforcement learning fail to perform optimally for the stochastic strategy. Spike-based population reinforcement learning, shown to follow the stochastic reward gradient, is therefore a viable candidate to explain automated decision learning of a Nash equilibrium in two-player games.

  14. Assessment of Some Adipo cytokines Levels In Serum of Egyptian Patients Suffering From Non-Alcoholic Steatohepatitis (NASH)

    International Nuclear Information System (INIS)

    Mohammed, A.A.

    2011-01-01

    In the present study, thirty five patients with biopsy proven NASH and twenty age and sex matched healthy individuals were enrolled. Serum adiponectin, ghrelin, TNF-α and leptin levels were estimated in the serum of NASH patients and control subjects. Also, fasting insulin and blood glucose levels were measured and insulin resistance (IR) were calculated. In addition, liver function enzymes (AST, ALT), total cholesterol and triglycerides were measured, and body mass index (BMI) was calculated. The results showed significant decrease in adiponectin and ghrelin levels and significant increase in TNF-α and leptin levels in NASH group as compared to controls. Ten patients were diabetic and seven patients had BMI > 30 kg/m 2 . Also, significant positive relationship was recorded between adiponectin and ghrelin and AST/ALT ratio in the NASH group, and significant negative relationship between them and BMI and HOMA-IR

  15. A periodic point-based method for the analysis of Nash equilibria in 2 x 2 symmetric quantum games

    International Nuclear Information System (INIS)

    Schneider, David

    2011-01-01

    We present a novel method of looking at Nash equilibria in 2 x 2 quantum games. Our method is based on a mathematical connection between the problem of identifying Nash equilibria in game theory, and the topological problem of the periodic points in nonlinear maps. To adapt our method to the original protocol designed by Eisert et al (1999 Phys. Rev. Lett. 83 3077-80) to study quantum games, we are forced to extend the space of strategies from the initial proposal. We apply our method to the extended strategy space version of the quantum Prisoner's dilemma and find that a new set of Nash equilibria emerge in a natural way. Nash equilibria in this set are optimal as Eisert's solution of the quantum Prisoner's dilemma and include this solution as a limit case.

  16. A Nash-game approach to joint image restoration and segmentation

    OpenAIRE

    Kallel, Moez; Aboulaich, Rajae; Habbal, Abderrahmane; Moakher, Maher

    2014-01-01

    International audience; We propose a game theory approach to simultaneously restore and segment noisy images. We define two players: one is restoration, with the image intensity as strategy, and the other is segmentation with contours as strategy. Cost functions are the classical relevant ones for restoration and segmentation, respectively. The two players play a static game with complete information, and we consider as solution to the game the so-called Nash Equilibrium. For the computation ...

  17. Nash equilibrium in a pay-as-bid electricity market: Part 1- existence and characterization

    Czech Academy of Sciences Publication Activity Database

    Aussel, D.; Bendotti, P.; Pištěk, Miroslav

    2017-01-01

    Roč. 66, č. 6 (2017), s. 1013-1025 ISSN 0233-1934 R&D Projects: GA ČR GA15-00735S Institutional support: RVO:67985556 Keywords : Electricity market * multi-leader-follower game * Nash equilibrium * best response Subject RIV: AH - Economics OBOR OECD: Economic Theory Impact factor: 0.943, year: 2016 http://library.utia.cas.cz/separaty/2016/MTR/pistek-0468195. pdf

  18. Placental extract ameliorates non-alcoholic steatohepatitis (NASH by exerting protective effects on endothelial cells

    Directory of Open Access Journals (Sweden)

    Akihiro Yamauchi

    2017-09-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is a severe form of fatty liver disease that is defined by the presence of inflammation and fibrosis, ultimately leading to cirrhosis and hepatocellular carcinoma. Treatment with human placental extract (HPE reportedly ameliorates the hepatic injury. We evaluated the effect of HPE treatment in a mouse model of NASH. In the methione- and choline-deficient (MCD diet-induced liver injury model, fibrosis started from regions adjacent to the sinusoids. We administered the MCD diet with high-salt loading (8% NaCl in the drinking water to mice deficient in the vasoprotective molecule RAMP2 for 5 weeks, with or without HPE. In both the HPE and control groups, fibrosis was seen in regions adjacent to the sinusoids, but the fibrosis was less pronounced in the HPE-treated mice. Levels of TNF-α and MMP9 expression were also significantly reduced in HPE-treated mice, and oxidative stress was suppressed in the perivascular region. In addition, HPE dose-dependently increased survival of cultured endothelial cells exposed to 100 μM H2O2, and it upregulated expression of eNOS and the anti-apoptotic factors bcl-2 and bcl-xL. From these observations, we conclude that HPE ameliorates NASH-associated pathologies by suppressing inflammation, oxidative stress and fibrosis. These beneficially effects of HPE are in part attributable to its protective effects on liver sinusoidal endothelial cells. HPE could thus be an attractive therapeutic candidate with which to suppress progression from simple fatty liver to NASH.

  19. The Impact of Fiscal Competition about International Double Taxation in a Nash Equilibrium Point of View

    OpenAIRE

    Trandafir Adina

    2010-01-01

    This paper examines international tax rules, with respect to both corporate income tax rates and tax rules for double taxation. This article assumes that governments set non-discriminatory tax rates on domesticand foreign-sourced corporate income and can choose no tax allowance as the tax rule. Consequently, the Nash equilibrium outcomes contradict the intuition underlying previous studies: no tax allowance is chosen as the tax rule where world economic welfare can be maximized. The purpose o...

  20. A symbolic shortest path algorithm for computing subgame-perfect Nash equilibria

    Directory of Open Access Journals (Sweden)

    Góngora Pedro A.

    2015-09-01

    Full Text Available Consider games where players wish to minimize the cost to reach some state. A subgame-perfect Nash equilibrium can be regarded as a collection of optimal paths on such games. Similarly, the well-known state-labeling algorithm used in model checking can be viewed as computing optimal paths on a Kripke structure, where each path has a minimum number of transitions. We exploit these similarities in a common generalization of extensive games and Kripke structures that we name “graph games”. By extending the Bellman-Ford algorithm for computing shortest paths, we obtain a model-checking algorithm for graph games with respect to formulas in an appropriate logic. Hence, when given a certain formula, our model-checking algorithm computes the subgame-perfect Nash equilibrium (as opposed to simply determining whether or not a given collection of paths is a Nash equilibrium. Next, we develop a symbolic version of our model checker allowing us to handle larger graph games. We illustrate our formalism on the critical-path method as well as games with perfect information. Finally, we report on the execution time of benchmarks of an implementation of our algorithms

  1. Detection of carcinogenic etheno-DNA adducts in children and adolescents with non-alcoholic steatohepatitis (NASH).

    Science.gov (United States)

    Teufel, Ulrike; Peccerella, Teresa; Engelmann, Guido; Bruckner, Thomas; Flechtenmacher, Christa; Millonig, Gunda; Stickel, Felix; Hoffmann, Georg F; Schirmacher, Peter; Mueller, Sebastian; Bartsch, Helmut; Seitz, Helmut K

    2015-12-01

    Carcinogenic exocyclic-DNA adducts like 1,N(6)-etheno-2'-deoxyadenosine (εdA) are formed through reactive intermediates of 4-hydroxynonenal (4-HNE) or other lipid peroxidation (LPO) products with the DNA bases A, C, methyl-C and G. High levels of hepatic etheno-DNA adducts have been detected in cancer prone liver diseases including alcoholic liver disease (ALD). In ALD εdA levels correlated significantly with cytochrome P-450 2E1 (CYP2E1) expression which is also induced in non-alcoholic steatohepatitis (NASH). We investigated the occurrence of εdA adducts in children with NASH as a DNA damage marker. Liver biopsies from 21 children/adolescents with histologically proven NASH were analysed for hepatic fat content, inflammation, and fibrosis. εdA levels in DNA, CYP2E1-expression and protein bound 4-hydroxynonenal (HNE) were semi-quantitatively evaluated by immunohistochemistry. Among 21 NASH children, εdA levels in the liver were high in 3, moderate in 5, weak in 9 and not elevated in 4 patients. There was a positive correlation between CYP2E1 and protein-bound 4-HNE (r=0.60; P=0.008) and a trend for a positive relationship for CYP2E1 vs. staining intensity of εdA (r=0.45; P=0.06). Inflammatory activity and fibrosis correlated significantly (r=0.49, P=0.023). Our results demonstrate for the first time the presence of elevated carcinogenic etheno-DNA lesions (εdA) in the majority (17/21) of liver biopsies from young NASH patients. Our data suggest that LPO-derived etheno-adducts are implicated in NASH. Whether these adducts may serve as predictive risk markers in NASH children to develop hepatocellular cancer later in life remains to be investigated.

  2. Patients with NASH and cryptogenic cirrhosis are less likely than those with hepatitis C to receive liver transplants.

    Science.gov (United States)

    O'Leary, Jacqueline G; Landaverde, Carmen; Jennings, Linda; Goldstein, Robert M; Davis, Gary L

    2011-08-01

    Many patients with cryptogenic cirrhosis (CC) have other conditions associated with nonalcoholic steatohepatitis (NASH) that put them at risk for complications that preclude orthotopic liver transplantation (OLT). We followed all patients with NASH and CC who were evaluated for OLT (n = 218) at Baylor Simmons Transplant Institute between March 2002 and May 2008. Data were compared with those from patients evaluated for OLT because of hepatitis C virus (HCV)-associated cirrhosis (n = 646). Patients with NASH and CC were older, more likely to be female, had a higher body mass index, and a greater prevalence of diabetes and hypertension, compared with patients with HCV-associated cirrhosis, but the 2 groups had similar model for end-stage liver disease (MELD) scores. NASH and CC in patients with MELD scores ≤15 were less likely to progress; these patients were less likely to receive OLT and more likely to die or be taken off the wait list because they were too sick, compared with patients with HCV-associated cirrhosis. The median progression rate among patients with NASH and CC was 1.3 MELD points per year versus 3.2 MELD points per year for the HCV group (P = .003). Among patients with MELD scores >15, there were no differences among groups in percentage that received transplants or rate of MELD score progression. Hepatocellular carcinoma occurred in 2.7% of patients with NASH and CC per year, compared with 4.7% per year among those with HCV-associated cirrhosis. Patients with NASH and CC and low MELD scores have slower disease progression than patients with HCV-associated cirrhosis and are less likely to receive OLT. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  3. A Simple Diet- and Chemical-Induced Murine NASH Model with Rapid Progression of Steatohepatitis, Fibrosis and Liver Cancer.

    Science.gov (United States)

    Tsuchida, Takuma; Lee, Youngmin A; Fujiwara, Naoto; Ybanez, Maria; Allen, Brittany; Martins, Sebastiao; Fiel, M Isabel; Goossens, Nicolas; Chou, Hsin-I; Hoshida, Yujin; Friedman, Scott L

    2018-03-20

    Although the majority of patients with nonalcoholic fatty liver disease (NAFLD) have only steatosis without progression, a sizable fraction develop non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis and hepatocellular carcinoma (HCC). Many established diet-induced mouse models for NASH require 24-52 weeks, which makes testing for drug response costly and time consuming. We have sought to establish a murine NASH model with rapid progression of extensive fibrosis and HCC by using a western diet (WD), which is high-fat, high-fructose and high-cholesterol, combined with low dose weekly intraperitoneal carbon tetrachloride (CCl 4 ), which served as an accelerator. C57BL/6J mice were fed a normal chow diet (ND) ± CCl 4 or WD ± CCl 4 for 12 and 24 weeks. Addition of CCl 4 exacerbated histological features of NASH, fibrosis, and tumor development induced by WD, which resulted in stage 3 fibrosis at 12 weeks and HCC development at 24 weeks. Furthermore, whole liver transcriptomic analysis indicated that dysregulated molecular pathways in WD/CCl 4 mice and immunologic features were closely similar to those of human NASH. Our mouse NASH model exhibits rapid progression of advanced fibrosis and HCC, and mimics histological, immunological and transcriptomic features of human NASH, suggesting that it will be a useful experimental tool for preclinical drug testing. A carefully characterized model has been developed in mice that recapitulates the progressive stages of human fatty liver disease, from simple steatosis, to inflammation, fibrosis and cancer. The functional pathways of gene expression and immune abnormalities in this model closely resemble human disease. The ease and reproducibility of this model makes it ideal to study disease pathogenesis and test new treatments. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  4. Predictive value of ALT levels for non-alcoholic steatohepatitis (NASH) and advanced fibrosis in non-alcoholic fatty liver disease (NAFLD).

    Science.gov (United States)

    Verma, Siddharth; Jensen, Donald; Hart, John; Mohanty, Smruti R

    2013-10-01

    Non-alcoholic fatty liver disease (NAFLD) patients with elevated serum alanine aminotransferase (ALT) generally undergo a liver biopsy to evaluate for possible non-alcoholic steatohepatitis (NASH) or advanced fibrosis. However, patients with normal ALT could also have advanced stages of NAFLD. To determine ALT value that will accurately predict NASH and advanced fibrosis using area under the receiver operating characteristics curve (AUROC) analysis. Demographic, clinical and laboratory data of an ethnically diverse cohort of biopsy proven NAFLD patients were retrospectively analysed under univariate and multivariate analyses. Liver biopsies were scored using NASH clinical research network (NASH CRN) system. AUROC were performed for NAFLD Activity Score ≥5 (NASH) and fibrosis score ≥2 (advanced fibrosis). Two hundred and twenty-two patients were analysed. Fifty six (23%) had normal ALT. There was no difference in the rate of advanced fibrosis between normal and elevated ALT (26.8% vs. 18.1%, P = 0.19). However, significantly lower percentage of normal ALT group had NASH compared with elevated ALT group (10.7% vs. 28.9%, P ALT group had NASH or advanced fibrosis, whereas 53% of elevated ALT had no NASH or advanced fibrosis. Higher ALT values correlated with higher specificity, but lower sensitivity for both NASH and advanced fibrosis. AUROC for ALT level correlating NASH and advanced fibrosis were 0.62 and 0.46 respectively. There is no optimal ALT level to predict NASH and advanced fibrosis. Metabolic risk factors should be evaluated to select patients for a liver biopsy to confirm NASH and advanced fibrosis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Predicting fibrosis worsening in obese patients with NASH through parenchymal fibronectin, HOMA-IR, and hypertension.

    Science.gov (United States)

    Sorrentino, Paolo; Terracciano, Luigi; D'Angelo, Salvatore; Ferbo, Umberto; Bracigliano, Alessandra; Vecchione, Raffaela

    2010-02-01

    Few published studies have examined the results obtained from repeat liver biopsies in obese patients with nonalcoholic fatty liver disease (NAFLD). The progressive form of this disease may be largely limited to a subgroup of NAFLD patients with nonalcoholic steatohepatitis (NASH). The presence of intralobular fibronectin (Fn) and other variables was investigated in relation to subsequent fibrosis progression. In this prospective study, 271 obese patients admitted to the hospital with NAFLD and abnormal liver enzymes were scheduled to undergo a repeat liver biopsy at least 5 years after the initial biopsy. After excluding cirrhotic patients, basal biopsy specimens obtained from patients who underwent a second liver biopsy were stained with antibodies against Fn. The progression of fibrosis in the follow-up sample was correlated with the amount of Fn and other clinicopathological variables. We obtained a second liver biopsy from 149 patients after a median time of 6.4 years. Of these, 132 showed suitable Fn staining for semi-quantitative assessments. In all, 44 out of 83 patients (53%) with basal NASH showed fibrosis progression by at least one stage in the second liver biopsy. The amount of Fn (odds ratio=14.1; PHOMA-IR) scores (>8, odds ratio=1.9; P=0.004) were independent predictive factors of worsening fibrosis. A semi-quantitative assessment of the amount of parenchymal Fn present at an early stage in obese patients with NASH is valuable for predicting the progression of fibrosis. Similarly, lobular Fn deposition may be a sensitive and early indicator of active fibrogenetic processes in the liver. Hypertension and higher HOMA-IR scores are other clinical independent risk factors that predict the progression of fibrosis.

  6. Key Inflammatory Processes in Human NASH Are Reflected in Ldlr-/-.Leiden Mice: A Translational Gene Profiling Study.

    Science.gov (United States)

    Morrison, Martine C; Kleemann, Robert; van Koppen, Arianne; Hanemaaijer, Roeland; Verschuren, Lars

    2018-01-01

    Introduction: It is generally accepted that metabolic inflammation in the liver is an important driver of disease progression in NASH and associated matrix remodeling/fibrosis. However, the exact molecular inflammatory mechanisms are poorly defined in human studies. Investigation of key pathogenic mechanisms requires the use of pre-clinical models, for instance for time-resolved studies. Such models must reflect molecular disease processes of importance in patients. Herein we characterized inflammation in NASH patients on the molecular level by transcriptomics and investigated whether key human disease pathways can be recapitulated experimentally in Ldlr -/- .Leiden mice, an established pre-clinical model of NASH. Methods: Human molecular inflammatory processes were defined using a publicly available NASH gene expression profiling dataset (GSE48452) allowing the comparison of biopsy-confirmed NASH patients with normal controls. Gene profiling data from high-fat diet (HFD)-fed Ldlr -/- .Leiden mice (GSE109345) were used for assessment of the translational value of these mice. Results: In human NASH livers, we observed regulation of 65 canonical pathways of which the majority was involved in inflammation (32%), lipid metabolism (16%), and extracellular matrix/remodeling (12%). A similar distribution of pathways across these categories, inflammation (36%), lipid metabolism (24%) and extracellular matrix/remodeling (8%) was observed in HFD-fed Ldlr -/- .Leiden mice. Detailed evaluation of these pathways revealed that a substantial proportion (11 out of 13) of human NASH inflammatory pathways was recapitulated in Ldlr -/- .Leiden mice. Furthermore, the activation state of identified master regulators of inflammation (i.e., specific transcription factors, cytokines, and growth factors) in human NASH was largely reflected in Ldlr -/- .Leiden mice, further substantiating its translational value. Conclusion: Human NASH is characterized by upregulation of specific

  7. Key Inflammatory Processes in Human NASH Are Reflected in Ldlr−/−.Leiden Mice: A Translational Gene Profiling Study

    Science.gov (United States)

    Morrison, Martine C.; Kleemann, Robert; van Koppen, Arianne; Hanemaaijer, Roeland; Verschuren, Lars

    2018-01-01

    Introduction: It is generally accepted that metabolic inflammation in the liver is an important driver of disease progression in NASH and associated matrix remodeling/fibrosis. However, the exact molecular inflammatory mechanisms are poorly defined in human studies. Investigation of key pathogenic mechanisms requires the use of pre-clinical models, for instance for time-resolved studies. Such models must reflect molecular disease processes of importance in patients. Herein we characterized inflammation in NASH patients on the molecular level by transcriptomics and investigated whether key human disease pathways can be recapitulated experimentally in Ldlr−/−.Leiden mice, an established pre-clinical model of NASH. Methods: Human molecular inflammatory processes were defined using a publicly available NASH gene expression profiling dataset (GSE48452) allowing the comparison of biopsy-confirmed NASH patients with normal controls. Gene profiling data from high-fat diet (HFD)-fed Ldlr−/−.Leiden mice (GSE109345) were used for assessment of the translational value of these mice. Results: In human NASH livers, we observed regulation of 65 canonical pathways of which the majority was involved in inflammation (32%), lipid metabolism (16%), and extracellular matrix/remodeling (12%). A similar distribution of pathways across these categories, inflammation (36%), lipid metabolism (24%) and extracellular matrix/remodeling (8%) was observed in HFD-fed Ldlr−/−.Leiden mice. Detailed evaluation of these pathways revealed that a substantial proportion (11 out of 13) of human NASH inflammatory pathways was recapitulated in Ldlr−/−.Leiden mice. Furthermore, the activation state of identified master regulators of inflammation (i.e., specific transcription factors, cytokines, and growth factors) in human NASH was largely reflected in Ldlr−/−.Leiden mice, further substantiating its translational value. Conclusion: Human NASH is characterized by upregulation of specific

  8. Nash Equilibria and the Price of Anarchy for Flows over Time

    Science.gov (United States)

    Koch, Ronald; Skutella, Martin

    We study Nash equilibria in the context of flows over time. Many results on static routing games have been obtained over the last ten years. In flows over time (also called dynamic flows), flow travels through a network over time and, as a consequence, flow values on edges are time-dependent. This more realistic setting has not been tackled from the viewpoint of algorithmic game theory yet; but there is a rich literature on game theoretic aspects of flows over time in the traffic community.

  9. COALITION-PROOF NASH EQUILIBRIA IN A NORMAL-FORM GAME AND ITS SUBGAMES

    OpenAIRE

    RYUSUKE SHINOHARA

    2010-01-01

    The relationship between coalition-proof (Nash) equilibria in a normal-form game and those in its subgame is examined. A subgame of a normal-form game is a game in which the strategy sets of all players in the subgame are subsets of those in the normal-form game. In this paper, focusing on a class of aggregative games, we provide a sufficient condition for the aggregative game under which every coalition-proof equilibrium in a subgame is also coalition-proof in the original normal-form game. ...

  10. Computing Nash Equilibrium in Wireless Ad Hoc Networks: A Simulation-Based Approach

    Directory of Open Access Journals (Sweden)

    Peter Bulychev

    2012-02-01

    Full Text Available This paper studies the problem of computing Nash equilibrium in wireless networks modeled by Weighted Timed Automata. Such formalism comes together with a logic that can be used to describe complex features such as timed energy constraints. Our contribution is a method for solving this problem using Statistical Model Checking. The method has been implemented in UPPAAL model checker and has been applied to the analysis of Aloha CSMA/CD and IEEE 802.15.4 CSMA/CA protocols.

  11. Prohibitin-induced, obesity-associated insulin resistance and accompanying low-grade inflammation causes NASH and HCC.

    Science.gov (United States)

    Ande, Sudharsana R; Nguyen, K Hoa; Grégoire Nyomba, B L; Mishra, Suresh

    2016-03-23

    Obesity increases the risk for nonalcoholic steatohepatitis (NASH) and hepatocarcinogenesis. However, the underlying mechanisms involved in the disease process remain unclear. Recently, we have developed a transgenic obese mouse model (Mito-Ob) by prohibitin mediated mitochondrial remodeling in adipocytes. The Mito-Ob mice develop obesity in a sex-neutral manner, but obesity-associated adipose inflammation and metabolic dysregulation in a male sex-specific manner. Here we report that with aging, the male Mito-Ob mice spontaneously develop obesity-linked NASH and hepatocellular carcinoma (HCC). In contrast, the female Mito-Ob mice maintained normal glucose and insulin levels and did not develop NASH and HCC. The anti-inflammatory peptide ghrelin was significantly upregulated in the female mice and down regulated in the male mice compared with respective control mice. In addition, a reduction in the markers of mitochondrial content and function was found in the liver of male Mito-Ob mice with NASH/HCC development. We found that ERK1/2 signaling was significantly upregulated whereas STAT3 signaling was significantly down regulated in the tumors from Mito-Ob mice. These data provide a proof-of-concept that the metabolic and inflammatory status of the adipose tissue and their interplay at the systemic and hepatic level play a central role in the pathogenesis of obesity-linked NASH and HCC.

  12. A methionine-choline-deficient diet elicits NASH in the immunodeficient mouse featuring a model for hepatic cell transplantation.

    Science.gov (United States)

    Pelz, Sandra; Stock, Peggy; Brückner, Sandra; Christ, Bruno

    2012-02-01

    Non-alcoholic staetohepatitis (NASH) is associated with fat deposition in the liver favoring inflammatory processes and development of fibrosis, cirrhosis and finally hepatocellular cancer. In Western lifestyle countries, NASH has reached a 20% prevalence in the obese population with escalating tendency in the future. Very often, liver transplantation is the only therapeutic option. Recently, transplantation of hepatocyte-like cells differentiated from mesenchymal stem cells was suggested a feasible alternative to whole organ transplantation to ameliorate donor organ shortage. Hence, in the present work an animal model of NASH was established in immunodeficient mice to investigate the feasibility of human stem cell-derived hepatocyte-like cell transplantation. NASH was induced by feeding a methionine/choline-deficient diet (MCD-diet) for up to 5 weeks. Animals developed a fatty liver featuring fibrosis and elevation of the proinflammatory markers serum amyloid A (SAA) and tumor necrosis factor alpha (TNFα). Hepatic triglycerides were significantly increased as well as alanine aminotransferase demonstrating inflammation-linked hepatocyte damage. Elevation of αSMA mRNA and collagen I as well as liver architecture deterioation indicated massive fibrosis. Both short- and long-term post-transplantation human hepatocyte-like cells resided in the mouse host liver indicating parenchymal penetration and most likely functional engraftment. Hence, the NASH model in the immunodeficient mouse is the first to allow for the assessment of the therapeutic impact of human stem cell-derived hepatocyte transplantation. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Spontaneous Time Symmetry Breaking in System with Mixed Strategy Nash Equilibrium: Evidences in Experimental Economics Data

    Science.gov (United States)

    Wang, Zhijian; Xu, Bin; Zhejiang Collaboration

    2011-03-01

    In social science, laboratory experiment with human subjects' interaction is a standard test-bed for studying social processes in micro level. Usually, as in physics, the processes near equilibrium are suggested as stochastic processes with time-reversal symmetry (TRS). To the best of our knowledge, near equilibrium, the breaking time symmetry, as well as the existence of robust time anti-symmetry processes, has not been reported clearly in experimental economics till now. By employing Markov transition method to analysis the data from human subject 2x2 Games with wide parameters and mixed Nash equilibrium, we study the time symmetry of the social interaction process near Nash equilibrium. We find that, the time symmetry is broken, and there exists a robust time anti-symmetry processes. We also report the weight of the time anti-symmetry processes in the total processes of each the games. Evidences in laboratory marketing experiments, at the same time, are provided as one-dimension cases. In these cases, time anti-symmetry cycles can also be captured. The proposition of time anti-symmetry processes is small, but the cycles are distinguishable.

  14. Nash Equilibrium of Social-Learning Agents in a Restless Multiarmed Bandit Game.

    Science.gov (United States)

    Nakayama, Kazuaki; Hisakado, Masato; Mori, Shintaro

    2017-05-16

    We study a simple model for social-learning agents in a restless multiarmed bandit (rMAB). The bandit has one good arm that changes to a bad one with a certain probability. Each agent stochastically selects one of the two methods, random search (individual learning) or copying information from other agents (social learning), using which he/she seeks the good arm. Fitness of an agent is the probability to know the good arm in the steady state of the agent system. In this model, we explicitly construct the unique Nash equilibrium state and show that the corresponding strategy for each agent is an evolutionarily stable strategy (ESS) in the sense of Thomas. It is shown that the fitness of an agent with ESS is superior to that of an asocial learner when the success probability of social learning is greater than a threshold determined from the probability of success of individual learning, the probability of change of state of the rMAB, and the number of agents. The ESS Nash equilibrium is a solution to Rogers' paradox.

  15. On Speech, Print, and New Media: Thomas Nashe and Marshall McLuhan

    Directory of Open Access Journals (Sweden)

    Neil Rhodes

    2009-10-01

    Full Text Available Marshall McLuhan, pioneer of modern media studies, wrote his Ph.D. thesis on the Elizabethan writer Thomas Nashe and the history of the classical trivium. This essay shows how McLuhan’s early exposure to Nashe influenced his later work on speech, print, and modern media. It argues that Nashe’s use of print to re-create oral conditions and his invention of personae drawn from fairground and marketplace helped shape McLuhan’s response to media and popular culture. Rhodes goes on to argue that it was Nashe’s attack on Ramus, to which McLuhan gave particular emphasis, that was the source of the idea that print promotes linear thinking and closure at the expense of the very different qualities associated with oral culture. He ends by countering some of the charges made against McLuhan that he sentimentalizes the oral by using it to represent an ideal of human wholeness.

  16. Characterizing the Nash equilibria of three-player Bayesian quantum games

    Science.gov (United States)

    Solmeyer, Neal; Balu, Radhakrishnan

    2017-05-01

    Quantum games with incomplete information can be studied within a Bayesian framework. We analyze games quantized within the EWL framework [Eisert, Wilkens, and Lewenstein, Phys Rev. Lett. 83, 3077 (1999)]. We solve for the Nash equilibria of a variety of two-player quantum games and compare the results to the solutions of the corresponding classical games. We then analyze Bayesian games where there is uncertainty about the player types in two-player conflicting interest games. The solutions to the Bayesian games are found to have a phase diagram-like structure where different equilibria exist in different parameter regions, depending both on the amount of uncertainty and the degree of entanglement. We find that in games where a Pareto-optimal solution is not a Nash equilibrium, it is possible for the quantized game to have an advantage over the classical version. In addition, we analyze the behavior of the solutions as the strategy choices approach an unrestricted operation. We find that some games have a continuum of solutions, bounded by the solutions of a simpler restricted game. A deeper understanding of Bayesian quantum game theory could lead to novel quantum applications in a multi-agent setting.

  17. Characterizing the Nash equilibria of a three-player Bayesian quantum game

    Science.gov (United States)

    Solmeyer, Neal; Dixon, Ricky; Balu, Radhakrishnan

    2017-06-01

    Quantum games with incomplete information can be studied within a Bayesian framework. We consider a version of prisoner's dilemma (PD) in this framework with three players and characterize the Nash equilibria. A variation of the standard PD game is set up with two types of the second prisoner and the first prisoner plays with them with probability p and 1-p, respectively. The Bayesian nature of the game manifests in the uncertainty that the first prisoner faces about his opponent's type which is encoded either in a classical probability or in the amplitudes of a wave function. Here, we consider scenarios with asymmetric payoffs between the first and second prisoner for different values of the probability, p, and the entanglement. Our results indicate a class of Nash equilibria (NE) with rich structures, characterized by a phase relationship on the strategies of the players. The rich structure can be exploited by the referee to set up rules of the game to push the players toward a specific class of NE. These results provide a deeper insight into the quantum advantages of Bayesian games over their classical counterpart.

  18. Ageing Fxr deficient mice develop increased energy expenditure, improved glucose control and liver damage resembling NASH.

    Directory of Open Access Journals (Sweden)

    Mikael Bjursell

    Full Text Available Nuclear receptor subfamily 1, group H, member 4 (Nr1h4, FXR is a bile acid activated nuclear receptor mainly expressed in the liver, intestine, kidney and adrenal glands. Upon activation, the primary function is to suppress cholesterol 7 alpha-hydroxylase (Cyp7a1, the rate-limiting enzyme in the classic or neutral bile acid synthesis pathway. In the present study, a novel Fxr deficient mouse line was created and studied with respect to metabolism and liver function in ageing mice fed chow diet. The Fxr deficient mice were similar to wild type mice in terms of body weight, body composition, energy intake and expenditure as well as behaviours at a young age. However, from 15 weeks of age and onwards, the Fxr deficient mice had almost no body weight increase up to 39 weeks of age mainly because of lower body fat mass. The lower body weight gain was associated with increased energy expenditure that was not compensated by increased food intake. Fasting levels of glucose and insulin were lower and glucose tolerance was improved in old and lean Fxr deficient mice. However, the Fxr deficient mice displayed significantly increased liver weight, steatosis, hepatocyte ballooning degeneration and lobular inflammation together with elevated plasma levels of ALT, bilirubin and bile acids, findings compatible with non-alcoholic steatohepatitis (NASH and cholestasis. In conclusion, ageing Fxr deficient mice display late onset leanness associated with elevated energy expenditure and improved glucose control but develop severe NASH-like liver pathology.

  19. Ageing Fxr deficient mice develop increased energy expenditure, improved glucose control and liver damage resembling NASH.

    Science.gov (United States)

    Bjursell, Mikael; Wedin, Marianne; Admyre, Therése; Hermansson, Majlis; Böttcher, Gerhard; Göransson, Melker; Lindén, Daniel; Bamberg, Krister; Oscarsson, Jan; Bohlooly-Y, Mohammad

    2013-01-01

    Nuclear receptor subfamily 1, group H, member 4 (Nr1h4, FXR) is a bile acid activated nuclear receptor mainly expressed in the liver, intestine, kidney and adrenal glands. Upon activation, the primary function is to suppress cholesterol 7 alpha-hydroxylase (Cyp7a1), the rate-limiting enzyme in the classic or neutral bile acid synthesis pathway. In the present study, a novel Fxr deficient mouse line was created and studied with respect to metabolism and liver function in ageing mice fed chow diet. The Fxr deficient mice were similar to wild type mice in terms of body weight, body composition, energy intake and expenditure as well as behaviours at a young age. However, from 15 weeks of age and onwards, the Fxr deficient mice had almost no body weight increase up to 39 weeks of age mainly because of lower body fat mass. The lower body weight gain was associated with increased energy expenditure that was not compensated by increased food intake. Fasting levels of glucose and insulin were lower and glucose tolerance was improved in old and lean Fxr deficient mice. However, the Fxr deficient mice displayed significantly increased liver weight, steatosis, hepatocyte ballooning degeneration and lobular inflammation together with elevated plasma levels of ALT, bilirubin and bile acids, findings compatible with non-alcoholic steatohepatitis (NASH) and cholestasis. In conclusion, ageing Fxr deficient mice display late onset leanness associated with elevated energy expenditure and improved glucose control but develop severe NASH-like liver pathology.

  20. Nash Equilibrium of an Energy Saving Strategy with Dual Rate Transmission in Wireless Regional Area Network

    Directory of Open Access Journals (Sweden)

    Zhanqiang Huo

    2017-01-01

    Full Text Available Wireless regional area network (WRAN adopts centralized network architecture and is currently one of the most typical cognitive radio networks. In order to reduce the energy consumption of the communication networks with the constraint of spectrum resource utilization, a working sleep mechanism is introduced into the base station (BS, and a novel energy saving strategy with dual rate transmission is proposed. Combining the multiple-vacation queue and priority queue, using the quasi-birth-death process and the matrix-geometric solution method, we assess the average latency and the forced termination probability of secondary user packets, as well as the energy saving ratio and the channel utilization of system. Based on the revenue-expenditure structure, a profit function is built, and then the Nash equilibrium behavior and the socially optimal behavior are investigated. With the help of the particle swarm optimization, an intelligent optimization algorithm to search the socially optimal arrival rate of secondary user packets is presented. In order to unify the arrival rates of secondary user packets with Nash equilibrium and social optimization, a reasonable pricing policy is formulated. In addition, system experiments are carried out to verify the effectiveness of the energy saving strategy and the rationality of the pricing policy.

  1. Nash equilibrium strategy in the deregulated power industry and comparing its lost welfare with Iran wholesale electricity market

    Science.gov (United States)

    Mousavi, Seyed Hosein; Nazemi, Ali; Hafezalkotob, Ashkan

    2016-09-01

    With the increasing use of different types of auctions in market designing, modeling of participants' behaviors to evaluate the market structure is one of the main discussions in the studies related to the deregulated power industries. In this article, we apply an approach of the optimal bidding behavior to the Iran wholesale electricity market as a restructured electric power industry and model how the participants of the market bid in the spot electricity market. The problem is formulated analytically using the Nash equilibrium concept composed of large numbers of players having discrete and very large strategy spaces. Then, we compute and draw supply curve of the competitive market in which all generators' proposed prices are equal to their marginal costs and supply curve of the real market in which the pricing mechanism is pay-as-bid. We finally calculate the lost welfare or inefficiency of the Nash equilibrium and the real market by comparing their supply curves with the competitive curve. We examine 3 cases on November 24 (2 cases) and July 24 (1 case), 2012. It is observed that in the Nash equilibrium on November 24 and demand of 23,487 MW, there are 212 allowed plants for the first case (plants are allowed to choose any quantity of generation except one of them that should be equal to maximum Power) and the economic efficiency or social welfare of Nash equilibrium is 2.77 times as much as the real market. In addition, there are 184 allowed plants for the second case (plants should offer their maximum power with different prices) and the efficiency or social welfare of Nash equilibrium is 3.6 times as much as the real market. On July 24 and demand of 42,421 MW, all 370 plants should generate maximum energy due to the high electricity demand that the economic efficiency or social welfare of the Nash equilibrium is about 2 times as much as the real market.

  2. Clinical Model for NASH and Advanced Fibrosis in Adult Patients With Diabetes and NAFLD: Guidelines for Referral in NAFLD.

    Science.gov (United States)

    Bazick, Jessica; Donithan, Michele; Neuschwander-Tetri, Brent A; Kleiner, David; Brunt, Elizabeth M; Wilson, Laura; Doo, Ed; Lavine, Joel; Tonascia, James; Loomba, Rohit

    2015-07-01

    Approximately 18 million people in the U.S. have coexisting type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). It is not known who among these patients has nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Therefore, we aimed to determine factors that are associated with both NASH and advanced fibrosis in patients with diabetes and NAFLD in order to identify who should be prioritized for referral to a hepatologist for further diagnostic evaluation and treatment. This study was derived from the NASH Clinical Research Network studies and included 1,249 patients with biopsy-proven NAFLD (including a model development cohort of 346 patients and an independent validation cohort of 100 patients with type 2 diabetes as defined by the American Diabetes Association criteria). Outcome measures were presence of NASH or advanced fibrosis (stage 3 or 4) using cross-validated, by jackknife method, multivariable-adjusted area under the receiver operating characteristic curve (AUROC) and 95% CI. The mean ± SD age and BMI of patients with diabetes and NAFLD was 52.5 ± 10.3 years and 35.8 ± 6.8 kg/m(2), respectively. The prevalence of NASH and advanced fibrosis was 69.2% and 41.0%, respectively. The model for NASH included white race, BMI, waist, alanine aminotransferase (ALT), Aspartate aminotransferase (AST), albumin, HbA1c, HOMA of insulin resistance, and ferritin with an AUROC of 0.80 (95% CI 0.75-0.84, P = 0.007). The specificity, sensitivity, negative predictive values (NPVs), and positive predictive values (PPVs) were 90.0%, 56.8%, 47.7%, and 93.2%, respectively, and the model correctly classified 67% of patients as having NASH. The model for predicting advanced fibrosis included age, Hispanic ethnicity, BMI, waist-to-hip ratio, hypertension, ALT-to-AST ratio, alkaline phosphatase, isolated abnormal alkaline phosphatase, bilirubin (total and direct), globulin, albumin, serum insulin, hematocrit, international normalized ratio, and platelet count with

  3. 77 FR 10553 - Match-E-Be-Nash-She-Wish Band of Pottawatomi Indians (Gun Lake)-Amendment to Liquor Beverage...

    Science.gov (United States)

    2012-02-22

    ... DEPARTMENT OF THE INTERIOR Bureau of Indian Affairs Match-E-Be-Nash-She-Wish Band of Pottawatomi Indians (Gun Lake)-- Amendment to Liquor Beverage Control Ordinance AGENCY: Bureau of Indian Affairs, Interior. ACTION: Notice SUMMARY: This notice publishes the amendments to the Match-E-Be-Nash- She-Wish...

  4. Two Monthly Continuous Dynamic Model Based on Nash Bargaining Theory for Conflict Resolution in Reservoir System.

    Directory of Open Access Journals (Sweden)

    Mehran Homayounfar

    Full Text Available So far many optimization models based on Nash Bargaining Theory associated with reservoir operation have been developed. Most of them have aimed to provide practical and efficient solutions for water allocation in order to alleviate conflicts among water users. These models can be discussed from two viewpoints: (i having a discrete nature; and (ii working on an annual basis. Although discrete dynamic game models provide appropriate reservoir operator policies, their discretization of variables increases the run time and causes dimensionality problems. In this study, two monthly based non-discrete optimization models based on the Nash Bargaining Solution are developed for a reservoir system. In the first model, based on constrained state formulation, the first and second moments (mean and variance of the state variable (water level in the reservoir is calculated. Using moment equations as the constraint, the long-term utility of the reservoir manager and water users are optimized. The second model is a dynamic approach structured based on continuous state Markov decision models. The corresponding solution based on the collocation method is structured for a reservoir system. In this model, the reward function is defined based on the Nash Bargaining Solution. Indeed, it is used to yield equilibrium in every proper sub-game, thereby satisfying the Markov perfect equilibrium. Both approaches are applicable for water allocation in arid and semi-arid regions. A case study was carried out at the Zayandeh-Rud river basin located in central Iran to identify the effectiveness of the presented methods. The results are compared with the results of an annual form of dynamic game, a classical stochastic dynamic programming model (e.g. Bayesian Stochastic Dynamic Programming model, BSDP, and a discrete stochastic dynamic game model (PSDNG. By comparing the results of alternative methods, it is shown that both models are capable of tackling conflict issues in

  5. Two Monthly Continuous Dynamic Model Based on Nash Bargaining Theory for Conflict Resolution in Reservoir System.

    Science.gov (United States)

    Homayounfar, Mehran; Zomorodian, Mehdi; Martinez, Christopher J; Lai, Sai Hin

    2015-01-01

    So far many optimization models based on Nash Bargaining Theory associated with reservoir operation have been developed. Most of them have aimed to provide practical and efficient solutions for water allocation in order to alleviate conflicts among water users. These models can be discussed from two viewpoints: (i) having a discrete nature; and (ii) working on an annual basis. Although discrete dynamic game models provide appropriate reservoir operator policies, their discretization of variables increases the run time and causes dimensionality problems. In this study, two monthly based non-discrete optimization models based on the Nash Bargaining Solution are developed for a reservoir system. In the first model, based on constrained state formulation, the first and second moments (mean and variance) of the state variable (water level in the reservoir) is calculated. Using moment equations as the constraint, the long-term utility of the reservoir manager and water users are optimized. The second model is a dynamic approach structured based on continuous state Markov decision models. The corresponding solution based on the collocation method is structured for a reservoir system. In this model, the reward function is defined based on the Nash Bargaining Solution. Indeed, it is used to yield equilibrium in every proper sub-game, thereby satisfying the Markov perfect equilibrium. Both approaches are applicable for water allocation in arid and semi-arid regions. A case study was carried out at the Zayandeh-Rud river basin located in central Iran to identify the effectiveness of the presented methods. The results are compared with the results of an annual form of dynamic game, a classical stochastic dynamic programming model (e.g. Bayesian Stochastic Dynamic Programming model, BSDP), and a discrete stochastic dynamic game model (PSDNG). By comparing the results of alternative methods, it is shown that both models are capable of tackling conflict issues in water allocation

  6. PPARα activation differently affects microparticle content in atherosclerotic lesions and liver of a mouse model of atherosclerosis and NASH.

    Science.gov (United States)

    Baron, Morgane; Leroyer, Aurélie S; Majd, Zouher; Lalloyer, Fanny; Vallez, Emmanuelle; Bantubungi, Kadiombo; Chinetti-Gbaguidi, Giulia; Delerive, Philippe; Boulanger, Chantal M; Staels, Bart; Tailleux, Anne

    2011-09-01

    Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) are complex pathologies characterized by lipid accumulation, chronic inflammation and extensive tissue remodelling. Microparticles (MPs), small membrane vesicles produced by activated and apoptotic cells, might not only be biomarkers, but also functional actors in these pathologies. The apoE2-KI mouse is a model of atherosclerosis and NAFLD. Activation of the nuclear receptor PPARα decreases atherosclerosis and components of non-alcoholic steatohepatitis (NASH) in the apoE2-KI mouse. (1) To determine whether MPs are present in atherosclerotic lesions, liver and plasma during atherosclerosis and NASH progression in apoE2-KI mice, and (2) to study whether PPARα activation modulates MP concentrations. ApoE2-KI mice were fed a Western diet to induce atherosclerosis and NASH. MPs were isolated from atherosclerotic lesions, liver and blood and quantified by flow cytometry. An increase of MPs was observed in the atherosclerotic lesions and in the liver of apoE2-KI mice upon Western diet feeding. PPARα activation with fenofibrate decreased MP levels in the atherosclerotic lesions in a PPARα-dependent manner, but did not influence MP concentrations in the liver. Here we report that MPs are present in atherosclerotic lesions and in the liver of apoE2-KI mice. Their concentration increased during atherosclerosis and NASH development. PPARα activation differentially modulates MP levels in a tissue-specific manner. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  7. Key Inflammatory Processes in Human NASH Are Reflected in Ldlr−/−.Leiden Mice: A Translational Gene Profiling Study

    NARCIS (Netherlands)

    Morrison, M.C.; Kleemann, R.; Koppen, A. van; Hanemaaijer, R.; Verschuren, L.

    2018-01-01

    Introduction: It is generally accepted that metabolic inflammation in the liver is an important driver of disease progression in NASH and associated matrix remodeling/fibrosis. However, the exact molecular inflammatory mechanisms are poorly defined in human studies. Investigation of key pathogenic

  8. Metabolically induced liver inflammation leads to NASH and differs from LPS- or IL-1 beta-induced chronic inflammation

    NARCIS (Netherlands)

    Liang, Wen; Lindeman, Jan H.; Menke, Aswin L.; Koonen, Debby P.; Morrison, Martine; Havekes, Louis M.; van den Hoek, Anita M.; Kleemann, Robert

    The nature of the chronic inflammatory component that drives the development of non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory triggers have not been investigated systematically. We examined the effect of non-metabolic triggers (lipopolysaccharide (LPS), interleukin-1 beta

  9. Metabolically induced liver inflammation leads to NASH and differs from LPS-or IL-1β-induced chronic inflammation

    NARCIS (Netherlands)

    Liang, W.; Lindeman, J.H.; Menke, A.L.; Koonen, D.P.; Morrison, M.; Havekes, L.M.; Hoek, A.M. van den; Kleemann, R.

    2014-01-01

    The nature of the chronic inflammatory component that drives the development of non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory triggers have not been investigated systematically. We examined the effect of non-metabolic triggers (lipopolysaccharide (LPS), interleukin-1β

  10. Canagliflozin, an SGLT2 inhibitor, attenuates the development of hepatocellular carcinoma in a mouse model of human NASH.

    Science.gov (United States)

    Shiba, Kumiko; Tsuchiya, Kyoichiro; Komiya, Chikara; Miyachi, Yasutaka; Mori, Kentaro; Shimazu, Noriko; Yamaguchi, Shinobu; Ogasawara, Naomi; Katoh, Makoto; Itoh, Michiko; Suganami, Takayoshi; Ogawa, Yoshihiro

    2018-02-05

    Sodium glucose cotransporter 2 (SGLT2) inhibitors, an antidiabetic drug, promotes urinary excretion of glucose by blocking its reabsorption in the renal proximal tubules. It is unclear whether SGLT2 inhibition could attenuate nonalcoholic steatohepatitis (NASH) and NASH-associated hepatocellular carcinoma. We examined the preventive effects of an SGLT2 inhibitor canagliflozin (CANA) in Western diet (WD)-fed melanocortin 4 receptor-deficient (MC4R-KO) mice, a mouse model of human NASH. An eight-week CANA treatment attenuated hepatic steatosis in WD-fed MC4R-KO mice, with increased epididymal fat mass without inflammatory changes. CANA treatment for 20 weeks inhibited the development of hepatic fibrosis in WD-fed MC4R-KO mice. After one year of CANA treatment, the number of liver tumors was significantly reduced in WD-fed MC4R-KO mice. In adipose tissue, CANA suppressed the ratio of oxidative to reduced forms of glutathiones (GSSG/GSH) in WD-fed MC4R-KO mice. Treatment with GSH significantly attenuated the H 2 O 2 -induced upregulation of genes related to NADPH oxidase in 3T3-L1 adipocytes, and that of Il6, Tgfb, and Pdgfb in RAW264.7 cells. This study provides evidence that SGLT2 inhibitors represent the unique class of drugs that can attenuate or delay the onset of NASH and eventually hepatocellular carcinoma, at least partly, through "healthy adipose expansion".

  11. Altered cellular redox status, sirtuin abundance and clock gene expression in a mouse model of developmentally primed NASH.

    Science.gov (United States)

    Bruce, Kimberley D; Szczepankiewicz, Dawid; Sihota, Kiran K; Ravindraanandan, Manoj; Thomas, Hugh; Lillycrop, Karen A; Burdge, Graham C; Hanson, Mark A; Byrne, Christopher D; Cagampang, Felino R

    2016-07-01

    We have previously shown that high fat (HF) feeding during pregnancy primes the development of non-alcoholic steatohepatits (NASH) in the adult offspring. However, the underlying mechanisms are unclear. Since the endogenous molecular clock can regulate hepatic lipid metabolism, we investigated whether exposure to a HF diet during development could alter hepatic clock gene expression and contribute to NASH onset in later life. Female mice were fed either a control (C, 7%kcal fat) or HF (45%kcal fat) diet. Offspring were fed either a C or HF diet resulting in four offspring groups: C/C, C/HF, HF/C and HF/HF. NAFLD progression, cellular redox status, sirtuin expression (Sirt1, Sirt3), and the expression of core clock genes (Clock, Bmal1, Per2, Cry2) and clock-controlled genes involved in lipid metabolism (Rev-Erbα, Rev-Erbβ, RORα, and Srebp1c) were measured in offspring livers. Offspring fed a HF diet developed NAFLD. However HF fed offspring of mothers fed a HF diet developed NASH, coupled with significantly reduced NAD(+)/NADH (pNASH in adulthood, involving altered cellular redox status, reduced sirtuin abundance, and desynchronized clock gene expression. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Obeticholic acid raises LDL-cholesterol and reduces HDL-cholesterol in the Diet-Induced NASH (DIN) hamster model.

    Science.gov (United States)

    Briand, François; Brousseau, Emmanuel; Quinsat, Marjolaine; Burcelin, Rémy; Sulpice, Thierry

    2018-01-05

    The use of rat and mouse models limits the translation to humans for developing novel drugs targeting nonalcoholic steatohepatitis (NASH). Obeticholic acid (OCA) illustrates this limitation since its dyslipidemic effect in humans cannot be observed in these rodents. Conversely, Golden Syrian hamsters have a lipoprotein metabolism mimicking human dyslipidemia since it does express the cholesteryl ester transfer protein (CETP). We therefore developed a Diet-Induced NASH (DIN) hamster model and evaluated the impact of OCA. Compared with chow fed controls, hamsters fed for 20 weeks with a free-choice (FC) diet, developed obesity, insulin resistance, dyslipidemia and NASH (microvesicular steatosis, inflammation, hepatocyte ballooning and perisinusoidal to bridging fibrosis). After 20 weeks of diet, FC fed hamsters were treated without or with obeticholic acid (15mg/kg/day) for 5 weeks. Although a non-significant trend towards higher dietary caloric intake was observed, OCA significantly lowered body weight after 5 weeks of treatment. OCA significantly increased CETP activity and LDL-C levels by 20% and 27%, and reduced HDL-C levels by 20%. OCA blunted hepatic gene expression of Cyp7a1 and Cyp8b1 and reduced fecal bile acids mass excretion by 64% (P DIN hamster replicates benefits and side effects of OCA as observed in humans, and should be useful for evaluating novel drugs targeting NASH. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Strategic trade between two regions with partial local consumer protection - General setup and nash equilibria

    Science.gov (United States)

    Iordanov, Iordan V.; Vassilev, Andrey A.

    2017-12-01

    We construct a model of the trade relations between two regions for the case when the trading entities (consumers) compete for a scarce good and there is an element of strategic interdependence in the trading process. Additionally, local consumers enjoy partial protection in the form of guaranteed access to a part of the locally-supplied quantity of the good. The model is formulated for the general asymmetric case, where the two regions differ in terms of parameters such as income, size of the local market supply, degree of protection and transportation costs. For this general model we establish the existence of Nash equilibria and obtain their form as a function of the model parameters, producing a typology of the equilibria. This is a required step in order to rigorously study various types of price dynamics for the model.

  14. Fishermen's profits maximization: case of generalized Nash equilibrium of a non-symmetrical game.

    Science.gov (United States)

    El Foutayeni, Y; Khaladi, M

    2014-09-01

    In the present paper, we consider a bio-economic equilibrium model which describes the dynamics of a fish population fished by several fishermen seeking to maximize their profits. Each fisherman tries to find the fishing effort which maximizes his profit at biological equilibrium without any consultation with others, but all of them have to respect two constraints: (1) the sustainable management of the resources ; and (2) the preservation of the biodiversity. With all these considerations, our problem leads to a generalized Nash equilibrium problem. The objective is to show that even when a fisherman (i) provides a fishing effort equal to twice the fishing effort of a fisherman (j), then the profit of fisherman (i) is not necessarily double that of fisherman (j).

  15. On the fair division of multiple stochastic pies to multiple agents within the Nash bargaining solution.

    Science.gov (United States)

    Karmperis, Athanasios C; Aravossis, Konstantinos; Tatsiopoulos, Ilias P; Sotirchos, Anastasios

    2012-01-01

    The fair division of a surplus is one of the most widely examined problems. This paper focuses on bargaining problems with fixed disagreement payoffs where risk-neutral agents have reached an agreement that is the Nash-bargaining solution (NBS). We consider a stochastic environment, in which the overall return consists of multiple pies with uncertain sizes and we examine how these pies can be allocated with fairness among agents. Specifically, fairness is based on the Aristotle's maxim: "equals should be treated equally and unequals unequally, in proportion to the relevant inequality". In this context, fairness is achieved when all the individual stochastic surplus shares which are allocated to agents are distributed in proportion to the NBS. We introduce a novel algorithm, which can be used to compute the ratio of each pie that should be allocated to each agent, in order to ensure fairness within a symmetric or asymmetric NBS.

  16. Quantum correlations and Nash equilibria of a bi-matrix game

    International Nuclear Information System (INIS)

    Iqbal, Azhar

    2004-01-01

    Playing a symmetric bi-matrix game is usually physical implemented by sharing pairs of 'objects' between two players. A new setting is proposed that explicitly shows effects of quantum correlations between the pairs on the structure of payoff relations and the 'solutions' of the game. The setting allows a re-expression of the game such that the players play the classical game when their moves are performed on pairs of objects having correlations that satisfy Bell's inequalities. If players receive pairs having quantum correlations the resulting game cannot be considered another classical symmetric bi-matrix game. Also the Nash equilibria of the game are found to be decided by the nature of the correlations. (letter to the editor)

  17. Mixed-strategy Nash equilibrium for a discontinuous symmetric N-player game

    Science.gov (United States)

    Hilhorst, H. J.; Appert-Rolland, C.

    2018-03-01

    We consider a game in which each player must find a compromise between more daring strategies that carry a high risk for him to be eliminated, and more cautious ones that, however, reduce his final score. For two symmetric players this game was originally formulated in 1961 by Dresher, who modeled a duel between two opponents. The game has also been of interest in the description of athletic competitions. We extend here the two-player game to an arbitrary number N of symmetric players. We show that there is a mixed-strategy Nash equilibrium and find its exact analytic expression, which we analyze in particular in the limit of large N, where mean-field behavior occurs. The original game with N  =  2 arises as a singular limit of the general case.

  18. A new geometrical approach to Nash equilibria organization in Eisert's quantum games

    International Nuclear Information System (INIS)

    Schneider, David

    2012-01-01

    We extend the periodic point-based method for Eisert's quantum games (Schneider 2011 J. Phys. A: Math. Theor. 44 095301) to games not previously analyzed. From the comparison of different cases, we observe that games sharing the same classical features (as for instance the symmetrized Battle of the Sexes and the Chicken game) can have different characteristics after the quantization, and conversely, games with different classical behaviors (the Chicken game and the Prisoner's dilemma), are completely equivalent within Eisert's protocol. This fact is reflected in the structure of the map that the periodic point-procedure associates to the quantum game (from which the Nash equilibria are deduced). In order to understand how these unexpected outcomes are generated, we give a geometrical description of our observations in terms of bifurcation theory for maps. (paper)

  19. HCC development is associated to peripheral insulin resistance in a mouse model of NASH.

    Directory of Open Access Journals (Sweden)

    Samuele De Minicis

    Full Text Available NAFLD is the most common liver disease worldwide but it is the potential evolution to NASH and eventually to hepatocellular carcinoma (HCC, even in the absence of cirrhosis, that makes NAFLD of such clinical importance.we aimed to create a mouse model reproducing the pathological spectrum of NAFLD and to investigate the role of possible co-factors in promoting HCC.mice were treated with a choline-deficient L-amino-acid-defined-diet (CDAA or its control (CSAA diet and subjected to a low-dose i.p. injection of CCl4 or vehicle. Insulin resistance was measured by the euglycemic-hyperinsulinemic clamp method. Steatosis, fibrosis and HCC were evaluated by histological and molecular analysis.CDAA-treated mice showed peripheral insulin resistance at 1 month. At 1-3 months, extensive steatosis and fibrosis were observed in CDAA and CDAA+CCl4 groups. At 6 months, equal increase in steatosis and fibrosis was observed between the two groups, together with the appearance of tumor. At 9 months of treatment, the 100% of CDAA+CCl4 treated mice revealed tumor versus 40% of CDAA mice. Insulin-like Growth Factor-2 (IGF-2 and Osteopontin (SPP-1 were increased in CDAA mice versus CSAA. Furthermore, Immunostaining for p-AKT, p-c-Myc and Glypican-3 revealed increased positivity in the tumors.the CDAA model promotes the development of HCC from NAFLD-NASH in the presence of insulin resistance but in the absence of cirrhosis. Since this condition is increasingly recognized in humans, our study provides a model that may help understanding mechanisms of carcinogenesis in NAFLD.

  20. HCC development is associated to peripheral insulin resistance in a mouse model of NASH.

    Science.gov (United States)

    De Minicis, Samuele; Agostinelli, Laura; Rychlicki, Chiara; Sorice, Gian Pio; Saccomanno, Stefania; Candelaresi, Cinzia; Giaccari, Andrea; Trozzi, Luciano; Pierantonelli, Irene; Mingarelli, Eleonora; Marzioni, Marco; Muscogiuri, Giovanna; Gaggini, Melania; Benedetti, Antonio; Gastaldelli, Amalia; Guido, Maria; Svegliati-Baroni, Gianluca

    2014-01-01

    NAFLD is the most common liver disease worldwide but it is the potential evolution to NASH and eventually to hepatocellular carcinoma (HCC), even in the absence of cirrhosis, that makes NAFLD of such clinical importance. we aimed to create a mouse model reproducing the pathological spectrum of NAFLD and to investigate the role of possible co-factors in promoting HCC. mice were treated with a choline-deficient L-amino-acid-defined-diet (CDAA) or its control (CSAA diet) and subjected to a low-dose i.p. injection of CCl4 or vehicle. Insulin resistance was measured by the euglycemic-hyperinsulinemic clamp method. Steatosis, fibrosis and HCC were evaluated by histological and molecular analysis. CDAA-treated mice showed peripheral insulin resistance at 1 month. At 1-3 months, extensive steatosis and fibrosis were observed in CDAA and CDAA+CCl4 groups. At 6 months, equal increase in steatosis and fibrosis was observed between the two groups, together with the appearance of tumor. At 9 months of treatment, the 100% of CDAA+CCl4 treated mice revealed tumor versus 40% of CDAA mice. Insulin-like Growth Factor-2 (IGF-2) and Osteopontin (SPP-1) were increased in CDAA mice versus CSAA. Furthermore, Immunostaining for p-AKT, p-c-Myc and Glypican-3 revealed increased positivity in the tumors. the CDAA model promotes the development of HCC from NAFLD-NASH in the presence of insulin resistance but in the absence of cirrhosis. Since this condition is increasingly recognized in humans, our study provides a model that may help understanding mechanisms of carcinogenesis in NAFLD.

  1. Liver transplantation for NASH cirrhosis is not performed at the expense of major post-operative morbidity.

    Science.gov (United States)

    van den Berg, Eline H; Douwes, Rianne M; de Meijer, Vincent E; Schreuder, Tim C M A; Blokzijl, Hans

    2018-01-01

    Non-alcoholic steatohepatitis (NASH) is an emerging indication for liver transplantation (LT) and coexists with multiple comorbidities. Obese and cirrhotic patients experience more perioperative complications. Limited data exist about short-term complications after LT for NASH cirrhosis. Investigate short-term complications in patients transplanted for NASH cirrhosis. Single center retrospective cohort study including patients >18years who underwent LT between 2009-2015. Exclusion criteria were LT for acute liver failure and non-cirrhotic disease. Post-operative complications and severity within 90-days were classified using the Clavien-Dindo classification of surgical complications and comprehensive complication index (CCI). P<0.05 was significant. Out of 169 eligible patients, 34 patients (20.1%) were transplanted for NASH cirrhosis. These patients were significantly older (59.2 vs. 54.8 years, P=0.01), more obese (61.8% vs. 8.1%, P<0.01), had more diabetes mellitus (73.5% vs. 20%, P<0.01), metabolic syndrome (83.3% vs. 37.8%, P<0.01) and cardiovascular disease (29.4% vs. 11.1%, P<0.01). More grade 1 complications (OR 1.64, 95%CI 1.03-2.63, P=0.04) and more grade 2 urogenital infections (OR 3.4, 95%CI 1.1-10.6, P=0.03) were found. Major complications, CCI, 90-day mortality and graft survival were similar. Despite significantly increased comorbidities in patients transplanted for NASH cirrhosis, major morbidity, mortality and graft survival after 90days were comparable to patients transplanted for other indications. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  2. DSS colitis promotes tumorigenesis and fibrogenesis in a choline-deficient high-fat diet-induced NASH mouse model.

    Science.gov (United States)

    Achiwa, Koichi; Ishigami, Masatoshi; Ishizu, Yoji; Kuzuya, Teiji; Honda, Takashi; Hayashi, Kazuhiko; Hirooka, Yoshiki; Katano, Yoshiaki; Goto, Hidemi

    2016-01-29

    Nonalcoholic steatohepatitis (NASH) patients progress to liver cirrhosis and even hepatocellular carcinoma (HCC). Several lines of evidence indicate that accumulation of lipopolysaccharide (LPS) and disruption of gut microbiota play contributory roles in HCC. Moreover, in a dextran sodium sulfate (DSS)-induced colitis model in mice, a high-fat diet increases portal LPS level and promotes hepatic inflammation and fibrosis. However, this diet-induced NASH model requires at least 50 weeks for carcinogenesis. In this study, we sought to determine whether increased intestinal permeability would aggravate liver inflammation and fibrosis and accelerate tumorigenesis in a diet-induced NASH model. Mice were fed a choline-deficient high-fat (CDHF) diet for 4 or 12 weeks. The DSS group was fed CDHF and intermittently received 1% DSS in the drinking water. Exposure to DSS promoted mucosal changes such as crypt loss and increased the number of inflammatory cells in the colon. In the DSS group, portal LPS levels were elevated at 4 weeks, and the proportions of Clostridium cluster XI in the fecal microbiota were elevated. In addition, levels of serum transaminase, number of lobular inflammatory cells, F4/80 staining-positive area, and levels of inflammatory cytokines were all elevated in the DSS group. Liver histology in the DSS group revealed severe fibrosis at 12 weeks. Liver tumors were detected in the DSS group at 12 weeks, but not in the other groups. Thus, DSS administration promoted liver tumors in a CDHF diet-induced NASH mouse over the short term, suggesting that the induction of intestinal inflammation and gut disruption of microbiota in NASH promote hepatic tumorigenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Progression and Regression of Hepatic Lesions in a Mouse Model of NASH Induced by Dietary Intervention and Its Implications in Pharmacotherapy

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    Zhi-Ming Ding

    2018-05-01

    Full Text Available Understanding of the temporal changes of hepatic lesions in the progression and regression of non-alcoholic steatohepatitis (NASH is vital to elucidation of the pathogenesis of NASH, and critical to the development of a strategy for NASH pharmacotherapy. There are challenges in studying hepatic lesion progression and regression in NASH patients due to the slow development of NASH in humans, one being the requirement for multiple biopsies during the longitudinal follow-up. Here we studied lesion progression and regression in the diet-induced animal model of NASH by application or removal of the pathogenic diet for multiple time periods. Male C57BL/6 mice fed Western diet developed progressive hepatic steatosis/macrovesicular vacuolation, inflammation, and hepatocyte degeneration, as well as perisinusoidal fibrosis and occasionally portal fibrosis as early as 2 months after initiation of the Western diet. In the same period, the mice exhibited elevated ALT (alanine aminotransferase and AST (aspartate aminotransferase enzyme activities, CK18 (cytokeratin−18, PIIINP (N-terminal propeptide of type III collagen, and TIMP-1 (tissue inhibitor of metalloproteinase−1. Hepatic steatosis diminished rapidly when the Western diet was replaced by normal rodent chow diet and hepatic inflammation and hepatocyte degeneration were also reduced. Interestingly, perisinusoidal fibrosis and portal fibrosis regressed 8 months after chow diet replacement. To understand pharmacotherapy for NASH, mice with established NASH hepatic lesions were treated with either FXR agonist obeticholic acid (Ocaliva, or CCR2/5 antagonist Cenicriviroc. Similar to the diet replacement, metabolic modulator Ocaliva markedly reduced steatosis/macrovesicular vacuolation, hepatic inflammation, and hepatocyte degeneration effectively, but exhibited no significant effect on liver fibrosis. Anti-inflammation drug Cenicriviroc, on the other hand, markedly decreased inflammation and hepatocyte

  4. Gut microbiome composition in lean patients with NASH is associated with liver damage independent of caloric intake: A prospective pilot study.

    Science.gov (United States)

    Duarte, S M B; Stefano, J T; Miele, L; Ponziani, F R; Souza-Basqueira, M; Okada, L S R R; de Barros Costa, F G; Toda, K; Mazo, D F C; Sabino, E C; Carrilho, F J; Gasbarrini, A; Oliveira, C P

    2018-04-01

    The aim of the study was to compare the gut microbiomes from obese and lean patients with or without NASH to outline phenotypic differences. We performed a cross-sectional pilot study comprising biopsy-proven NASH patients grouped according to BMI. Microbiome DNA was extracted from stool samples, and PCR amplification was performed using primers for the V4 region of the 16S rRNA gene. The amplicons were sequenced using the Ion PGM Torrent platform, and data were analyzed using QIIME software. Macronutrient consumption was analyzed by a 7-day food record. Liver fibrosis ≥ F2 was associated with increased abundance of Lactobacilli (p = 0.0007). NASH patients showed differences in Faecalibacterium, Ruminococcus, Lactobacillus and Bifidobacterium abundance compared with the control group. Lean NASH patients had a 3-fold lower abundance of Faecalibacterium and Ruminococcus (p = 0.004), obese NASH patients were enriched in Lactobacilli (p = 0.002), and overweight NASH patients had reduced Bifidobacterium (p = 0.018). Moreover, lean NASH patients showed a deficiency in Lactobacillus compared with overweight and obese NASH patients. This group also appeared similar to the control group with regard to gut microbiome alpha diversity. Although there were qualitative differences between lean NASH and overweight/obese NASH, they were not statistically significant (p = 0.618). The study limitations included a small sample size, a food questionnaire that collected only qualitative and semi-quantitative data, and variations in group gender composition that may influence differences in FXR signaling, bile acids metabolism and the composition of gut microbiota. Our preliminary finding of a different pathogenetic process in lean NASH patients needs to be confirmed by larger studies, including those with patient populations stratified by sex and dietary habits. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the

  5. A Bidding Methodology by Nash Equilibrium for Finite Generators Participating in Imperfect Electricity Markets

    Science.gov (United States)

    Satyaramesh, P. V.

    2014-01-01

    This paper presents an application of finite n-person non-cooperative game theory for analyzing bidding strategies of generators in a deregulated energy marketplace with Pool Bilateral contracts so as to maximize their net profits. A new methodology to build bidding methodology for generators participating in oligopoly electricity market has been proposed in this paper. It is assumed that each generator bids a supply function. This methodology finds out the coefficients in the supply function of generators in order to maximize benefits in an environment of competing rival bidders. A natural choice for developing strategies is Nash Equilibrium (NE) model incorporating mixed strategies, for solving the bidding problem of electrical market. Associated optimal profits are evaluated for a combination of set of pure strategies of bidding of generators, and payoff matrix has been constructed. The optimal payoff is calculated by using NE. An attempt has also been made to minimize the gap between the optimal payoff and the payoff obtained by a possible mixed strategies combination. The algorithm is coded in MATLAB. A numerical example is used to illustrate the essential features of the approach and the results are proved to be the optimal values.

  6. Robust Nash Dynamic Game Strategy for User Cooperation Energy Efficiency in Wireless Cellular Networks

    Directory of Open Access Journals (Sweden)

    Shuhuan Wen

    2012-01-01

    Full Text Available Recently, there is an emerging trend of addressing “energy efficiency” aspect of wireless communications. It has been shown that cooperating users relay each other's information to improve data rates. The energy is limited in the wireless cellular network, but the mobile users refuse to relay. This paper presents an approach that encourages user cooperation in order to improve the energy efficiency. The game theory is an efficient method to solve such conflicts. We present a cellular framework in which two mobile users, who desire to communicate with a common base station, may cooperate via decode-and-forward relaying. In the case of imperfect information assumption, cooperative Nash dynamic game is used between the two users' cooperation to tackle the decision making problems: whether to cooperate and how to cooperate in wireless networks. The scheme based on “cooperative game theory” can achieve general pareto-optimal performance for cooperative games, and thus, maximize the entire system payoff while maintaining fairness.

  7. The Combination of Blueberry Juice and Probiotics Ameliorate Non-Alcoholic Steatohepatitis (NASH) by Affecting SREBP-1c/PNPLA-3 Pathway via PPAR-α

    Science.gov (United States)

    Ren, Tingting; Zhu, Juanjuan; Zhu, Lili; Cheng, Mingliang

    2017-01-01

    Nonalcoholic steatohepatitis (NASH) is liver inflammation and a major threat to public health. Several pharmaceutical agents have been used for NASH therapy but their high-rate side effects limit the use. Blueberry juice and probiotics (BP) have anti-inflammation and antibacterial properties, and may be potential candidates for NASH therapy. To understand the molecular mechanism, Sprague Dawley rats were used to create NASH models and received different treatments. Liver tissues were examined using HE (hematoxylin and eosin) and ORO (Oil Red O) stain, and serum biochemical indices were measured. The levels of peroxisome proliferators-activated receptor (PPAR)-α, sterol regulatory element binding protein-1c (SREBP-1c), Patatin-like phospholipase domain-containing protein 3 (PNPLA-3), inflammatory cytokines and apoptosis biomarkers in liver tissues were measured by qRT-PCR and Western blot. HE and ORO analysis indicated that the hepatocytes were seriously damaged with more and larger lipid droplets in NASH models while BP reduced the number and size of lipid droplets (p < 0.05). Meanwhile, BP increased the levels of SOD (superoxide dismutase), GSH (reduced glutathione) and HDL-C (high-density lipoprotein cholesterol), and reduced the levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), TG (triglycerides), LDL-C (low-density lipoprotein cholesterol) and MDA (malondialdehyde) in NASH models (p < 0.05). BP increased the level of PPAR-α (Peroxisome proliferator-activated receptor α), and reduced the levels of SREBP-1c (sterol regulatory element binding protein-1c) and PNPLA-3 (Patatin-like phospholipase domain-containing protein 3) (p < 0.05). BP reduced hepatic inflammation and apoptosis by affecting IL-6 (interleukin 6), TNF-α (Tumor necrosis factor α), caspase-3 and Bcl-2 in NASH models. Furthermore, PPAR-α inhibitor increased the level of SREBP-1c and PNPLA-3. Therefore, BP prevents NASH progression by affecting SREBP-1c/PNPLA-3 pathway

  8. Advanced Oil Recovery Technologies for Improved Recovery from Slope Basin Clastic Reservoirs, Nash Draw Brushy Canyon Pool, Eddy County, NM

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, Mark B.

    1999-02-24

    The Nash Draw Brushy Canyon Pool in Eddy County New Mexico is a cost-shared field demonstration project in the US Department of Energy Class II Program. A major goal of the Class III Program is to stimulate the use of advanced technologies to increase ultimate recovery from slope-basin clastic reservoirs. Advanced characterization techniques are being used at the Nash Draw project to develop reservoir management strategies for optimizing oil recovery from this Delaware reservoir. Analysis, interpretation, and integration of recently acquired geologic, geophysical, and engineering data revealed that the initial reservoir characterization was too simplistic to capture the critical features of this complex formation. Contrary to the initial characterization, a new reservoir description evolved that provided sufficient detail regarding the complexity of the Brushy Canyon interval at Nash Draw. This new reservoir description is being used as a risk reduction tool to identify ''sweet spots'' for a development drilling program as well as to evaluate pressure maintenance strategies. The reservoir characterization, geological modeling, 3-D seismic interpretation, and simulation studies have provided a detailed model of the Brushy Canyon zones. This model was used to predict the success of different reservoir management scenarios and to aid in determining the most favorable combination of targeted drilling, pressure maintenance, well simulation, and well spacing to improve recovery from this reservoir.

  9. A longitudinal study of whole body, tissue, and cellular physiology in a mouse model of fibrosing NASH with high fidelity to the human condition.

    Science.gov (United States)

    Krishnan, Anuradha; Abdullah, Tasduq Sheikh; Mounajjed, Taofic; Hartono, Stella; McConico, Andrea; White, Thomas; LeBrasseur, Nathan; Lanza, Ian; Nair, Sreekumaran; Gores, Gregory; Charlton, Michael

    2017-06-01

    The sequence of events that lead to inflammation and fibrosing nonalcoholic steatohepatitis (NASH) is incompletely understood. Hence, we investigated the chronology of whole body, tissue, and cellular events that occur during the evolution of diet-induced NASH. Male C57Bl/6 mice were assigned to a fast-food (FF; high calorie, high cholesterol, high fructose) or standard-chow (SC) diet over a period of 36 wk. Liver histology, body composition, mitochondrial respiration, metabolic rate, gene expression, and hepatic lipid content were analyzed. Insulin resistance [homeostasis model assessment-insulin resistance (HOMA-IR)] increased 10-fold after 4 wk. Fibrosing NASH was fully established by 16 wk. Total hepatic lipids increased by 4 wk and remained two- to threefold increased throughout. Hepatic triglycerides declined from sixfold increase at 8 wk to threefold increase by 36 wk. In contrast, hepatic cholesterol levels steadily increased from baseline at 8 wk to twofold by 36 wk. The hepatic immune cell population altered over time with macrophages persisting beyond 16 wk. Mitochondrial oxygen flux rates of FF mice diet were uniformly lower with all the tested substrates (13-276 pmol·s -1 ·ml -1 per unit citrate synthase) than SC mice (17-394 pmol·s -1 ·ml -1 per unit citrate synthase) and was accompanied by decreased mitochondrial:nuclear gene copy number ratios after 4 wk. Metabolic rate was lower in FF mice. Mitochondrial glutathione was significantly decreased at 24 wk in FF mice. Expression of dismutases and catalase was also decreased in FF mice. The evolution of NASH in the FF diet-induced model is multiphasic, particularly in terms of hepatic lipid composition. Insulin resistance precedes hepatic inflammation and fibrosis. Mitochondrial dysfunction and depletion occur after the histological features of NASH are apparent. Collectively, these observations provide a unique overview of the sequence of changes that coevolve with the histological evolution of

  10. Metabolomic profiling to identify predictors of response to vitamin E for non-alcoholic steatohepatitis (NASH.

    Directory of Open Access Journals (Sweden)

    Jianfeng Cheng

    Full Text Available Vitamin E was recently shown to improve hepatic histology in a randomized controlled trial of pioglitazone or vitamin E for nonalcoholic steatohepatitis (PIVENS. The current study utilized samples collected in the PIVENS trial to identify: (1 baseline metabolomic profiles that could identify who would respond to vitamin E treatment and (2 end of treatment metabolomic profiles reflective of histologic improvement. A comprehensive analysis of metabolomics profiles (n = 547 quantified by mass spectrometry was performed in vitamin E responders (n = 16, vitamin E non-responders (n = 15, and placebo responders (n = 15. At baseline, phenyl-propionic acid (Odds ratio: 29.4, p<0.01, indole-propionic acid levels (Odds ratio: 16.2, p<0.01 were directly associated with a subsequent histologic response to vitamin E treatment whereas γ-carboxyethylhydroxychroman (CEHC levels were inversely related to histologic response. Adjusting for baseline values by analysis of covariance, the end of treatment levels of gamma-glutamyl leucine (Fold change: 0.82, p<0.02 and gamma-glutamyl valine (Fold change: 0.8, p<0.03 were significantly lower in vitamin E responders compared to non-responders. The levels of gamma-glutamyl transpeptidase were not significantly different across the two groups. Subjects receiving placebo who demonstrated a histologic improvement also demonstrated lower levels of gamma-glutamylated amino acids (leucine, valine and isoleucine compared to vitamin E non-responders. These data provide exploratory proof that there are measurable differences in the metabolic profile of subjects who are likely (vs unlikely to respond to vitamin E treatment for NASH and in those experiencing histologic improvement (vs no improvement on treatment and support further studies to validate these biomarkers.

  11. Efficient Nash Equilibrium Resource Allocation Based on Game Theory Mechanism in Cloud Computing by Using Auction.

    Science.gov (United States)

    Nezarat, Amin; Dastghaibifard, G H

    2015-01-01

    One of the most complex issues in the cloud computing environment is the problem of resource allocation so that, on one hand, the cloud provider expects the most profitability and, on the other hand, users also expect to have the best resources at their disposal considering the budget constraints and time. In most previous work conducted, heuristic and evolutionary approaches have been used to solve this problem. Nevertheless, since the nature of this environment is based on economic methods, using such methods can decrease response time and reducing the complexity of the problem. In this paper, an auction-based method is proposed which determines the auction winner by applying game theory mechanism and holding a repetitive game with incomplete information in a non-cooperative environment. In this method, users calculate suitable price bid with their objective function during several round and repetitions and send it to the auctioneer; and the auctioneer chooses the winning player based the suggested utility function. In the proposed method, the end point of the game is the Nash equilibrium point where players are no longer inclined to alter their bid for that resource and the final bid also satisfies the auctioneer's utility function. To prove the response space convexity, the Lagrange method is used and the proposed model is simulated in the cloudsim and the results are compared with previous work. At the end, it is concluded that this method converges to a response in a shorter time, provides the lowest service level agreement violations and the most utility to the provider.

  12. "Jezhi" v bolshom gorode / Tatjana Pissareva

    Index Scriptorium Estoniae

    Pissareva, Tatjana

    2004-01-01

    Loomingulise ühenduse "Jezhi" liikmete tööde näitus on Viru Keskuse neljandal korrusel. Osalevad Arnold Repin, Dmitri Lazjuk, Anzhela Belenova, Juri Ivanov, Juri Sedõhh, Konstantin Tsherenkov ja teised

  13. Pomosh sobakam, koshkam i loshadjam / Tatjana Pissareva

    Index Scriptorium Estoniae

    Pissareva, Tatjana

    2006-01-01

    Mittetulundusühing Pets aitab hüljatud koertele ja kassidele uut kodu leida, samuti aidatakse varjupaiku üle Eesti korjates toitu ning pakkudes veterinaarset abi. Petsil on aktiivseid liikmeid Soomes ja Rootsis

  14. Lotmani seminar / Tatjana Stepanishtsheva ; tlk. Mall Jõgi

    Index Scriptorium Estoniae

    Stepaništševa, Tatjana, 1973-

    2007-01-01

    Tartu Ülikoolis vene kirjanduse õppetooli korraldatud iga-aastasest Lotmani seminarist. 2007. aastal tähistati Juri Lotmani 85. sünniaastapäeva, Zara Mintsi 80. sünniaastapäeva ja vene kirjanduse kateedri 60. aastapäeva

  15. Kruglõi stol / Tatjana Iljina

    Index Scriptorium Estoniae

    Iljina, Tatjana

    2002-01-01

    Presidendi juurest tegutsev rahvusvähemuste ümarlaud pidas järjekordset istungit. Põhiteemaks pühapäevakoolide finantseerimine. Osalesid ka Arnold Rüütel, Andra Veidemann, Eldar Efendijev, Edgar Savisaar

  16. Hip-hop, Onegin - pop! / Tatjana Aleksandrova

    Index Scriptorium Estoniae

    Aleksandrova, Tatjana, 1945-

    2004-01-01

    Erateatrikooli KS, mida juhib Svetlana Krassman, lavastus A. Pushkini poeemi "Jevgeni Onegin" motiividel. Noortelavastuse muusikalises seades kasutatakse klassikalise muusika aranzheeringuid ja räppi, kostüümidraamat koos hip-hop rõivastiiliga

  17. Nash Bargaining Game-Theoretic Framework for Power Control in Distributed Multiple-Radar Architecture Underlying Wireless Communication System

    Directory of Open Access Journals (Sweden)

    Chenguang Shi

    2018-04-01

    Full Text Available This paper presents a novel Nash bargaining solution (NBS-based cooperative game-theoretic framework for power control in a distributed multiple-radar architecture underlying a wireless communication system. Our primary objective is to minimize the total power consumption of the distributed multiple-radar system (DMRS with the protection of wireless communication user’s transmission, while guaranteeing each radar’s target detection requirement. A unified cooperative game-theoretic framework is proposed for the optimization problem, where interference power constraints (IPCs are imposed to protect the communication user’s transmission, and a minimum signal-to-interference-plus-noise ratio (SINR requirement is employed to provide reliable target detection for each radar. The existence, uniqueness and fairness of the NBS to this cooperative game are proven. An iterative Nash bargaining power control algorithm with low computational complexity and fast convergence is developed and is shown to converge to a Pareto-optimal equilibrium for the cooperative game model. Numerical simulations and analyses are further presented to highlight the advantages and testify to the efficiency of our proposed cooperative game algorithm. It is demonstrated that the distributed algorithm is effective for power control and could protect the communication system with limited implementation overhead.

  18. An analysis of capacity and price trajectories for the Ontario electricity market using dynamic Nash equilibrium under uncertainty

    International Nuclear Information System (INIS)

    Genc, T.S.; Suvrajeet Sen

    2008-01-01

    This paper studies investments in the Ontario Electricity Market which is currently being restructured. Our methodology is based on the concept of S-adapted open-loop Nash equilibrium. We examine the evolution of capital investments and pricing behavior of suppliers as uncertain electricity demand evolves over time (in Ontario). This study is particularly interesting since we compare the implications of two policies: (i) the current setting in which Ontario Power Generation (OPG) retains its generation units; (ii) the policy (set up in 2003) that required the divestiture of the largest supplier, OPG, and aimed to increase the number of independent suppliers in Ontario. We mainly focus on the independent generators like Bruce Nuclear. We use the tools of Stochastic Programming to compute the S-adapted open-loop Nash equilibrium market outcomes. We find that in the three-player market total capacity installation and market prices are higher than the ones in the five-player market. That is higher capacity may not necessarily alleviate exercise of market power. We also confirm the prediction by the National Energy Board that in a market with five major players, OPG's market share may reduce to a percentage between 35% and 40%. (author)

  19. Screening for therapeutic trials and treatment indication in clinical practice: MACK-3, a new blood test for the diagnosis of fibrotic NASH.

    Science.gov (United States)

    Boursier, J; Anty, R; Vonghia, L; Moal, V; Vanwolleghem, T; Canivet, C M; Michalak, S; Bonnafous, S; Michielsen, P; Oberti, F; Iannelli, A; Van Gaal, L; Patouraux, S; Blanchet, O; Verrijken, A; Gual, P; Rousselet, M-C; Driessen, A; Hunault, G; Bertrais, S; Tran, A; Calès, P; Francque, S

    2018-03-25

    The composite histological endpoint comprising nonalcoholic steatohepatitis (NASH) and NAFLD activity score ≥4 and advanced fibrosis (F ≥ 2) ("fibrotic NASH") is becoming an important diagnostic target in NAFLD: it is currently used to select patients for inclusion in phase III therapeutic trials and will ultimately be used to indicate treatment in clinical practice once the new drugs are approved. To develop a new blood test specifically dedicated for this new diagnostic target of interest. Eight Hundred and forty-six biopsy-proven NAFLD patients from three centres (Angers, Nice, Antwerp) were randomised into derivation and validation sets. The blood fibrosis tests BARD, NFS and FIB4 had poor accuracy for fibrotic NASH with respective AUROC: 0.566 ± 0.023, 0.654 ± 0.023, 0.732 ± 0.021. In the derivation set, fibrotic NASH was independently predicted by AST, HOMA and CK18; all three were combined in the new blood test MACK-3 (hoMa, Ast, CK18) for which 90% sensitivity and 95% specificity cut-offs were calculated. In the validation set, MACK-3 had a significantly higher AUROC (0.847 ± 0.030, P ≤ 0.002) than blood fibrosis tests. Using liver biopsy in the grey zone between the two cut-offs (36.0% of the patients), MACK-3 provided excellent accuracy for the diagnosis of fibrotic NASH with 93.3% well-classified patients, sensitivity: 90.0%, specificity: 94.2%, positive predictive value: 81.8% and negative predictive value: 97.0%. The new blood test MACK-3 accurately diagnoses fibrotic NASH. This new test will facilitate patient screening and inclusion in NAFLD therapeutic trials and will enable the identification of patients who will benefit from the treatments once approved. © 2018 John Wiley & Sons Ltd.

  20. The balance between IL-17 and IL-22 produced by liver-infiltrating T-helper cells critically controls NASH development in mice.

    Science.gov (United States)

    Rolla, Simona; Alchera, Elisa; Imarisio, Chiara; Bardina, Valentina; Valente, Guido; Cappello, Paola; Mombello, Cristina; Follenzi, Antonia; Novelli, Francesco; Carini, Rita

    2016-02-01

    The mechanisms responsible for the evolution of steatosis towards NASH (non-alcoholic steatohepatitis) and fibrosis are not completely defined. In the present study we evaluated the role of CD4(+) T-helper (Th) cells in this process. We analysed the infiltration of different subsets of CD4(+) Th cells in C57BL/6 mice fed on a MCD (methionine choline-deficient) diet, which is a model reproducing all phases of human NASH progression. There was an increase in Th17 cells at the beginning of NASH development and at the NASH-fibrosis transition, whereas levels of Th22 cells peaked between the first and the second expansion of Th17 cells. An increase in the production of IL (interleukin)-6, TNFα (tumour necrosis factor α), TGFβ (transforming growth factor β) and CCL20 (CC chemokine ligand 20) accompanied the changes in Th17/Th22 cells. Livers of IL-17(-/-) mice were protected from NASH development and characterized by an extensive infiltration of Th22 cells. In vitro, IL-17 exacerbated the JNK (c-Jun N-terminal kinase)-dependent mouse hepatocyte lipotoxicity induced by palmitate. IL-22 prevented lipotoxicity through PI3K (phosphoinositide 3-kinase)-mediated inhibition of JNK, but did not play a protective role in the presence of IL-17, which up-regulated the PI3K/Akt inhibitor PTEN (phosphatase and tensin homologue deleted on chromosome 10). Consistently, livers of IL-17(-/-) mice fed on the MCD diet displayed decreased activation of JNK, reduced expression of PTEN and increased phosphorylation of Akt compared with livers of wild-type mice. Hepatic infiltration of Th17 cells is critical for NASH initiation and development of fibrosis in mice, and reflects an infiltration of Th22 cells. Th22 cells are protective in NASH, but only in the absence of IL-17. These data strongly support the potentiality of clinical applications of IL-17 inhibitors that can prevent NASH by both abolishing the lipotoxic action of IL-17 and allowing IL-22-mediated protection. © 2016 Authors

  1. Defining the Polar Vortex Edge Using an N2O: Potential Temperature Correlation Versus the Nash Criterion: A Comparison

    Science.gov (United States)

    Greenblatt, Jeffery B.; Jost, Hans-Juerg; Loewenstein, Max; Podolske, James R.; Bui, T. Paul; Hurst, Dale F.; Elkins, James W.; Herman, Robert L.; Webster, Christopher R.; Schauffler, Sue M.; hide

    2001-01-01

    A prerequisite to study phenomena in the winter stratospheric polar vortex is the separation of measurements inside and outside the dynamical barrier of the vortex edge. We describe a technique to accurately determine the inner edge of the vortex boundary region from measurements of potential temperature and a trace gas, such as N2O, and apply it to in situ aircraft and balloon measurements from the SOLVE/THESE02000 Arctic campaign. The method may be used to refine the Nash algorithm, which, due to the inherently coarser resolution of potential vorticity on which it is dependent, may misidentify the inner edge by up to 466 km, and omit the identification of small, extra-vortex filaments within the vortex.

  2. From rationality to cooperativeness: The totally mixed Nash equilibrium in Markov strategies in the iterated Prisoner's Dilemma.

    Directory of Open Access Journals (Sweden)

    Ivan S Menshikov

    Full Text Available In this research, the social behavior of the participants in a Prisoner's Dilemma laboratory game is explained on the basis of the quantal response equilibrium concept and the representation of the game in Markov strategies. In previous research, we demonstrated that social interaction during the experiment has a positive influence on cooperation, trust, and gratefulness. This research shows that the quantal response equilibrium concept agrees only with the results of experiments on cooperation in Prisoner's Dilemma prior to social interaction. However, quantal response equilibrium does not explain of participants' behavior after social interaction. As an alternative theoretical approach, an examination was conducted of iterated Prisoner's Dilemma game in Markov strategies. We built a totally mixed Nash equilibrium in this game; the equilibrium agrees with the results of the experiments both before and after social interaction.

  3. [Effects and mechanisms of the inflammatory reaction related to NASH and induced by activation of the cholinergic anti-inflammatory pathway].

    Science.gov (United States)

    Zhou, Zhou; Chen, Xiaomei; Li, Fuqiang; Tang, Cuilan

    2015-01-01

    To investigate the effects and mechanisms of the inflammatory reaction related to nonalcoholic steatohepatitis (NASH) and induced by activation of the cholinergic anti-inflammatory pathway. A mouse model of NASH was established by feeding a high-fat and high-sugar diet.Activation of the cholinergic anti-inflammatory pathway was achieved by nicotine administration to the NASH modeled mice and normal controls. Liver biopsies were taken and the concentrations of cytokines were measured. Isolated liver primary Kupffer cells and RAw264.7 cells were cultured, pre-treated or not with lipopolysaccharide (LPS) and exposed to nicotine, after which the supernatant concentrations of IL-6 and TNFa were determined by ELISA. The protein expression levels of phosphorylated (p)-NF-kB and I k B were detected in primary cultured Kupffer cells by western blotting. The mouse model of NASH was successfully established, as evidenced by findings from liver biopsy and serum liver function tests. The degree of liver inflammation in the NASH mice decreased after nicotine administration, and the level of serum TNFa also significantly decreased. The levels of serum TNFa were 21.95+/-0.8 pg/mL in nicotine-treated mice and 38.07+/-1.7 pg/mL in the non-nicotine-treated NASH mice (P less than 0.05). The nicotine treatment also significantly reduced the concentration of TNFa in the culture supernatants of Kupffer cells after LPS stimulation; moreover, the supernatant level of TNFa decreased significantly after the nicotine treatment (Pless than 0.05). LPS stimulation of the RAw264.7 cells led to an increased level ofp-NF-kB and a reduced level ofI-kB, suggesting that the NF-kB pathway had been activated; different doses of nicotine pre-treatment led to down-regulation of the p-NF-kB level and up-regulation of the I-kB level, both in dose-dependent manners. Activating the cholinergic anti-inflammatory pathway inhibits the NASH-related inflammatory reaction, and the mechanism for this inhibition

  4. Computing the Stackelberg/Nash equilibria using the extraproximal method: Convergence analysis and implementation details for Markov chains games

    Directory of Open Access Journals (Sweden)

    Trejo Kristal K.

    2015-06-01

    Full Text Available In this paper we present the extraproximal method for computing the Stackelberg/Nash equilibria in a class of ergodic controlled finite Markov chains games. We exemplify the original game formulation in terms of coupled nonlinear programming problems implementing the Lagrange principle. In addition, Tikhonov’s regularization method is employed to ensure the convergence of the cost-functions to a Stackelberg/Nash equilibrium point. Then, we transform the problem into a system of equations in the proximal format. We present a two-step iterated procedure for solving the extraproximal method: (a the first step (the extra-proximal step consists of a “prediction” which calculates the preliminary position approximation to the equilibrium point, and (b the second step is designed to find a “basic adjustment” of the previous prediction. The procedure is called the “extraproximal method” because of the use of an extrapolation. Each equation in this system is an optimization problem for which the necessary and efficient condition for a minimum is solved using a quadratic programming method. This solution approach provides a drastically quicker rate of convergence to the equilibrium point. We present the analysis of the convergence as well the rate of convergence of the method, which is one of the main results of this paper. Additionally, the extraproximal method is developed in terms of Markov chains for Stackelberg games. Our goal is to analyze completely a three-player Stackelberg game consisting of a leader and two followers. We provide all the details needed to implement the extraproximal method in an efficient and numerically stable way. For instance, a numerical technique is presented for computing the first step parameter (λ of the extraproximal method. The usefulness of the approach is successfully demonstrated by a numerical example related to a pricing oligopoly model for airlines companies.

  5. Usefulness of the index of NASH - ION for the diagnosis of steatohepatitis in patients with non-alcoholic fatty liver: An external validation study.

    Science.gov (United States)

    Younes, Ramy; Rosso, Chiara; Petta, Salvatore; Cucco, Monica; Marietti, Milena; Caviglia, Gian Paolo; Ciancio, Alessia; Abate, Maria Lorena; Cammà, Carlo; Smedile, Antonina; Craxì, Antonio; Saracco, Giorgio Maria; Bugianesi, Elisabetta

    2017-10-13

    The non-invasive identification of steatohepatitis (NASH) in patients with Non-Alcoholic Fatty Liver Disease is an unmet need in clinical practice. Index of NASH (ION) is a new tool for the prediction of NASH. We aimed to externally validate ION and to compare it with CK-18. Since necroinflammation precedes fibrosis, we also tested ION in combination with non-invasive tools for fibrosis. We analysed data from 292 Italian patients (169 Southern cohort, and 123 Northern cohort) with an histological diagnosis of NAFLD. The ION, FIB-4 and NFS scores were calculated according to published algorithms. Serum cytokeratin18-Aspartate396 levels and liver stiffness (LS) by Fibroscan were assessed within three months from liver biopsy. The diagnostic accuracy of ION for the identification of NASH was not as satisfactory as reported (area under the ROC curve, AUROC = 0.687 [95% CI = 0.62-0.75]). The proposed cut-off value ≥50 showed a poor sensitivity (Se) (28%) and a good specificity (Sp) (92%), with a positive predictive value (PPV) of 91% and a negative predictive value (NPV) of 30%. A new cut-off value >26 improved Se (73%) but decreased Sp (60%) (PPV of 84% and a NPV of 43%). ION performed slightly better in obese NAFLD (AUROC = 0.700). The combination of ION and markers of fibrosis did not improve the identification of advanced liver disease. ION is not feasible for the non-invasive diagnosis of NASH across different populations of NAFLD patients, mainly because its limited reproducibility in non-obese subjects. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Loss of miR-141/200c ameliorates hepatic steatosis and inflammation by reprogramming multiple signaling pathways in NASH

    Science.gov (United States)

    Tran, Melanie; Lee, Sang-Min; Shin, Dong-Ju

    2017-01-01

    Accumulation of lipid droplets and inflammatory cell infiltration is the hallmark of nonalcoholic steatohepatitis (NASH). The roles of noncoding RNAs in NASH are less known. We aim to elucidate the function of miR-141/200c in diet-induced NASH. WT and miR-141/200c–/– mice were fed a methionine and choline deficient (MCD) diet for 2 weeks to assess markers of steatosis, liver injury, and inflammation. Hepatic miR-141 and miR-200c RNA levels were highly induced in human patients with NASH fatty liver and in WT MCD mice. miR-141/200c–/– MCD mice had reduced liver weights and triglyceride (TG) levels, which was associated with increased microsomal TG transfer protein (MTTP) and PPARα but reduced SREBP1c and FAS expression. Inflammation was attenuated and F4/80 macrophage activation was suppressed in miR-141/200c–/– mice, as evidenced by decreased serum aminotransferases and IL-6 and reduced hepatic proinflammatory, neutrophil, and profibrotic genes. Treatment with LPS in BM-derived macrophages isolated from miR-200c/141–/– mice polarized macrophages toward the M2 antiinflammatory state by increasing Arg1 and IL-10 levels while decreasing the M1 marker iNOS. In addition, elevated phosphorylated AMPK (p-AMPK), p-AKT, and p-GSK3β and diminished TLR4 and p-mTOR/p-4EBP1 proteins were observed. Lipidomics and metabolomics revealed alterations of TG and phosphatidylcholine (PC) lipid species by miR-141/200c deficiency. In summary, miR-141/200c deficiency diminished NASH-associated hepatic steatosis and inflammation by reprogramming lipid and inflammation signaling pathways. PMID:29093267

  7. 3, 3'-Diindolylmethane alleviates steatosis and the progression of NASH partly through shifting the imbalance of Treg/Th17 cells to Treg dominance.

    Science.gov (United States)

    Liu, Yun; She, Weimin; Wang, Fuping; Li, Jing; Wang, Jiyao; Jiang, Wei

    2014-12-01

    This study was designed to discuss the effects of 3, 3'-diindolylmethane (DIM) on methionine-choline-deficient (MCD)-diet induced mouse nonalcoholic steatohepatitis (NASH) and the potential mechanisms. NASH mice were administrated with or without DIM at different concentrations for 8 weeks. Both the in-vivo and in-vitro effects of DIM on Treg/Th17 imbalance during NASH progression were analyzed. The in-vivo blocking of CD25 or IL-17 was performed to respectively deplete respective function of Treg or Th17 subset. Besides, with the assistance of AhR antagonist CH223191 and anti-TLR4 neutralizing antibody, we designed the in-vitro DIM-incubation experiments to discuss the roles of aryl hydrocarbon receptor (AhR) (CYP1A1, CYP1B1) and toll-like receptor 4 (TLR4) on DIM's effects when shifting Treg/Th17 imbalance. Notably, in NASH mouse models, DIM alleviated hepatic steatosis and inflammation, and shifted the Treg/Th17 imbalance from MCD diet-induced Th17 dominance to Treg dominance. In-vitro, DIM not only significantly up-regulated the mRNAs of Foxp3 (Treg-specific) in purified spleen CD4(+) T cells, but also enhanced the immunosuppressive function of these Treg cells. Besides, DIM significantly up-regulated the proteins of CYP1A1 and CYP1B1 whereas down-regulated those of TLR4 on CD4(+) T cells from MCD-diet mice. Moreover, blocking AhR attenuated while blocking TLR4 enhanced the effects of DIM when regulating Treg/Th17 imbalance. Conclusively, DIM could be used as a potential therapeutic candidate to treat NASH based on its dramatic induction of Treg dominance to alleviate intra-hepatic inflammation, suggesting us a clue that the dietary cruciferous vegetables (containing abundant DIM) might exist as a protective factor for patients with NASH-related liver diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Gd-EOB-DTPA-enhanced-MR imaging in the inflammation stage of nonalcoholic steatohepatitis (NASH) in mice.

    Science.gov (United States)

    Yamada, Tomomi; Obata, Atsushi; Kashiwagi, Yuto; Rokugawa, Takemi; Matsushima, Shuuichi; Hamada, Tadateru; Watabe, Hiroshi; Abe, Kohji

    2016-07-01

    The purpose of this study is to investigate the correlation between the liver kinetics of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) and liver histopathology in a mouse model of NASH by using dynamic contrast-enhanced MRI. Twenty male C57/BL6 mice aged 8weeks were fed a methionine-choline-deficient (MCD) diet for 2, 4 and 6weeks (MCD groups: MCD 2w, 4w, or 6w). Gd-EOB-DTPA-enhanced MR imaging of the liver was performed at 2, 4 and 6weeks after the MCD feeding. The signal intensity of the liver was obtained from dynamic MR images and relative enhancement (RE), and the time to maximum RE (Tmax) and half-life of elimination RE (T1/2) were calculated. After MRI scan, histopathological scores of hepatic steatosis and inflammation and blood biochemistry data, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, were obtained. Plasma AST and ALT levels were significantly increased in mice fed MCD. Histopathological scores indicated that steatohepatitis progressed with the MCD feeding period from 2 to 6weeks, but significant fibrosis was observed only in mice fed MCD for 6weeks. Gd-EOB-DTPA-enhanced MRI showed that Tmax was significantly prolonged in the livers of the 6-week group compared to the control group (control, 4.0±0.7min; MCD 6w, 12.1±1.6min), although there was no alteration in the 2- and 4-week groups. T1/2 was significantly prolonged in mice fed MCD for 4 and 6weeks compared to the control group (control, 19.9±2.0min; MCD 4w, 46.7±8.7min; MCD 6w, 65.4±8.8min). The parameters of Gd-EOB-DTPA kinetics (Tmax and T1/2) in the liver were positively correlated with the liver histopathological score (steatosis vs Tmax, rho=0.69, P=0.0007; inflammation vs Tmax, rho=0.66, P=0.00155; steatosis vs T1/2, rho=0.77, Pmouse model of NASH, suggesting the possibility of detecting the steatohepatitis stage without fibrosis by Gd-EOB-DTPA-enhanced MR imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Tatjana Manevskaja : nagradõ za tet-a-tet / Tatjana Manevskaja ; interv. Boris Tuch

    Index Scriptorium Estoniae

    Manevskaja, Tatjana

    2004-01-01

    Näitlejanna sai oma rolli eest lavastuses "Lou - geeniuste innustaja" diplomi Moskvas toimunud monoetenduste VI Rahvusvahelisel festivalil "Ühe näitleja teater" ja Volgogradis toimunud festivalil "Üks ja kõik"

  10. Game Theory: The Nash Equilibrium Point Identification In Bi-Matrix Games Of Economic And Social Indicators

    Directory of Open Access Journals (Sweden)

    Fernanda Kreuzberg

    2015-12-01

    Full Text Available Currently companies have to think about its management system to meet not only their economic interests but also their social interests aiming at the activities’ sustainability and longevity. In this research, the goal is to identify the Nash equilibrium point in the bi-matrix game of economic and social indicators of the companies of Public Utilities sector listed on the BM & FBovespa. The research was conducted with a sample of 26 companies. To evaluate the economic performance it was used the profitability and market indicators; for evaluating the social performance, it was used the indicators derived from the VAD (Value Added Statement. In the estimation of earnings among indicators, it was used the standard parameters of the multiple linear regression. The obtained results highlighted the existence of at least one point of equilibrium for the years analyzed and, especially in the models, two points of equilibrium were proposed for 2009 and 2011 and three for 2010. It is noteworthy that, in the proposed model it was confirmed the hypothesis of the existence of at least one point of equilibrium. Thus, it was possible to meet the research objective, namely, that it is possible to meet both economic aspects and the social aspects of the companies when the indicators are taken as basic information.

  11. Nash and integrated solutions in a just-in-time seller-buyer supply chain with buyer's ordering cost reductions

    Science.gov (United States)

    Lou, Kuo-Ren; Wang, Lu

    2016-05-01

    The seller frequently offers the buyer trade credit to settle the purchase amount. From the seller's prospective, granting trade credit increases not only the opportunity cost (i.e., the interest loss on the buyer's purchase amount during the credit period) but also the default risk (i.e., the rate that the buyer will be unable to pay off his/her debt obligations). On the other hand, granting trade credit increases sales volume and revenue. Consequently, trade credit is an important strategy to increase seller's profitability. In this paper, we assume that the seller uses trade credit and number of shipments in a production run as decision variables to maximise his/her profit, while the buyer determines his/her replenishment cycle time and capital investment as decision variables to reduce his/her ordering cost and achieve his/her maximum profit. We then derive non-cooperative Nash solution and cooperative integrated solution in a just-in-time inventory system, in which granting trade credit increases not only the demand but also the opportunity cost and default risk, and the relationship between the capital investment and the ordering cost reduction is logarithmic. Then, we use a software to solve and compare these two distinct solutions. Finally, we use sensitivity analysis to obtain some managerial insights.

  12. Supply Chains Competition under Uncertainty Concerning Player’s Strategies and Customer Choice Behavior: A Generalized Nash Game Approach

    Directory of Open Access Journals (Sweden)

    A. Hafezalkotob

    2012-01-01

    Full Text Available Decision makers in a supply chain confront two main sources of uncertainty in market environment including uncertainty about customers purchasing behaviors and rival chains strategies. Focusing on competition between two supply chains, it is considered that each customer as an independent player selects products of these chains based on random utility model. Similar to quantal response equilibrium approach, we take account of customer rationality as an exogenous parameter. Moreover, it is assumed that decision makers in a supply chain can perceive an estimation of rival strategies about price and service level formulated in the model by fuzzy strategies. In the competition model, chain’s decision makers consider a subjective probability for wining each customer which is formulated by coupled constraints. These constraints connect chains strategies regarding to each customer and yield a generalized Nash equilibrium problem. Since price cutting and increasing service level are main responses to rival supply chain, after calculating optimal strategies, we show that more efficient responses depend on customer preferences.

  13. The Phytocomplex from Fucus vesiculosus and Ascophyllum nodosum Controls Postprandial Plasma Glucose Levels: An In Vitro and In Vivo Study in a Mouse Model of NASH

    Directory of Open Access Journals (Sweden)

    Daniela Gabbia

    2017-02-01

    Full Text Available Edible seaweeds have been consumed by Asian coastal communities since ancient times. Fucus vesiculosus and Ascophyllum nodosum extracts have been traditionally used for the treatment of obesity and several gastrointestinal diseases. We evaluated the ability of extracts obtained from these algae to inhibit the digestive enzymes α-amylase and α-glucosidase in vitro, and control postprandial plasma glucose levels in a mouse model of non-alcoholic steatohepatitis (NASH; a liver disease often preceding the development of Type 2 diabetes (T2DM. This model was obtained by the administration of a high-fat diet. Our results demonstrate that these algae only delayed and reduced the peak of blood glucose (p < 0.05 in mice fed with normal diet, without changing the area under the blood glucose curve (AUC. In the model of NASH, the phytocomplex was able to reduce both the postprandial glycaemic peak, and the AUC. The administration of the extract in a diet particularly rich in fat is associated with a delay in carbohydrate digestion, but also with a decrease in its assimilation. In conclusion, our results indicate that this algal extract may be useful in the control of carbohydrate digestion and absorption. This effect may be therapeutically exploited to prevent the transition of NASH to T2DM.

  14. The Phytocomplex from Fucus vesiculosus and Ascophyllum nodosum Controls Postprandial Plasma Glucose Levels: An In Vitro and In Vivo Study in a Mouse Model of NASH.

    Science.gov (United States)

    Gabbia, Daniela; Dall'Acqua, Stefano; Di Gangi, Iole Maria; Bogialli, Sara; Caputi, Valentina; Albertoni, Laura; Marsilio, Ilaria; Paccagnella, Nicola; Carrara, Maria; Giron, Maria Cecilia; De Martin, Sara

    2017-02-15

    Edible seaweeds have been consumed by Asian coastal communities since ancient times. Fucus vesiculosus and Ascophyllum nodosum extracts have been traditionally used for the treatment of obesity and several gastrointestinal diseases. We evaluated the ability of extracts obtained from these algae to inhibit the digestive enzymes α-amylase and α-glucosidase in vitro, and control postprandial plasma glucose levels in a mouse model of non-alcoholic steatohepatitis (NASH); a liver disease often preceding the development of Type 2 diabetes (T2DM). This model was obtained by the administration of a high-fat diet. Our results demonstrate that these algae only delayed and reduced the peak of blood glucose ( p NASH, the phytocomplex was able to reduce both the postprandial glycaemic peak, and the AUC. The administration of the extract in a diet particularly rich in fat is associated with a delay in carbohydrate digestion, but also with a decrease in its assimilation. In conclusion, our results indicate that this algal extract may be useful in the control of carbohydrate digestion and absorption. This effect may be therapeutically exploited to prevent the transition of NASH to T2DM.

  15. Kupffer cell depletion attenuates leptin-mediated methoxamine-stimulated portal perfusion pressure and thromboxane A2 release in a rodent model of NASH-cirrhosis.

    Science.gov (United States)

    Yang, Ying-Ying; Huang, Yi-Tsau; Tsai, Tung-Hu; Hou, Ming-Chih; Lee, Fa-Yauh; Lee, Shou-Dong; Lin, Han-Chieh

    2012-12-01

    Cirrhotic portal hypertension is characterized by increased hepatic oxidative stress, AA (arachidonic acid)-derived TXA(2) (thromboxane A(2)) release and exaggerated hepatic response to the α-adrenergic agonist MTX (methoxamine). Besides promoting hepatic fibrosis, the role of hyperleptinaemia in the modulation of vascular response in NASH (non-alcoholic steatohepatitis) rat livers remains unknown. The aim of the present study was to explore the possible links between hyperleptinaemia and the disarrangement in the hepatic microcirculation. NASH-cirrhosis with hyperleptinaemia was induced in lean rats by feeding with an HF/MCD (high-fat/methionine-choline-deficient) diet. Portal haemodynamics, various substances, protein and mRNA expression and PUFA (polyunsaturated fatty acid) composition were measured. Finally, the effects of leptin pre-infusion on TXA(2) release and concentration-PPP (portal perfusion pressure) curves in response to MTX were evaluated by simultaneously pre-treatment with the Kupffer cell inactivators GdCl(3) (gadolinium chloride) or EC (encapsulated clodronate), the TXS (TXA(2) synthase) inhibitor furegrelate, the TP receptor (TXA(2) receptor) antagonist SQ29548 and the dual TXS/TP receptor antagonist BM567. In HF/MCD+leptin-lean rats, cirrhosis-induced PPP and MTX hyper-responsiveness were associated with increased hepatic TXA(2) production, TBARS (thiobarbituric acid-reacting substances) levels and the AA (arachidonic acid)/n-3 PUFA ratio, and up-regulation of hepatic leptin, FAS (fatty acid synthase), NADPH oxidase subunits, TXS, TP receptor, TGFβ(1) (transforming growth factor β(1)) proteins and mRNAs. Pre-infusion of leptin significantly enhanced MTX-stimulated PPP elevation and TXA(2) release, which were attenuated by GdCl(3) and EC pre-treatment. Concomitantly pre-incubation with BM567, but not furegrelate or SQ29548, significantly abolished the leptin-enhanced MTX-stimulated increase in PPP in NASH-cirrhotic rats. Hyperleptinaemia

  16. Advanced Oil Recovery Technologies for Improved Recovery from Slope Basin Clastic Reservoirs, Nash Draw Brushy Canyon Pool, Eddy County, NM

    Energy Technology Data Exchange (ETDEWEB)

    Mark B. Murphy

    2005-09-30

    The Nash Draw Brushy Canyon Pool in Eddy County New Mexico was a cost-shared field demonstration project in the U.S. Department of Energy Class III Program. A major goal of the Class III Program was to stimulate the use of advanced technologies to increase ultimate recovery from slope-basin clastic reservoirs. Advanced characterization techniques were used at the Nash Draw Pool (NDP) project to develop reservoir management strategies for optimizing oil recovery from this Delaware reservoir. The objective of the project was to demonstrate that a development program, which was based on advanced reservoir management methods, could significantly improve oil recovery at the NDP. Initial goals were (1) to demonstrate that an advanced development drilling and pressure maintenance program can significantly improve oil recovery compared to existing technology applications and (2) to transfer these advanced methodologies to other oil and gas producers. Analysis, interpretation, and integration of recently acquired geological, geophysical, and engineering data revealed that the initial reservoir characterization was too simplistic to capture the critical features of this complex formation. Contrary to the initial characterization, a new reservoir description evolved that provided sufficient detail regarding the complexity of the Brushy Canyon interval at Nash Draw. This new reservoir description was used as a risk reduction tool to identify 'sweet spots' for a development drilling program as well as to evaluate pressure maintenance strategies. The reservoir characterization, geological modeling, 3-D seismic interpretation, and simulation studies have provided a detailed model of the Brushy Canyon zones. This model was used to predict the success of different reservoir management scenarios and to aid in determining the most favorable combination of targeted drilling, pressure maintenance, well stimulation, and well spacing to improve recovery from this reservoir. An

  17. CHIP−/−-Mouse Liver: Adiponectin-AMPK-FOXO-Activation Overrides CYP2E1-Elicited JNK1-Activation, Delaying Onset of NASH: Therapeutic Implications

    Science.gov (United States)

    Kim, Sung-Mi; Grenert, James P.; Patterson, Cam; Correia, Maria Almira

    2016-01-01

    Genetic ablation of C-terminus of Hsc70-interacting protein (CHIP) E3 ubiquitin-ligase impairs hepatic cytochrome P450 CYP2E1 degradation. Consequent CYP2E1 gain of function accelerates reactive O2 species (ROS) production, triggering oxidative/proteotoxic stress associated with sustained activation of c-Jun NH2-terminal kinase (JNK)-signaling cascades, pro-inflammatory effectors/cytokines, insulin resistance, progressive hepatocellular ballooning and microvesicular steatosis. Despite this, little evidence of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) was found in CHIP−/−-mice over the first 8–9-months of life. We herein document that this lack of tissue injury is largely due to the concurrent up-regulation and/or activation of the adiponectin-5′-AMP-activated protein kinase (AMPK)-forkhead box O (FOXO)-signaling axis stemming from at the least three synergistic features: Up-regulated expression of adipose tissue adiponectin and its hepatic adipoR1/adipoR2 receptors, stabilization of hepatic AMPKα1-isoform, identified herein for the first time as a CHIP-ubiquitination substrate (unlike its AMPKα2-isoform), as well as nuclear stabilization of FOXOs, well-known CHIP-ubiquitination targets. Such beneficial predominance of the adiponectin-AMPK-FOXO-signaling axis over the sustained JNK-elevation and injurious insulin resistance in CHIP−/−-livers apparently counteracts/delays rapid progression of the hepatic microvesicular steatosis to the characteristic macrovesicular steatosis observed in clinical NASH and/or rodent NASH-models. PMID:27406999

  18. Investigation of pharmacological responses to anti-diabetic drugs in female Spontaneously Diabetic Torii (SDT) fatty rats, a new nonalcoholic steatohepatitis (NASH) model.

    Science.gov (United States)

    Toriniwa, Yasufumi; Saito, Tomoyuki; Miyajima, Katsuhiro; Ishii, Yukihito; Uno, Kinuko; Maekawa, Tatsuya; Matsui, Tohru; Kume, Shinichi; Yamada, Takahisa; Ohta, Takeshi

    2018-04-10

    Nonalcoholic steatohepatitis (NASH) is a progressive liver disease, and some patients develop hepatic cirrhosis/carcinoma. Animal models play key roles in the development of new therapies for NASH. In this study, the pharmacological effects of metformin and pioglitazone were investigated in female Spontaneously Diabetic Torii (SDT) fatty rats to verify the utility of this model. The anti-diabetic drugs were administered to SDT fatty rats fed a cholesterol-enriched diet from 4 to 25 weeks, and changes in food intake, body weight, and blood chemistry parameters were evaluated every 4 weeks. The hepatic lipid content, mRNA expression in relation to lipid synthesis, inflammation, and fibrosis, and histopathological analyses were performed at 25 weeks. Pioglitazone improved hyperglycemia, hyperlipidemia, and abnormalities in hepatic parameters. The insulin levels were lower than those in the control rats before 16 weeks. Plasma glucose levels in the metformin-treated rats were lower than those in the control rats, and plasma triglyceride and alanine aminotransferase levels temporarily decreased. The lipid content and some mRNA expression in relation to fibrosis in the liver decreased with pioglitazone treatment, and the mRNA expression of microsomal triglyceride transfer protein increased. Hepatic fibrosis observed in the SDT fatty rats improved with pioglitazone treatment; however, the effect with metformin treatment was partial. These results in both drugs are in line with results in the human study, suggesting that the SDT fatty rat is useful for developing new anti-NASH drugs that show potential to regulate glucose/lipid metabolism.

  19. Eplerenone ameliorates the phenotypes of metabolic syndrome with NASH in liver-specific SREBP-1c Tg mice fed high-fat and high-fructose diet.

    Science.gov (United States)

    Wada, Tsutomu; Miyashita, Yusuke; Sasaki, Motohiro; Aruga, Yusuke; Nakamura, Yuto; Ishii, Yoko; Sasahara, Masakiyo; Kanasaki, Keizo; Kitada, Munehiro; Koya, Daisuke; Shimano, Hitoshi; Tsuneki, Hiroshi; Sasaoka, Toshiyasu

    2013-12-01

    Because the renin-angiotensin-aldosterone system has been implicated in the development of insulin resistance and promotion of fibrosis in some tissues, such as the vasculature, we examined the effect of eplerenone, a selective mineralocorticoid receptor (MR) antagonist, on nonalcoholic steatohepatitis (NASH) and metabolic phenotypes in a mouse model reflecting metabolic syndrome in humans. We adopted liver-specific transgenic (Tg) mice overexpressing the active form of sterol response element binding protein-1c (SREBP-1c) fed a high-fat and fructose diet (HFFD) as the animal model in the present study. When wild-type (WT) C57BL/6 and liver-specific SREBP-1c Tg mice grew while being fed HFFD for 12 wk, body weight and epididymal fat weight increased in both groups with an elevation in blood pressure and dyslipidemia. Glucose intolerance and insulin resistance were also observed. Adipose tissue hypertrophy and macrophage infiltration with crown-like structure formation were also noted in mice fed HFFD. Interestingly, the changes noted in both genotypes fed HFFD were significantly ameliorated with eplerenone. HFFD-fed Tg mice exhibited the histological features of NASH in the liver, including macrovesicular steatosis and fibrosis, whereas HFFD-fed WT mice had hepatic steatosis without apparent fibrotic changes. Eplerenone effectively ameliorated these histological abnormalities. Moreover, the direct suppressive effects of eplerenone on lipopolysaccharide-induced TNFα production in the presence and absence of aldosterone were observed in primary-cultured Kupffer cells and bone marrow-derived macrophages. These results indicated that eplerenone prevented the development of NASH and metabolic abnormalities in mice by inhibiting inflammatory responses in both Kupffer cells and macrophages.

  20. Effects of N-3 Fish Oil on Metabolic and Histological Parameters in NASH: A Double-Blind, Randomized, Placebo-Controlled Trial

    Science.gov (United States)

    Argo, Curtis K.; Patrie, James T.; Lackner, Carolin; Henry, Thomas D.; deLange, Eduard E.; Weltman, Arthur L.; Shah, Neeral L.; Al-Osaimi, Abdullah M.; Pramoonjago, Patcharin; Jayakumar, Saumya; Binder, Lukas P.; Simmons-Egolf, Winsor D.; Burks, Sandra G.; Bao, Yongde; Taylor, Anne Gill; Rodriguez, Jessica; Caldwell, Stephen H.

    2014-01-01

    This study’s aim was to assess the histological and metabolic effects of N-3 polyunsaturated fatty acids (PUFA) versus placebo while adjusting for the impact of age and weight change in NASH patients. (ClinicalTrials.gov: NCT00681408). Methods Forty-one subjects with non-cirrhotic NASH were enrolled, and 34 completed the study. 17 received N-3 fish oil 3000 mg/day and 17 received placebo daily for 1 year with typical counseling on caloric intake and physical activity for all subjects. Results N-3- and placebo-treated groups showed no significant difference for the primary endpoint of NAS reduction ≥ 2 points without fibrosis progression after adjustment for known covariates (N-3, 4/17 (23.5%); placebo, 3/17, (17.6%), p=0.99). Among subjects with increased or stable weight, N-3 subjects showed a larger decrease in liver fat content by MRI than placebo-treated subjects (p=0.014 for 2nd quartile, p=0.003 for 3rd quartile of weight change). N-3 treatment showed significant fat reduction on paired analysis of image-assisted fat morphometry regardless of weight loss or gain. Exercise capacity remained markedly reduced in all subjects. No independent effects on markers of hepatocyte injury or insulin sensitivity indices were observed. Conclusion N-3 PUFA at 3000 mg/day for one year did not lead to improvement in the primary outcome of histological activity in NASH patients (≥ 2 point NAS reduction). N-3 led to reduced liver fat by multiple measures. Other metabolic effects were not seen, although no detrimental effects were apparent. Whether longer duration, higher dose, or different composition of N-3 therapy would lead to additional benefit is uncertain. PMID:25195547

  1. MicroRNA expression analysis in high fat diet-induced NAFLD-NASH-HCC progression: study on C57BL/6J mice.

    Science.gov (United States)

    Tessitore, Alessandra; Cicciarelli, Germana; Del Vecchio, Filippo; Gaggiano, Agata; Verzella, Daniela; Fischietti, Mariafausta; Mastroiaco, Valentina; Vetuschi, Antonella; Sferra, Roberta; Barnabei, Remo; Capece, Daria; Zazzeroni, Francesca; Alesse, Edoardo

    2016-01-05

    Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Non-alcoholic fatty liver disease (NAFLD) is a frequent chronic liver disorder in developed countries. NAFLD can progress through the more severe non alcoholic steatohepatitis (NASH), cirrhosis and, lastly, HCC. Genetic and epigenetic alterations of coding genes as well as deregulation of microRNAs (miRNAs) activity play a role in HCC development. In this study, the C57BL/6J mouse model was long term high-fat (HF) or low-fat (LF) diet fed, in order to analyze molecular mechanisms responsible for the hepatic damage progression. Mice were HF or LF diet fed for different time points, then plasma and hepatic tissues were collected. Histological and clinical chemistry assays were performed to assess the progression of liver disease. MicroRNAs' differential expression was evaluated on pooled RNAs from tissues, and some miRNAs showing dysregulation were further analyzed at the individual level. Cholesterol, low and high density lipoproteins, triglycerides and alanine aminotransferase increase was detected in HF mice. Gross anatomical examination revealed hepatomegaly in HF livers, and histological analysis highlighted different degrees and levels of steatosis, inflammatory infiltrate and fibrosis in HF and LF animals, demonstrating the progression from NAFLD through NASH. Macroscopic nodules, showing typical neoplastic features, were observed in 20% of HF diet fed mice. Fifteen miRNAs differentially expressed in HF with respect to LF hepatic tissues during the progression of liver damage, and in tumors with respect to HF non tumor liver specimens were identified. Among them, miR-340-5p, miR-484, miR-574-3p, miR-720, whose expression was never described in NAFLD, NASH and HCC tissues, and miR-125a-5p and miR-182, which showed early and significant dysregulation in the sequential hepatic damage process. In this study, fifteen microRNAs which were modulated in hepatic tissues and in tumors during

  2. 02 Nash 02.pmd

    African Journals Online (AJOL)

    Owner

    2009-06-23

    Jun 23, 2009 ... of political activity, divested of the more mundane horse-trading and compromise of everyday politics,” which ..... elements towards a strategy for revolution in South Africa”, which is in many ways a precursor to the Okhela ... conflict and resistance are made necessary, in Breytenbach's argument. The Okhela.

  3. A Generalized Nash-Cournot Model for the North-Western European Natural Gas Markets with a Fuel Substitution Demand Function: The GaMMES Model

    International Nuclear Information System (INIS)

    Abada, Ibrahim; Briat, Vincent; GABRIEL, Steve A.; MASSOL, Olivier

    2011-01-01

    This article presents a dynamic Generalized Nash-Cournot model to describe the evolution of the natural gas markets. The major players along the gas chain are depicted including: producers, consumers, storage and pipeline operators, as well as intermediate local traders. Our economic structure description takes into account market power and the demand representation tries to capture the possible fuel substitution that can be made between the consumption of oil, coal, and natural gas in the overall fossil energy consumption. We also take into account long-term contracts in an endogenous way, which makes the model a Generalized Nash Equilibrium problem. We discuss some means to solve such problems. Our model has been applied to represent the European natural gas market and forecast, until 2030, after a calibration process, consumption, prices, production, and natural gas dependence. A comparison between our model, a more standard one that does not take into account energy substitution, and the European Commission natural gas forecasts is carried out to analyze our results. Finally, in order to illustrate the possible use of fuel substitution, we studied the evolution of the natural gas price as compared to the coal and oil prices. (authors)

  4. Mood and psychosis in schizophrenia : exploring diagnostic frontiers with the Operational Criteria Checklist for Psychotic Illness (OPCRIT) and Jonh Nash case

    OpenAIRE

    Belmonte-de-Abreu, Paulo Silva; Martins, Cristiane Damacarena Nunes; Gil, Alexei; Lobato, Maria Inês Rodrigues

    2004-01-01

    INTRODUÇÃO: Utilizamos uma simulação diagnóstica no caso John Nash, Prêmio Nobel de Matemática de 1994 e descrito como portador de esquizofrenia, para apresentar o Inventário de Critérios Operacionais para Doenças Psicóticas (OPCRIT) e discutir as frágeis delimitações dos diagnósticos categóricos, bem como o uso de diagnósticos dimensionais em psiquiatria. MÉTODO: Baseados na biografia escrita por Sylvia Nasar e no filme Uma mente brilhante, os autores discutiram a sintomatologia e preenchera...

  5. Development of hepatocellular cancer induced by long term low fat-high carbohydrate diet in a NAFLD/NASH mouse model.

    Science.gov (United States)

    Tessitore, Alessandra; Mastroiaco, Valentina; Vetuschi, Antonella; Sferra, Roberta; Pompili, Simona; Cicciarelli, Germana; Barnabei, Remo; Capece, Daria; Zazzeroni, Francesca; Capalbo, Carlo; Alesse, Edoardo

    2017-08-08

    Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease. It can progress to nonalcoholic steatohepatitis (NASH) and, in a percentage of cases, to hepatocarcinogenesis. The strong incidence in western countries of obesity and metabolic syndrome, whose NAFLD is the hepatic expression, is thought to be correlated to consumption of diets characterized by processed food and sweet beverages. Previous studies described high-fat diet-induced liver tumors. Conversely, the involvement of low-fat/high-carbohydrate diet in the progression of liver disease or cancer initiation has not been described yet. Here we show for the first time hepatic cancer formation in low-fat/high-carbohydrate diet fed NAFLD/NASH mouse model. Animals were long term high-fat, low-fat/high-carbohydrate or standard diet fed. We observed progressive liver damage in low-fat/high-carbohydrate and high-fat animals after 12 and, more, 18 months. Tumors were detected in 20% and 50% of high-fat diet fed mice after 12 and 18 months and, interestingly, in 30% of low-fat/high-carbohydrate fed animals after 18 months. No tumors were detected in standard diet fed mice. Global increase of hepatic interleukin-1β, interleukin-6, tumor necrosis factor-α and hepatocyte growth factor was detected in low-fat/high-carbohydrate and high-fat with respect to standard diet fed mice as well as in tumor with respect to non-tumor bearing mice. A panel of 15 microRNAs was analyzed: some of them revealed differential expression in low-fat/high-carbohydrate with respect to high-fat diet fed groups and in tumors. Data here shown provide the first evidence of the involvement of low-fat/high-carbohydrate diet in hepatic damage leading to tumorigenesis.

  6. Estudo comparativo da medida da rotação vertebral pelos métodos de Nash & Moe e método de Raimondi Comparative study of the measurements of the vertebral rotation using Nash & Moe and Raimondi methods

    Directory of Open Access Journals (Sweden)

    Helton L. A. Defino

    2004-09-01

    Full Text Available Neste estudo foram avaliados a sensibilidade e precisão dos métodos de Nash e Moe e de Raimondi para a medida da rotação da vértebra torácica e lombar.Três cirurgiões de coluna avaliaram, independentemente, as radiografias de uma vértebra torácica (T9 e de uma vértebra lombar (L2 com graus de rotação que variaram de 0º a 60º e estabeleceram valores de acordo com o método de Nash e Moe e o método de Raimondi.Foram estudadas a concordância entre os examinadores para um determinado método, a variação das medidas obtidas na vértebra torácica e lombar a partir de uma mesma rotação real conhecida e a correlação entre um valor real conhecido de rotação vertebral e a sua estimativa pelos métodos utilizados no estudo . Os resultados mostraram boa concordância entre os examinadores para o método de Nash e Moe, tanto para a vértebra torácica (k médio = 0,66, quanto para a lombar (k médio = 0,80. Pelo método de Raimondi não houve diferença significativa entre os examinadores para a vértebra torácica, no entanto, para a vértebra lombar houve baixa reprodutibilidade do método.Para uma mesma rotação na vértebra torácica e lombar os resultados foram não concordantes pelo método de Nash e Moe, e pelo método de Raimondi os valores observados para a vértebra torácica foram significativamente maiores que os da vértebra lombar. A correlação entre os valores reais e as estimados pelo método de Raimondi para a vértebra torácica mostrou que houve diferença significativa produzida em função da rotação até 20º graus, já para a vértebra lombar, os valores obtidos foram muito próximos do real.The sensibility and precision of the Nash and Moe and Raimondi methods were evaluated in this study for the measurement of the rotation of the thoracic and the lumbar vertebra. Three spine surgeons evaluated, independently, the x-rays of a thoracic vertebra (T9 and of a lumbar vertebra (L2 with varying rotational

  7. Jeshtshjo odin shag vpravo / Raivo Vetik ; interv. Tatjana Opekina

    Index Scriptorium Estoniae

    Vetik, Raivo

    2003-01-01

    TPÜ Rahvusvaheliste ja Sotsiaaluuringute Instituudi direktor Raivo Vetik jagab mõtteid valimistulemustest, uuest valitsuskoalitsioonist, uuest põlvkonnast poliitikas, Keskerakonna poliitikast, riigi sotsiaalarengust

  8. Tõ menja uvazhajesh? / Liina Tõnisson ; interv. Tatjana Opekina

    Index Scriptorium Estoniae

    Tõnisson, Liina, 1940-

    2003-01-01

    Pikaajalise kogemusega Riigikogu liikme Liina Tõnissoni arvates on Eesti ühiskonnal veel pikk tee tõelise demokraatiani. Koostööst Reformierakonnaga, partei liidrist Edgar Savisaarest, paremliberaalsest poliitikast

  9. Klubok problem Jevrosojuza / Toomas Hendrik Ilves ; interv. Tatjana Opekina

    Index Scriptorium Estoniae

    Ilves, Toomas Hendrik, 1953-

    2006-01-01

    Europarlamendi väliskomisjoni aseesimees puudutab järgmisi teemasid: Euroopa julgeolek, Lissaboni strateegia, Euroopa Liidu uued ja vanad liikmed, traditsiooniline perekond ja sündimus, Euroopa islamiseerimine, globaliseerumisprotsesside mõju, Eesti-Vene piirilepe

  10. Kak trudno ponjat drug druga / Trivimi Velliste ; interv. Tatjana Opekina

    Index Scriptorium Estoniae

    Velliste, Trivimi, 1947-

    2006-01-01

    Riigikoguliige, Isamaa ja Res Publica liidu juhatuse liige vastab küsimustele, mis puudutavad tema kohta Eesti poliitilisel maastikul, osalemist Sinimägedes toimunud 20. Eesti relvagrenaderide diviisi veteranide kokkutulekul ja kokkutuleku mõju poliitilisele stabiilsusele ühiskonnas, pronkssõduri probleemi ja eelseivaid parlamendivalimisi, pangalaenude kasvu Eestis ning Nõukogude okupatsiooni andestamise võimalikkust

  11. Doroga k zvezdam / Tatjana Antsiferova ; interv. Nikolai Hrustaljov

    Index Scriptorium Estoniae

    Antsiferova, Tatjana

    2003-01-01

    Venemaal Gatshina filmifestivalil "Kirandus ja kino" ("Literatura i kino") sai žürii eriauhinna populaarteaduslike filmide stuudio "Lennautshfilm" film poeet Vassili Zhukovskist "Rohkem kui poeet" ("Bolshe, tshem poet") : režissöör Dolores Hmelnitskaja. Stuudiost selle 70. aastapäeva puhul räägib peatoimetaja

  12. Gollandtsõ pomogut nashim portam / Tatjana Merkulova

    Index Scriptorium Estoniae

    Merkulova, Tatjana

    2000-01-01

    Koostöös AS-iga Tallinna Sadam töötab Hollandi firma Tebodin Consultants & Engineers B.V. välja Tallinna Sadama pikaajalise arenguprogrammi. Tabel: AS Tallinna Sadama veosekäive 1999/2000 jaan-juuli

  13. Pamela sovsem ohhamela / Javier Bardem ; interv. Maria Davtjan, Tatjana Pinskaja

    Index Scriptorium Estoniae

    Bardem, Javier

    2007-01-01

    60-nda Cannes'i filmifestivalilt. Näitleja lühendatud intervjuu oma osalemisest Ethan ja Joel Coen'i filmis "Pole maad vanadele meestele" ("No Country for Old Men" ; Ameerika Ühendriigid). Ka ajakirjanike tähelepanekuid festivali külastavate staaride kohta (Leonardo DiCaprio kui stsenarist ja produtsent dokfilmile "Üheteistkümnes tund")

  14. Dozhivjom do võborov / Ain Seppik ; interv. Tatjana Opekina

    Index Scriptorium Estoniae

    Seppik, Ain, 1952-

    2007-01-01

    Riigikogu liige vastab küsimustele, mis puudutavad Keskerakonna poliitikat, parlamendivalimisi, aprillisündmusi, korruptsiooni, riigieelarvet. Ain Seppik leiab, et Keskerakonna missiooniks on arendada riiki ja kaitsta nõrku

  15. Ravnopravnõi Peeter / Vello Tafenau ; interv. Tatjana Opekina

    Index Scriptorium Estoniae

    Tafenau, Vello, 1952-

    2007-01-01

    Riigikogu rahanduskomisjoni aseesimees vastab küsimustele, kuidas ERL viib oma valimisprogrammi potentsiaalsete valijateni, kas Eesti on lõpuks teel sotsiaalse riigi poole, kuidas ERL-il õnnestus säilitada aastatel 2003-2005 koalitsioonis olles oma nägu, kuidas muuta ERL-i ideed profülaktilisest suunast meditsiinis tegelikkuseks, kuidas praegustes tingimustes parandada majandussuhteid Venemaaga, kas Erakonna Eestimaa Rohelised tulek ei meenuta Res Publica tulekut

  16. Izbirateli razotsharovalis v respublikantsahh? / Raivo Vetik ; interv. Tatjana Opekina

    Index Scriptorium Estoniae

    Vetik, Raivo

    2004-01-01

    Rahvusvaheliste ja sotsiaaluuringute instituudi direktor vastab küsimustele, mis puudutavad hinnangut valitsusele, Res Publica kampaaniat Euroopa Parlamendi valimiste eel ja valimistulemusi Eestis, Res Publica juhte, Res Publica endise juhi Rein Taagepera artiklit "Res Publica teelahkmel", Keskerakonna juhti Edgar Savisaart

  17. Aeromagnetic Surveying with a Rotary-Wing Unmanned Aircraft System: A Case Study from a Zinc Deposit in Nash Creek, New Brunswick, Canada

    Science.gov (United States)

    Cunningham, Michael; Samson, Claire; Wood, Alan; Cook, Ian

    2017-12-01

    Unmanned aircraft systems (UASs) have been under rapid development for applications in the mineral exploration industry, mainly for aeromagnetic surveying. They provide improved detection of smaller, deeper and weaker magnetic targets. A traditional system flying an altitude of 100 m above ground level (AGL) can detect a spherical ore body with a radius of 16 m and a magnetic susceptibility of 10-4 buried at a depth of 40 m. A UAS flying at an altitude of 50 or 2 m AGL would require the radius to be 11 or 5 m, respectively. A demonstration survey was performed using the SkyLance rotary-wing UAS instrumented with a cesium vapour magnetometer in Nash Creek, New Brunswick, Canada. The UAS flew over a zinc deposit featuring three magnetic anomalies. It acquired repeatable data that compared well with upward continuation maps of ground magnetic data. Dykes or faults that are dipping eastward at 25° and are approximately 1.5 m wide fit the observed response of the three anomalies captured on the UAS magnetic data.

  18. Advanced oil recovery technologies for improved recovery from slope basin clastic reservoirs, Nash Draw Brushy Canyon Pool, Eddy County, New Mexico. Annual report, September 25, 1995--September 24, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, M.B.

    1997-08-01

    The basic driver for this project is the low recovery observed in Delaware reservoirs, such as the Nash Draw Pool (NDP). This low recovery is caused by low reservoir energy, less than optimum permeabilities and porosities, and inadequate reservoir characterization and reservoir management strategies which are typical of projects operated by independent producers. Rapid oil decline rates and high gas/oil ratios are typically observed in the first year of primary production. Based on the production characteristics that have been observed in similar Delaware fields, pressure maintenance is a likely requirement at the Nash Pool. Three basic constraints to producing the Nash Draw Brushy Canyon Reservoir are: (1) limited areal and interwell geologic knowledge, (2) lack of an engineering tool to evaluate the various producing strategies, and (3) limited surface access prohibiting development with conventional drilling. The limited surface access is caused by the proximity of underground potash mining and surface playa lakes. The objectives of this project are: (1) to demonstrate that a development drilling program and pressure maintenance program, based on advanced reservoir management methods, can significantly improve oil recovery compared with existing technology applications and (2) to transfer these advanced methodologies to oil and gas producers, especially in the Permian Basin.

  19. Microbiota Modulation With Synbiotic Decreases Liver Fibrosis in a High Fat Choline Deficient Diet Mice Model of Non-Alcoholic Steatohepatitis (NASH).

    Science.gov (United States)

    Cortez-Pinto, Helena; Borralho, Paula; Machado, Jorge; Lopes, Maria T; Gato, Inês V; Santos, António M; Guerreiro, António S

    2016-01-01

    Gut microbiota may play a role in non-alcoholic steatohepatitis (NASH). Previous studies showed that prebiotics and probiotics might halt the progression of steatohepatitis. To clarify the potential effect of Synbiotic 2000 ® Forte (Synb) in preventing or ameliorating diet induced steatohepatitis, particularly in fibrosis progression and how this intervention correlates with gut microbiota composition and endotoxinemia. Twenty-seven C57BL/6 mice were divided into three groups: chow diet (CD, n = 7); high-fat choline deficient diet (HFCD, n = 10) and HFCD diet supplemented with Synbiotic 2000 ® Forte (four probiotic strains and four prebiotics mixture) (HFCD + Synb, n = 10). At 6 and 18 weeks, blood samples (lipopolysaccharides assay - LPS), cecal feaces (gut microbiota) and liver tissue (histology) were collected for analysis. Both HCFD diet mice developed steatohepatitis with ballooning at 6 and 18 weeks, opposite to CD. Comparison of histological scores in HFCD and HFCD + Synb, at 6 and 18 weeks showed no significant difference regarding steatosis, inflammation, or ballooning. Evaluating fibrosis with Sirius Red, and degree of smooth-muscle cell activation, HFCD mice had significantly more fibrosis; addition of Synb significantly reduced fibrosis at 6 weeks and 18 weeks. Serum endotoxin levels were similarly increased in HFCD and HFCD + Synb at week 6; however at week 18 HFCD + Synb had significantly lower endotoxin levels than HFCD. Gut microbiota of HFCD vs CD, showed no significant differences regarding the phyla Firmicutes and Bacteroidetes , either at 6 or 18 weeks; Proteobacteria increased at 6 week (3.3) and 18 week (7.5), while the addition of Synb resulted in a decrease at week 18 (-3.90). Fusobacteria markedly increase at week 18 (10.0), but less so with the addition of Synb (5.2). Synbiotic 2000 ® Forte is able to modulate the mouse gut microbiota reducing the degree of fibrosis while simultaneously decreasing endotoxemia.

  20. O equilíbrio de Nash como uma solução para o conflito entre eficiência e custo na escolha de sistemas de tratamento de esgoto sanitário com o auxílio de um modelo de tomada de decisão The Nash equilibrium as a solution to the conflict between efficiency and cost in the choice of systems for sanitary sewage treatment using a decision making model

    Directory of Open Access Journals (Sweden)

    Alexandre Bevilacqua Leoneti

    2010-03-01

    Full Text Available A escolha de estações de tratamento de esgoto pode, dentre outras coisas, envolver um conflito entre a eficiência e o custo, pois para o menor custo possível esta escolha também deverá satisfazer várias exigências ambientais. Para auxiliar na escolha de uma estação de menor custo, um modelo baseado em técnicas de tomada de decisão foi desenvolvido por Oliveira (2004. Todavia, se não forem levados em consideração os outros critérios envolvidos, a interação entre os tomadores de decisão e suas respectivas estratégias podem fazer com que a escolha do sistema de tratamento não seja a mais adequada. Para estes casos, o equilíbrio de Nash pode oferece uma solução, construída com base na interação entre os jogadores, a qual poderia satisfazer razoavelmente os interesses conflitantes. Desta forma, o objetivo desta pesquisa foi, com base nos dados de saída do modelo de Oliveira (2004, encontrar o equilíbrio de Nash para propor uma solução para o conflito entre a eficiência e o custo nas escolhas do sistema de tratamento de esgoto sanitário. A comparação entre os diferentes resultados alcançados, quando apenas considerado o critério de menor custo ou de maior eficiência, demonstrou que a adoção do equilíbrio de Nash pode ser uma alternativa viável para solucionar o conflito entre a eficiência e o custo nas escolhas das estações de tratamento de esgoto sanitário.The choice of sewage treatment plants may, among others, involve a conflict between efficiency and cost, because for the lowest possible cost, this choice should meet some environmental requirements. To assist in the choice of a treatment system for municipal sanitary sewer, a model based on techniques of decision making was developed by Oliveira (2004. However, if the other criteria involved are not considered, the interaction between decision makers and their strategies can turn the choice of the treatment system into an inadequate one. For these

  1. Numerical and Statistical Analysis of Fractures in Mechanically Dissimilar Rocks of Limestone Interbedded with Shale from Nash Point in Bristol Channel, South Wales, UK.

    Science.gov (United States)

    Adeoye-Akinde, K.; Gudmundsson, A.

    2017-12-01

    Heterogeneity and anisotropy, especially with layered strata within the same reservoir, makes the geometry and permeability of an in-situ fracture network challenging to forecast. This study looks at outcrops analogous to reservoir rocks for a better understanding of in-situ fracture networks and permeability, especially fracture formation, propagation, and arrest/deflection. Here, fracture geometry (e.g. length and aperture) from interbedded limestone and shale is combined with statistical and numerical modelling (using the Finite Element Method) to better forecast fracture network properties and permeability. The main aim is to bridge the gap between fracture data obtained at the core level (cm-scale) and at the seismic level (km-scale). Analysis has been made of geometric properties of over 250 fractures from the blue Lias in Nash Point, UK. As fractures propagate, energy is required to keep them going, and according to the laws of thermodynamics, this energy can be linked to entropy. As fractures grow, entropy increases, therefore, the result shows a strong linear correlation between entropy and the scaling exponent of fracture length and aperture-size distributions. Modelling is used to numerically simulate the stress/fracture behaviour in mechanically dissimilar rocks. Results show that the maximum principal compressive stress orientation changes in the host rock as the fracture-induced stress tip moves towards a more compliant (shale) layer. This behaviour can be related to the three mechanisms of fracture arrest/deflection at an interface, namely: elastic mismatch, stress barrier and Cook-Gordon debonding. Tensile stress concentrates at the contact between the stratigraphic layers, ahead of and around the propagating fracture. However, as shale stiffens with time, the stresses concentrated at the contact start to dissipate into it. This can happen in nature through diagenesis, and with greater depth of burial. This study also investigates how induced

  2. Jantarnaja komnata : neuzheli jejo nashli?

    Index Scriptorium Estoniae

    2008-01-01

    Teise maailmasõja ajal Tsarskoje Selo Katariina lossist röövitud Merevaigutoa otsingutest. Merevaigutoa aarded arvatakse asuvat Deutschneudorfis Tšehhi-Saksa piiri lähedal. On alustatud otsimistöödega

  3. Zdorovje - nash ressurss / Anna Litvinjuk

    Index Scriptorium Estoniae

    Litvinjuk, Anna

    2005-01-01

    Ülemaailmse Tervishoiuorganisatsiooni (WHO) andmetel on keskmine eluiga Eestis tunduvalt lühem kui teistes EL-i riikides. Samuti on Eesti elanike tervis võrreldes teiste EL-i riikide elanike tervisega tunduvalt halvem. WHO toetusel toimunud tervisefoorumist Eestis. Diagramm

  4. What Is NAFLD and NASH?

    Science.gov (United States)

    ... Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información ... Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información ...

  5. Humor e psicose em esquizofrenia: explorando fronteiras diagnósticas com o Inventário de Critérios Operacionais para Doenças Psicóticas (OPCRIT) e o caso John Nash

    OpenAIRE

    Martins, Cristiane Damacarena; Gil, Alexei; Abreu, Paulo Silva Belmonte de; Lobato, Maria Inês

    2004-01-01

    INTRODUÇÃO: Utilizamos uma simulação diagnóstica no caso John Nash, Prêmio Nobel de Matemática de 1994 e descrito como portador de esquizofrenia, para apresentar o Inventário de Critérios Operacionais para Doenças Psicóticas (OPCRIT) e discutir as frágeis delimitações dos diagnósticos categóricos, bem como o uso de diagnósticos dimensionais em psiquiatria. MÉTODO: Baseados na biografia escrita por Sylvia Nasar e no filme Uma mente brilhante, os autores discutiram a sintomatologia e preenchera...

  6. Humor e psicose em esquizofrenia: explorando fronteiras diagnósticas com o Inventário de Critérios Operacionais para Doenças Psicóticas (OPCRIT e o caso John Nash Ánimo y psicosis en esquizofrenia: explorando fronteras diagnósticas con el Inventario de Criterios Operacionales para Enfermedades Psicóticas (OPCRIT y el caso John Nash Mood and psychosis in schizophrenia: exploring diagnostic frontiers with the Operational Criteria Checklist for Psychotic Illness (OPCRIT and John Nash case

    Directory of Open Access Journals (Sweden)

    Cristiane Damacarena Martins

    2004-08-01

    Full Text Available INTRODUÇÃO: Utilizamos uma simulação diagnóstica no caso John Nash, Prêmio Nobel de Matemática de 1994 e descrito como portador de esquizofrenia, para apresentar o Inventário de Critérios Operacionais para Doenças Psicóticas (OPCRIT e discutir as frágeis delimitações dos diagnósticos categóricos, bem como o uso de diagnósticos dimensionais em psiquiatria. MÉTODO: Baseados na biografia escrita por Sylvia Nasar e no filme Uma mente brilhante, os autores discutiram a sintomatologia e preencheram o OPCRIT. Devido à ausência inicial de consenso, repetiu-se a simulação mais duas vezes, modificando-se os itens que avaliam a presença de pensamentos acelerados (item 31, a ocorrência de aumento de sociabilidade (item 53 e o balanço entre sintomas psicóticos e de humor (item 52, a fim de verificar as repercussões dessas mudanças no diagnóstico. RESULTADOS: Os diagnósticos obtidos em duas simulações foram esquizofrenia (DSM-IV e esquizofrenia indiferenciada (CID-10, corroborando o diagnóstico de John Nash em sua biografia. Outra simulação apresentou os diagnósticos de transtorno esquizoafetivo tipo bipolar (DSM-IV e transtorno esquizoafetivo tipo maníaco (CID-10. Apenas a mudança do critério de proporcionalidade entre sintomas psicóticos e de humor (item 52 alterou o diagnóstico de esquizofrenia para transtorno esquizoafetivo. DISCUSSÃO: As fronteiras que separam os diagnósticos de esquizofrenia e transtorno esquizoafetivo são muito tênues, o que explica a freqüente dificuldade diagnóstica. CONCLUSÕES: Ressaltamos a importância do estudo detalhado do curso da doença, enfatizando o balanço entre sintomas psicóticos e de humor, para a definição diagnóstica dos transtornos psicóticos conforme as classificações atuais. Por fim, destacamos a importância dos diagnósticos dimensionais e a necessidade de mais estudos para a validação das categorias diagnósticas atuais.INTRODUCCÍON: Utilizamos una

  7. Nashe obshtshestvo osnovano na lzhi / Arnold Takkin

    Index Scriptorium Estoniae

    Takkin, Arnold

    2007-01-01

    Eesti ühiskonna vastuoludest. Autor leiab, et Eesti pole olnud NSV Liidu poolt okupeeritud, vaid annekteeritud, ning selgitab, miks oli vaja okupatsioonivalet. Mitte-eestlaste demokraatlike õiguste piiramisega piiratakse Eestis demokraatlikku riigielu korraldamist, tuues soovitusi demokraatlikeks parlamendivalimisteks

  8. On Nash Equilibria in Stochastic Games

    Science.gov (United States)

    2003-10-01

    Traditionally automata theory and veri cation has considered zero sum or strictly competitive versions of stochastic games . In these games there are two players...zero- sum discrete-time stochastic dynamic games . SIAM J. Control and Optimization, 19(5):617{634, 1981. 18. R.J. Lipton, E . Markakis, and A. Mehta...Playing large games using simple strate- gies. In EC 03: Electronic Commerce, pages 36{41. ACM Press, 2003. 19. A. Maitra and W. Sudderth. Finitely

  9. Pure Nash Equilibria in Restricted Budget Games

    NARCIS (Netherlands)

    Drees, Maximilian Werner; Feldotto, Matthias; Riechers, Sören; Skopalik, Alexander

    2017-01-01

    In budget games, players compete over resources with finite budgets. For every resource, a player has a specific demand and as a strategy, he chooses a subset of resources. If the total demand on a resource does not exceed its budget, the utility of each player who chose that resource equals his

  10. Gde ono, nashe mesto? / Nelli Kuznetsova

    Index Scriptorium Estoniae

    Kuznetsova, Nelli

    2007-01-01

    Tallinnas toimus siinse vene kogukonna esindajate konverents, kus arutati venelaste probleeme Eestis. Konverentsist võttis osa ka Venemaa suursaadik Eestis Nikolai Uspenski. Vt. samas intervjuud Nikolai Uspenskiga

  11. Nash Equilibria in Shared Effort Games

    NARCIS (Netherlands)

    Polevoy, G.; Trajanovski, S.; De Weerdt, M.M.

    2014-01-01

    Shared effort games model people's contribution to projects and sharing the obtained profits. Those games generalize both public projects like writing for Wikipedia, where everybody shares the resulting benefits, and all-pay auctions such as contests and political campaigns, where only the winner

  12. Third Worldism | Nash | African Sociological Review / Revue ...

    African Journals Online (AJOL)

    African Sociological Review / Revue Africaine de Sociologie. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 7, No 1 (2003) >. Log in or Register to get access to full text downloads.

  13. Nash tshelovek v Milane / Ksenia Repson

    Index Scriptorium Estoniae

    Repson, Ksenia

    2006-01-01

    Eesti Kunstiakadeemia tööstusdisaini eriala III kursuse tudeng Pavel Sidorenko sai I koha ja kursusekaaslane Anna-Maria Einla II koha noorte disainerite konkursil Massimo Martini Design Award Milanos. Konkursi korraldusest, Sidorenko ja Einla konkursitöödest

  14. Nash equilibria via duality and homological selection

    Indian Academy of Sciences (India)

    Zr. The (m−1)-skeleton of ×rSm−1 is ∨rSm−1. (under the standard CW complex structure on the product induced from the CW complex structure on Sm−1 with one m−1-cell). The projection map induces ir on each factor. Therefore the projection map on Hm−1 is the sum Zr → Z given by (a1,...,ar) ↦→ a1 +···+ ar. Therefore.

  15. Nash equilibria via duality and homological selection

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... Given a multifunction from to the -fold symmetric product Symk(X), we use the Dold–Thom theorem to establish a homological selection theorem. ... The domain part of the email address of all email addresses used by the office of Indian Academy of Sciences, including those of the staff, the journals, ...

  16. The Embedding Theorems of Whitney and Nash

    Indian Academy of Sciences (India)

    IAS Admin

    axis or the y-axis. It is nat- ural to ask whether such a bijection can be given for all points of the circle in a single stroke without having to resort to a two-step approach given above. The answer is no. Let us look at another example. We consider ...

  17. Stability and perfection of nash equilibria

    CERN Document Server

    Damme, Eric

    1991-01-01

    I have been pleased with the favourable reception of the first edition of this book and I am grateful to have the opportunity to prepare this second edition. In this revised and enlarged edition I corrected some misprints and errors that occurred in the first edition (fortunately I didn't find too many) and I added a large number of notes that give the reader an impression of what kind of results have been obtained since the first edition was printed and that give an indication of the direction the subject is taking. Many of the notes discuss (or refer to papers discussing) applications of the refinements that are considered. Of course, it is the quantity and the quality of the insights and the applications that lend the refinements their validity. Although the guide to the applications is far from complete, the notes certainly allow the reader to form a good judgement of which refinements have really yielded new insights. Hence, as in the first edition, I will refrain from speculating on which refinements of...

  18. How Do Doctors Treat NAFLD and NASH?

    Science.gov (United States)

    ... Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información ... Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información ...

  19. How Do Doctors Diagnose NAFLD and NASH?

    Science.gov (United States)

    ... Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información ... Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información ...

  20. God v Jevrosojuze. Poteri i priobretenija / Ivar Raig ; interv. Tatjana Opekina

    Index Scriptorium Estoniae

    Raig, Ivar, 1953-

    2005-01-01

    Professor Ivar Raig arutleb muudatuste üle, mida on toonud Eestile esimene aasta Euroopa Liidus. Suhkrutrahvi põhjustest, talunike toetuste võimalustest Euroopa Liidu fondidest, kapitali rahvusest, tööjõu vabast liikumisest, põhiseaduslikust leppest, maailma demograafiliste protsesside mõjust Euroopa ja USA suhetele

  1. Kadriorus voolivad mitme maa skulptorid jääst kujusid / Tatjana Bratoljubova

    Index Scriptorium Estoniae

    Bratoljubova, Tatjana

    2008-01-01

    Kadrioru pargi 290. sünnipäeva puhul loovad kunstnikud Tallinnas Luigetiigi ääres jääskulptuure. Taieseid teostavad Kate Robinson Shotimaalt, Natalia Tshistjakova ja Jevgeni Zavjalov Peterburist ning Tiiu Kirsipuu, Ekke Väli ja Kalle Pruuden Eestist

  2. Muusikaalane õppekirjandus ühiskonnaväärtuste edasikandjana / Tatjana Lindeberg, Maia Muldma

    Index Scriptorium Estoniae

    Lindeberg, Tatjana

    2008-01-01

    Artiklis on analüüsitud aastatel 1991-2007 Eesti ja Soome muusikaõpikute laulurepertuaaris olevaid väärtusi (sotsiaalsed-, esteetilised ja eetilised ning etnokultuurilised väärtused). Võrdluseks tagasivaade nõukogude aastatesse 1985-1990/91

  3. Skoro nam pjatnadtsat. Mõ belõje i pushistõje? / Arvo Sirendi ; interv. Tatjana Opekina

    Index Scriptorium Estoniae

    Sirendi, Arvo, 1939-

    2006-01-01

    Põllumajandusdoktor, ERL-i liige vastab küsimustele, mis on seotud Eesti taasiseseisvumisega, toimunud muutustega maaelus ja põllumajanduses ning tervishoius viimasel viieteistkümnel aastal, Eesti-Vene suhetega

  4. Russkaja diaspora : vzgljad iz Moskvõ / Tatjana Poloskova ; interv. Nelli Kuznetsova

    Index Scriptorium Estoniae

    Poloskova, Tatjana

    2004-01-01

    Mõningates endistes NSVL liiduvabariikides, ka Eestis, viidi läbi monitooring venelaste olukorra selgitamiseks. Uuringu tulemusi arutati Moskvas, Peterburis ning kokkuvõtvat aruannet Venemaa välisministeeriumis. Venemaa kaasmaalaste poliitikast

  5. Educando le figlie di Tat'jana: governanti vittoriane in Russia

    Directory of Open Access Journals (Sweden)

    Daria Parisi

    2013-12-01

    Full Text Available In this article, after a short description of the phenomenon of British governesses’ emigration to Russia, three novels are analysed. These novels belong to the “governess abroad literature” and were published shortly after the Crimean War, due to the increasing interest of readers towards books about Russia. From the analysis of themes and techniques in the three texts, the importance of the British imperialist project in its relation with travel literature and fiction emerges, as well as the contribution to this project of the character of the British governess, represented as an educator of foreigners, an evangelist, a cultural mediator and a proud symbol of Englishness.

  6. Filosofija finansovõhh prestuplenii / Tatjana Merkulova, Martinsh Naglis, Vaidotas Vishnjauskas

    Index Scriptorium Estoniae

    Merkulova, Tatjana

    2001-01-01

    Eesti, Läti, Leedu suuremad finantsskandaalid: Eesti rublade müük Tsetseeniasse, 10 miljoni krooni kadumine Eesti Pangast, Maapanga ja ERA Panga pankrotistumine; Lätis Latvijas tautas banka, Olimpija ja Banka Baltija pankrotid, Saksa firmaga ZUS seotud 18 miljoni afäär; Leedus Lietovos akcinis inovacinis bankas (LAIB), Litimpeks panga ja Vakaru bankas'e pankrotid

  7. Prebõvanije v Jevrosojuze objazõvajet igrat po pravilam / Armands Gutmanis ; interv. Tatjana Komorskaja

    Index Scriptorium Estoniae

    Gutmanis, Armands

    2004-01-01

    Intervjuu Läti saadikuga Leedus Baltimaade ühistest transpordiprojektidest ning konkurentsist, muutustest koostöös seoses liitumisega EL-iga, rahvusliku identiteedi säilimisest globaliseerumise käigus

  8. EU-Russia : towards the four spaces / Tatjana Romanova, Natalia Zaslavskaya

    Index Scriptorium Estoniae

    Romanova, Tatjana

    2004-01-01

    Ülevaade Euroopa Liidu ja Venemaa suhetest aastatel 1991-2003. Koostöö aluseks olevast 1997. a. sõlmitud Partnerluse ja Koostöö Lepingust. Koostöö perspektiividest Euroopa ühise majandus-, õigus-, julgeoleku- ning teadus- ja haridusruumi raames

  9. Ivangorodtsõ zarabotali na lutshshii za dvadtsat let prazdnik / Aleksei Shanin ; interv. Tatjana Zavjalova

    Index Scriptorium Estoniae

    Shanin, Aleksei

    2004-01-01

    Ivangorodi eelarve on kahe aasta jooksul kümnekordistunud, juba kaks aastat pole linnas tööpuudust. Linn lahendab spetsialistide korteriprobleeme ning võimaldab pensionäridele tasuta kasutada ühistransporti

  10. Molodõje litsa partii / Karel Rüütli ; interv. Tatjana Opekina

    Index Scriptorium Estoniae

    Rüütli, Karel, 1978-

    2008-01-01

    Intervjuu Riigikogu Rahvaliidu fraktsiooni esimehe Karel Rüütliga, kes vastab küsimustele, mis puudutavad tööd Riigikogus, Eestimaa Rahvaliidu positsiooni ühiskonnas, noorte osalust poliitikas ja erakonnas

  11. Kruglõi stol semeistva Tshuhrajev / Pavel Tshuhrai, Anastassia Tshuhrai ; interv. Tatjana Petrenko

    Index Scriptorium Estoniae

    Tshuhrai, Pavel

    2006-01-01

    Perekond Tshuhrai'de vestlusring : režissöör ja stsenarist Pavel Tshuhrai räägib oma isast, režissöör Grigori Tshuhraist, meenutab oma lapsepõlve. Tema tütar Anastassia oma isast ja vanaisast. Pavel Tshuhrai abikaasa Maria Zvereva perekonna eraelust

  12. "Nizkii reiting - eto problema" / Taavi Veskimägi ; interv. Tatjana Opekina

    Index Scriptorium Estoniae

    Veskimägi, Taavi, 1974-

    2006-01-01

    Res Publica liidri Taavi Veskimägi suhtumisest president Arnold Rüütli võimalikku jätkamisse, hinnangutest tuntud poliitikute lahkumisele Res Publicast, ühenduse kujunemisest parteiks, partei reitingust, valitseva koalitsiooni kriitika

  13. Baltimaade parim konstaabel töötab Maidlas ja Sondas / Tatjana Leppik

    Index Scriptorium Estoniae

    Leppik, Tatjana

    2007-01-01

    Ilmunud ka: Severnoje Poberezhje : Subbota, 10. nov. 2007, lk. 2. Leedus toimunud politseinike võistlusel selgusid Baltimaade parimad korravalvurid. Individuaalarvestuses tunnistati parimaks Paul Kriisa

  14. Aplodismentõ i kriki "bravo!" do polunotshi / Tatjana Laada, Liina Poobus

    Index Scriptorium Estoniae

    Laada, Tatjana

    2004-01-01

    Jõhvi Vene gümnaasiumi teatristuudio esinemisest VII õpetajate teatrifestivalil Viljandis, kus etendati V. Sologubi vodevilli "Häda õrna südame pärast". Oma muljeid jagavad toimetusele lavastaja T. Laada ja helirežissöör L. Poobus

  15. Budushtsheje za Business Travel / Olga Pavuk, Anzhela Rzhishtsheva, Tatjana Komorskaja...[jt.

    Index Scriptorium Estoniae

    2006-01-01

    Ülevaade Balti riikide konverentsi- ja äriturismist. Konverentsikeskustest hotellides ja mujal, Eesti suurematest äriturismiga tegelevatest ettevõtetest, Eestit külastanud turistide statistikast. Tabelid

  16. Russki "Tjulpan" pokoril lazurnõi bereg / Maria Davtjan, Tatjana Pinskaja

    Index Scriptorium Estoniae

    Davtjan, Maria

    2008-01-01

    61. Cannes'i filmifestival on lõppenud. Vaatenurga preemia sai Kasahstani režissöör Sergei Dvortsevoi filmi "Tulp" ("Tjulpan") eest. Lisatud ka lühiintervjuu režissööriga. Ka mõnest filmist, nii auhinnatuist (Steven Soderbergh'i "Che", Clint Eastwoodi "Changeling") kui ilmajäänuist (Atom Egoyani "Adoration", Wim Wendersi "Palermo Shooting"), Sharon Stone'i juhitud heategevast AIDSi ravi toetavast oksjonist

  17. Tarvo Hanno Varres, Mari-Leen Kiipli / Merilin Talumaa, Hanno Soans, Tatjana Kozlova-Johannes

    Index Scriptorium Estoniae

    Talumaa, Merilin, 1986-

    2015-01-01

    Vaatluse alla on võetud Tarvo Hanno Varrese heli- ja videoinstallatsioon "Lindistav põrand" (2015) ja heli- ja videoteos "Betweenland" (2014) ning Mari-Leen Kiipli fotoseeria "The school of dreams" (2012-2015)

  18. Lutshije muzhtshinõ-aktjorõ - v Rossii. A lutsheje kino - v Rumõnii / Maria Davtjan, Tatjana Pinskaja

    Index Scriptorium Estoniae

    Davtjan, Maria

    2007-01-01

    60-nda Cannes'i filmifestivali auhindadest : Kuldse Palmioksa saanud Christian Mungiu "4 kuud, 3 nädalat ja 2 päeva" (Rumeenia), Konstantin Lavronenko parima näitleja auhind Andrei Zvjagintsevi filmis "Pagendus" (Izgnanije") jt

  19. Maksim Danilov : "Ida-Virus näen rohkem perspektiivi kui Tallinnas." / Maksim Danikov ; interv. Tatjana Lepik

    Index Scriptorium Estoniae

    Danikov, Maksim

    2006-01-01

    Ilmunud ka: Severnoje Poberezhje Ilmunud ka: Severnoje Poberezhje : Subbota 10. juuni lk. 5. Kiviõli aselinnapea kommunaalmajanduse alal oma tööst, linna arengust ja tulevikust. Arvamust avaldavad Kiviõli linnapea Voldemar Trumm ja OÜ Formet Grupp juht Pavel Suslov

  20. The role of banking sector, Mortgage and Land Bank in further economic development in Latvia / Brigita Baltaca, Tatjana Volkova

    Index Scriptorium Estoniae

    Baltaca, Brigita

    2004-01-01

    Läti pangandussektori kujunemisest. Riikliku hüpoteekpanga (Latvija Hipoteku un zemes banka) osast riigi majanduslikus arengus: väikeettevõtetele, naisettevõtjatele, elamuehitusele, põllumajandusele suunatud laenuprogrammid. Tabelid. Diagrammid

  1. Information Structures in Nash and Leader-Follower Strategies.

    Science.gov (United States)

    1981-01-01

    OICkASSIPICATION/ OOWNGRAOING IS. OISTNIIIUTION STATEMINT (ao tD. esPort ) * Approved for public release; distribution unlimited. 17. DISTRIBUTION STATEMENT...y Y " Q i [ " Q , ".. .z Qi3 Rii., Rij are symmetric, positive definite riatrices, E(y )0O; E(yoyo )I - where I is the identity matrix. Let player...B22 722 (0) assuming that Ac22 is nonsingular.* It is noticed that equations (2.3), (2.6) and (2.7) are identical to equa- tions (2.11), (2.10) and

  2. Alternating minima and maxima, Nash equilibria and bounded arithmetic

    Czech Academy of Sciences Publication Activity Database

    Pudlák, Pavel; Thapen, Neil

    2012-01-01

    Roč. 163, č. 5 (2012), s. 604-614 ISSN 0168-0072 R&D Projects: GA AV ČR IAA100190902 Institutional research plan: CEZ:AV0Z10190503 Keywords : proof complexity * bounded arithmetic * search problems Subject RIV: BA - General Mathematics Impact factor: 0.504, year: 2012 http://www.sciencedirect.com/science/article/pii/S016800721100090X

  3. On Cournot-Nash equilibria with exogenous uncertainty

    NARCIS (Netherlands)

    Aaftink, J.; Ireland, N.; Sertel, M.

    1986-01-01

    A large body of literature has accumulated which examines how the optimal solution of an agent maximizing the expectation of a real-valued function, depending on a random parameterp and the agent's behaviorx, reacts to perturbations in the first and second moments ofp. Here, by an approximation

  4. From Nash to Lindahl in Climate Change Policy

    NARCIS (Netherlands)

    Groot, L.F.M.; Swart, J.

    2015-01-01

    To reach an international agreement on the cost of abatement of climate change, one needs to specify a fair burden sharing rule. This paper evaluates different burden sharing rules in terms of their redistributive impact and by the extent to which they realize the aim of optimal abatement. It is

  5. What are the symptoms of NAFLD and NASH?

    Science.gov (United States)

    ... may be closely linked to metabolic syndrome. Doctors define metabolic syndrome as the presence of any three ... Grants & Grant History Research Resources Research at NIDDK Technology Advancement & Transfer Meetings & Workshops Health Information Diabetes Digestive ...

  6. Properties of feedback Nash equilibria in scalar LQ differential games

    NARCIS (Netherlands)

    Engwerda, Jacob

    In this paper we study the scalar linear quadratic differential game with state feedback information structure. Using a geometric approach, we present a complete characterization when this game will have no, one or multiple equilibria. Furthermore, we investigate the effect on this solution

  7. Nash sovremennik Tammsaare / Elmo Nüganen ; interv. Nikolai Hrustaljov

    Index Scriptorium Estoniae

    Nüganen, Elmo, 1962-

    2006-01-01

    Tallinna Linnateatris 12. märtsil esietendunud Elmo Nüganeni Tammsaare-lavastusest, mis põhineb "Tõe ja õiguse" neljandal osal. Dramatiseeringu on teinud Elmo Nüganen, peaosades Indrek Sammul ja Hele Kõre

  8. Britanskaja objektivnost i nash võbor / Boris Tuch

    Index Scriptorium Estoniae

    Tuch, Boris, 1946-

    2007-01-01

    Kaks uut teatriraamatut : "Oxfordi illustreeritud teatriajalugu", mille eestikeelse tõlke aluseks on 1995. aastal kirjastuses Oxford University Press ilmunud samanimeline raamat, koostajaks John Russell Brown ja Reet Neimari koostatud ja kommenteeritud teatriraamat "Sajandi sada sõnalavastust" (Eesti Entsüklopeediakirjastus, 2007)

  9. Balts react to anti-NATO magazine article / Andris Straumanis

    Index Scriptorium Estoniae

    Straumanis, Andris

    2002-01-01

    Moskva korrespondent Jeffrey Tayler kirjutas Ameerika ajalehes The Atlantic Monthly artikli venelaste diskrimineerimisest Balti riikides ja et sellepärast ei peaks Eestit, Leedut ja Lätit NATO-sse võtma

  10. Briti ajakirjanik sai Moskvast hundipassi / Heiki Suurkask

    Index Scriptorium Estoniae

    Suurkask, Heiki, 1972-

    2011-01-01

    Briti ajalehe Guardian Moskva-korrespondent Luke Harding saadeti kodumaale tagasi. Guardian peab põhjuseks seda, et Harding mainis Wikileaksist artikleid kirjutades, kuidas USA diplomaadid peavad Putini Venemaad maffiariigiks

  11. Free zones on the fence

    Index Scriptorium Estoniae

    2001-01-01

    Euroopa Liiduga liitumisega võib kaasneda vabakaubandustsoonide kadumine Baltimaade sadamates. Sellega seonduvatest probleemidest. Koostanud Olga Pavuk, Jelena Narushevich, Gediminas Pilaitis, Tatjana Merkulova

  12. Iz zolushki - v modeli / Olga Grigorjeva

    Index Scriptorium Estoniae

    Grigorjeva, Olga, 1983-

    2007-01-01

    Esimene rahvusvaheline laste ja noorte moeteatrite festival "Max Moda 2007" Tallinnas. Festivali peakorraldajast, moeteatrist Max Moda. Asutaja ja kunstiline juht on Maksim Hlebnikov. Kommenteerib Tatjana Hlebnikova

  13. Strategic Generation Capacity Choice under Demand Uncertainty : Analysis of Nash Equilibria in Electricity Markets

    NARCIS (Netherlands)

    Gürkan, G.; Ozdemir, O.; Smeers, Y.

    2013-01-01

    Abstract: We analyze a two-stage game of strategic firms facing uncertain demand and exerting market power in decentralized electricity markets. These firms choose their generation capacities at the first stage while anticipating a perfectly competitive future electricity spot market outcome at the

  14. A Critical Assessment of Cost-Based Nash Methods for Demand Scheduling in Smart Grids

    OpenAIRE

    Najy, Waleed K. A.; Crandall, Jacob W.; Zeineldin, H. H.

    2013-01-01

    Demand-side management (DSM) is becoming an increasingly important component of the envisioned smart grid. The ability to improve the efficiency of energy use in the power system by altering demand is widely viewed as being not merely promising but in fact essential. However, while the advantages of DSM are clear, arriving at an efficient implementation has so far proven to be less straightforward. There have recently been many proposals put forth in the literature to tackle the demand schedu...

  15. Pricing of Vehicle-to-Grid Services in a Microgrid by Nash Bargaining Theory

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Sarparandeh

    2017-01-01

    Full Text Available Owners of electric vehicles (EVs can offer the storage capacity of their batteries to the operator of a microgrid as a service called vehicle-to-grid (V2G to hold the balance between supply and demand of electricity, particularly when the microgrid has intermittent renewable energy sources. Literature review implies that V2G has economic benefits for both microgrid operator and EV owners, but it is unclear how these benefits are divided between them. The challenge grows when the policy makers rely on the V2G revenue as an incentive for expanding the penetration of EVs in the automotive market. This paper models the interaction between microgrid operator and EV owners as a bargaining game to determine how the benefits of V2G should be divided. The method has been implemented on a hybrid power system with high wind penetration in addition to diesel generators in Manjil, Iran. The results indicate that, in addition to V2G benefits, government subsidies are necessary to promote the use of EVs.

  16. A Line in the Sand: Prospect Theory and Nash Arbitration in Resolving Territorial Disputes

    Science.gov (United States)

    2012-12-01

    productive and diversified fishery. The rocky island coasts also shelter dense kelp and seaweed forests. Virtually all economic activity within the...along the Red Sea between the borders of Egypt and Sudan (Figure 34). The land is predominantly rocky and sandy, and has little inherent value at the...surface. Oil and gas reserves, however, are likely offshore in the Red Sea.188 The triangle was created as a result of the misalignment of two

  17. A Nash-Hörmander iteration and boundary elements for the Molodensky problem

    DEFF Research Database (Denmark)

    Costea, Adrian; Gimperlein, Heiko; Stephan, Ernst P.

    2014-01-01

    We investigate the numerical approximation of the nonlinear Molodensky problem, which reconstructs the surface of the earth from the gravitational potential and the gravity vector. The method, based on a smoothed Nash–Hörmander iteration, solves a sequence of exterior oblique Robin problems...... evaluation of the Hessian of the gravitational potential on the surface, using a representation in terms of a hypersingular integral.Aboundary element method is used to solve the exterior problem. Numerical results compare the error between the approximation and the exact solution in a model problem....

  18. Pigeons ("Columba Livia") Approach Nash Equilibrium in Experimental Matching Pennies Competitions

    Science.gov (United States)

    Sanabria, Federico; Thrailkill, Eric

    2009-01-01

    The game of Matching Pennies (MP), a simplified version of the more popular Rock, Papers, Scissors, schematically represents competitions between organisms with incentives to predict each other's behavior. Optimal performance in iterated MP competitions involves the production of random choice patterns and the detection of nonrandomness in the…

  19. Cholesterol crystallization within hepatocyte lipid droplets and its role in murine NASH.

    Science.gov (United States)

    Ioannou, George N; Subramanian, Savitha; Chait, Alan; Haigh, W Geoffrey; Yeh, Matthew M; Farrell, Geoffrey C; Lee, Sum P; Savard, Christopher

    2017-06-01

    We recently reported that cholesterol crystals form in hepatocyte lipid droplets (LDs) in human and experimental nonalcoholic steatohepatitis. Herein, we assigned WT C57BL/6J mice to a high-fat (15%) diet for 6 months, supplemented with 0%, 0.25%, 0.5%, 0.75%, or 1% dietary cholesterol. Increasing dietary cholesterol led to cholesterol loading of the liver, but not of adipose tissue, resulting in fibrosing steatohepatitis at a dietary cholesterol concentration of ≥0.5%, whereas mice on lower-cholesterol diets developed only simple steatosis. Hepatic cholesterol crystals and crown-like structures also developed at a dietary cholesterol concentration ≥0.5%. Crown-like structures consisted of activated Kupffer cells (KCs) staining positive for NLRP3 and activated caspase 1, which surrounded and processed cholesterol crystal-containing remnant LDs of dead hepatocytes. The KCs processed LDs at the center of crown-like structures in the extracellular space by lysosomal enzymes, ultimately transforming into lipid-laden foam cells. When HepG2 cells were exposed to LDL cholesterol, they developed cholesterol crystals in LD membranes, which caused activation of THP1 cells (macrophages) grown in coculture; upregulation of TNF-alpha , NLRP3, and interleukin 1beta ( IL1β ) mRNA; and secretion of IL-1beta. In conclusion, cholesterol crystals form on the LD membrane of hepatocytes and cause activation and cholesterol loading of KCs that surround and process these LDs by lysosomal enzymes.

  20. Nashe vremja nuzhdajetsja v Gamlete / Борис Тух

    Index Scriptorium Estoniae

    Тух, Борис, 1946-

    2004-01-01

    Poola linnas Gdanskis toimunud VIII rahvusvahelisest Shakespeare'le pühendatud teatrifestivalist ja konverentsist. Theatrum mängis 2. ja 3. aug. festivali raames oma lavastust "Hamlet" L. Petersoni lavastuses

  1. Planeta Zemlja - matritsa ili nash metafizitsheski dom? / Peeter Liiv ; tõlk. Marina Tervonen

    Index Scriptorium Estoniae

    Liiv, Peeter, 1953-

    2005-01-01

    Metafüüsika nõrkusest Eesti kultuuris. Kannatuse ja rõõmu religioonidest, valgustumisest, "Brahma ööst" ja "Brahma päevast", miks ja kuidas on Jumal maailma loonud. Osho, Ken Wilberi, Maharishi Mahesh Yogi jt. mõtteid

  2. Cytokeratin 18 as a non invasive marker in diagnosis of NASH and ...

    African Journals Online (AJOL)

    Mohsen M. Maher

    2014-12-19

    Dec 19, 2014 ... fibrosis, supporting its usefulness in clinical practice. Abbreviations: ALT, alanine transaminase; ANA, antinuclear anti- body; Anti LKM Ab,anti-liver kidney microsomal antibodies; ASMA, anti smooth muscle antibody; AST, aspartate transaminase; BMI, body mass index; CBC, complete blood count; CK-18, ...

  3. How Can My Diet Help Prevent or Treat NAFLD and NASH?

    Science.gov (United States)

    ... which can damage your liver . For men, experts define heavy alcohol use as more than 4 drinks ... Grants & Grant History Research Resources Research at NIDDK Technology Advancement & Transfer Meetings & Workshops Health Information Diabetes Digestive ...

  4. Takova zhizn, ili nash tshelovek v Pompidu / Ene Rämmeld ; interv. Boris Tuch

    Index Scriptorium Estoniae

    Rämmeld, Ene, 1947-

    2004-01-01

    Pariisis elav näitlejanna esitles oma autobiograafilist raamatut "C'est la vie. Elu on selline", milles juttu kolmest kunstnikust : L. Laiusest, E. Hermakülast ja V.G. Karassev-Orgussaarest - kuidas nad kõik mõjutasid näitlejanna arengut. Ka oma elust ja elufilosoofiast praegu

  5. Nash tshelovek v Moskve - laureat vserossiiskoi premii / Erki Aule ; interv. Boris Tuch

    Index Scriptorium Estoniae

    Aule, Erki

    2004-01-01

    1. novembril kuulutati Venemaal välja iga-aastase näidendivõistluse "Deistvujushtshije litsa" laureaadid. Võistlusele saabunud 219 näidendi hulgast osutusid väljavalituiks kümme paremat. Nende hulgas ka Salong-Teatri lavastaja ning Venemaa Teatriakadeemia magistrantuuris lavastamist õppiva Erki Aule näidend "Vorobji uleteli" (Varblased läinud), mis sai ka ajakirja "Ogonjok" eripreemia

  6. On Quasinormal Modes for Scalar Perturbations of Static Spherically Symmetric Black Holes in Nash Embedding Framework

    Directory of Open Access Journals (Sweden)

    Sergio C. Ulhoa

    2017-01-01

    Full Text Available In this paper we investigate scalar perturbations of black holes embedded in a five-dimensional bulk space. The quasinormal frequencies of such black holes are calculated using the third order of Wentzel, Kramers, and Brillouin (WKB approximation for scalar perturbations. The high overtones of quasinormal modes indicate a resonant-like set of black holes suggesting a serious constraint of embedding models in five dimensions.

  7. Three Players Nash Equilibrium Game Concerning the Charging Time and Place of Employee Electric Vehicles

    DEFF Research Database (Denmark)

    Fetene, Gebeyehu Manie; Hirte, Georg; Tscharaktschiew, Stefan

    In this study, we model the demand for and supply of charging facility at workplace, and the associated consequences on social welfare. We found that both employers and workers benefit from the accessibility of workplace charging when: i) they agree to pay for workplace charging out of gross salary......) helping to predict the choice of time and place of charging of employees’ EVs, (ii) supporting employers to understand the implications of workplace charging provision, (iii) providing electricity suppliers with information for better electricity demand predictions, and (iv) revealing to policy makers...... the non-taxed fringe benefit problem of charging at the workplace....

  8. Abelovu cenu za matematiku z í skali v roce 2015 John F. Nash a Louis Nirenberg

    Czech Academy of Sciences Publication Activity Database

    Křížek, Michal

    2015-01-01

    Roč. 60, č. 4 (2015), s. 277-283 ISSN 0032-2423 Institutional support: RVO:67985840 Keywords : Riemannian manifolds * regularity * Navier-Stokes equations * nonlinear elliptic problem Subject RIV: BA - General Mathematics http://hdl.handle.net/10338.dmlcz/144483

  9. The other Side of Objectivity

    DEFF Research Database (Denmark)

    Bjerregaard, Peter

    2009-01-01

    Artiklen følger en korrespondance mellem forfatteren og Alexandra Schüssler under sidstnævntes etablering af udstillingen "Villa Sovietica" på Musée d'ethnographie de Genève. Ved at følge AS' overvejelser om den udstilling, hun er ved at etablere fokuserer artiklen på, hvordan etnografiske museer...

  10. Pressivabaduse indeks nõuab pimedat usaldust / Tarmu Tammerk

    Index Scriptorium Estoniae

    Tammerk, Tarmu, 1961-

    2006-01-01

    Eelmisel nädalal avaldas Pariisis peakorterit omav ajakirjanduse pressivabaduse organisatsioon Reporters sans frontieres (RSF) maailma riikide pressivabaduse indeksid. Eesti on tõusnud mulluselt 11. kohalt 6. kohale. Selgitab Avaliku Sõna Nõukogu ja Pressinõukogu esimees, praegune Agence France Presse'i korrespondent Tarmu Tammerk. Lisa: Tabel

  11. Emmaste kell pälvis üleilmset tähelepanu / Priit Pullerits

    Index Scriptorium Estoniae

    Pullerits, Priit, 1965-

    2001-01-01

    Lugu Emmaste kiriku kellast jõudis Associated Pressi kaudu paljudesse maailma infokanalitesse. Kalifornia firma Critical Mass Films kavatseb vändata mängufilmi Hiiumaal Emmaste kiriku kella peitmise loost II Maailmasõja ja järgnenud okupatsiooni ajal. Kella peitmise ja leidmise loo pani kirja AP Balti korrespondent M. Tarm

  12. Edward Lucas : Eesti parim kaitse on kontrast Venemaaga / Edward Lucas ; interv. Liisa Past

    Index Scriptorium Estoniae

    Lucas, Edward

    2008-01-01

    The Economist Kesk- ja Ida-Euroopa korrespondent vastab küsimustele, mis puudutavad tema raamatut "Uus külm sõda", võimuvahetust Venemaal ja vene raha mõju maailmapoliitikale, USA uue administratsiooni Vene-poliitikat ning Eesti-Venemaa suhteid

  13. "Eesti elab varasemate saavutuste arvel" / Edward Lucas ; interv. Argo Ideon

    Index Scriptorium Estoniae

    Lucas, Edward

    2007-01-01

    Briti nädalalehe The Economist Kesk- ja Ida-Euroopa korrespondent avaldab arvamust Eesti senise valitsuse, peaminister Andrus Ansipi kohta. Ta tunneb muret, et majanduskasv pöörab langusele, haavatavaks kohaks peab ta jooksevkonto puudujääki. Tema hinnangul on Eestil väga tähtis minna edasi haridusreformiga

  14. The Attalid Kingdom and the Cult of Cybele at Pessinous

    DEFF Research Database (Denmark)

    Rasmussen, Anders Holm

    2002-01-01

    Artiklen diskuterer den status præsterne for Cybelekulten i Pessinous havde i samfundet i hellenistisk tid. Dette belyses bl.a. gennem en overleveret korrespondance mellem disse præster og de attalidiske konger. Det hævdes, at præsterne besad en fremtrædende position i Pessinous....

  15. Tracking lichen community composition changes due to declining air quality over the last century: the Nash legacy in Southern California

    Science.gov (United States)

    Jennifer Riddell; Sarah Jovan; Pamela E. Padgett; Ken. Sweat

    2011-01-01

    Southern California's South Coast Air Basin includes the heavily urbanized Los Angeles and Orange counties, the inland urban and suburban areas, and the surrounding mountain ranges. Historically high air pollution makes the region a natural laboratory for investigating human impacts on natural systems. Regional lichen distribution records from the early 1900s...

  16. High fat, high fructose, high cholesterol feeding causes severe NASH and cecal microbiota dysbiosis in juvenile Ossabaw swine

    Science.gov (United States)

    Female Ossabaw swine (5 weeks old) were fed WD (43.0% fat; 17.8% high fructose corn syrup; 2% cholesterol) or low-fat diet (CON/lean; 10.5% fat) for 16 wks (n=6 each) or 36 wks (n=4 each). WD-fed pigs developed obesity, dyslipidemia, and systemic insulin resistance compared with CON pigs. In additio...

  17. Domino effects within a chemical cluster : A game-theoretical modeling approach by using Nash-equilibrium

    NARCIS (Netherlands)

    Reniers, Genserik; Dullaert, Wout; Karel, Soudan

    2009-01-01

    Every company situated within a chemical cluster faces domino effect risks, whose magnitude depends on every company's own risk management strategies and on those of all others. Preventing domino effects is therefore very important to avoid catastrophes in the chemical process industry. Given that

  18. Domino effects within a chemical cluster: a game-theoretical modeling approach by using Nash-equilibrium.

    Science.gov (United States)

    Reniers, Genserik; Dullaert, Wout; Karel, Soudan

    2009-08-15

    Every company situated within a chemical cluster faces domino effect risks, whose magnitude depends on every company's own risk management strategies and on those of all others. Preventing domino effects is therefore very important to avoid catastrophes in the chemical process industry. Given that chemical companies are interlinked by domino effect accident links, there is some likelihood that even if certain companies fully invest in domino effects prevention measures, they can nonetheless experience an external domino effect caused by an accident which occurred in another chemical enterprise of the cluster. In this article a game-theoretic approach to interpret and model behaviour of chemical plants within chemical clusters while negotiating and deciding on domino effects prevention investments is employed.

  19. Igor Maslennikov : Kogda snimalsja nash Holms, prihhodili pisma - trebovali prodolzhenija, ugrozhali dazhe / Igor Maslennikov ; interv. Nina Kovalenko

    Index Scriptorium Estoniae

    Maslennikov, Igor

    2006-01-01

    Tuntud vene filmirežissöör tähistas 26. oktoobril oma 75. aastast juubelit. Teleseriaalist "Sherlock Holmes'i ja doktor Watsoni seiklused", filmist "Talvised kirsid" (1985), teistest tema filmidest ja seriaalidest

  20. Identification of Biochemical Pathways Associated with Lead Tolerance and Detoxification in Chrysopogon zizanioides L. Nash (Vetiver) by Metabolic Profiling.

    Science.gov (United States)

    Pidatala, Venkataramana R; Li, Kefeng; Sarkar, Dibyendu; Ramakrishna, Wusirika; Datta, Rupali

    2016-03-01

    Lead (Pb) is a major urban pollutant, due to deteriorating lead-based paint in houses built before 1978. Phytoremediation is an inexpensive and effective technique for remediation of Pb-contaminated homes. Vetiver (Chrysopogon zizanioides), a noninvasive, fast-growing grass with high biomass, can tolerate and accumulate large quantities of Pb in its tissues. Lead is known to induce phytochelatins and antioxidative enzymes in vetiver; however, the overall impact of Pb stress on metabolic pathways of vetiver is unknown. In the current study, vetiver plants were treated with different concentrations of Pb in a hydroponic setup. Metabolites were extracted and analyzed using LC/MS/MS. Multivariate analysis of metabolites in both root and shoot tissue showed tremendous induction in key metabolic pathways including sugar metabolism, amino acid metabolism, and an increase in production of osmoprotectants, such as betaine and polyols, and metal-chelating organic acids. The data obtained provide a comprehensive insight into the overall stress response mechanisms in vetiver.

  1. Un análisis estadístico del equilibrio de nash en juegos repetidos usando implementaciones computacionales

    OpenAIRE

    Necco, Claudia Mónica; Quintas, Luis Guillermo

    1998-01-01

    En este trabajo se realiza un análisis de situaciones de conflicto estratégico que se producen periódicamente y que se modelan como juegos repetidos, bajo supuestos de racionalidad acotada y usando implementaciones computacionales (estrategias implementadas por autómatas de tamaño 2). Sin estas restricciones hay típicamente infinitos equilibrios lo cual naturalmente dificulta la posibilidad de saber que tipo de conductas (todas razonables) podrán tomar los agentes. En este caso, se hace...

  2. Romantiline ajareis olevikust tulevikku mineviku kaudu / Gerhard Lock

    Index Scriptorium Estoniae

    Lock, Gerhard, 1978-

    2011-01-01

    26. veebruaril Eesti muusika päevade ja programmi "Tallinn - Euroopa kultuuripealinn 2011" raames Salme kultuurikeskuses toimunud Tatjana Kozlova autorikontserdist, kus kaasa tegid Annamaria Morini (flööt, Itaalia), Enzo Porta (viiul, Itaalia) ja ansambel Resonabilis

  3. Dancing at Lughnasa / Jekaterina Kondakova

    Index Scriptorium Estoniae

    Kondakova, Jekaterina

    2006-01-01

    Brian Frieli "Lõikuspeo tantsud" Vene Teatris, lavastaja Mihhail Feigin Moskvast. Esietendus 16. sept. Näitlejannad Ljubov Agapova, Tatjana Manevskaja, Jelena Tarassenko, Ksenia Agarkova ja Larissa Savankova tutvustavad oma tegelaskujusid. Ajakirja esikaanel kuupäev Detsember 2006/Jaanuar 2007

  4. Irina Muravjova nabila sinjakov na rolikahh / Oksana Truhhan

    Index Scriptorium Estoniae

    Truhhan, Oksana

    2006-01-01

    Muusikaline komöödia "Karneval" : režissöör Tatjana Lioznova : osades Irina Muravjova, Aleksandr Abdulov, Jekaterina Zhemtshuzhnaja : NSV Liit 1981. Lavastaja ja näitlejad meenutavad filmi valmimise käiku

  5. Standartenführer von Stirlitz - nõukogude ekraani-iidol / Aigi Viira

    Index Scriptorium Estoniae

    Viira, Aigi

    2004-01-01

    1973. aastal vändatud kultusseriaal "Seitseteist kevadist hetke", režissöör Tatjana Lioznova. Lisaks kommentaarid Ilmar Raagilt "Fenomen omas ajas", Peeter Ribalt "Seriaal parem kui Stirlitzi-anekdoodid"

  6. Forma odezhdõ - v tsvetotshek / Ksenia Repson

    Index Scriptorium Estoniae

    Repson, Ksenia

    2003-01-01

    Tatjana Tridvornova organiseeritud lilleballist Tallinnas. Algas lillekleitide defileega Saku Suurhallis ja jätkus lillekleitide konkursiga klubis Opium. Žürii koosseis. Võitja on läti florist Druvis Ciritis lillekleidiga "Puudutus"

  7. Katja Mosendz i Lena Arno sozdali devushku s koromõslom / Vilena Makaritsh

    Index Scriptorium Estoniae

    Makaritsh, Vilena

    2005-01-01

    Jekaterina Mosendz ja Jelena Arno võitsid fantaasiasoengute konkursi Riias. Võistlus toimus Baltimaade esimese ühisprojekti "Baltic Beauty World" raames. Oma loomingut (lillekleiti) näitas ka Tatjana Tridvornova

  8. Augustitantsud kanade ja põtradega / Kairi Prints

    Index Scriptorium Estoniae

    Prints, Kairi

    2008-01-01

    21.-23. aug. Tallinna Kanuti Gildi saalis toimunud Augusti tantsufestivali lavastustest - Sonia G̤mezi "Mi madre y yo', Frédéric Giesi "Dance (Practicable), Tatjana Gordejeva "Gallina Aquatica", Iguan Dance Theatre tantsulavastus "Radiodance"

  9. Ekskursioon Kozlova tämbrimaailma / Igor Garšnek

    Index Scriptorium Estoniae

    Garšnek, Igor, 1958-

    2011-01-01

    26. veebruaril Eesti muusika päevade ja programmi "Tallinn - Euroopa kultuuripealinn 2011" raames Salme kultuurikeskuses toimunud Tatjana Kozlova autorikontserdist, kus kaasa tegid Annamaria Morini (flööt, Itaalia), Enzo Porta (viiul, Itaalia) ja ansambel Resonabilis

  10. Ves aprel "Aprelju" ver / Lidija Tolmatshova

    Index Scriptorium Estoniae

    Tolmatshova, Lidija

    2001-01-01

    Kunstnike rühmituse "Aprill" - Aleksandr ja Nadezhda Popolitov, Vladislav ja Jelena Kuznetsov, Tatjana Petsheritsa, Igor Lukjanov, Sergei Kolesnikov, Aleksandr Orlov, Eduard Zentshik, Vladimir Zujev, German Jershov - näituse avamisest Sillamäel kehamaalingutega

  11. Sunflower Beauty Contest : tsvetõ zimoi / Marina Poltavtseva

    Index Scriptorium Estoniae

    Poltavtseva, Marina

    2001-01-01

    Lillekleitide võistlusest Sunflower Beauty Contest Tallinna klubis Decolte. Konkursi idee on florist Tatjana Tridvornovalt. Esimese koha sai Viimsi lilleäri lilleseadjate Meri-Liis Kõivu ja Triinu Põlderi lillekleit "Talvepruut"

  12. Starost ne radost / Jevgenija Garanzha, Jekaterina Rodina

    Index Scriptorium Estoniae

    Garanža, Jevgenija, 1979-

    2006-01-01

    Rahvusvaheline reitinguagentuur Standard & Poor's hoiatas oma raportis, et rahvastiku vananemine Eestis hakkab survet avaldama Eesti majandusele ja riigireitingule, mis võib edasiste reformideta langeda 2035. aastaks spekulatiivsesse kategooriasse. Vt. samas: Tatjana Lavrova. Vastastikune väljaaitamine pensionide osas

  13. Moda po maksimumu

    Index Scriptorium Estoniae

    2008-01-01

    Teisest rahvusvahelisest noorte moeteatrite festival-konkursist "Max Moda 2008" Tallinnas Salme Kultuurikeskuses 10.-11. aprillil. Demonstreeriti Maksim Hlebnikovi uut kollektsiooni. Kommenteerivad ürituse korraldajad Tatjana ja Maksim Hlebnikov

  14. Moeteater õpetab stiili tabama / Anneli Sihvart

    Index Scriptorium Estoniae

    Sihvart, Anneli, 1964-

    2011-01-01

    Kultuuripealinna programmi kuuluv 5. rahvusvaheline laste ja noorte moeteatrite festival "Max Moda 2011" Tallinnas Salme kultuurikeskuses 24.-26. märtsini. Festivali korraldavast moeteatrist Max Moda, mille kunstiline juht ja direktor on Maksim Hlebnikov. Tatjana Hlebnikova kommentaarid

  15. Russkije Jevropeiskogo Sojuza splotiliss v Narve / Nikolai Andrejev

    Index Scriptorium Estoniae

    Andrejev, Nikolai

    2005-01-01

    Narvas toimunud konverentsil osalesid Euroopa Liidu 16 liikmesriigi vene kogukonna, organisatsiooni ja ajalehe esindajad, nende hulgas Euroopa Parlamendi saadik Tatjana Zhdanova ja krahv Pjotr Sheremetjev. Esmakordselt kogunesid siia Euroopa Vene alliansi liikmed

  16. Uudised : Balleti võlumaailm. Agent M sai maha uue plaadi, singli ja videoga

    Index Scriptorium Estoniae

    2007-01-01

    Rahvusooper Estonia, eesotsas Mai Murdmaa, Tatjana Järvi ja Lemme Järviga, korraldab põhikoolinoortele balletti tutvustavaid etendusi. Alternatiivrokki viljeleva ansambli Agent M heliplaadist "Spionaazh" ja videost laulule "Queen of the World" (www.agentm.pri.ee)

  17. Korova Makarevitsha - samaja stojashtshaja

    Index Scriptorium Estoniae

    2005-01-01

    Rahvusvahelisest kunstifestivalist "Cowparade" Moskvas. Projekti algatajaks on Jerome D. Elbaum. Esimene Cowparade toimus 1998. a. Zürichis. Moskva oksjonil müüdi kõige kallimalt Andrei Makarevitshi, kunstnik Tatjana Nazarenko ja skulptor Zurab Tsereteli maalitud lehmad

  18. Mõ interesnõ drug drugu / Aleksandr Ikonnikov

    Index Scriptorium Estoniae

    Ikonnikov, Aleksandr

    2000-01-01

    Sillamäe kunstnike tööde näitusest Kärdla kultuurikeskuses. Esinesid Igor Lukjanov, German Jershov, Aleksandr Orlov, Vladimir ja Jelena Kuznetsovid, Aala Gitt, Tatjana Petsheritsa, Aleksandr Popolitov, Eduard Zenitski

  19. Pramana – Journal of Physics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    frequency elliptical laser field · Miladinovic Tatjana B Petrovic Violeta M .... Spin polarization of electrons in a magnetic impurity doped semiconductor quantum dot – The effect of electron–phonon interaction · Misra Deepanjali Tripathy Sukanta ...

  20. Vozmozhen li "russkii mir"? / Vladimir Stroi

    Index Scriptorium Estoniae

    Stroi, Vladimir

    2004-01-01

    Lätist valitud europarlamendisaadiku Tatjana Zhdanoki kohtumisest Vene kaasmaalaskonna rahvusvahelise ühenduse presidendi Pjotr Sheremetjeviga. Arutelu põhiküsimuseks oli võimaluste otsimine üleeuroopalise vene partei loomiseks

  1. Kommunist mittekommunisti ei usalda / David Satter ; interv. Viktor Niitsoo

    Index Scriptorium Estoniae

    Satter, David

    2005-01-01

    Tallinnas esitles oma raamatut "Meeletuste ajastu. Nõukogude Liidu allakäik ja langus" Finacial Times'i endine Moskva korrespondent David Satter, tegemist on NL-i viimase viieteistkümne aasta koondkroonikaga. Intervjuus meenutab David Satter oma tööaastaid Moskvas 1976-1982. a., kus ta keskendus põhiliselt ühiskondlik-poliitilistele teemadele, kaasa arvatud dissidentlik liikumine. Suhted võimudega, KGB provokatsioonid

  2. He skenothesia mias gnorimias

    DEFF Research Database (Denmark)

    Nørgaard, Lars

    2007-01-01

    I artiklen diskuteres mødet mellem Nikos Kazantzakis og Johannes Jørgensen i Assisi foråret 1924. I  Jørgensens dagbøger, nu på Det Kongelige Bibliotek i København, omtales mødet meget kort. Kazantzakis derimod refererer til mødet i sin korrespondance samt udførligt i forordet til sin oversættels...

  3. Individual Vaccination as Nash Equilibrium in a SIR Model with Application to the 2009-2010 Influenza A (H1N1) Epidemic in France.

    Science.gov (United States)

    Laguzet, Laetitia; Turinici, Gabriel

    2015-10-01

    The vaccination against ongoing epidemics is seldom compulsory but remains one of the most classical means to fight epidemic propagation. However, recent debates concerning the innocuity of vaccines and their risk with respect to the risk of the epidemic itself lead to severe vaccination campaign failures, and new mass behaviors appeared driven by individual self-interest. Prompted by this context, we analyze, in a Susceptible-Infected-Recovered model, whether egocentric individuals can reach an equilibrium with the rest of the society. Using techniques from the "Mean Field Games" theory, we extend previous results and show that an equilibrium exists and characterizes completely the individual best vaccination strategy (with or without discounting). We also compare with a strategy based only on overall societal optimization and exhibit a situation with nonnegative price of anarchy. Finally, we apply the theory to the 2009-2010 Influenza A (H1N1) vaccination campaign in France and hint that a group of individuals stopped vaccinating at levels that indicated a pessimistic perception of the risk of the vaccine.

  4. Nash equilibrium strategies of generating companies (Gencos) in the simultaneous operation of active and reactive power market, with considering voltage stability margin

    International Nuclear Information System (INIS)

    Soleymani, S.

    2013-01-01

    Highlights: ► We model the behavior of Gencos in the active and reactive power markets. ► Genco’s strategy is modeled as a bi-level optimization problem. ► The ISO’s market clearing model is modified with applying generator APFs. ► Good forecast of Genco’s information will increase the accuracy of proposed method. ► Obtained profit of Gencos depend on their bidding strategy. - Abstract: As Gencos are responsible for providing active and reactive power generation, they should devise good bidding strategies for energy and reactive power market. The paper describes a method for analyzing the competition among transmission-constrained Gencos with incomplete information. The proposed methodology employs the Supply Function Equilibrium (SFE) for modeling a Genco’s bidding strategy in energy market and uses Expected Payment Function (EPF) to construct a bidding framework in the reactive power market. The problem of finding the optimum strategy of Gencos is modeled as a bi-level optimization problem, where the upper sub-problem represents individual Genco’s payoff and the lower sub-problem solves the ISO’s market clearing problem. The ISO’s market clearing model is modified with applying generator Active Participation Factors to improve the voltage stability margin. The IEEE 39 bus test system is used to verify the effectiveness of the proposed method.

  5. SphK1 mediates hepatic inflammation in a mouse model of NASH induced by high saturated fat feeding and initiates proinflammatory signaling in hepatocytes.

    Science.gov (United States)

    Geng, Tuoyu; Sutter, Alton; Harland, Michael D; Law, Brittany A; Ross, Jessica S; Lewin, David; Palanisamy, Arun; Russo, Sarah B; Chavin, Kenneth D; Cowart, L Ashley

    2015-12-01

    Steatohepatitis occurs in up to 20% of patients with fatty liver disease and leads to its primary disease outcomes, including fibrosis, cirrhosis, and increased risk of hepatocellular carcinoma. Mechanisms that mediate this inflammation are of major interest. We previously showed that overload of saturated fatty acids, such as that which occurs with metabolic syndrome, induced sphingosine kinase 1 (SphK1), an enzyme that generates sphingosine-1-phosphate (S1P). While data suggest beneficial roles for S1P in some contexts, we hypothesized that it may promote hepatic inflammation in the context of obesity. Consistent with this, we observed 2-fold elevation of this enzyme in livers from humans with nonalcoholic fatty liver disease and also in mice with high saturated fat feeding, which recapitulated the human disease. Mice exhibited activation of NFκB, elevated cytokine production, and immune cell infiltration. Importantly, SphK1-null mice were protected from these outcomes. Studies in cultured cells demonstrated saturated fatty acid induction of SphK1 message, protein, and activity, and also a requirement of the enzyme for NFκB signaling and increased mRNA encoding TNFα and MCP1. Moreover, saturated fat-induced NFκB signaling and elevation of TNFα and MCP1 mRNA in HepG2 cells was blocked by targeted knockdown of S1P receptor 1, supporting a role for this lipid signaling pathway in inflammation in nonalcoholic fatty liver disease.

  6. The Effect of Metformin and Standard Therapy Versus Standard Therapy Alone in Nondiabetic Patients with Insulin Resistance and Nonalcoholic Steatohepatitis (NASH): A Pilot Trial

    Science.gov (United States)

    2009-01-01

    Bailey and Turner, 1996]. Previous studies of metformin have shown bio - chemical improvement in NAFLD patients and suggest histologic improvement [Loomba...liver patients. Aliment Pharmacol Ther 23: 1643–1647. Hamaguchi, M., Kojima, T., Takeda, N., Nakagawa, T., Taniguchi, H., Fujii, K. et al. (2005) The...J.J. et al. (2009) Clinical trial: pilot study of metformin for the treatment of non-alcoholic steato- hepatitis. Aliment Pharmacol Ther 29: 172–182

  7. Effect of disease progression on liver apparent diffusion coefficient values in a murine model of NASH at 11.7 Tesla MRI.

    Science.gov (United States)

    Anderson, Stephan W; Soto, Jorge A; Milch, Holly N; Ozonoff, Al; O'Brien, Michael; Hamilton, James A; Jara, Hernan J

    2011-04-01

    To evaluate the apparent diffusion coefficient (ADC) values of liver in a murine model of non-alcoholic steatohepatitis using 11.7 Tesla (T) MRI. This animal study was IACUC approved. Seventeen male C57BL/6 mice were divided into control (n = 3) and experimental groups (n = 14) fed a methionine-deficient choline-deficient (MCD) diet to induce steatohepatitis. Livers underwent ex vivo diffusion-weighted MR imaging and ADC maps were calculated. A pathologist determined subjective scores of steatosis, classified from 0 to 3. Digital image analysis was used to determine percentage areas of steatosis. Graphs comparing ADC to subjective and digital image analysis (DIA) determinations of steatosis were plotted. Subjective assessments of steatosis ranged up to values of 3 and DIA determined areas of steatosis to range up to approximately 16%. ADC values approximated 800 × 10(-6) mm(2) /s (range, 749-811 × 10(-6) mm(2) /s, mean 786 × 10(-6) mm(2) /s) in controls and 500 × 10(-6) mm(2) /s (range, 478-733 × 10(-6) mm(2) /s, mean 625 × 10(-6) mm(2) /s) in experimental mice. Moderate correlation between ADC and subjective scores of steatosis (R = -0.56) was observed. Strong correlation between ADC values and percentage areas of steatosis was between ADC values and percentage areas of steatosis was observed greater (R = -0.81) and very strong correlation was observed with the exclusion of a single outlying data point (R = -0.91). Based on the comparison of ADC values and steatosis determinations by DIA, increasing degrees of steatosis are seen to result in decreased hepatic ADC values. Copyright © 2011 Wiley-Liss, Inc.

  8. Metabolic and hepatic effects of liraglutide, obeticholic acid and elafibranor in diet-induced obese mouse models of biopsy-confirmed nonalcoholic steatohepatitis

    DEFF Research Database (Denmark)

    Tølbøl, Kirstine S; Kristiansen, Maria Nb; Hansen, Henrik H

    2018-01-01

    AIM: To evaluate the pharmacodynamics of compounds in clinical development for nonalcoholic steatohepatitis (NASH) in obese mouse models of biopsy-confirmed NASH. METHODS: Male wild-type C57BL/6J mice (DIO-NASH) and Lep ob/ob (ob/ob-NASH) mice were fed a diet high in trans-fat (40%), fructose (20...... by global gene expression (RNA sequencing) and liver lipid biochemistry. CONCLUSION: DIO-NASH andob/ob-NASH mouse models show distinct treatment effects of liraglutide, OCA, and elafibranor, being in general agreement with corresponding findings in clinical trials for NASH. The present data therefore...... further supports the clinical translatability and utility of DIO-NASH andob/ob-NASH mouse models of NASH for probing the therapeutic efficacy of compounds in preclinical drug development for NASH....

  9. Aktuaalsetest tendentsidest elektroakustilise muusika alal Eestis / Gerhard Lock

    Index Scriptorium Estoniae

    Lock, Gerhard, 1978-

    2007-01-01

    Elektroakustilise muusika lähiajaloost, elektroakustilist muusikat viljelevatest Eesti heliloojatest. Age Hirv, Raun Juurikas, Liis Jürgens, Andrus Kallastu, Tatjana Kozlova, Ülo Krigul, Margo Kõlar, Märt-Matis Lill, Gerhard Lock, Hans-Gunter Lock, Malle Maltis, Jüri Reinvere, Mart Siimer, Mirjam Tally, Toomas Trass, Lauri-Dag Tüür oma muusikast

  10. Minsk ja RAM 7 / Evelyn Müürsepp

    Index Scriptorium Estoniae

    Müürsepp, Evelyn

    2005-01-01

    Minskis toimunud RAM 7-st (Reapproaching New Media. Models of Collaboration / Ümberhinnates uut meediat. Koostöömudelid". Korraldajad Tatjana Dushina ja Denis Romanovski üritavad luua uue meedia keskust Valgevene kunstiakadeemiasse. Eestit esindasid Evelin Müürsepp ja John Grzinich (modereeris vabade ülikoolide kursust). Osalemisest fotomängus "FotoOhota"

  11. Tihhonov viksis Stirlitzi maha ohvitserist naabrimehe pealt / Triin Tael

    Index Scriptorium Estoniae

    Tael, Triin

    2008-01-01

    8. veebruaril täitub 80 eluaastat Vene näitlejal Vjatsheslav Tihhonovil, keda tuntakse eelkõige Stirlitzina Tatjana Lioznova poolt filmitud legendaarses teleseriaalis "Seitseteist kevadist hetke". Lisaks põnevussarjast "Issajev", režissöör Sergei Ursuljak : "Uues sarjas Stirlitzi noorusest mängib ka Lembit Ulfsak"

  12. Stirlitzit polnud vaja Berliini saata / Mati Õun

    Index Scriptorium Estoniae

    Õun, Mati, 1942-

    2011-01-01

    Eesti Televisioon hakkab 8. juunist näitama nõukogudeaegset seriaali "Seitseteist kevadist hetke" (režissöör Tatjana Lioznova, Stirlitzi rollis Vjatšeslav Tihhonov, NSV Liit 1973). Seriaalist, filmi tegelaste prototüüpidest

  13. Shtirlits vstretil jubilei v bolnitse / Boris Tuch

    Index Scriptorium Estoniae

    Tuch, Boris, 1946-

    2008-01-01

    8. veebruaril täitub 80 eluaastat Vene näitlejal Vjatsheslav Tihhonovil, keda tuntakse eelkõige Stirlitzina Tatjana Lioznova poolt filmitud legendaarses teleseriaalis "Seitseteist kevadist hetke". Kokkuvõtvalt loominguteest ja hetkeolukorrast. Lisatud fotod V. Tihhonovist Tallinnas

  14. "Sinjaja ptitsa" - shedevr stoletnei võderzhki / Anatoli Korolev

    Index Scriptorium Estoniae

    Korolev, Anatoli

    2008-01-01

    Moskva Kunstiteater tähistab Maurice Maeterlincki näidendi "Sinilind" lavastuse 100. juubelit. Esmalavastus Moskva Kunstiteatris 1908, lavastaja Konstantin Stanislavski. "Sinilind" on vene reformaatori ainus lavastus, mis on säilinud meie päevini. Praegu mängitakse seda Gorki-nim. Kunstiteatris Tatjana Doronina lavastuses

  15. Moskva pisaraid ei usu : 5. Venemaa rahvuslik teatrifestival "Zolotaja Maska" 10. märtsist 5. aprillini 1999 Moskvas / Juri Ljubimov, Kadi Herkül ; interv. Olga Jero

    Index Scriptorium Estoniae

    Ljubimov, Juri, 1917-2014

    1999-01-01

    Vaadeldakse lavastusi - A. Tshehhovi "Tatjana Repina" (lav. Valeri Fokin), W. Shakespeare'i "Talvemuinasjutt" (lav. Declan Donnellan), A. Ostrovski "Äike" (lav.Henrietta Janovskaja), A. Krutshjonõhhi "Võit päikese üle" (lav. Aleksandr Ponomarjov), W. Gombrowiczi "Iwona, Burgundia printsess" (lav. Oleg Rõbkin) ja H. Pinteri "Majahoidja" (lav. Juri Butussov)

  16. I eto vsjo o njom... / Valentin Zvegintsev

    Index Scriptorium Estoniae

    Zvegintsev, Valentin

    2005-01-01

    Res Publica nõuniku Nikolai Stelmachi sõnul ei saa Res Publica valimisreklaami Tallinnas kuidagi plagiaadiks nimetada, tema hinnangul on Reformierakonna ja Res Publica valimisplakatid Tallinnas sisult erinevad, kuid Reformierakond võttis üle Res Publica idee lastevanemate toetamise kohta. Reformierakonna liikme Tatjana Muravjova arvamus

  17. Üliõpilased soovivad Eesti valitsuselt toetust Valgevene tudengile / Hannes Krause

    Index Scriptorium Estoniae

    Krause, Hannes

    2005-01-01

    Reedel saatis Eesti Üliõpilaskondade Liit kirja peaministrile ja välisministrile, paludes toetust tudeng Tatjana Homale, kes heideti välja Valgene Riiklikust Majandusülikoolist, sest ta ei teavitanud oma ülikooli sõidust Prantsusmaale Euroopa üliõpilasliitude katusorganisatsiooni üldkogule

  18. Vid na himkombinat v Maardu so stenõ Hudozhestvennoi galerei / A. Orshanskaja

    Index Scriptorium Estoniae

    Orshanskaja, A.

    1999-01-01

    Eesti akvarellistide ühingu vabariiklikust näitusest Narva kunstigaleriis : akvarelle aastatest 1960 - 1999 eri põlvkondade 43 kunstnikult. Esinevad ka 6 Narva kunstnikku : Igor Gordin, Vera Lantsova, Anne Pärtel, Jelena Sabinina, Tatjana Sonina, Irina Sopina.

  19. Eraeluks pole aega / Marianne Mikko ; interv. Paavo Kangur

    Index Scriptorium Estoniae

    Mikko, Marianne, 1961-

    2008-01-01

    Euroopa Parlamendi saadik Marianne Mikko Pakistani endise peaministri Benazir Bhutto mõrvast, tutvusest Euroopa Parlamendi India delegatsiooni juhi Neena Gilliga ja Eesti presidendi Toomas Hendrik Ilvesega, Läti eurosaadikust Tatjana Zdanokast, oma tööst, teest poliitikasse, isiklikust elust, muusikaeelistustest. Lisa: Marianne Mikko

  20. Kaitstud magistri- ja doktoritööd 2014

    Index Scriptorium Estoniae

    2015-01-01

    Magistritööd kaitsesid: Ekaterina Ermolaeva, Helena Haller, Kadri Kallast, Ville-Matti Aleksi Kataja, Laura Kiiroja, Alina-Ruxanda Mircea, Tatjana Pilipoveca, Liina Sieberk, Katsiaryna Suryna, Fatemeh Tavakoli, Ele Viskus; doktoritööd kaitses Vadim Verenitš

  1. Narva narkomaanid jätavad oma lapsed nime ja dokumentideta / Tanel Mazur, Mari Kodres

    Index Scriptorium Estoniae

    Mazur, Tanel, 1971-

    2008-01-01

    Probleemidest, mida tõstatas narkomaanide ja alkohoolikute rehabilitatsiooniga tegeleva MTÜ Sind Ei Jäeta Üksi juht Tatjana Magerova kohtumisel Narvas külaskäigul viibinud presidendi Toomas Hendrik Ilvesega. Vabariigi President Ida-Virumaal 19.-20.11.2008. Ilmunud ka Narva Postiljon 22. nov. lk. 1, autor ainult Tanel Mazur

  2. Südame poolest sinimustvalge / Kristel Kossar

    Index Scriptorium Estoniae

    Kossar, Kristel

    2012-01-01

    Edukatest ja andekatest noortest venelastest Eestis - jalgpallur Konstantin Vassiljev, internetiäri looja ja poliitik Andrei Korobeinik, helilooja Tatjana Kozlova, Tallinna Ülikooli Katariina kolledži direktor Dimitri Mironov, sõjaajaloolane, õpetaja ja Tallinna Ülikooli doktorant Igor Kopõtin. Nende arvamused Eestist ja venelaste osalusest Eesti ühiskonnaelus

  3. "Põhþamaa talv..." : [luuletused] / Niina Obrezkova

    Index Scriptorium Estoniae

    Obrezkova, Niina, 1965-

    2005-01-01

    Sisu: "Põhþamaa talv..." / Pauli Lesoneni venekeelse tõlke järgi võru keelde tõlkinud Kauksi Ülle ; "Kuke vuod dorad bdzõm adjamien..." ; "Kõlburjosõ mõnam..." / komi keelest tõlkinud udmurdi keelde Tatjana Prokopjeva

  4. Naperegonki s modoi / Aleksandra Manukjan

    Index Scriptorium Estoniae

    Manukjan, Aleksandra

    2004-01-01

    Kõrgema disainikooli ruumikujunduse III kursuse üliõpilaste maalinäitus "Seda suudad sinagi" ja IV kursuse üliõpilaste tööde näitus "Test" galeriis Kullo. Näituse aitas kujundada õppejõud Tatjana Sidorenko

  5. Jevropeiskii biznes gorko platshet / Alexander Rahr

    Index Scriptorium Estoniae

    Rahr, Alexander

    2008-01-01

    Ilmunud ka: Den za Dnjom 2. mai lk. 20, Stolitsa 5. mai lk. 5. Venemaale ja Ida-Euroopa riikidele spetsialiseerunud Saksa politoloogi ettekanne Tallinna linna korraldatud Kodurahu Foorumil, kus põhitähelepanu oli Euroopa riikide suhetel, sh suhetel Venemaaga ning Euroopa poliitika tulevikuperspektiividel. Vahendanud Tatjana Opekina

  6. Pärilik armastusejanu / Aita Kivi

    Index Scriptorium Estoniae

    Kivi, Aita, 1954-

    2001-01-01

    Sisu : John Steinbeck. Hommiku pool Eedenit; Rosamunde Pilcher. Talvine pööripäev; Joan Hohl. Võib-olla homme; Tatjana Muravskaja. Beatrice. Võõras. Kriminaalne kolmik: Håkan Nesser. Karambool, Selma Eichler. Mõrv võib tappa su seltsielu, John Dickson Carr. Kadunud võllapuu; Simon Beesley, Sheena Joughin. 20. sajandi kirjandus; Maailma parimad seltskonnamängud

  7. "Автопортреты Ю. М. Лотмана": ученый в истории культуры / Людмила Глушковская

    Index Scriptorium Estoniae

    Глушковская, Людмила, 1937-

    2016-01-01

    Arvustus: Juri Lotmani autoportreed = Автопортреты Ю. М. Лотмана = Juri Lotman's self-portraits / koostajad: Tatjana Kuzovkina, Sergei Daniel. Tallinn : Tallinna Ülikooli Kirjastus, 2016. (Bibliotheca Lotmaniana)

  8. Tsvetotshnaja skazka / Anna Litvinjuk

    Index Scriptorium Estoniae

    Litvinjuk, Anna

    2003-01-01

    Tatjana Tridvornova organiseeritud lilleballist Tallinnas. Algas lillekleitide defileega Saku Suurhallis ja jätkus lillekleitide konkursiga klubis Opium. Žürii koosseis. Osalejad Eestist, Lätist ja Soomest. Võitja on läti florist Druvis Ciritis lillekleidiga "Puudutus"

  9. Otvedaite "Ljubovnõi napitok"

    Index Scriptorium Estoniae

    1999-01-01

    Majakovski nim. Akadeemilise Teatri külalisetendused Tallinnas 16. ja 17. mail Vene Draamateatris.Etendatakase Tatjana Ahramkova lavastuses "Armujooki" Peter Shafferi näidendi "Lettice and Lovage" järgi. Peaosas näitleja Natalja Gundareva

  10. Питерской "Пышке" рукоплескали на родине Ги де Мопассана / Ирина Кивисельг ; комментировал Андрей Лобанов

    Index Scriptorium Estoniae

    Кивисельг, Ирина, 1961-

    2009-01-01

    Peterburi Riikliku Draamateatri Liteinõil direktor Andrei Lobanov räägib teatrist ja juuni alguses Jõhvis ning Tallinnas etenduvast Guy de Maupassant'i novelli "Rasvarull" ainetel lavastatud muusikalist "Пышка". Lavastaja Vladislav Pazi, muusika autor Nikolai Orlovski, peaosas Tatjana Tuzova

  11. Presidendi teenetemärgi pälvis viis spordiinimest

    Index Scriptorium Estoniae

    2008-01-01

    Vt. ka Linnaleht : Tartu 7. veebr., lk. 7. Eesti riigile osutatud teenete eest pälvisid president Toomas Hendrik Ilveselt teenetemärgi viis spordieluga seotud inimest: jalgpallikoondise ekstreenerid Jelle Goes ja Arno Pijpers, kergejõustikutreener Vésteinn Hafsteinsson, sõudetreener Tatjana Jaanson ning spordielu edendaja Nora Kutti. Juuresoleval fotol Jelle Goes

  12. Teachers, nurses face widespread cuts / Kate Mclntosh

    Index Scriptorium Estoniae

    Mclntosh, Kate

    2009-01-01

    Läti haridusminister Tatjana Koke kommenteerib pärast valitsuse erakorralist istungit meditsiini- ja haridustöötajate palkade kärpimise plaani ning kinnitab, et tööta jäänud õpetajatele hakatakse ümberõpet korraldama Euroopa Liidu sotsiaalfondi rahade abil

  13. Meri, munklus ja tööstusmaastik / Kaire Nurk

    Index Scriptorium Estoniae

    Nurk, Kaire, 1960-

    2003-01-01

    Video-tegevuskunsti sündmus "Saar 2003" 5. juulil Viinistus ja Mohnil. Osa võtsid Erik Alalooga, sakslased Uwe Schloen ja Georg Janthur, Jaan Toomik, Jaan Paavle, Silja Saarepuu, Villu Plink, Jüri Ojaver, venelanna Tatjana Goloviznina, lõuna-aafriklane Steven Cohen

  14. Propaganda i kontrpropaganda / Aleksandr Tshaplõgin

    Index Scriptorium Estoniae

    Tšaplõgin, Aleksandr, 1964-

    2007-01-01

    Europarlamendis esines Öise Vahtkonna liige Juri Zhuravljov informatsiooniga väidetavast politsei vägivallast pronksööl. Riigikogu eurokomisjoni esimees Marko Mihkelson on väitnud, et ürituse organisaatoriks on Läti eurosaadik Tatjana Zhdanok. Europarlamendi liikme Katrin Saksa väiteid

  15. Kaks head prantslast korraga / Peeter Künstler

    Index Scriptorium Estoniae

    Künstler, Peeter, 1958-2009

    1996-01-01

    Arvustus: Guibert, Hervé. Sõbrale, kes ei päästnud mu elu / Prantsuse k. tlk. T. Arot. Tln. : Kupar, 1996; Modiano, Patrick. Hämarate poodide tänav / Prantsuse k. tlk. Tatjana Hallap. Tln. : Kupar, 1996

  16. Narva mälestuseks / Tanel Mazur

    Index Scriptorium Estoniae

    Mazur, Tanel, 1971-

    2005-01-01

    6. märtsil möödub 61 aastat pommirünnakust Narvale, mis hävitas linna. Meenutavad: Tatjana Gontsharenko, endine narvalanna ja rüütliristi kavaler, Narva kaitse juhataja Harald Riipalu. Ilmunud ka: Narvskaja Gazeta, 5. märts 2005, lk 2

  17. "Aprel" v aprele ! / Aala Gitt

    Index Scriptorium Estoniae

    Gitt, Aala

    2000-01-01

    Sillamäe kunstnike rühmituse "Aprel" [Aprill] tegevusest 1999. aastal ja nende valmistumisest aprilli-näituseks Sillamäe näitusesaalis, kus osalevad grupi liikmed Aleksandr Popolitov, Aala Gitt, Igor Lukjanov, Tatjana Petsheritsa, Sergei Kolesnikov, German Jershov, Aleksandr Orlov, Nadezhda Popolitova, Eduard Zentshik, Jelena ja Vladislav Kuznetsovid

  18. Behaviour of tunnelling transition rate of argon atom exposed to ...

    Indian Academy of Sciences (India)

    physics pp. 565–573. Behaviour of tunnelling transition rate of argon atom exposed to strong low-frequency elliptical laser field. TATJANA B MILADINOVI ´C and VIOLETA M ... There are two laser field polarizations, linear and circular, as ... is the electron momentum [1], expressed using the field strength F and the parabolic.

  19. Tvortsheski duhh i teatralnõje bratstvo / Kristiina Nurme

    Index Scriptorium Estoniae

    Nurme, Kristiina

    2008-01-01

    Vene Kultuurikeskuse teater ART-Grotesk osales rahvusvahelisel noorte harrastusteatrite festivalil Leedus ja võitis esikoha oma lavastusega "Õnnelik" Oscar Wilde'i teose "Õnnelik prints" järgi. Teose on lavale seadnud Tatjana Buinova

  20. Iskusstvo iz-za bolnitshnoi stenõ / Svetlana Karabut

    Index Scriptorium Estoniae

    Karabut, Svetlana

    2008-01-01

    Autsaiderite kunsti näitus "Kunst ühendab" Viljandis Ugala teatri fuajees. Näidatakse eesti taastuskeskuste Singel ja Vinger ning Peterburi psühhiaatriahaigla kunstistuudio töid. Kommenteerib Linda Luhse. Intervjuu Peterburi haigla kunstistuudio juhendajate Tatjana ja Vladimir Barsukovidega

  1. Piiteri "Uue draama" märgistik hakkab selguma / Andres Keil

    Index Scriptorium Estoniae

    Keil, Andres, 1974-

    2004-01-01

    Peterburi teatrifestivalist "Novaja drama" (Uus draama), kus M. Karusoo lavastus "Eestisse sündinud" tekitas furoori. Pikemalt peatutakse ka K. Kostenko "Klaustrofoobial" - Koljada-Teatri ja Teatroni koostööl, samuti gruusia autori L. Bugadze näidendi "Šokeeritud Tatjana" lavastusel.

  2. Revisitando a Estratégia de Execução das Reformas Gerenciais no Setor Público: uma abordagem à luz do equilíbrio de Nash

    Directory of Open Access Journals (Sweden)

    Saulo Felipe Costa

    2017-07-01

    Full Text Available A década de 1990 inaugurou um conjunto de políticas públicas marcadas pela busca do aumento da eficiência governamental na geração e execução de suas ações. Às políticas orientadas para o mercado seguiram-se esforços de descentralização do processo decisório com vistas ao aprimoramento da gestão pública, onde se buscou combinar ajuste fiscal (eficiência orçamentária com mudança institucional (instituições voltadas para os resultados. Entretanto, o problema da falha sequencial das reformas administrativas, decorrente do dilema do controle, se constituiu no vetor de constrangimento para a implementação exitosa dessas concepções gerencialistas. Qual a natureza dos conflitos e a estratégia de ação dos policy-makers no interior da “coalizão reformadora”? Este trabalho, em uma tentativa de responder tal questão, apresenta uma abordagem analítica do dilema do controle baseada na teoria dos jogos. Objetivou-se com isto, apresentar uma formalização do problema da falha sequencial, via dilema do controle, como esforço analítico para o desenvolvimento de modelos formais para fenômenos decisórios na área das Ciências Sociais em geral, e da Ciência Política em particular.

  3. Hepatic artery resistive index (HARI) and non-alcoholic fatty liver disease (NAFLD) fibrosis score in NAFLD patients: cut-off suggestive of non-alcoholic steatohepatitis (NASH) evolution.

    Science.gov (United States)

    Tana, Claudio; Tana, Marco; Rossi, Stefano; Silingardi, Mauro; Schiavone, Cosima

    2016-09-01

    Conventional ultrasound (US) is reliable to reveal the presence of non-alcoholic fatty liver disease (NAFLD), but it is neither sensitive nor specific to reveal fibrosis clues, except in advanced stages where signs of cirrhosis are evident. NALFD fibrosis score is a non-invasive parameter that predicts well the presence of significant fibrosis, but correlations with US parameters are lacking. The aim of this study was, therefore, to compare resistive index of hepatic artery (HARI) of NAFLD patients with different severity degrees of diffuse fatty liver disease vs HARI of controls, and to compare HARI of NAFLD patients with different NAFLD fibrosis scores vs HARI of controls. This was a spontaneous, no-profit observational study conducted in our US department between December 2013 and July 2014. Patients with NAFLD with different severity of disease and healthy controls were included. Echogenicity and size of liver and spleen, maximum portal vein velocity, RI, peak systolic velocity (PSV), and end diastolic velocity (EDV) of splenic artery, PSV, EDV, and RI of hepatic artery, and NAFLD fibrosis score were acquired and compared between groups. HARI was significantly lower in NAFLD patients than controls (p steatosis, might suggest the execution of biopsy to predict the risk of progression to steatohepatitis and fibrous tissue accumulation. Low values of HARI may be expression of lower risk, which does not necessitate any biopsy.

  4. Advanced oil recovery technologies for improved recovery from slope basin clastic reservoirs, Nash Draw Brushy Canyon Pool, Eddy County, NM. Quarterly technical progress report, April 1, 1996--June 30, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, M.B.

    1996-07-26

    The overall objective of this project is to demonstrate that a development program based on advanced reservoir management methods can significantly improve oil recovery. The demonstration plan includes developing a control area using standard reservoir management techniques and comparing the performance of the control area with an area developed using advanced reservoir management methods. Specific goals to attain the objective are: (1) to demonstrate that a development drilling program and pressure maintenance program, based on advanced reservoir management methods, can significantly improve oil recovery compared with existing technology applications, and (2) to transfer the advanced methodologies to oil and gas producers in the Permian Basin and elsewhere in the U.S. oil and gas industry.

  5. Mary Nash; Susanna Tavera (orgs., Las mujeres y las guerras: el papel de las mujeres en las guerras de la Edad Antígua a la Contemporánea

    Directory of Open Access Journals (Sweden)

    Tatiana Moura

    2012-10-01

    Full Text Available I am tired of being the blood, the earth and the scream. I address the storyteller and those who have passed the tale down, written it down, recited and believed it. Is that all? I ask the storyteller. Where am I then? Do I have to be Abel if I don’t want to be Cain? Is there no other way?Dorothee Solle Ao longo dos séculos, as experiências das mulheres foram marginalizadas e secundarizadas nos acontecimentos históricos mais relevantes, em particular nas guerras, contrastando com o protagonis...

  6. PEMIKIRAN IBNU AL-QAYYIM TENTANG PENDIDIKAN KRISTOLOGI (Studi Terhadap Kitab Hidāyah al-Hayārā fī Ajwibah al-Yahūd wa al-Nashārā

    Directory of Open Access Journals (Sweden)

    Rahendra Maya

    2017-06-01

    Full Text Available Perbedaan konsepsi di antara agama-agama yang ada adalah sebuah realitas, satu kenyataan yang tidak dapat dipungkiri oleh siapapun. Perbedaan –bahkan benturan konsepsi– itu terjadi pada hampir semua aspek dalam agama, baik bidang konsepsi tentang Tuhan maupun konsepsi sistem pengaturan kehidupan. Sejak munculnya manusia di muka bumi, mulailah perbedaan itu muncul. Manusia dikarunia akal dengan kadar kemampuan dan jenis serta jumlah informasi yang berbeda, sehingga berkemungkinan memahami sesuatu dengan berbeda pula. Itu hal yang alami dalam kehidupan manusia. Sumber-sumber informasi yang dialami setiap manusia juga berbeda. Belum lagi sikap apriori atau fanatisme –karena berbagai faktor– yang menyebabkan munculnya perbedaan pandangan dan sikap. Perbedaan pendapat dan konsepsi keagamaan tidaklah otomatis memunculkan konflik pada level praktis. Sepanjang sejarah, kehidupan damai dan harmonis lebih banyak dijalani umat beragama, dibandingkan periode-periode konflik. Setidaknya, demikianlah titik tolak dan landasan bagi sebuah telaah (perbandingan atau bahkan dialog sekalipun.

  7. Every finite strategic form game has at least one mixed strategy ...

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Every finite strategic form game has at least one mixed strategy Nash equilibrium. Every finite strategic form game has at least one mixed strategy Nash equilibrium.

  8. Plasma Cathepsin D Levels : A Novel Tool to Predict Pediatric Hepatic Infl ammation

    NARCIS (Netherlands)

    Walenbergh, Sofie M. A.; Houben, Tom; Hendrikx, Tim; Jeurissen, Mike L. J.; van Gorp, Patrick J.; Vreugdenhil, Anita C. E.; Adriaanse, Marlou P.; Buurman, Wim A.; Hofker, Marten H.; Mosca, Antonella; Lindsey, Patrick J.; Alisi, Anna; Liccardo, Daniela; Panera, Nadia; Koek, Ger H.; Nobili, Valerio; Shiri-Sverdlov, Ronit

    OBJECTIVES: Nonalcoholic steatohepatitis (NASH) is the most severe form of a hepatic condition known as nonalcoholic fatty liver disease (NAFLD). NASH is histologically characterized by hepatic fat accumulation, inflammation, and ballooning, and eventually coupled with fibrosis that, in turn, may

  9. Üks doktor ja kaks magistrit / Halliki Uibu

    Index Scriptorium Estoniae

    Uibu, Halliki

    2001-01-01

    18. juunil 2001 toimus TPÜ kultuuriajaloo kaitsmisnõukogus Lauri Lindströmi doktoritöö "Album Academicum Universitatis Tartuensis 1918-1944. Rahvus, sugu, sünni- ja keskhariduse omandamise koht üliõpilaskonna kujunemist ja kõrghariduse omandamist mõjutavate teguritena" kaitsmine. Lauri Lindströmile omistati teaduskraad doctor philosophiae (PhD) kultuuriajaloo alal. TPÜ kultuuriajaloo magistrikraadi kaitsmisnõukogus kaitsesid 18. juunil 2001 Igor Tõnurist magistritööd "Pillid ja pillimäng eesti külaelus" ja Tatjana Tšervova magistritööd "Vene kogukonna ühiskondlikust ja kultuurielust Tallinnas 1880-1905". Igor Tõnuristile ja Tatjana Tšervovale omistati teaduskraad magister artium kultuuriajaloo alal hindega cum laude

  10. In vivo cytochrome P450 activity alterations in diabetic nonalcoholic steatohepatitis mice

    OpenAIRE

    Li, Hui; Clarke, John D.; Dzierlenga, Anika L.; Bear, John; Goedken, Michael J.; Cherrington, Nathan J.

    2016-01-01

    Nonalcoholic steatohepatitis (NASH) has been identified as a source of significant interindividual variation in drug metabolism. A previous ex vivo study demonstrated significant changes in hepatic Cytochrome P450 (CYP) activity in human NASH. This study evaluated the in vivo activities of multiple CYP isoforms simultaneously in prominent diabetic NASH mouse models. The pharmacokinetics of CYP selective substrates: caffeine, losartan, and omeprazole changed significantly in a diabetic NASH mo...

  11. Karakteriga hotell - L'Ermitage : Toompuiestee 19, Tallinn = A Hotel with Character - L'Ermitage : Toompuiestee 19, Tallinn / Regina Viljasaar

    Index Scriptorium Estoniae

    Viljasaar, Regina

    2004-01-01

    Hoone esifassaad on kaetud tumepruuniks patineerunud vasega, hoovipoolne külg on roosa. Uuenduslikud on õhukesed põrandaküttega vahelaed. Projekteerija: Arhitektuuribüroo Pluss. Autor Indrek Allmann. Konstruktor: Inseneribüroo Pike. Sisekujundaja Tatjana Jakobson. I korruse avaliku tsooni kujundas Pille Lausmäe. Projekt 2003, valmis 2004. I ja tüüpkorruse plaan, sisevaade, 5 välisvaadet

  12. Victory celebrations mark 1945 peace

    Index Scriptorium Estoniae

    2011-01-01

    Riia vennaskalmistul 8. mail peetud Teises maailmasõjas langenute mälestamistseremooniast võtsid osa ka Läti president Valdis Zatlers, spiiker Solvita Aboltina, kaitseminister Artis Pabriks, riiklike relvajõudude juhataja Raimond Graube ja Riia linnapea Nils Usakovs. 30 000 inimest tähistas Riias 9. mai võidupüha, kohal olid ka Euroopa Parlamendi saadikud Tatjana Zdanoka, Alfreds Rubiks ja Vladimirs Buzajevs

  13. Kas nüüd ka sinu pisarad, Moskva? / Ants Juske

    Index Scriptorium Estoniae

    Juske, Ants, 1956-2016

    1998-01-01

    Moskva kunstielu. Kriitikutest-kuraatoritest - Viktor Misiano, Josif Bakstein, Georgi Nikitsh, Andrei Kovaljov -, kunstnikest - Oleg Kulik, Aleksandr Brener, Tanja Antoshina, Anatoli Osmõlovski, Ilja Kabakov -, Marat Gelmani galeriist, Josif Baksteini kureeritud näitusest "Medialisatsioonid" Stockholmis, kunstnikegrupist AES (Tatjana Arzamasova, Lev Jevzovitsh, Jevgeni Svjatski) ja Misiano grupist (koostööd teeb filosoof Vladimir Sorokin), osalemisvõimalustest rahvusvahelistel näitustel

  14. Ryska nobelpriskandidater i Svenska Akademiens arkiv 1914-1937

    OpenAIRE

    Maier, Ingrid; Martjenko, Tatjana

    2002-01-01

    Ingrid Maier, Tatjana Martjenko, Russian Nobel Prize Candidates in the Archives of the Swedish Academy. This study tries to answer the question why the first Nobel prize in literature was awarded to Ivan Bunin (1933), a writer whose oeuvre now is almost totally unknown outside Russia, while some of the more internationally well-known Russian writers such as Leo Tolstoy and Maxim Gorki were overlooked. The main source for our analysis are the records kept in the archives of the Swedish Academy...

  15. Mälupuutuja puudutus / Reet Varblane

    Index Scriptorium Estoniae

    Varblane, Reet, 1952-

    1998-01-01

    Ando Keskküla kuraatornäitus "Puutujad" Tallinna Kunstihoones, näituse lähtekohtadest. Moskvalaste AESi rühmituse (Tatjana Arzamazova, Lev Jevzotovitch, Jevgeni Svjatski), hiina kunstniku Zhang¡Dali, Teemu Mäki, vene kunstniku Juri Alberti, Izabella Gustowska, Saara Ekströmi, Mart Viljuse töödest, poola kunstniku Maciej Toporowiczi videost "Kinnisidee".

  16. Kunst aitab klisheesid lõhkuda : prostitutsioon / Reet Varblane

    Index Scriptorium Estoniae

    Varblane, Reet, 1952-

    2007-01-01

    Prostitutsiooniteemast kunstis, praeguste prostitutsiooni käsitlevate näituste ("Sex Work. Kunst. Mythos. Realität" Berliinis, Ann-Sofi Sideni projekt "Warte mal! Prostitutsion after the Velvet Revolution" jt.) rollist. Pikemalt näitusest "Kehaturg / Sex market" Tallinna Kunstihoones. Anu Juuraku, Foxy Haze'i, Teemu Mäki, Tatjana Antoshina, Kari Bie Erenurme, Sandra Jõgeva, Shula Kesheti, Deimantas Narkeviciuse ja Pal Hollenderi töödest

  17. Concert - piano duo - Potevska/ Djorleva

    OpenAIRE

    Potevska, Emilija; Dzorleva, Tatjana

    2012-01-01

    Emilija Potevska and Tatjana Djorleva began playing together while students at Faculty of music arts in Skopje, later developing into professional ensemble with the international carrier. They both finished the graduate and master studies in piano with a highest grades in the class of professor Stela Slejanska and currently working on their doctoral thesis in piano performance. As one of their great achievement as a piano duo is the first prize and golden medal at the International piano comp...

  18. Prevalence of Non-Alcoholic Fatty Liver Disease in Morbidly Obese Patients Undergoing Sleeve Bariatric Surgery in Iran and Association With Other Comorbid Conditions

    OpenAIRE

    Karimi-Sari; Mousavi-Naeini; Ramezani-Binabaj; Najafizadeh-Sari; Mir-Jalili; Dolatimehr

    2015-01-01

    Background Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease including simple steatosis to nonalcoholic steatohepatitis (NASH). NASH could progress to cirrhosis and liver cancer. The prevalence of NAFLD is increasing by increasing the prevalence of obesity. Objectives This study was designed to determine the prevalence of NASH in morbidly obese patients undergoing sleeve bariatric s...

  19. LDL receptor knock-out mice are a physiological model particularly vulnerable to study the onset of inflammation in non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Bieghs, Veerle; van Gorp, Patrick J.; Wouters, Kristiaan; Hendrikx, Tim; Gijbels, Marion J.; van Bilsen, Marc; Bakker, Jaap; Binder, Christoph J.; Lütjohann, Dieter; Staels, Bart; Hofker, Marten H.; Shiri-Sverdlov, Ronit

    2012-01-01

    Non-alcoholic steatohepatitis (NASH) involves steatosis combined with inflammation, which can progress into fibrosis and cirrhosis. Exploring the molecular mechanisms of NASH is highly dependent on the availability of animal models. Currently, the most commonly used animal models for NASH imitate

  20. Biochemical parameters response to weight loss in patients with non ...

    African Journals Online (AJOL)

    Background: Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that is capable of progressing to end-stage liver disease, but generally has a benign course. Non-alcoholic steatohepatitis (NASH) is a growing public health problem with no approved therapy. NASH projected to be the leading cause of liver ...

  1. Ursodeoxycholic Acid and Atorvastatin in the Treatment of Nonalcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Murat Kiyici

    2003-01-01

    Full Text Available BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH is a serious disorder with the potential to gradually progress to cirrhosis. It is generally associated with obesity, diabetes and hyperlipidemia. Currently, there is no established therapy for NASH. The aim of the present study was to evaluate the effectiveness of atorvastatin and ursodeoxycholic acid (UDCA in the treatment of NASH.

  2. Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy

    Science.gov (United States)

    Kristiansen, Maria Nicoline Baandrup; Veidal, Sanne Skovgård; Rigbolt, Kristoffer Tobias Gustav; Tølbøl, Kirstine Sloth; Roth, Jonathan David; Jelsing, Jacob; Vrang, Niels; Feigh, Michael

    2016-01-01

    AIM: To characterize development of diet-induced nonalcoholic steatohepatitis (NASH) by performing liver biopsy in wild-type and genetically obese mice. METHODS: Male wild-type C57BL/6J (C57) mice (DIO-NASH) and male Lepob/Lepob (ob/ob) mice (ob/ob-NASH) were maintained on a diet high in trans-fat (40%), fructose (22%) and cholesterol (2%) for 26 and 12 wk, respectively. A normal chow diet served as control in C57 mice (lean chow) and ob/ob mice (ob/ob chow). After the diet-induction period, mice were liver biopsied and a blinded histological assessment of steatosis and fibrosis was conducted. Mice were then stratified into groups counterbalanced for steatosis score and fibrosis stage and continued on diet and to receive daily PO dosing of vehicle for 8 wk. Global gene expression in liver tissue was assessed by RNA sequencing and bioinformatics. Metabolic parameters, plasma liver enzymes and lipids (total cholesterol, triglycerides) as well as hepatic lipids and collagen content were measured by biochemical analysis. Non-alcoholic fatty liver disease activity score (NAS) (steatosis/inflammation/ballooning degeneration) and fibrosis were scored. Steatosis and fibrosis were also quantified using percent fractional area. RESULTS: Diet-induction for 26 and 12 wk in DIO-NASH and ob/ob-NASH mice, respectively, elicited progressive metabolic perturbations characterized by increased adiposity, total cholesterol and elevated plasma liver enzymes. The diet also induced clear histological features of NASH including hepatosteatosis and fibrosis. Overall, the metabolic NASH phenotype was more pronounced in ob/ob-NASH vs DIO-NASH mice. During the eight week repeated vehicle dosing period, the metabolic phenotype was sustained in DIO-NASH and ob/ob-NASH mice in conjunction with hepatomegaly and increased hepatic lipids and collagen accumulation. Histopathological scoring demonstrated significantly increased NAS of DIO-NASH mice (0 vs 4.7 ± 0.4, P NASH mice (2.4 ± 0.3 vs 6.3

  3. Recognition and enforcement of foreign judgements in the Republic of Lithuania = Признание и приведение к исполнению решений иностранных судов в Литовской Республике / Tatjana

    Index Scriptorium Estoniae

    Žukauskienė, Tatjana

    2010-01-01

    Tunnustamisprotseduuridest (eksekvaaturi väljaandmine ; registreerimine), neljast mudelist välisriigi kohtulahendite tunnustamisel ja täitmiseks lubamisel, Leedu tsiviilkohtumenetluse seadustikust ja rahvusvahelistest lepingutest

  4. Non-alcoholic fatty liver disease - histological scoring systems: a large cohort single-center, evaluation study.

    Science.gov (United States)

    Rastogi, Archana; Shasthry, Saggere Muralikrishna; Agarwal, Ayushi; Bihari, Chhagan; Jain, Priyanka; Jindal, Ankur; Sarin, Shiv

    2017-11-01

    Non-alcoholic fatty liver disease (NAFLD) is an increasingly common cause of chronic liver disease. Till date, liver biopsy remains the gold standard for identification and quantification of the wide histological spectra of NAFLD. Histological scorings are very useful and widely applied for the diagnosis and management in clinical trials and follow-up studies of non-alcoholic steatohepatitis (NASH). However, in view of scarce published literature, there is a need to evaluate them in large cohort of NAFLD. This study was aimed to evaluate the two histological scoring systems (NAS-CRN, SAF) in the diagnosis of NAFLD and to assess the role of histological characteristics as injury markers in NAFLD. Retrospective histological study of liver biopsies of 1000 patients diagnosed as NAFLD, between 2010 and 2016, was conducted. Histopathologic evaluation and semiquantiative scoring based on NAS-CRN and SAF algorithm and their correlation with serum aminotransferase and fibrosis were performed. Liver biopsies were classified according to the NAS-CRN scoring, as NAS <3 (not NASH) in 72 (7.2%), NAS 3-4 (borderline NASH) in 310 (31%), and NAS ≥5 (definite NASH) in 618 (61.8%), and SAF classified 117 (11.7%) not NASH and 883 (88.3%) definite NASH. There was excellent concordance for definite NASH and not NASH; however, 88.06% of borderline NASH was classified as NASH by SAF. 76.39% by NAS and 78.63% by SAF algorithm who were diagnosed as not NASH showed the presence of fibrosis; however, higher stages of fibrosis were significantly more prevalent in definite NASH, excluding burnt-out cirrhosis. Serum ALT was significantly associated with increasing stages of fibrosis (p < 0.001) and the three categories (not NASH, borderline NASH, and definite NASH) when classified as with/without fibrosis (p < 0.001). Steatosis of higher grades, more ballooned cells, and more foci of Lobular Inflammation were found in significantly higher proportion of patients with NASH (p < 0

  5. Over-expressing the soluble gp130-Fc does not ameliorate methionine and choline deficient diet-induced non alcoholic steatohepatitis in mice.

    Directory of Open Access Journals (Sweden)

    Helene L Kammoun

    Full Text Available Non-alcoholic steatohepatitis (NASH is a liver disease with the potential to lead to cirrhosis and hepatocellular carcinoma. Interleukin-6 (IL-6 has been implicated in the pathogenesis of NASH, with the so-called IL-6 'trans-signaling' cascade being responsible for the pro-inflammatory actions of this cytokine. We aimed to block IL-6 'trans-signaling', using a transgenic mouse that overexpresses human soluble glycoprotein130 (sgp130Fc Tg mice fed a commonly used dietary model of inducing NASH (methionine and choline deficient-diet; MCD diet and hypothesized that markers of NASH would be ameliorated in such mice. Sgp130Fc Tg and littermate control mice were fed a MCD or control diet for 4 weeks. The MCD diet induced many hallmarks of NASH including hepatomegaly, steatosis, and liver inflammation. However, in contrast with other mouse models and, indeed, human NASH, the MCD diet model did not increase the mRNA or protein expression of IL-6. Not surprisingly, therefore, markers of MCD diet-induced NASH were unaffected by sgp130Fc transgenic expression. While the MCD diet model induces many pathophysiological markers of NASH, it does not induce increased IL-6 expression in the liver, a key hallmark of human NASH. We, therefore, caution the use of the MCD diet as a viable mouse model of NASH.

  6. Plasma cathepsin D correlates with histological classifications of fatty liver disease in adults and responds to intervention.

    Science.gov (United States)

    Walenbergh, Sofie M A; Houben, Tom; Rensen, Sander S; Bieghs, Veerle; Hendrikx, Tim; van Gorp, Patrick J; Oligschlaeger, Yvonne; Jeurissen, Mike L J; Gijbels, Marion J J; Buurman, Wim A; Vreugdenhil, Anita C E; Greve, Jan Willem M; Plat, Jogchum; Hofker, Marten H; Kalhan, Satish; Pihlajamäki, Jussi; Lindsey, Patrick; Koek, Ger H; Shiri-Sverdlov, Ronit

    2016-12-06

    Non-alcoholic steatohepatitis (NASH) is characterized by liver lipid accumulation and inflammation. The mechanisms that trigger hepatic inflammation are poorly understood and subsequently, no specific non-invasive markers exist. We previously demonstrated a reduction in the plasma lysosomal enzyme, cathepsin D (CatD), in children with NASH compared to children without NASH. Recent studies have raised the concept that non-alcoholic fatty liver disease (NAFLD) in adults is distinct from children due to a different histological pattern in the liver. Yet, the link between plasma CatD to adult NASH was not examined. In the current manuscript, we investigated whether plasma CatD in adults correlates with NASH development and regression. Biopsies were histologically evaluated for inflammation and NAFLD in three complementary cohorts of adults (total n = 248). CatD and alanine aminotransferase (ALT) were measured in plasma. Opposite to our previous observations with childhood NASH, we observed increased levels of plasma CatD in patients with NASH compared to adults without hepatic inflammation. Furthermore, after surgical intervention, we found a reduction of plasma CatD compared to baseline. Our observations highlight a distinct pathophysiology between NASH in children and adults. The observation that plasma CatD correlated with NASH development and regression is promising for NASH diagnosis.

  7. Metabolic and hepatic effects of liraglutide, obeticholic acid and elafibranor in diet-induced obese mouse models of biopsy-confirmed nonalcoholic steatohepatitis

    Science.gov (United States)

    Tølbøl, Kirstine S; Kristiansen, Maria NB; Hansen, Henrik H; Veidal, Sanne S; Rigbolt, Kristoffer TG; Gillum, Matthew P; Jelsing, Jacob; Vrang, Niels; Feigh, Michael

    2018-01-01

    AIM To evaluate the pharmacodynamics of compounds in clinical development for nonalcoholic steatohepatitis (NASH) in obese mouse models of biopsy-confirmed NASH. METHODS Male wild-type C57BL/6J mice (DIO-NASH) and Lepob/ob (ob/ob-NASH) mice were fed a diet high in trans-fat (40%), fructose (20%) and cholesterol (2%) for 30 and 21 wk, respectively. Prior to treatment, all mice underwent liver biopsy for confirmation and stratification of liver steatosis and fibrosis, using the nonalcoholic fatty liver disease activity score (NAS) and fibrosis staging system. The mice were kept on the diet and received vehicle, liraglutide (0.2 mg/kg, SC, BID), obeticholic acid (OCA, 30 mg/kg PO, QD), or elafibranor (30 mg/kg PO, QD) for eight weeks. Within-subject comparisons were performed on changes in steatosis, inflammation, ballooning degeneration, and fibrosis scores. In addition, compound effects were evaluated by quantitative liver histology, including percent fractional area of liver fat, galectin-3, and collagen 1a1. RESULTS Liraglutide and elafibranor, but not OCA, reduced body weight in both models. Liraglutide improved steatosis scores in DIO-NASH mice only. Elafibranor and OCA reduced histopathological scores of hepatic steatosis and inflammation in both models, but only elafibranor reduced fibrosis severity. Liraglutide and OCA reduced total liver fat, collagen 1a1, and galectin-3 content, driven by significant reductions in liver weight. The individual drug effects on NASH histological endpoints were supported by global gene expression (RNA sequencing) and liver lipid biochemistry. CONCLUSION DIO-NASH and ob/ob-NASH mouse models show distinct treatment effects of liraglutide, OCA, and elafibranor, being in general agreement with corresponding findings in clinical trials for NASH. The present data therefore further supports the clinical translatability and utility of DIO-NASH and ob/ob-NASH mouse models of NASH for probing the therapeutic efficacy of compounds in

  8. Effect of pioglitazone, quercetin and hydroxy citric acid on extracellular matrix components in experimentally induced non-alcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Surapaneni Krishna Mohan

    2015-08-01

    Results:The experimental NASH rats treated with pioglitazone showed significant decrease in the levels of hyaluronic acid and significant increase in adiponectin levels when compared to experimentally induced NASH group, but did not show any effect on the levels of leptin. Contrary to these two drugs, viz. pioglitazone and hydroxy citric acid, the group treated with quercetin showedsignificant decrease in the levels of hyaluronic acid and leptin and significant decrease in adiponectin levels compared with that of experimentally induced NASH NASH group, offering maximum protection against NASH. Conclusion: Considering our findings, it could be concluded that quercetin may offer maximum protection against NASH by significantly increasing the levels of adiponectin, when compared to pioglitazone and hydroxy citric acid.

  9. Prisoners' dilemma in the presence of collective dephasing

    International Nuclear Information System (INIS)

    Nawaz, Ahmad

    2012-01-01

    We quantize prisoners' dilemma in the presence of collective dephasing with a dephasing rate γ. It is shown that for a two-parameter set of strategies, Q⊗Q is Nash equilibrium below a cut-off value of time. Beyond this cut-off it bifurcates into two new Nash equilibria Q⊗D and D⊗Q. Furthermore, for the maximum value of decoherence C⊗D and D⊗C also become Nash equilibria. At this stage the game has four Nash equilibria. On the other hand, for a three-parameter set of strategies, there is no pure strategy Nash equilibrium; however, there is a mixed strategy (non-unique) Nash equilibrium that is not affected by collective dephasing. (paper)

  10. Prisoners' dilemma in the presence of collective dephasing

    Science.gov (United States)

    Nawaz, Ahmad

    2012-05-01

    We quantize prisoners' dilemma in the presence of collective dephasing with a dephasing rate γ. It is shown that for a two-parameter set of strategies, Q⊗Q is Nash equilibrium below a cut-off value of time. Beyond this cut-off it bifurcates into two new Nash equilibria Q⊗D and D⊗Q. Furthermore, for the maximum value of decoherence C⊗D and D⊗C also become Nash equilibria. At this stage the game has four Nash equilibria. On the other hand, for a three-parameter set of strategies, there is no pure strategy Nash equilibrium; however, there is a mixed strategy (non-unique) Nash equilibrium that is not affected by collective dephasing.

  11. Low incidence of non-alcoholic steatohepatitis in a Danish liver unit

    DEFF Research Database (Denmark)

    Semb, Synne; Dam-Larsen, Sanne; Mogensen, Anne Mellon

    2012-01-01

    Non-alcoholic fatty liver disease encompasses a spectrum of histological lesions ranging from steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. Simple steatosis is generally benign, while NASH can progress to severe liver disease. The aim of the present study was to quantify the nu...... the number of patients with NASH and assess the prognosis associated with the condition in a large Danish referral centre for liver disease....

  12. Modeling Human Nonalcoholic Steatohepatitis-Associated Changes in Drug Transporter Expression Using Experimental Rodent Models

    OpenAIRE

    Canet, Mark J.; Hardwick, Rhiannon N.; Lake, April D.; Dzierlenga, Anika L.; Clarke, John D.; Cherrington, Nathan J.

    2014-01-01

    Nonalcoholic fatty liver disease is a prevalent form of chronic liver disease that can progress to the more advanced stage of nonalcoholic steatohepatitis (NASH). NASH has been shown to alter drug transporter regulation and may have implications in the development of adverse drug reactions. Several experimental rodent models have been proposed for the study of NASH, but no single model fully recapitulates all aspects of the human disease. The purpose of the current study was to determine whic...

  13. Plasma cathepsin D correlates with histological classifications of fatty liver disease in adults and responds to intervention

    OpenAIRE

    Walenbergh, Sofie M. A.; Houben, Tom; Rensen, Sander S.; Bieghs, Veerle; Hendrikx, Tim; van Gorp, Patrick J.; Oligschlaeger, Yvonne; Jeurissen, Mike L. J.; Gijbels, Marion J. J.; Buurman, Wim A.; Vreugdenhil, Anita C. E.; Greve, Jan Willem M.; Plat, Jogchum; Hofker, Marten H.; Kalhan, Satish

    2016-01-01

    Non-alcoholic steatohepatitis (NASH) is characterized by liver lipid accumulation and inflammation. The mechanisms that trigger hepatic inflammation are poorly understood and subsequently, no specific non-invasive markers exist. We previously demonstrated a reduction in the plasma lysosomal enzyme, cathepsin D (CatD), in children with NASH compared to children without NASH. Recent studies have raised the concept that non-alcoholic fatty liver disease (NAFLD) in adults is distinct from childre...

  14. State Manipulation and Asymptotic Inefficiency in a Dynamic Model of Monetary Policy

    DEFF Research Database (Denmark)

    Jensen, Henrik; Lockwood, Ben

    2000-01-01

    A simple folk theorem of repeated games states that Pareto-efficient outcomes can be achieved in a perfect equilibrium where deviations are punished by a reversion to Nash equilibrium of the associated stage game (Nash threats equilibrium), provided that players are sufficiently patient. In a dyn......A simple folk theorem of repeated games states that Pareto-efficient outcomes can be achieved in a perfect equilibrium where deviations are punished by a reversion to Nash equilibrium of the associated stage game (Nash threats equilibrium), provided that players are sufficiently patient...

  15. Lessons from Mouse Models of High-Fat Diet-Induced NAFLD

    Directory of Open Access Journals (Sweden)

    Yasuo Terauchi

    2013-10-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD encompasses a clinicopathologic spectrum of diseases ranging from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH, the more aggressive form of fatty liver disease that may progress to cirrhosis and cirrhosis-related complications, including hepatocellular carcinoma. The prevalence of NAFLD, including NASH, is also increasing in parallel with the growing epidemics of obesity and diabetes. However, the causal relationships between obesity and/or diabetes and NASH or liver tumorigenesis have not yet been clearly elucidated. Animal models of NAFLD/NASH provide crucial information, not only for elucidating the pathogenesis of NAFLD/NASH, but also for examining therapeutic effects of various agents. A high-fat diet is widely used to produce hepatic steatosis and NASH in experimental animals. Several studies, including our own, have shown that long-term high-fat diet loading, which can induce obesity and insulin resistance, can also induce NASH and liver tumorigenesis in C57BL/6J mice. In this article, we discuss the pathophysiology of and treatment strategies for NAFLD and subsequent NAFLD-related complications such as NASH and liver tumorigenesis, mainly based on lessons learned from mouse models of high-fat diet-induced NAFLD/NASH.

  16. Investeerimisel tuleb õigesti otsustada / Meelis Atonen

    Index Scriptorium Estoniae

    Atonen, Meelis, 1966-

    2007-01-01

    Ilmunud ka: Molodjozh Estonii : Zolotoi Vestnik, 18. dets. 2007, lk. 3; Delovõje Vedomosti : Zolotoi Vestnik, 19. dets. 2007, lk. 3; Den za Dnjom : Zolotoi Vestnik, 21. dets. 2007, lk. 3; Postimees : na russkom jazõke : Zolotoi Vestnik, 28. dets. 2007, lk. 3. Majanduse jahenemisele ja tarbimisbuumile järgnevaks ajaks valmistumisel on tähtis teha õigeid otsuseid tulevikku investeerimisel ning et investeeritud raha säiliks ja ühtlasi ka kasvaks. Kommenteerivad: Hannes Võrno, Jürgen Ligi, Peep Aru, Indrek Neivelt ja Aune Past. Ajal. Molodjozh Estonii : Zolotoi Vestnik, Delovõje Vedomosti : Zolotoi Vestnik kommenteerivad: Indrek Neivelt, Olga Sõtnik, Tatjana Muravjova

  17. Combined aesthetic interventions for prevention of facial ageing, and restoration and beautification of face and body

    OpenAIRE

    Fabi, Sabrina; Pavicic, Tatjana; Braz, André; Green, Jeremy B; Seo, Kyle; van Loghem, Jani AJ

    2017-01-01

    Sabrina Fabi,1 Tatjana Pavicic,2 André Braz,3 Jeremy B Green,4,5 Kyle Seo,6 Jani AJ van Loghem7 1Cosmetic Laser Dermatology, San Diego, CA, USA; 2Private Practice for Dermatology and Aesthetics, Munich, Germany; 3Division of the Policlínica Geral do Rio de Janeiro (PGRJ), Rio de Janeiro, Brazil; 4Skin Associates of South Florida, Miami, 5University of Miami Department of Dermatology, Miami, FL, USA; 6Seoul National University, Seoul, South Korea; 7Doctors Inc., Amsterdam...

  18. Ökodisainist futuristlike tudengite silmade läbi

    Index Scriptorium Estoniae

    2007-01-01

    Electroluxi Design Lab'i 2007. a. ülemaailsel disainivõistlusel Pariisis kujundasid tootedisaini üliõpilased keskkonnasõbralikke kodumasinaid aastaks 2020. Tutvustatakse finaliste: pesumasin E-wash (I koht - Levente Szabo), päikeseenergial töötav toiduvalmistaja Pebble (II - Laura Pandelle), kärjekujulistest sahtlitest koosnev külmik Go Fresh (III - He Cheng Fei), õhupuhastaja Nature Wind (Bae Won-Ho), plastikut kodustes tingimustes lagundav seade Return Pot (Juan Ying-Hao), nõudepesumasin Pure Washer (Tatjana Voronova), ududushsh Fog Shower (Joao Diego Schimansky), kompostiseade Circompo (Thanat Tengamnuay)

  19. Tööjõuvahetus viib teise keskkonda : mida kogesid Ida-Virumaa raamatukoguhoidjad Pärnus ja Rakveres töötades / Ene Riet

    Index Scriptorium Estoniae

    Riet, Ene, 1954-

    2010-01-01

    Integratsiooni ja Migratsiooni Sihtasutuse Meie Inimesed tööjõuvahetusprogrammis osalenud räägivad oma muljetest. Pärnu Keskraamatukogus töötasid Kohtla-Järve Keskraamatukogu töötajad Tatjana Agafonova ja Alla Rõtova ning vastuvõtjateks ja tugiisikuteks olid Lenna Eliste, Krista Visas ja Heinike Sinijärv. Lääne-Virumaa Keskraamatukogus olid Jõhvi Keskraamatukogu töötajad Natalja Jakovleva ja Tamara Saar, vastu võtsid Leigi Kütt ja Lea Lehtmets

  20. Вышел первый том переписки Лотмана с Егоровым

    Index Scriptorium Estoniae

    2012-01-01

    Tutvustus: Лотман, Юрий Михайлович ; Минц, Зара Гиршевна ; Егоров, Борис Федорович. Переписка 1954-1965 / teksti on ette valmistanud ja kommenteerinud Boriss Jegorov, Tatjana Kuzovkina, Nikolai Poseljagin, eessõna Boriss Jegorov. Tallinn : Tallinna Ülikooli Kirjastus, 2012. (Bibliotheca Lotmaniana)

  1. President tunnustab Eesti riigi edendajate elutööd / Silja Joon, Ester Vilgats, Eno-Gerrit Link

    Index Scriptorium Estoniae

    Joon, Silja, 1966-

    2008-01-01

    Pärnumaalased, kes pälvivad iseseisvuspäeva puhul ja Eesti riigile osutatud teenete tunnustamiseks president Toomas Hendrik Ilveselt riiklikud autasud. Juuresolevatel fotodel Valgetähe V klassi ordeni pälvinud koorijuht ja muusikaõpetaja Toomas Voll ja Kotkaristi IV klassi teenetemärgi pälvinud Lääne prefektuuri politseiametnik Kalvi Almosen. Vt. ka lk. 1: Enn Hallik. Tatjana Jaanson üllatus suurest aust. Sõudetreener pälvib Valgetähe IV klassi teenetemärgi

  2. Tallinna Linnateatri 5. rahvusvaheline teatrifestival "Talveöö unenägu" 28.-30. detsembril 2008 / Laur Kaunissaare

    Index Scriptorium Estoniae

    Kaunissaare, Laur, 1982-

    2008-01-01

    Festivalilavastustest - Fjodor Dostojevski "Vendade Karamazovite" järgi "Suurinkvisiitor" (Théatre des Bouffes du Nord, lavastaja Peter Brook), Tom Peuckerti "Artaud meenutab Adolf Hitlerit ja Romanische Café'd" (Berliner Ensemble, lavastaja Paul Plamper), Tatjana Tolstaja "Sonja" (Riia Uus Teater, lavastaja Alvis Hermanis), Lot Vekemansi "Tema õde" (NT Gent, lavastaja Allan Zipson), Jan Jönsoni "Tõelushetked" (autor, lavastaja ja esitaja ühes isikus) ja festivalil esinevatest erakordsetest näitlejatest Peter Wuttkest, Bruce Myersist, Elsie de Brauwist, Jan Jönsonist

  3. Research of Adults Lifelong Learning

    OpenAIRE

    Ingrīda Muraškovska

    2013-01-01

    The doctoral thesis of Ingrida Muraškovska in pedagogy science, Pedagogy of adult education sub-discipline “Investigation of Adult’s Lifelong Learning” has been worked out in the Pedagogy department of the Faculty of Education, Psychology and Art, University of Latvia, under the supervision of Dr. habil. paed. professor Tatjana Koķe from 2004 till 2012. The topicality of the study is determined by human development problems in the transition to a knowledge society in which the ability of all ...

  4. Cultural Resources Intensive Survey and Testing of Mississippi River Levee Berms Crittenden and Desha Counties, Arkansas and Mississippi, Scott, Cape Girardeau and Pemiscot Counties, Missouri. Item R-48.87 A.C. Nash; Missouri, Relief Well Ditches Cape Girardeau and Scott Counties, Missouri

    Science.gov (United States)

    1983-07-01

    honey locust (Gleditsia aquatica), Planer tree or water elm (Planera aquatica), wisteria (Wisteria macrostachya), grape (Vitispalmata) and Corkwood...hickory nuts, in addition to the berries found in the understory, such as haws, blueberries, blackberries and grapes . Plants in the backwater and the...of bean stalk and dried mud, cut but uncollected crops (e.g., corn). Controlled surface collections were made at each location. These were tape and

  5. Estimação de metas estratégicas por meio de análise por envoltória de dados e modelo da Barganha de Nash: aplicação na área de saúde publica

    OpenAIRE

    Santos, Marco Aurélio Reis dos [UNESP

    2014-01-01

    This work focuses the empirical estimation of targets for internal medicine from UBS (Basic Health Unit) in Guaratinguetá city. It was proposed a method that can help Public Health service managers to identify problems and best practices in each Basic Health Units where people are attended. In the first step, under the guidance system of strategic management BSC it was defined performance indicators based on its four perspectives that translate the vision and the strategic of health service. ...

  6. Screening for nonalcoholic steatohepatitis by using cytokeratin 18 and transient elastography in HIV mono-infection.

    Directory of Open Access Journals (Sweden)

    Amine Benmassaoud

    Full Text Available HIV-infected individuals are at high risk of developing nonalcoholic steatohepatitis (NASH, a leading cause of end-stage liver disease in Western countries. Nonetheless, due to the invasiveness of liver biopsy, NASH remains poorly understood in HIV mono-infection. We aimed to characterize the prevalence and predictors of NASH in unselected HIV mono-infected patients by means of non-invasive diagnostic tools.HIV-infected adults without significant alcohol intake or co-infection with hepatitis B or C underwent a routine screening program employing transient elastography (TE with controlled attenuation parameter (CAP and the serum biomarker cytokeratin-18 (CK-18. NASH was diagnosed non-invasively as the coexistence of fatty liver (CAP ≥248 dB/m and CK-18 >246 U/L. Identified cases of NASH were offered a diagnostic liver biopsy. Predictors of NASH were determined by multivariate logistic regression analysis.202 consecutive HIV mono-infected patients were included. NASH was non-invasively diagnosed in 23 cases (11.4%. Among them, 17 underwent a liver biopsy, and histology confirmed NASH in all cases. The prevalence of NASH was higher in patients with hypertriglyceridemia (17.1%, insulin resistance defined by homeostasis model for assessment of insulin resistance (HOMA-IR (25%, those with detectable HIV viral load (42.9% and those with elevated ALT (53.6%. After adjustment, higher HOMA-IR (adjusted odds ratio [aOR] = 1.20, 95% CI 1.01-1.43; p = 0.03 and ALT (aOR = 2.39, 95% CI 1.50-3.79; p<0.001 were independent predictors of NASH.NASH, diagnosed by a non-invasive diagnostic approach employing CK-18 and TE with CAP, is common in unselected HIV mono-infected individuals, particularly in the presence of insulin resistance and elevated ALT.

  7. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: cherrington@pharmacy.arizona.edu [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  8. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.

    2013-01-01

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  9. A preliminary study of inflammatory markers in non-alcoholic ...

    African Journals Online (AJOL)

    In the present preliminary study an attempt was made to study whether there is an increase in the levels of CRP in CAD patients associated with NASH. CAD patients showed an increase in CRP and serum ferritin levels. In CAD patients with NASH along with an increase in the levels of serum ferittin (p<0.001), the levels of ...

  10. Commuting for meetings

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Engelson, Leonid; Franklin, Joel P.

    2014-01-01

    until both are present. Players prefer to depart later and also to arrive sooner, provided they do not have to wait for the other player. We find a unique Nash equilibrium, and a continuum of Pareto optima that are strictly better than the Nash equilibrium for both players. Pareto optima may...

  11. The impact of advertising in a duopoly model

    NARCIS (Netherlands)

    Schoonbeek, Lambert; Kooreman, Peter

    1999-01-01

    We investigate the impact of advertising in a simple static differentiated duopoly model. First, we consider the Nash equilibrium of the situation in which the duopolistic firms compete simultaneously with two instruments, i.e. the prices and the advertising expenditures. Second, we examine the Nash

  12. Slide 1

    Indian Academy of Sciences (India)

    Game Theory · Strategic Form Games (Normal Form Games) · Example : Prisoner's Dilemma · Dominant Strategy Equilibrium · Nash Equilibrium · Nash's Theorem · Slide 17 · Slide 18 · Example 1: Mechanism Design Fair Division of a Cake · Example 2: Mechanism Design Truth Elicitation through an Indirect Mechanism.

  13. Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis

    NARCIS (Netherlands)

    Cabrera, Daniel; Wree, Alexander; Povero, Davide; Solís, Nancy; Hernandez, Alejandra; Pizarro, Margarita; Moshage, Han; Torres, Javiera; Feldstein, Ariel E; Cabello-Verrugio, Claudio; Brandan, Enrique; Barrera, Francisco; Arab, Juan Pablo; Arrese, Marco

    2017-01-01

    Therapy for nonalcoholic steatohepatitis (NASH) is limited. Andrographolide (ANDRO), a botanical compound, has a potent anti-inflammatory activity due to its ability to inhibit NF-kB. ANDRO has been also shown to inhibit the NLRP3 inflammasome, a relevant pathway in NASH. Our aim was to evaluate the

  14. Antioxidant and Hepatoprotective Effects of Silibinin in a Rat Model of Nonalcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Yara Haddad

    2011-01-01

    Full Text Available Nonalcoholic steatohepatitis (NASH is a progressive liver disease related to the metabolic syndrome, obesity and diabetes. The rising prevalence of NASH and the lack of efficient treatments have led to the exploration of different therapeutic approaches. Milk thistle (Silibum marianum is a medicinal plant used for its hepatoprotective properties in chronic liver disease since the 4th century BC. We explored the therapeutic effect of silibinin, the plant's most biologically active extract, in an experimental rat NASH model. A control group was fed a standard liquid diet for 12 weeks. The other groups were fed a high-fat liquid diet for 12 weeks without (NASH or with simultaneous daily supplement with silibinin–phosphatidylcholine complex (Silibinin 200 mg kg−1 for the last 5 weeks. NASH rats developed all key hallmarks of the pathology. Treatment with silibinin improved liver steatosis and inflammation and decreased NASH-induced lipid peroxidation, plasma insulin and TNF-α. Silibinin also decreased O2∙- release and returned the relative liver weight as well as GSH back to normal. Our results suggest that milk thistle's extract, silibinin, possesses antioxidant, hypoinsulinemic and hepatoprotective properties that act against NASH-induced liver damage. This medicinal herb thus shows promising therapeutic potential for the treatment of NASH.

  15. Beneficial effects of mineralocorticoid receptor blockade in experimental non-alcoholic steatohepatitis

    NARCIS (Netherlands)

    Pizarro, Margarita; Solis, Nancy; Quintero, Pablo; Barrera, Francisco; Cabrera, Daniel; Rojas-de Santiago, Pamela; Arab, Juan P.; Padilla, Oslando; Roa, Juan C.; Moshage, Han; Wree, Alexander; Inzaugarat, Eugenia; Feldstein, Ariel E.; Fardella, Carlos E.; Baudrand, Rene; Riquelme, Arnoldo; Arrese, Marco

    BackgroundTherapeutic options to treat Non-alcoholic steatohepatitis (NASH) are limited. Mineralocorticoid receptor (MR) activation could play a role in hepatic fibrogenesis and its modulation could be beneficial for NASH. AimTo investigate whether eplerenone, a specific MR antagonist, ameliorates

  16. Chemokine-Like Receptor 1 mRNA Weakly Correlates with Non-Alcoholic Steatohepatitis Score in Male but Not Female Individuals

    Directory of Open Access Journals (Sweden)

    Maximilian Neumann

    2016-08-01

    Full Text Available The chemokine-like receptor 1 (CMKLR1 ligands resolvin E1 and chemerin are known to modulate inflammatory response. The progression of non-alcoholic fatty liver disease (NAFLD to non-alcoholic steatohepatitis (NASH is associated with inflammation. Here it was analyzed whether hepatic CMKLR1 expression is related to histological features of NASH. Therefore, CMKLR1 mRNA was quantified in liver tissue of 33 patients without NAFLD, 47 patients with borderline NASH and 38 patients with NASH. Hepatic CMKLR1 mRNA was not associated with gender and body mass index (BMI in the controls and the whole study group. CMKLR1 expression was similar in controls and in patients with borderline NASH and NASH. In male patients weak positive correlations with inflammation, fibrosis and NASH score were identified. In females CMKLR1 was not associated with features of NAFLD. Liver CMKLR1 mRNA tended to be higher in type 2 diabetes patients of both genders and in hypercholesterolemic women. In summary, this study shows that hepatic CMKLR1 mRNA is weakly associated with features of NASH in male patients only.

  17. LDL Receptor Knock-Out Mice Are a Physiological Model Particularly Vulnerable to Study the Onset of Inflammation in Non-Alcoholic Fatty Liver Disease

    NARCIS (Netherlands)

    Bieghs, Veerle; Van Gorp, Patrick J.; Wouters, Kristiaan; Hendrikx, Tim; Gijbels, Marion J.; van Bilsen, Marc; Bakker, Jaap; Binder, Christoph J.; Luetjohann, Dieter; Staels, Bart; Hofker, Marten H.; Shiri-Sverdlov, Ronit

    2012-01-01

    Background & Aims: Non-alcoholic steatohepatitis (NASH) involves steatosis combined with inflammation, which can progress into fibrosis and cirrhosis. Exploring the molecular mechanisms of NASH is highly dependent on the availability of animal models. Currently, the most commonly used animal models

  18. How Many Formative Assessment Angels Can Dance on the Head of a Meta-Analytic Pin: 0.2

    Science.gov (United States)

    Kingston, Neal; Nash, Brooke

    2012-01-01

    In their critique of Kingston and Nash (2011), Briggs, Ruiz-Primo, Furtak, Shepard, and Yin (2012) make several major points. First, Kingston and Nash's conclusions about the state of research on the efficacy of formative assessment are similar to other researchers, "including some of the authors." Second, their research may be unique in that they…

  19. Slide 1

    Indian Academy of Sciences (India)

    Problem 1: Direct Materials Procurement at GM · Slide 8 · Slide 9 · Slide 10 · Game Theory · Strategic Form Games (Normal Form Games) · Example : Prisoner's Dilemma · Dominant Strategy Equilibrium · Nash Equilibrium · Nash's Theorem · Slide 17 · Slide 18 · Example 1: Mechanism Design Fair Division of a Cake.

  20. The LXR inverse agonist SR9238 suppresses fibrosis in a model of non-alcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Kristine Griffett

    2015-04-01

    Conclusions: Here, we demonstrate that an LXR inverse agonist, SR9238, is effective in reduction of hepatic steatosis, inflammation and fibrosis in an animal model of NASH. These results have important implications for the development of therapeutics for treatment NASH in humans.

  1. Role of scavenger receptor A and CD36 in diet-induced nonalcoholic steatohepatitis in hyperlipidemic mice

    NARCIS (Netherlands)

    Bieghs, Veerle; Wouters, Kristiaan; van Gorp, Patrick J.; Gijbels, Marion J. J.; de Winther, Menno P. J.; Binder, Christoph J.; Lütjohann, Dieter; Febbraio, Maria; Moore, Kathryn J.; van Bilsen, Marc; Hofker, Marten H.; Shiri-Sverdlov, Ronit

    2010-01-01

    Nonalcoholic steatohepatitis (NASH) is a disorder that consists of steatosis and hepatic inflammation. It is not known why only some people with steatosis develop NASH. Recently, we identified dietary cholesterol as a factor that directly leads to hepatic inflammation and hepatic foam cell

  2. Role of Scavenger Receptor A and CD36 in Diet-Induced Nonalcoholic Steatohepatitis in Hyperlipidemic Mice

    NARCIS (Netherlands)

    Bieghs, Veerle; Wouters, Kristiaan; Van Gorp, Patrick J.; Gijbels, Marion J. J.; De Winther, Menno P. J.; Binder, Christoph J.; Luetjohann, Dieter; Febbraio, Maria; Moore, Kathryn J.; Van Bilsen, Marc; Hofker, Marten H.; Shiri-Sverdlov, Ronit

    BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is a disorder that consists of steatosis and hepatic inflammation. It is not known why only some people with steatosis develop NASH. Recently, we identified dietary cholesterol as a factor that directly leads to hepatic inflammation and hepatic

  3. Mouse Models of Diet-Induced Nonalcoholic Steatohepatitis Reproduce the Heterogeneity of the Human Disease

    Science.gov (United States)

    Machado, Mariana Verdelho; Michelotti, Gregory Alexander; Xie, Guanhua; de Almeida, Thiago Pereira; Boursier, Jerome; Bohnic, Brittany; Guy, Cynthia D.; Diehl, Anna Mae

    2015-01-01

    Background and aims Non-alcoholic steatohepatitis (NASH), the potentially progressive form of nonalcoholic fatty liver disease (NAFLD), is the pandemic liver disease of our time. Although there are several animal models of NASH, consensus regarding the optimal model is lacking. We aimed to compare features of NASH in the two most widely-used mouse models: methionine-choline deficient (MCD) diet and Western diet. Methods Mice were fed standard chow, MCD diet for 8 weeks, or Western diet (45% energy from fat, predominantly saturated fat, with 0.2% cholesterol, plus drinking water supplemented with fructose and glucose) for 16 weeks. Liver pathology and metabolic profile were compared. Results The metabolic profile associated with human NASH was better mimicked by Western diet. Although hepatic steatosis (i.e., triglyceride accumulation) was also more severe, liver non-esterified fatty acid content was lower than in the MCD diet group. NASH was also less severe and less reproducible in the Western diet model, as evidenced by less liver cell death/apoptosis, inflammation, ductular reaction, and fibrosis. Various mechanisms implicated in human NASH pathogenesis/progression were also less robust in the Western diet model, including oxidative stress, ER stress, autophagy deregulation, and hedgehog pathway activation. Conclusion Feeding mice a Western diet models metabolic perturbations that are common in humans with mild NASH, whereas administration of a MCD diet better models the pathobiological mechanisms that cause human NAFLD to progress to advanced NASH. PMID:26017539

  4. Word Meaning Selection in Multiprocess Language Understanding Programs,

    Science.gov (United States)

    1981-02-01

    powerful knowledge sources use "semantic," "contextual" and " pragmat - ic" features. Surface semantics exploits the constraints which certain words...Report No. 74, Yale Univer- sity, New Haven, Cr. [Nash78] Nash-Webber, B. L., "Syntax beyond the Sentence: Anaphora ," in Spiro, Bruce & Brewer (eds

  5. Impact of Renal Impairment on Cardiovascular Disease Mortality After Liver Transplantation for Nonalcoholic Steatohepatitis Cirrhosis

    Science.gov (United States)

    VanWagner, Lisa B.; Lapin, Brittany; Skaro, Anton I.; Lloyd-Jones, Donald M.; Rinella, Mary E.

    2016-01-01

    BACKGROUND & AIMS Non-alcoholic steatohepatitis (NASH) is an independent risk factor for cardiovascular disease (CVD) morbidity after liver transplantation, but its impact on CVD mortality is unknown. We sought to assess the impact of NASH on CVD mortality after liver transplantation and to predict which NASH recipients are at highest risk of a CVD-related death following a liver transplant. METHODS Using the Organ Procurement and Transplantation Network database we examined associations between NASH and post liver transplant CVD mortality, defined as primary cause of death from thromboembolism, arrhythmia, heart failure, myocardial infarction, or stroke. A physician panel reviewed cause of death. RESULTS Of 48,360 liver transplants (2/2002–12/2011), 5,057 (10.5%) were performed for NASH cirrhosis. NASH recipients were more likely to be older, female, obese, diabetic, and have history of renal failure or prior CVD versus non-NASH (ptransplant diabetes, renal impairment or CVD. A risk score comprising age ≥ 55, male sex, diabetes and renal impairment was developed for prediction of post liver transplant CVD mortality (c-statistic 0.60). CONCLUSION NASH recipients have an increased risk of CVD mortality after liver transplantation explained by a high prevalence of co-morbid cardiometabolic risk factors that in aggregate identify those at highest risk of post-transplant CVD mortality. PMID:25977117

  6. Uniqueness Conditions for the Infinite-Planning Horizon Open-Loop Linear Quadratic Differential Game

    NARCIS (Netherlands)

    Engwerda, J.C.

    2005-01-01

    In this note we consider the open-loop Nash linear quadratic differential game with an infinite planning horizon.The performance function is assumed to be indefinite and the underlying system affine.We derive both necessary and sufficient conditions under which this game has a unique Nash

  7. Early diet-induced non-alcoholic steatohepatitis in APOE2 knock-in mice and its prevention by fibrates

    NARCIS (Netherlands)

    Shiri-Sverdlov, Ronit; Wouters, Kristiaan; van Gorp, Patrick J.; Gijbels, Marion J.; Noel, Benoit; Buffat, Laurent; Staels, Bart; Maeda, Nobuyo; van Bilsen, Marc; Hofker, Marten H.

    2006-01-01

    The molecular mechanisms leading to Non-Alcoholic Steatohepatitis (NASH) are not fully understood. In mice, NASH can be inhibited by fenofibrate, a synthetic agonist for the nuclear receptor peroxisome proliferator activated receptor alpha, which regulates hepatic triglyceride metabolism. This study

  8. Proteome Characteristics of Non-Alcoholic Steatohepatitis Liver Tissue and Associated Hepatocellular Carcinomas

    Directory of Open Access Journals (Sweden)

    Anna Kakehashi

    2017-02-01

    Full Text Available To uncover mechanisms of nonalcoholic steatohepatitis (NASH associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs and HCCs of HCV+ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed. Similar changes in the proteome spectrum such as overexpression of enzymes involved in lipid, cholesterol and bile acid biosynthesis and examples associated with suppression of fatty acid oxidation and catabolism, alcohol metabolism, mitochondrial function as well as low expression levels of cytokeratins 8 and 18 were observed in both human NASH biopsies and NASH HCCs, but not HCV+ HCCs. Alterations in downstream protein expression pointed to significant activation of transforming growth factor β, SMAD family member 3, β-catenin, Nrf2, SREBP-LXRα and nuclear receptor-interacting protein 1 (NRIP1, and inhibition of PPARs and p53 in human NASH biopsies and/or HCCs, suggesting their involvement in accumulation of lipids, development of fibrosis, oxidative stress, cell proliferation and suppression of apoptosis in NASH hepatocarcinogenesis. In STAM mice, PPARs inhibition was not obvious, while expression of cytokeratins 8 and 18 was elevated, indicative of essential differences between human and mouse NASH pathogenesis.

  9. Mouse models of diet-induced nonalcoholic steatohepatitis reproduce the heterogeneity of the human disease.

    Directory of Open Access Journals (Sweden)

    Mariana Verdelho Machado

    Full Text Available Non-alcoholic steatohepatitis (NASH, the potentially progressive form of nonalcoholic fatty liver disease (NAFLD, is the pandemic liver disease of our time. Although there are several animal models of NASH, consensus regarding the optimal model is lacking. We aimed to compare features of NASH in the two most widely-used mouse models: methionine-choline deficient (MCD diet and Western diet.Mice were fed standard chow, MCD diet for 8 weeks, or Western diet (45% energy from fat, predominantly saturated fat, with 0.2% cholesterol, plus drinking water supplemented with fructose and glucose for 16 weeks. Liver pathology and metabolic profile were compared.The metabolic profile associated with human NASH was better mimicked by Western diet. Although hepatic steatosis (i.e., triglyceride accumulation was also more severe, liver non-esterified fatty acid content was lower than in the MCD diet group. NASH was also less severe and less reproducible in the Western diet model, as evidenced by less liver cell death/apoptosis, inflammation, ductular reaction, and fibrosis. Various mechanisms implicated in human NASH pathogenesis/progression were also less robust in the Western diet model, including oxidative stress, ER stress, autophagy deregulation, and hedgehog pathway activation.Feeding mice a Western diet models metabolic perturbations that are common in humans with mild NASH, whereas administration of a MCD diet better models the pathobiological mechanisms that cause human NAFLD to progress to advanced NASH.

  10. 76 FR 27173 - Carolina Coastal Railway, Inc.-Acquisition and Operation Exemption-Rocky Mount & Western Railroad...

    Science.gov (United States)

    2011-05-10

    ... Surface Transportation Board Carolina Coastal Railway, Inc.--Acquisition and Operation Exemption--Rocky Mount & Western Railroad Co., Inc. d/b/a Nash County Railroad Carolina Coastal Railway, Inc. (CLNA), a... Rocky Mount & Western Railroad Co., Inc. d/b/a Nash County Railroad (NCR), and to operate, approximately...

  11. Moderate alcohol consumption aggravates high fat-diet induced steatohepatitis in rats

    Science.gov (United States)

    Background: Nonalcoholic steatohepatitis (NASH) develops in the absence of chronic and excessive alcohol consumption. However, it remains unknown whether moderate alcohol consumption aggravates liver inflammation in pre-existing NASH condition. Methods: Sprague-Dawley rats were first fed ad libitum...

  12. Hepatocellular carcinoma and non-alcoholic steatohepatitis: The state of play.

    Science.gov (United States)

    Charrez, Bérénice; Qiao, Liang; Hebbard, Lionel

    2016-02-28

    Hepatocellular carcinoma (HCC) is now the fifth cancer of greatest frequency and the second leading cause of cancer related deaths worldwide. Chief amongst the risks of HCC are hepatitis B and C infection, aflatoxin B1 ingestion, alcoholism and obesity. The latter can promote non-alcoholic fatty liver disease (NAFLD), that can lead to the inflammatory form non-alcoholic steatohepatitis (NASH), and can in turn promote HCC. The mechanisms by which NASH promotes HCC are only beginning to be characterized. Here in this review, we give a summary of the recent findings that describe and associate NAFLD and NASH with the subsequent HCC progression. We will focus our discussion on clinical and genomic associations that describe new risks for NAFLD and NASH promoted HCC. In addition, we will consider novel murine models that clarify some of the mechanisms that drive NASH HCC formation.

  13. Potential for dietary ω-3 fatty acids to prevent nonalcoholic fatty liver disease and reduce the risk of primary liver cancer.

    Science.gov (United States)

    Jump, Donald B; Depner, Christopher M; Tripathy, Sasmita; Lytle, Kelli A

    2015-11-01

    Nonalcoholic fatty liver disease (NAFLD) has increased in parallel with central obesity, and its prevalence is anticipated to increase as the obesity epidemic remains unabated. NAFLD is now the most common cause of chronic liver disease in developed countries and is defined as excessive lipid accumulation in the liver, that is, hepatosteatosis. NAFLD ranges in severity from benign fatty liver to nonalcoholic steatohepatitis (NASH), and NASH is characterized by hepatic injury, inflammation, oxidative stress, and fibrosis. NASH can progress to cirrhosis, and cirrhosis is a risk factor for primary hepatocellular carcinoma (HCC). The prevention of NASH will lower the risk of cirrhosis and NASH-associated HCC. Our studies have focused on NASH prevention. We developed a model of NASH by using mice with the LDL cholesterol receptor gene ablated fed the Western diet (WD). The WD induces a NASH phenotype in these mice that is similar to that seen in humans and includes robust induction of hepatic steatosis, inflammation, oxidative stress, and fibrosis. With the use of transcriptomic, lipidomic, and metabolomic approaches, we examined the capacity of 2 dietary ω-3 (n-3) polyunsaturated fatty acids, eicosapentaenoic acid (20:5ω-3; EPA) and docosahexaenoic acid (22:6ω-3; DHA), to prevent WD-induced NASH. Dietary DHA was superior to EPA at attenuating WD-induced changes in plasma lipids and hepatic injury and at reversing WD effects on hepatic metabolism, oxidative stress, and fibrosis. The outcome of these studies suggests that DHA may be useful in preventing NASH and reducing the risk of HCC. © 2015 American Society for Nutrition.

  14. Dynamical and thermodynamical coupling between the North Atlantic subtropical high and the marine boundary layer clouds in boreal summer

    Science.gov (United States)

    Wei, Wei; Li, Wenhong; Deng, Yi; Yang, Song; Jiang, Jonathan H.; Huang, Lei; Liu, W. Timothy

    2018-04-01

    This study investigates dynamical and thermodynamical coupling between the North Atlantic subtropical high (NASH), marine boundary layer (MBL) clouds, and the local sea surface temperatures (SSTs) over the North Atlantic in boreal summer for 1984-2009 using NCEP/DOE Reanalysis 2 dataset, various cloud data, and the Hadley Centre sea surface temperature. On interannual timescales, the summer mean subtropical MBL clouds to the southeast of the NASH is actively coupled with the NASH and local SSTs: a stronger (weaker) NASH is often accompanied with an increase (a decrease) of MBL clouds and abnormally cooler (warmer) SSTs along the southeast flank of the NASH. To understand the physical processes between the NASH and the MBL clouds, the authors conduct a data diagnostic analysis and implement a numerical modeling investigation using an idealized anomalous atmospheric general circulation model (AGCM). Results suggest that significant northeasterly anomalies in the southeast flank of the NASH associated with an intensified NASH tend to induce stronger cold advection and coastal upwelling in the MBL cloud region, reducing the boundary surface temperature. Meanwhile, warm advection associated with the easterly anomalies from the African continent leads to warming over the MBL cloud region at 700 hPa. Such warming and the surface cooling increase the atmospheric static stability, favoring growth of the MBL clouds. The anomalous diabatic cooling associated with the growth of the MBL clouds dynamically excites an anomalous anticyclone to its north and contributes to strengthening of the NASH circulation in its southeast flank. The dynamical and thermodynamical couplings and their associated variations in the NASH, MBL clouds, and SSTs constitute an important aspect of the summer climate variability over the North Atlantic.

  15. The xanthine oxidase inhibitor febuxostat suppresses development of nonalcoholic steatohepatitis in a rodent model.

    Science.gov (United States)

    Nakatsu, Yusuke; Seno, Yasuyuki; Kushiyama, Akifumi; Sakoda, Hideyuki; Fujishiro, Midori; Katasako, Aya; Mori, Keiichi; Matsunaga, Yasuka; Fukushima, Toshiaki; Kanaoka, Ryuhei; Yamamotoya, Takeshi; Kamata, Hideaki; Asano, Tomoichiro

    2015-07-01

    Xanthine oxidase (XO) is an enzyme involved in the production of uric acid (UA) from purine nucleotides. Numerous recent studies have revealed the likelihood of metabolic syndrome including nonalcoholic fatty liver disease (NAFLD) or steatohepatitis (NASH) to be related to hyperuricemia. However, it remains unclear whether elevated serum UA during the development of NAFLD or NASH is a cause or a consequence of these diseases. In this study, the XO inhibitor febuxostat was administered to two types of NASH model mice. Febuxostat exerted a strong protective effect against NASH development induced by a high-fat diet containing trans fatty acid (HFDT). In contrast, methionine choline-deficient-diet-induced NASH development not accompanied by hyperuricemia showed no UA normalization, suggesting that the ameliorating effect of febuxostat occurs via the normalization of hyperuricemia itself and/or accompanying molecular mechanism(s) such as oxidative stress. In the HFDT-fed mice, hyperuricemia, elevated alanine aminotransferase, and increased Tunnel-positive cells in the liver were normalized by febuxostat administration. In addition, upregulation of fatty acid oxidation-related genes, fibrotic change, and increases in collagen deposition, inflammatory cytokine expressions, and lipid peroxidation in the HFDT-fed mice were also normalized by febuxostat administration. Taken together, these observations indicate that administration of febuxostat has a protective effect against HFDT-induced NASH development, suggesting the importance of XO in its pathogenesis. Thus XO inhibitors are potentially potent therapies for patients with NASH, particularly that associated with hyperuricemia. Copyright © 2015 the American Physiological Society.

  16. Diagnostic Value of CK-18, FGF-21, and Related Biomarker Panel in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Lei He

    2017-01-01

    Full Text Available Liver biopsy still remains the gold standard for diagnosing nonalcoholic steatohepatitis (NASH, but with limitations. There is an urgent need to develop noninvasive tests that accurately distinguish NASH from simple steatosis. The purpose of this meta-analysis was to evaluate the diagnostic value of serum biomarkers including cytokeratin 18 (CK-18, fibroblast growth factor 21 (FGF-21, and combined biomarker panel (CBP in the diagnosis of NAFLD, especially NASH. A total of 25 studies met the inclusion criteria. Pooled sensitivity and specificity values for chosen serum markers for diagnosing NASH are as follows: CK-18 (M30, 0.75 and 0.77; CK-18 (M65, 0.71 and 0.77; FGF-21, 0.62 and 0.78; and CBP, 0.92 and 0.85. CBP demonstrated better accuracy with higher sensitivity and specificity than those tested individually. Furthermore, the AUROC of CBP was 0.94 (95% CI, 0.92–0.96, compared to CK-18 or FGF-21 assay, which showed the most significant ability to distinguish NASH from simple steatosis. The results suggest that increased circulating CK-18 and FGF-21 are associated with NASH and may be used for initial assessment, but not enough. Importantly, CBP is potentially used as accurate diagnostic tools for NASH. Further prospective designed studies are warranted to confirm our findings.

  17. The histologic spectrum of liver disease in African-American, non-Hispanic white, and Hispanic obesity surgery patients.

    Science.gov (United States)

    Kallwitz, Eric R; Guzman, Grace; TenCate, Veronica; Vitello, Joseph; Layden-Almer, Jennifer; Berkes, Jamie; Patel, Roshan; Layden, Thomas J; Cotler, Scott J

    2009-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a prominent cause of chronic liver disease in African Americans, non-Hispanic whites, and Hispanics. The aim of this study was to evaluate ethnic differences in the prevalence of NAFLD and non-alcoholic steatohepatitis (NASH) and to compare the severity of histologic features of NASH in obesity surgery patients. Subjects consisted of 238 patients who had a routine liver biopsy at the time of obesity surgery. Demographic and clinical variables pertaining to the metabolic syndrome were collected retrospectively. Liver biopsies were evaluated according to the scoring system proposed by the Nonalcoholic Steatohepatitis Clinical Research Network and NASH was defined as a NASH activity score > or =5. African Americans had lower rates of steatosis than non-Hispanic whites (P or =F2 than non-Hispanic whites (P=0.002) and Hispanics (P=0.04). Ethnic differences in rates of NAFLD, NASH, and fibrosis > or =F2 persisted when controlling for demographic variables and features of the metabolic syndrome in logistic regression analysis. There were no significant differences in steatosis, NASH, or fibrosis > or =F2 between non-Hispanic whites and Hispanics. African-American obesity surgery patients have a lower rate of NAFLD, NASH, and less severe fibrosis than non-Hispanic whites and Hispanics.

  18. Development of a Representative Mouse Model with Nonalcoholic Steatohepatitis.

    Science.gov (United States)

    Verbeek, Jef; Jacobs, Ans; Spincemaille, Pieter; Cassiman, David

    2016-06-01

    Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the Western world. It represents a disease spectrum ranging from isolated steatosis to non-alcoholic steatohepatitis (NASH). In particular, NASH can evolve to fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. The development of novel treatment strategies is hampered by the lack of representative NASH mouse models. Here, we describe a NASH mouse model, which is based on feeding non-genetically manipulated C57BL6/J mice a 'Western style' high-fat/high-sucrose diet (HF-HSD). HF-HSD leads to early obesity, insulin resistance, and hypercholesterolemia. After 12 weeks of HF-HSD, all mice exhibit the complete spectrum of features of NASH, including steatosis, hepatocyte ballooning, and lobular inflammation, together with fibrosis in the majority of mice. Hence, this model closely mimics the human disease. Implementation of this mouse model will lead to a standardized setup for the evaluation of (i) underlying mechanisms that contribute to the progression of NAFLD to NASH, and (ii) therapeutic interventions for NASH. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

  19. Berberine Reduces Neurotoxicity Related to Nonalcoholic Steatohepatitis in Rats

    Directory of Open Access Journals (Sweden)

    Doaa A. Ghareeb

    2015-01-01

    Full Text Available Berberine is a plant alkaloid that has several pharmacological effects such as antioxidant, antilipidemic, and anti-inflammatory effects. Nonalcoholic steatohepatitis (NASH triggers different aspects of disorders such as impaired endogenous lipid metabolism, hypercholesterolemia, oxidative stress, and neurotoxicity. In this study, we examined the mechanism by which NASH induces neurotoxicity and the protective effect of berberine against both NASH and its associated neurotoxicity. NASH induced rats showed significant impairments in lipid metabolism with increased serum triglycerides, cholesterol, and low-density lipoprotein (LDL. The NASH induced group also demonstrated a significant oxidative stress which is characterized by increased TBARs level and decreased antioxidant capacity such as GSH and SOD levels. Moreover, the NASH induction was associated with inflammation which was demonstrated by increased TNFα and nitric oxide levels. Hyperglycemia and hyperinsulinemia were observed in the NASH induced group. Also, our results showed a significant increase in the expression of the acetylcholine esterase (AChE and amyloid beta precursor protein (AβPP. These changes were significantly correlated with decreased insulin degrading enzyme (IDE and beta-amyloid40 (Aβ40 and increased beta-amyloid42 (Aβ42 in the hippocampal region. Daily administration of berberine (50 mg/kg for three weeks ameliorated oxidative stress, inflammation, hyperlipidemia, hyperglycemia, hyperinsulinemia, and the observed neurotoxicity.

  20. Anti-oxidative and anti-inflammatory effects of spirulina on rat model of non-alcoholic steatohepatitis

    Science.gov (United States)

    Pak, Wing; Takayama, Fusako; Mine, Manaka; Nakamoto, Kazuo; Kodo, Yasumasa; Mankura, Mitsumasa; Egashira, Toru; Kawasaki, Hiromu; Mori, Akitane

    2012-01-01

    The pathogenesis of nonalcoholic steatohepatitis (NASH) remains unclear, but accumulating data suggest oxidative stress and the relationship between inflammation and immunity plays a crucial role. The aim of this study is to investigate the spirulina, which is a blue-green algae rich in proteins and other nutritional elements, and its component-phycocyanin effect on a rat model of NASH. NASH model rats were established by feeding male Wistar rats with choline-deficient high-fat diet (CDHF) and intermittent hypoxemia by sodium nitrite challenge after 5 weeks of CDHF. After experimental period of 10 weeks, blood and liver were collected to determine oxidative stress injuries and efficacies of spirulina or phycocyanin on NASH model rats. In the NASH model rats, increase in plasma liver enzymes and liver fibrosis, increases in productions of reactive oxygen species from liver mitochondria and from leukocytes, the activation of nuclear factor-kappa B, and the change in the lymphocyte surface antigen ratio (CD4+/CD8+) were observed. The spirulina and phycocyanin administration significantly abated these changes. The spirulina or phycocyanin administration to model rats of NASH might lessen the inflammatory response through anti-oxidative and anti-inflammatory mechanisms, breaking the crosstalk between oxidative stress and inflammation, and effectively inhibit NASH progression. PMID:23170052

  1. Proteomic analysis of serum in patients with non-alcoholic steatohepatitis using matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

    Science.gov (United States)

    Ulukaya, Engin; Yilmaz, Yusuf; Moshkovskii, Sergei; Karpova, Maria; Pyatnitskiy, Mikhail; Atug, Ozlen; Dolar, Enver

    2009-01-01

    We sought to investigate whether serum proteomic pattern analysis obtained using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI TOF-MS) may help to diagnose non-alcoholic steatohepatitis (NASH) in the setting of non-alcoholic fatty liver disease (NAFLD). We enrolled 80 patients with biopsy-proven NAFLD and 19 healthy comparison subjects. Patients with NAFLD were classified according to their liver histology as having definite NASH (n = 48), borderline NASH (n = 22) or simple steatosis (n = 10). Liver ultrasound scanning was performed to assess the degree of steatosis. Mass spectra of serum samples were obtained using a Ultraflex II mass spectrometer. The highest accuracy for NASH diagnostics was reached using 15 peaks. Corresponding sensitivity and specificity values were 73.95% +/- 3.38% and 88.71% +/- 1.39%, respectively. However, mass spectra did not allow us to distinguish NASH from simple steatosis. We conclude that proteomic analyses of serum samples from NAFLD patients by MALDI TOF-MS do not seem to have a major clinical value for diagnosing NASH. However, the identification of 15 peaks in our study may help to further elucidate the pathophysiology of NASH and merits further investigation.

  2. Vitamin B5 and N-Acetylcysteine in Nonalcoholic Steatohepatitis: A Preclinical Study in a Dietary Mouse Model.

    Science.gov (United States)

    Machado, Mariana Verdelho; Kruger, Leandi; Jewell, Mark L; Michelotti, Gregory Alexander; Pereira, Thiago de Almeida; Xie, Guanhua; Moylan, Cynthia A; Diehl, Anna Mae

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the number one cause of chronic liver disease and second indication for liver transplantation in the Western world. Effective therapy is still not available. Previously we showed a critical role for caspase-2 in the pathogenesis of nonalcoholic steatohepatitis (NASH), the potentially progressive form of NAFLD. An imbalance between free coenzyme A (CoA) and acyl-CoA ratio is known to induce caspase-2 activation. We aimed to evaluate CoA metabolism and the effects of supplementation with CoA precursors, pantothenate and cysteine, in mouse models of NASH. CoA metabolism was evaluated in methionine-choline deficient (MCD) and Western diet mouse models of NASH. MCD diet-fed mice were treated with pantothenate and N-acetylcysteine or placebo to determine effects on NASH. Liver free CoA content was reduced, pantothenate kinase (PANK), the rate-limiting enzyme in the CoA biosynthesis pathway, was down-regulated, and CoA degrading enzymes were increased in mice with NASH. Decreased hepatic free CoA content was associated with increased caspase-2 activity and correlated with worse liver cell apoptosis, inflammation, and fibrosis. Treatment with pantothenate and N-acetylcysteine did not inhibit caspase-2 activation, improve NASH, normalize PANK expression, or restore free CoA levels in MCD diet-fed mice. In mice with NASH, hepatic CoA metabolism is impaired, leading to decreased free CoA content, activation of caspase-2, and increased liver cell apoptosis. Dietary supplementation with CoA precursors did not restore CoA levels or improve NASH, suggesting that alternative approaches are necessary to normalize free CoA during NASH.

  3. Liver microRNA-21 is overexpressed in non-alcoholic steatohepatitis and contributes to the disease in experimental models by inhibiting PPARα expression

    Science.gov (United States)

    Loyer, Xavier; Paradis, Valérie; Hénique, Carole; Vion, Anne-Clémence; Colnot, Nathalie; Guerin, Coralie L; Devue, Cécile; On, Sissi; Scetbun, Jérémy; Romain, Mélissa; Paul, Jean-Louis; Rothenberg, Marc E; Marcellin, Patrick; Durand, François; Bedossa, Pierre; Prip-Buus, Carina; Baugé, Eric; Staels, Bart; Boulanger, Chantal M; Tedgui, Alain; Rautou, Pierre-Emmanuel

    2016-01-01

    Objective Previous studies suggested that microRNA-21 may be upregulated in the liver in non-alcoholic steatohepatitis (NASH), but its role in the development of this disease remains unknown. This study aimed to determine the role of microRNA-21 in NASH. Design We inhibited or suppressed microRNA-21 in different mouse models of NASH: (a) low-density lipoprotein receptor-deficient (Ldlr−/−) mice fed a high-fat diet and treated with antagomir-21 or antagomir control; (b) microRNA-21-deficient and wild-type mice fed a methionine-choline-deficient (MCD) diet; (c) peroxisome proliferation-activator receptor α (PPARα)-deficient mice fed an MCD diet and treated with antagomir-21 or antagomir control. We assessed features of NASH and determined liver microRNA-21 levels and cell localisation. MicroRNA-21 levels were also quantified in the liver of patients with NASH, bland steatosis or normal liver and localisation was determined. Results Inhibiting or suppressing liver microRNA-21 expression reduced liver cell injury, inflammation and fibrogenesis without affecting liver lipid accumulation in Ldlr−/− fed a high-fat diet and in wild-type mice fed an MCD diet. Liver microRNA-21 was overexpressed, primarily in biliary and inflammatory cells, in mouse models as well as in patients with NASH, but not in patients with bland steatosis. PPARα, a known microRNA-21 target, implicated in NASH, was decreased in the liver of mice with NASH and restored following microRNA-21 inhibition or suppression. The effect of antagomir-21 was lost in PPARα-deficient mice. Conclusions MicroRNA-21 inhibition or suppression decreases liver injury, inflammation and fibrosis, by restoring PPARα expression. Antagomir-21 might be a future therapeutic strategy for NASH. PMID:26338827

  4. Screening for nonalcoholic steatohepatitis by using cytokeratin 18 and transient elastography in HIV mono-infection.

    Science.gov (United States)

    Benmassaoud, Amine; Ghali, Peter; Cox, Joseph; Wong, Philip; Szabo, Jason; Deschenes, Marc; Osikowicz, Maria; Lebouche, Bertrand; Klein, Marina B; Sebastiani, Giada

    2018-01-01

    HIV-infected individuals are at high risk of developing nonalcoholic steatohepatitis (NASH), a leading cause of end-stage liver disease in Western countries. Nonetheless, due to the invasiveness of liver biopsy, NASH remains poorly understood in HIV mono-infection. We aimed to characterize the prevalence and predictors of NASH in unselected HIV mono-infected patients by means of non-invasive diagnostic tools. HIV-infected adults without significant alcohol intake or co-infection with hepatitis B or C underwent a routine screening program employing transient elastography (TE) with controlled attenuation parameter (CAP) and the serum biomarker cytokeratin-18 (CK-18). NASH was diagnosed non-invasively as the coexistence of fatty liver (CAP ≥248 dB/m) and CK-18 >246 U/L. Identified cases of NASH were offered a diagnostic liver biopsy. Predictors of NASH were determined by multivariate logistic regression analysis. 202 consecutive HIV mono-infected patients were included. NASH was non-invasively diagnosed in 23 cases (11.4%). Among them, 17 underwent a liver biopsy, and histology confirmed NASH in all cases. The prevalence of NASH was higher in patients with hypertriglyceridemia (17.1%), insulin resistance defined by homeostasis model for assessment of insulin resistance (HOMA-IR) (25%), those with detectable HIV viral load (42.9%) and those with elevated ALT (53.6%). After adjustment, higher HOMA-IR (adjusted odds ratio [aOR] = 1.20, 95% CI 1.01-1.43; p = 0.03) and ALT (aOR = 2.39, 95% CI 1.50-3.79; pmono-infected individuals, particularly in the presence of insulin resistance and elevated ALT.

  5. Neonatal monosodium glutamate treatment causes obesity, diabetes, and macrovesicular steatohepatitis with liver nodules in DIAR mice.

    Science.gov (United States)

    Tsuneyama, Koichi; Nishida, Takeshi; Baba, Hayato; Taira, Shu; Fujimoto, Makoto; Nomoto, Kazuhiro; Hayashi, Shinichi; Miwa, Shigeharu; Nakajima, Takahiko; Sutoh, Mitsuko; Oda, Emu; Hokao, Ryoji; Imura, Johji

    2014-09-01

    Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome (MS). Monosodium glutamate (MSG)-treated ICR mice is a useful model of MS and NASH, but it shows the different patterns of steatosis from human NASH. Because inbred aged DIAR (ddY, Institute for Animal Reproduction) mice spontaneously show the similar pattern of steatosis as NASH, we analyzed their liver pathology after administering MSG. MSG-treated DIAR mice (DIAR-MSG) and untreated DIAR mice (DIAR-controls) were sacrificed and assessed histopathologically at 29, 32, 40, 48, and 54 weeks of age. The NASH activity score, body mass index, blood glucose level, and oral glucose tolerance test were also assessed. The body mass index and blood glucose levels of DIAR-MSG were significantly higher than controls. The oral glucose tolerance test revealed a type 2 diabetes pattern in DIAR-MSG. The livers of DIAR-MSG mice showed macrovesicular steatosis, lobular inflammation with neutrophils, and ballooning degeneration after 29 weeks. At 54 weeks, mild fibrosis was observed in 5/6 DIAR-MSG and 2/5 DIAR-control mice. In imaging mass spectrometry analysis, cholesterol as well as triglyceride accumulated in the liver of DIAR-MSG mice. Atypical liver nodules were also observed after 32 weeks in DIAR-MSG, some with cellular and structural atypia mimicking human hepatocellular carcinoma. The NASH activity score of DIAR-MSG after 29 weeks was higher than that of control mice, suggesting the development of NASH. DIAR-MSG had NASH-like liver pathology and liver nodules typically associated with MS symptoms. DIAR-MSG provides a valuable animal model to analyze NASH pathogenesis and carcinogenesis. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  6. Desenvolvimento de um modelo experimental de esteatohepatite induzida pelo antineoplÃsico irinotecano

    OpenAIRE

    Marcelo Leite Vieira Costa

    2012-01-01

    IntroduÃÃo: A esteatohepatite nÃo alcoÃlica (NASH) à um evento adverso do quimioterÃpico irinotecano extremamente relevante, pois associa-se a uma maior mortalidade apÃs ressecÃÃes hepÃticas. Atà o momento nÃo hà na literatura um modelo experimental bem estabelecido de NASH induzido por irinotecano. Objetivo: Estabelecer um modelo experimental de NASH induzida pelo irinotecano em camundongos que simule os aspectos histopatolÃgicos encontrados na clÃnica. Estudar os mecanismos e mediadores env...

  7. On signaling games with quantum chance move

    International Nuclear Information System (INIS)

    Frackiewicz, Piotr

    2015-01-01

    We give formal conditions for a perfect Bayesian-type equilibrium in a quantum signaling game. We show that the conditions imply a classical perfect Bayesian equilibrium if the quantum game coincides with the classical one. Next, we extend the signaling game to include a quantum chance move. We prove that the classical relation between Nash equilibria and perfect Bayesian equilibria is preserved in that case—every perfect Bayesian-type equilibrium implies a Nash equilibrium, but the converse is not true. Lastly, we give a condition for equivalence between Nash equilibria and perfect Bayesian-type equilibria. (paper)

  8. Role of peroxisome proliferators-activated receptors in the pathogenesis and treatment of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Kallwitz, Eric R; McLachlan, Alan; Cotler, Scott J

    2008-01-07

    Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can result in nonalcoholic steatohepatitis (NASH) and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of literature implicates the peroxisome proliferators-activated receptors (PPARs) in the pathogenesis and treatment of NAFLD. These nuclear hormone receptors impact on hepatic triglyceride accumulation and insulin resistance. The aim of this review is to describe the data linking PPAR alpha and PPAR gamma to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH.

  9. Docosahexaenoic acid blocks progression of western diet-induced nonalcoholic steatohepatitis in obese Ldlr-/- mice.

    Science.gov (United States)

    Lytle, Kelli A; Wong, Carmen P; Jump, Donald B

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major public health concern in western societies. Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, is characterized by hepatic steatosis, inflammation, oxidative stress and fibrosis. NASH is a risk factor for cirrhosis and hepatocellular carcinoma. NASH is predicted to be the leading cause of liver transplants by 2020. Despite this growing public health concern, there remain no Food and Drug Administration (FDA) approved NASH treatments. Using Ldlr -/- mice as a preclinical model of western diet (WD)-induced NASH, we previously established that dietary supplementation with docosahexaenoic acid (DHA, 22:6,ω3) attenuated WD-induced NASH in a prevention study. Herein, we evaluated the capacity of DHA supplementation of the WD and a low fat diet to fully reverse NASH in mice with pre-existing disease. Ldlr -/- mice fed the WD for 22 wks developed metabolic syndrome (MetS) and a severe NASH phenotype, including obesity, dyslipidemia, hyperglycemia, hepatic steatosis, inflammation, fibrosis and low hepatic polyunsaturated fatty acid (PUFA) content. These mice were randomized to 5 groups: a baseline group (WDB, sacrificed at 22 wks) and 4 treatments: 1) WD + olive oil (WDO); 2) WD + DHA (WDD); 3) returned to chow + olive oil (WDChO); or 4) returned to chow + DHA (WDChD). The four treatment groups were maintained on their respective diets for 8 wks. An additional group was maintained on standard laboratory chow (Reference Diet, RD) for the 30-wk duration of the study. When compared to the WDB group, the WDO group displayed increased hepatic expression of genes linked to inflammation (Opn, Il1rn, Gdf15), hepatic fibrosis (collagen staining, Col1A1, Thbs2, Lox) reflecting disease progression. Mice in the WDD group, in contrast, had increased hepatic C20-22 ω3 PUFA and no evidence of NASH progression. MetS and NASH markers in the WDChO or WDChD groups were significantly attenuated and marginally different from

  10. Remarks on Hierarchic Control for a Linearized Micropolar Fluids System in Moving Domains

    Energy Technology Data Exchange (ETDEWEB)

    Jesus, Isaías Pereira de, E-mail: isaias@ufpi.edu.br [Universidade Federal do Piauí, Dpto. Matemática (Brazil)

    2015-12-15

    We study a Stackelberg strategy subject to the evolutionary linearized micropolar fluids equations in domains with moving boundaries, considering a Nash multi-objective equilibrium (non necessarily cooperative) for the “follower players” (as is called in the economy field) and an optimal problem for the leader player with approximate controllability objective. We will obtain the following main results: the existence and uniqueness of Nash equilibrium and its characterization, the approximate controllability of the linearized micropolar system with respect to the leader control and the existence and uniqueness of the Stackelberg–Nash problem, where the optimality system for the leader is given.

  11. Atomic routing in a deterministic queuing model

    Directory of Open Access Journals (Sweden)

    T.L. Werth

    2014-03-01

    We also consider the makespan objective (arrival time of the last user and show that optimal solutions and Nash equilibria in these games, where every user selfishly tries to minimize her travel time, can be found efficiently.

  12. Radiology examination as a diagnostic aid in presentations with ...

    African Journals Online (AJOL)

    Radiology examination as a diagnostic aid in presentations with wide differential diagnoses: Case report of new Hodgkin's lymphoma on a background of poorly controlled HIV. Rachel Hubbard, Jalpa Kotecha, Thomas Nash, Yu Jin Lee, Nasir Khan, Farhat Kazmi ...

  13. Plaadid / Margit Tõnson

    Index Scriptorium Estoniae

    Tõnson, Margit, 1978-

    2005-01-01

    Uute heliplaatide Gorillaz "Demon Days", Nine Inch Nails "With Teeth", Weezer "Make Believe", CDOASS "Extra Fingers", System Of A Down "Mezmerize", Crosby Stills & Nash "Createst Hits 2005", "The Others"

  14. Weight Management

    Science.gov (United States)

    ... Health Information Weight Management English English Español Weight Management Obesity is a chronic condition that affects more ... Liver (NASH) Heart Disease & Stroke Sleep Apnea Weight Management Topics About Food Portions Bariatric Surgery for Severe ...

  15. Plaadid / Andri Maimets

    Index Scriptorium Estoniae

    Maimets, Andri, 1979-

    2005-01-01

    Uutest heliplaatidest Jennifer Lopez "Rebirth", Crosby Stills & Nash "Greatest Hits", "Verve/Remixe", Thirteen Senses "The Invitation", "Amos Lee", Mari Boine "Gula Gula", dZihan & Kamien "Fakes", Hot Hot Heat "Elevator"

  16. Complimentary Advanced Fusion Exploration

    National Research Council Canada - National Science Library

    Alford, Mark G; Jones, Eric C; Bubalo, Adnan; Neumann, Melissa; Greer, Michael J

    2005-01-01

    .... The focus areas were in the following regimes: multi-tensor homographic computer vision image fusion, out-of-sequence measurement and track data handling, Nash bargaining approaches to sensor management, pursuit-evasion game theoretic modeling...

  17. Bisphenol A levels in multimedia samples

    Data.gov (United States)

    U.S. Environmental Protection Agency — Levels of bisphenol A in multimedia samples. This dataset is associated with the following publication: Morgan, M., M. Nash, D. Boyd Barr, J. Starr, M. Clifton, and...

  18. Small intestinal bacterial overgrowth in nonalcoholic steatohepatitis: association with toll-like receptor 4 expression and plasma levels of interleukin 8.

    LENUS (Irish Health Repository)

    Shanab, Ahmed Abu

    2011-05-01

    Experimental and clinical studies suggest an association between small intestinal bacterial overgrowth (SIBO) and nonalcoholic steatohepatitis (NASH). Liver injury and fibrosis could be related to exposure to bacterial products of intestinal origin and, most notably, endotoxin, including lipopolysaccharide (LPS).

  19. Effect of resveratrol on experimental non-alcoholic fatty liver disease depends on severity of pathology and timing of treatment

    DEFF Research Database (Denmark)

    Heebøll, Sara; El-Houri, Rime Bahij; Hellberg, Ylva Erika Kristina

    2016-01-01

    BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease with few therapeutic options. RSV prevents the development of steatosis in a number of experimental fatty liver (NAFL) models but the preventive or therapeutic effects on experimental NASH...... model. The preventive and therapeutic potential of RSV was tested by adding RSV to the HF and HFC diet from study start or after one week of the diets. Animals were sacrificed after 8 weeks with appropriate controls. Blood and liver were harvested for analysis, including measurement of RSV metabolites.......01), while there was no effect on biochemical, histopathological, or transcriptional NASH changes. Further, RSV had no therapeutic effect on established NASH. We found RSV metabolites but no parent RSV in serum or liver tissue, confirming low bioavailability. CONCLUSIONS: These experimental findings suggest...

  20. The Open-Loop Linear Quadratic Differential Game Revisited

    NARCIS (Netherlands)

    Engwerda, J.C.

    2005-01-01

    In this note we reconsider the indefinite open-loop Nash linear quadratic differential game with an infinite planning horizon.In particular we derive both necessary and sufficient conditions under which the game will have a unique equilibrium.

  1. Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis

    NARCIS (Netherlands)

    Wouters, Kristiaan; van Gorp, Patrick J.; Bieghs, Veerle; Gijbels, Marion J.; Duimel, Hans; Lütjohann, Dieter; Kerksiek, Anja; van Kruchten, Roger; Maeda, Nobuyo; Staels, Bart; van Bilsen, Marc; Shiri-Sverdlov, Ronit; Hofker, Marten H.

    2008-01-01

    Nonalcoholic steatohepatitis (NASH) involves liver lipid accumulation (steatosis) combined with hepatic inflammation. The transition towards hepatic inflammation represents a key step in pathogenesis, because it will set the stage for further liver damage, culminating in hepatic fibrosis, cirrhosis,

  2. 75 FR 31347 - Proposed Flood Elevation Determinations

    Science.gov (United States)

    2010-06-03

    ... Seward, Kenai Resurrection Bay. Peninsula Borough. Approximately 1.3 mile None +183 upstream of Nash Road..., MO 63670. McHenry County, North Dakota, and Incorporated Areas Mouse River Approximately 1.25 mile...

  3. Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis

    NARCIS (Netherlands)

    Wouters, Kristiaan; van Gorp, Patrick J.; Bieghs, Veerle; Gijbels, Marion J.; Duimel, Hans; Luetjohann, Dieter; Kerksiek, Anja; van Kruchten, Roger; Maeda, Nobuyo; Staels, Bart; van Bilsen, Marc; Shiri-Sverdlov, Ronit; Hofker, Marten H.

    Nonalcoholic steatohepatitis (NASH) involves liver lipid accumulation (steatosis) combined with hepatic inflammation. The transition towards hepatic inflammation represents a key step in pathogenesis, because it will set the stage for further liver damage, culminating in hepatic fibrosis, cirrhosis,

  4. Immunological Mechanisms in the Pathophysiology of Non-Alcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Sven Francque

    2013-10-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is characterized by the presence of steatosis, inflammation and hepatocyte injury and constitutes hepatic manifestation of the metabolic syndrome. The pathogenesis of NASH is complex and implicates cross-talk between different metabolically active sites, such as liver and adipose tissue. Obesity is considered a chronic low-grade inflammatory state and the liver has been recognized as being an “immunological organ”. The complex role of the immune system in the pathogenesis of NASH is currently raising great interest, also in view of the possible therapeutic potential of immunotherapy in NASH. This review focuses on the disturbances of the cells constituting the innate and adaptive immune system in the liver and in adipose tissue.

  5. Characterizing Solution Concepts in Terms of Common Knowledge of Rationality

    OpenAIRE

    Halpern, Joseph Y.; Moses, Yoram

    2016-01-01

    Characterizations of Nash equilibrium, correlated equilibrium, and rationalizability in terms of common knowledge of rationality are well known. Analogous characterizations of sequential equilibrium, (trembling hand) perfect equilibrium, and quasi-perfect equilibrium using results of Halpern [2009].

  6. Aed, imelise rahu paik / Merilen Mentaal

    Index Scriptorium Estoniae

    Mentaal, Merilen, 1972-

    2008-01-01

    Chelsea Flower Show 2008 võistelnud aedadest. Kujundajateks Philip Nash, Andy Sturgeon, Buono Gazerwitz, Trevor Tooth, Philip Nixon, Thomas Hoblyn, Robert Myers, Tom Stuart-Smith, Yvonne Innes ja Olivia Harrison. 11 värv. ill

  7. Differences in innate immune signaling between alcoholic and non-alcoholic steatohepatitis.

    Science.gov (United States)

    Petrasek, Jan; Csak, Timea; Ganz, Michal; Szabo, Gyongyi

    2013-08-01

    The similar histopathological characteristics of alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH), and the crucial role of the innate immune response in both conditions may lead to the assumption that ASH and NASH represent the same pathophysiological entities caused by different risk factors. In this review paper, we elaborate on the pathophysiological differences between these two entities and highlight the disease-specific involvement of signaling molecules downstream of the Toll-like receptor 4, and the differential mechanism by which the inflammasome contributes to ASH versus NASH. Our findings emphasize that ASH and NASH have disease-specific mechanisms and therefore represent distinct biological entities. Further studies are needed to dissect the emerging differences in pathogenesis of these two conditions. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  8. Les auteurs du numéro

    Directory of Open Access Journals (Sweden)

    2010-04-01

    Full Text Available Tatjana Barazon est docteur en philosophie et a soutenu sa thèse « Création et participation : le monde au seuil de l’être » en 2003 à Paris IV- Sorbonne. Elle a traduit La vie de Jésus de G.W.F. Hegel (Vrin, 2009 en collaboration avec Ari Simhon, avec qui elle travaille, ainsi qu’avec Jean-Marie Lardic, sur une autre traduction de Hegel « Les leçons de la Logique (1817 ». Elle s’intéresse à la question de la réception de la pensée de Bergson dans la phénoménologie et les neurosciences (htt...

  9. Barnumi tsirkus ja kultuurkapitali vene preemia / P. I. Filimonov

    Index Scriptorium Estoniae

    Filimonov, P. I., pseud., 1975-

    2009-01-01

    Artikkel vaidlustab Eesti Kultuurkapitali venekeelse autori kirjandusauhinna žürii selleaastase valiku: Tatjana Kašneva (Zolotova) "Земная коротка наша память..." (kirj. Aleksandra) ja Josef Katsi "Старый Таллинн : четыре времени города" (КПД). T. Kašneva memuaaride esitrükk ilmus 1993. a., J. Katsi raamat aga ei mahu esseežanri alla

  10. Divadlo on teater, Nitra on linn / Tiina Talts

    Index Scriptorium Estoniae

    Talts, Tiina

    2006-01-01

    Rahvusvahelisest teatrifestivalist "Divadelna Nitra" ("Teatraalne Nitra") Slovakkias 22. - 27. septembrini. Lühidalt lavastustest Georg Brüchner "Woyzeck" (Wojciech Boguslawski teater, Poola, lavastaja Maja Kleczewska); Thomas Bernhard "Before retirement" (Slovakkia teater Astorka-Korzo'90, lavastaja Juraj Nvota); Tatjana Tolstaja "Sonja" (Läti Riia Uus Teater, lavastaja Alvis Hermanis); Michel Houllebecq "Platform" (Belgia NTGent, lavastaja Johan Simons); William Shakespeare "Richard III" (Tšehhi Rahvusteater, lavastaja Michal Docekal); Neil LaBute "The shape of things" (Slovakkia Andrej Bagari Teater, lavastajad Roman Olekshak ja Maja Hrieshik); Rainald Goetz-Martin Heidegger "The consolation of the country path" (Tšehhi kodanike ühendus Mezery, lavastaja Miroslav Bambushek); Mark Ravenhill "Product" (Inglismaa Paines Plough, lavastaja Ravenhill); Anton Tshehhov "Ivanov" (Slovakkia Kammerteater, lavastaja Roman Polak)

  11. Vanadust käsitlev projekt Tallinna Kunstihoones

    Index Scriptorium Estoniae

    2005-01-01

    Tallinna Kunstihoones Reet Varblase kureeritud näitus "Homo grandis natu", mis käsitleb vanaduse ja vananemise tähendust ja rolli praeguses ühiskonnas. Osalejaid: Boaz Tal, Eveli Varik, Ly Lestberg, Mare Mikof, Aili Vahtrapuu, Jaan Paavle, Terje Ojaver, Marge Monko, Terje Tunis, Tatjana Antoshina, Valeri Vinogradov, Peeter Laurits, Toomas Kalve, Jüri Ojaver. 15. IV toimuva seminari "Eesti vananemispoliitika täna ja homme" ning 21., 28. IV, 5., 12. V toimuva loengusarja kava. 16. IV peab Boaz Tal loengu arhetüüpidest ja mälust, tutvustab oma töid. 21. IV avatakse Katarzyna Kozyra videoinstallatsioon "Naiste saun". 2. V performance'i-festival "Diverse universe", loetletud osalejaid

  12. New clinical score to diagnose nonalcoholic steatohepatitis in obese patients

    Directory of Open Access Journals (Sweden)

    Pulzi Fernanda BU

    2011-02-01

    Full Text Available Abstract Background Nonalcoholic fatty liver disease (NAFLD is the most frequent disease associated with abnormal liver tests that is characterized by a wide spectrum of liver damage, ranging from simple macro vesicular steatosis to steatohepatitis (NASH, cirrhosis or liver carcinoma. Liver biopsy is the most precise test to differentiate NASH from other stages of NAFLD, but it is an invasive and expensive method. This study aimed to create a clinical laboratory score capable of identify individual with NASH in severely obese patients submitted to bariatric surgery. Methods The medical records from 66 patients submitted to gastroplasty were reviewed. Their chemistry profile, abdominal ultrasound (US and liver biopsy done during the surgical procedure were analyzed. Patients were classified into 2 groups according to liver biopsy: Non-NASH group - those patients without NAFLD or with grade I, II or III steatosis; and NASH group - those with steatohepatitis or fibrosis. The t-test was used to compare each variable with normal distribution between NASH and Non-NASH groups. When comparing proportions of categorical variables, we used chi-square or z-test, where appropriate. A p-value Results 83% of patients with obesity grades II or III showed NAFLD, and the majority was asymptomatic. Total Cholesterol (TC≥200 mg/dL, alanine aminotransferase (ALT ≥30, AST/ALT ratio (AAR≤ 1, gammaglutaril-transferase (γGT≥30 U/L and abdominal US, compatible with steatosis, showed association with NASH group. We proposed 2 scores: Complete score (TC, ALT, AAR, γGT and US and the simplified score, where US was not included. The combination of biochemical and imaging results improved accuracy to 84.4% the recognition of NASH (sensitivity 70%, specificity 88.6%, NPV 91.2%, PPV 63. 6%. Conclusion Alterations in TC, ALT, AAR, γGT and US are related to the most risk for NASH. The combination of biochemical and imaging results improved accuracy to 84.4% the

  13. Empagliflozin (an SGLT2 inhibitor), alone or in combination with linagliptin (a DPP-4 inhibitor), prevents steatohepatitis in a novel mouse model of non-alcoholic steatohepatitis and diabetes

    OpenAIRE

    Jojima, Teruo; Tomotsune, Takanori; Iijima, Toshie; Akimoto, Kazumi; Suzuki, Kunihiro; Aso, Yoshimasa

    2016-01-01

    Background Sodium-glucose co-transporter-2 (SGLT2) inhibitors are new oral antidiabetic drugs that reduce hyperglycemia by promoting urinary glucose excretion. Glycosuria produced by SGLT2 inhibitors is associated with weight loss, mainly due to reduced fat volume. We investigated the effects of empagliflozin (selective SGLT2 inhibitor) and linagliptin (DPP-4 inhibitor) on steatohepatitis and fibrosis in a mouse model of non-alcoholic steatohepatitis (NASH) with diabetes. Methods A novel NASH...

  14. Strategic Design of Mobile Agents

    OpenAIRE

    Vulkan, Nir

    2002-01-01

    Much of the economic value of electronic commerce comes from the automation of interactions between businesses and individuals. Game theory is a useful set of tools that can be used by designers of electronic-commerce applications in analyzing and engineering of automated agents and communication protocols. The central theoretical concept used in game theory is the Nash equilibrium. In this article, I show how the outcomes supported by a Nash equilibrium can positively be enlarged using autom...

  15. Role of gut microbiota and oxidative stress in the progression of non-alcoholic fatty liver disease to hepatocarcinoma: Current and innovative therapeutic approaches.

    Science.gov (United States)

    Borrelli, Antonella; Bonelli, Patrizia; Tuccillo, Franca Maria; Goldfine, Ira D; Evans, Joseph L; Buonaguro, Franco Maria; Mancini, Aldo

    2018-05-01

    Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in industrialized countries. NAFLD progresses through the inflammatory phase of non-alcoholic steatohepatitis (NASH) to fibrosis and cirrhosis, with some cases developing liver failure or hepatocellular carcinoma (HCC). Liver biopsy remains the gold standard approach to a definitive diagnosis of NAFLD and the distinction between simple steatosis and NASH. The pathogenesis of NASH is still not clear. Several theories have been proposed ranging from the "Two Hit Theory" to the "Multiple Hit Theory". However, the general consensus is that the gut microbiota, oxidative stress, and mitochondrial damage play key roles in the pathogenesis of NASH. The interaction between the gut epithelia and some commensal bacteria induces the rapid generation of reactive oxygen species (ROS). The main goal of any therapy addressing NASH is to reverse or prevent progression to liver fibrosis/cirrhosis. This problem represents the first "Achilles' heel" of the new molecules being evaluated in most ongoing clinical trials. The second is the inability of these molecules to reach the mitochondria, the primary sites of energy production and ROS generation. Recently, a variety of non-pharmacological and pharmacological treatment approaches for NASH have been evaluated including vitamin E, the thiazolidinediones, and novel molecules related to NASH pathogenesis (including obeticholic acid and elafibranor). Recently, a new isoform of human manganese superoxide dismutase (MnSOD) was isolated and obtained in a synthetic recombinant form designated rMnSOD. This protein has been shown to be a powerful antioxidant capable of mediating ROS dismutation, penetrating biological barriers via its uncleaved leader peptide, and reducing portal hypertension and fibrosis in rats affected by liver cirrhosis. Based on these distinctive characteristics, it can be hypothesized that this novel recombinant protein (r

  16. Role of gut microbiota and oxidative stress in the progression of non-alcoholic fatty liver disease to hepatocarcinoma: Current and innovative therapeutic approaches

    Directory of Open Access Journals (Sweden)

    Antonella Borrelli

    2018-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD represents the most common chronic liver disease in industrialized countries. NAFLD progresses through the inflammatory phase of non-alcoholic steatohepatitis (NASH to fibrosis and cirrhosis, with some cases developing liver failure or hepatocellular carcinoma (HCC. Liver biopsy remains the gold standard approach to a definitive diagnosis of NAFLD and the distinction between simple steatosis and NASH. The pathogenesis of NASH is still not clear. Several theories have been proposed ranging from the “Two Hit Theory” to the “Multiple Hit Theory”. However, the general consensus is that the gut microbiota, oxidative stress, and mitochondrial damage play key roles in the pathogenesis of NASH. The interaction between the gut epithelia and some commensal bacteria induces the rapid generation of reactive oxygen species (ROS. The main goal of any therapy addressing NASH is to reverse or prevent progression to liver fibrosis/cirrhosis. This problem represents the first “Achilles’ heel” of the new molecules being evaluated in most ongoing clinical trials. The second is the inability of these molecules to reach the mitochondria, the primary sites of energy production and ROS generation. Recently, a variety of non-pharmacological and pharmacological treatment approaches for NASH have been evaluated including vitamin E, the thiazolidinediones, and novel molecules related to NASH pathogenesis (including obeticholic acid and elafibranor. Recently, a new isoform of human manganese superoxide dismutase (MnSOD was isolated and obtained in a synthetic recombinant form designated rMnSOD. This protein has been shown to be a powerful antioxidant capable of mediating ROS dismutation, penetrating biological barriers via its uncleaved leader peptide, and reducing portal hypertension and fibrosis in rats affected by liver cirrhosis. Based on these distinctive characteristics, it can be hypothesized that this novel

  17. Insulin resistance and neurodegeneration: Roles of obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis

    OpenAIRE

    de la Monte, Suzanne M; Longato, Lisa; Tong, Ming; Wands, Jack R

    2009-01-01

    Recent studies have linked obesity, type 2 diabetes mellitus (T2DM) or non-alcoholic steatohepatitis (NASH) to insulin resistance in the brain, cognitive impairment and neurodegeneration. Insulin resistance compromises cell survival, metabolism and neuronal plasticity, and increases oxidative stress, cytokine activation and apoptosis. T2DM/NASH has been demonstrated to be associated with increased ceramide generation, suggesting a mechanistic link between peripheral insulin resistance and neu...

  18. Gene Expression of Tumor Necrosis Factor α and TNF-α Receptors (p55 and p75) in Nonalcoholic Steatohepatitis Patients

    International Nuclear Information System (INIS)

    Soliman, S.ET.; Abo-Madyan, A.A.

    2010-01-01

    The main objective of this study was to analyze the pathogenic role of the tumor necrosis factor (TNF-) system in the development of nonalcoholic steatohepatitis (NASH). Fifty obese patients were studied. We investigated: 1) the expression of mRNA of TNF- and their p55 and p75 receptors by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in hepatic and adipose tissues; and 2) the relationship between TNF-, p55, and p75 and the severity of NASH. Obese patients without NASH were the control group. A remarkable increase in the expression of mRNA of TNF- was found in patients with NASH in hepatic tissue (0.65 ± 0.54) and in peripheral fat (0.43 ± 0.45); in the control samples, the mRNA expression was 0.30 ± 0.32, P < .006, and 0.28 ± 0.22, P < .016, respectively. Furthermore, we found significant increase in the mRNA levels of p55 receptor (2.94 ± 1.71 vs. 1.46 ± 1.27; P<.04); however, the mRNA expression of the p75 receptor was similar in both patients. Those patients with NASH with significant fibrosis presented an increase in the expression of mRNA TNF- in comparison with those with slight or nonexistent fibrosis. The levels of mRNA-p55 are increased in the liver tissue of NASH patients. This over expression is more elevated in patients with more advanced NASH. These findings suggest that the TNF- system may be involved in the pathogenesis of NASH.

  19. Sequential bargaining in a market with one seller and two different buyers

    DEFF Research Database (Denmark)

    Tranæs, Torben; Hendon, Ebbe

    1991-01-01

    A matching and bargaining model in a market with one seller and two buyers, differing only in their reservation price, is analyzed. No subgame perfect equilibrium exists for stationary strategies. We demonstrate the existence of inefficient equilibria in which the low buyer receives the good...... with large probability, even as friction becomes negligible. We investigate the relationship between the use of Nash and sequential bargaining. Nash bargaining seems applicable only when the sequential approach yields a unique stationary strategy subgame perfect equilibrium...

  20. Sequential bargaining in a market with one seller and two different buyers

    DEFF Research Database (Denmark)

    Hendon, Ebbe; Tranæs, Torben

    1991-01-01

    A matching and bargaining model in a market with one seller and two buyers, differing only in their reservation price, is analyzed. No subgame perfect equilibrium exists for stationary strategies. We demonstrate the existence of inefficient equilibria in which the low buyer receives the good...... with large probability, even as friction becomes negligible. We investigate the relationship between the use of Nash and sequential bargaining. Nash bargaining seems applicable only when the sequential approach yields a unique stationary strategy subgame perfect equilibrium....

  1. Pro-Inflammatory Cytokines but Not Endotoxin-Related Parameters Associate with Disease Severity in Patients with NAFLD.

    Directory of Open Access Journals (Sweden)

    Johannie du Plessis

    Full Text Available Intestinal dysbiosis and elevated lipopolysaccharides (LPS levels have been implicated in the development of obesity, insulin resistance and non-alcoholic steatohepatitis (NASH. In order to determine if LPS levels are elevated in patients with NASH compared to patients with non-alcoholic fatty liver (NAFL and, if elevated LPS levels correlated with histological severity of non-alcoholic fatty liver disease (NAFLD we compared LPS, markers of LPS bioactivity and pro-inflammatory cytokines/chemokines in patients undergoing bariatric surgery. At the time of surgery a liver biopsy was taken allowing the stratification into well-delineated subgroups including: No NAFL/NAFL; NASH; NASH with fibrosis and NASH cirrhotics, using the NAFLD Activity Score (NAS. Anthropometric data and plasma were collected for assessment of LPS, lipopolysaccharide binding protein (LBP, soluble CD14 (sCD14, intestinal-type fatty acid binding protein (iFABP, Toll-like receptors 2 and 4 (TLR2, 4 and a panel of cytokines/chemokines. Similar analysis was performed on plasma from a cohort of healthy controls. Our data indicate elevated levels of LPS, LBP, sCD14, iFABP and TLR2,4 in obese patients compared to healthy controls, however, these parameters remained unaltered within patients with limited liver disease (NAFL compared to NASH/NASH with fibrosis subgroups. Hierarchic cluster analysis using endotoxin-related parameters failed to discriminate between lean controls, NAFLD. While similar cluster analysis implementing inflammation-related parameters clearly distinguished lean controls, NALFD subgroups and NASH cirrhotics. In addition, LPS levels was not associated with disease severity while TNFα, IL8, and CCL3 featured a clear correlation with transaminase levels and the histological severity of NALFD. In conclusion our data indicate a stronger correlation for circulating inflammatory- rather than endotoxin-related parameters in progression of NAFLD and highlights the need

  2. Fatty acid metabolism is altered in non-alcoholic steatohepatitis independent of obesity.

    Science.gov (United States)

    Walle, Paula; Takkunen, Markus; Männistö, Ville; Vaittinen, Maija; Lankinen, Maria; Kärjä, Vesa; Käkelä, Pirjo; Ågren, Jyrki; Tiainen, Mika; Schwab, Ursula; Kuusisto, Johanna; Laakso, Markku; Pihlajamäki, Jussi

    2016-05-01

    Non-alcoholic steatohepatitis (NASH) is associated with changes in fatty acid (FA) metabolism. However, specific changes in metabolism and hepatic mRNA expression related to NASH independent of simple steatosis, obesity and diet are unknown. Liver histology, serum and liver FA composition and estimated enzyme activities based on the FA ratios in cholesteryl esters and triglycerides were assessed in 92 obese participants of the Kuopio Obesity Surgery Study (KOBS) divided to those with normal liver, steatosis or NASH (30 men and 62 women, age 46.8±9.5years (mean±SD), BMI 44.2±6.2kg/m(2)). Plasma FA composition was also investigated in the Metabolic Syndrome in Men (METSIM) Study (n=769), in which serum alanine aminotransferase (ALT) was used as a marker of liver disease. Obese individuals with NASH had higher activity of estimated activities of delta-6 desaturase (D6D, pliver. Estimated activities of D5D, D6D and SCD1 correlated positively between liver and serum indicating that serum estimates reflected liver metabolism. Accordingly, NASH was associated with higher hepatic mRNA expression of corresponding genes FADS1, FADS2 and SCD. Finally, differences in FA metabolism that associated with NASH in obese individuals were also associated with high ALT in the METSIM Study. We demonstrated alterations in FA metabolism and endogenous desaturase activities that associate with NASH, independent of obesity and diet. This suggests that changes in endogenous FA metabolism are related to NASH and that they may contribute to the progression of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. The relationship between advanced oxidation protein products (AOPP) and biochemical and histopathological findings in patients with nonalcoholic steatohepatitis.

    Science.gov (United States)

    Ozenirler, Seren; Erkan, Gulbanu; Konca Degertekin, Ceyla; Ercin, Ugur; Cengiz, Mustafa; Bilgihan, Ayse; Yilmaz, Guldal; Akyol, Gulen

    2014-03-01

    To investigate the correlation between advanced oxidation protein products (AOPP) levels and biochemical and histopathological findings in patients with nonalcoholic steatohepatitis (NASH). Sixty biopsy-proven NASH patients and 60 individuals with ultrasonographically healthy liver (the control group) were included in the study. AOPP levels were determined in all the participants and liver histopathological examination based on liver biopsy was performed in NASH patients. The NASH activity score (NAS), hepatosteatosis, liver inflammation and fibrosis were evaluated. Serum AOPP level was significantly higher in the NASH group than that in the control group (461.8 ± 201.9 μmol/L vs 191.7 ± 152.5 μmol/L, P < 0.001). The receiver operating characteristic (ROC) curve revealed a sensitivity of 73.3% and a specificity of 88.3% for the diagnosis of NASH with an AOPP cut-off value of 332 μmol/L (the area under ROC curve 0.88, 95% confidence interval 0.82-0.94, P < 0.01). AOPP levels were positively correlated with NAS (r = 0.27, P = 0.035), fibrosis (r = 0.27, P = 0.037) and inflammation (r = 0.34, P = 0.008), but not the grade of steatosis (r = 0.02, P = 0.83) or ballooning (r = 0.02, P = 0.55). AOPP levels are significantly higher in patients with NASH than in those with ultrasonographically healthy liver. AOPP levels are positively correlated with biochemical and histopathological findings (NAS, liver inflammation and fibrosis), indicating that AOPP may play a role in the development of liver fibrosis and inflammation and may predict liver histopathology in NASH. © 2013 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  4. Comparison of clinical, biochemical and histological features of alcoholic steatohepatitis and non-alcoholic steatohepatitis in Asian Indian patients

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    Singh Deepak

    2010-07-01

    Full Text Available Background: Alcoholic steatohepatitis (ASH and non-alcoholic steatohepatitis (NASH are significant forms of liver disease and may progress to end-stage liver disease, cirrhosis and potentially malignant complications. The most difficult aspect of establishing a diagnosis of NASH is distinguishing it from ASH. Laboratory markers such as AST, ALT and GGT lack sufficient sensitivity and specificity. Aim: To study the clinical, biochemical and histological differences between non-alcoholic steatohepatitis (NASH and alcoholic steatohepatitis (ASH. Materials and Methods: Sixty histologically confirmed cases of non-alcoholic steatohepatitis and 38 cases of alcoholic steatohepatitis were included in the study. A modified form of scoring system proposed by Yip and Burt was used to grade histological features of NASH and ASH. Results: Mean age was 42.85 ± 12.36 years in ASH group and 35.07 ± 8.06 years for NASH group. Male: Female ratio was 37:1 in ASH and 4:1 in NASH. The mean ALT (P = 0.012, SAP (P = 0.003, serum bilirubin (P = 0.001, AST/ALT ratio (P = 0.03, steatosis (P < 0.001, ballooning degeneration of hepatocytes (P < 0.001, portal inflammation (P < 0.001, Mallory hyaline (P = 0.001, ductular proliferation and fibrosis (P < 0.001 showed a significant difference between ASH and NASH cases. Discussion: Older age, male sex, larger derangement of serum biochemistry, high serum bilirubin, AST/ALT > 1, more ballooning degeneration, portal inflammation, Mallory′s hyaline, hepatocytic and ductular cholestasis, ductular proliferation and higher stage of fibrosis favors a diagnosis of ASH. Younger age, high ALT, AST/ALT < 1, higher grade of steatosis and absence of extensive neutrophilic portal inflammation favors a diagnosis of NASH.

  5. On a numerical solving of random generated hexamatrix games

    Science.gov (United States)

    Orlov, Andrei; Strekalovskiy, Alexander

    2016-10-01

    In this paper, we develop a global search method for finding a Nash equilibrium in a hexamatrix game (polymatrix game of three players). The method, on the one hand, is based on the equivalence theorem of the problem of finding a Nash equilibrium in the game and a special mathematical optimization problem, and, on the other hand, on the usage of Global Search Theory for solving the latter problem. The efficiency of this approach is demonstrated by the results of computational testing.

  6. Prevalence and significance of autoantibodies in patients with non-alcoholic steatohepatitis.

    Science.gov (United States)

    Cotler, Scott J; Kanji, Kiran; Keshavarzian, Ali; Jensen, Donald M; Jakate, Shriram

    2004-10-01

    The aim of this study is to evaluate the prevalence and the clinical and histologic correlates of autoantibodies in patients with nonalcoholic steatohepatitis (NASH). Antinuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) have been identified in patients with NASH. The significance of autoantibodies in NASH is uncertain. Clinical data from patients with a histologic diagnosis of NASH at a university hospital in Chicago, Illinois between January 1999 and April 2003 were reviewed retrospectively. Seventy-four patients who were tested for autoantibodies and had no history of alcohol abuse or a systemic autoimmune disease were included. Demographic information and laboratory data were collected. Autoantibody titers > or = 1:40 were considered positive. A single pathologist reviewed all liver biopsies and scored features of NASH and identified characteristics of autoimmune hepatitis. Thirty-four percent of patients with NASH had positive ANA titers and 6% were ASMA positive. Demographic and laboratory parameters did not differ by ANA status, except that women were more frequently ANA positive then men (P = 0.01). The severity of steatosis, inflammation, and fibrosis on liver biopsy were similar in the ANA positive and negative groups. Only 15% of ANA positive patients with NASH had a plasma cell infiltrate on liver biopsy and there was no difference in the frequency of histologic features of autoimmune hepatitis between ANA positive and negative patients. Antinuclear antibodies are common in patients with NASH and most frequently represent a nonspecific antibody response that is not associated with the pattern or severity of injury on liver biopsy.

  7. Lessons from Mouse Models of High-Fat Diet-Induced NAFLD

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    Nakamura, Akinobu; Terauchi, Yasuo

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) encompasses a clinicopathologic spectrum of diseases ranging from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), the more aggressive form of fatty liver disease that may progress to cirrhosis and cirrhosis-related complications, including hepatocellular carcinoma. The prevalence of NAFLD, including NASH, is also increasing in parallel with the growing epidemics of obesity and diabetes. However, the causal relationships between obesi...

  8. Human mesenchymal stem cells towards non-alcoholic steatohepatitis in an immunodeficient mouse model

    International Nuclear Information System (INIS)

    Winkler, Sandra; Borkham-Kamphorst, Erawan; Stock, Peggy; Brückner, Sandra; Dollinger, Matthias; Weiskirchen, Ralf; Christ, Bruno

    2014-01-01

    Non-alcoholic steatohepatitis (NASH) is a frequent clinical picture characterised by hepatic inflammation, lipid accumulation and fibrosis. When untreated, NASH bears a high risk of developing liver cirrhosis and consecutive hepatocellular carcinoma requiring liver transplantation in its end-stage. However, donor organ scarcity has prompted the search for alternatives, of which hepatocyte or stem cell-derived hepatocyte transplantation are regarded auspicious options of treatment. Mesenchymal stem cells (MSC) are able to differentiate into hepatocyte-like cells and thus may represent an alternative cell source to primary hepatocytes. In addition these cells feature anti-inflammatory and pro-regenerative characteristics, which might favour liver recovery from NASH. The aim of this study was to investigate the potential benefit of hepatocyte-like cells derived from human bone marrow MSC in a mouse model of diet-induced NASH. Seven days post-transplant, human hepatocyte-like cells were found in the mouse liver parenchyma. Triglyceride depositions were lowered in the liver but restored to normal in the blood. Hepatic inflammation was attenuated as verified by decreased expression of the acute phase protein serum amyloid A, inflammation-associated markers (e.g. lipocalin 2), as well as the pro-inflammatory cytokine TNFα. Moreover, the proliferation of host hepatocytes that indicate the regenerative capacity in livers receiving cell transplants was enhanced. Transplantation of MSC-derived human hepatocyte-like cells corrects NASH in mice by restoring triglyceride depositions, reducing inflammation and augmenting the regenerative capacity of the liver. - Highlights: • First time to show NASH in an immune-deficient mouse model. • Human MSC attenuate NASH and improve lipid homeostasis. • MSC act anti-fibrotic and augment liver regeneration by stimulation of proliferation. • Pre-clinical assessment of human MSC for stem cell-based therapy of NASH

  9. Human mesenchymal stem cells towards non-alcoholic steatohepatitis in an immunodeficient mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Winkler, Sandra, E-mail: sandra.pelz@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Borkham-Kamphorst, Erawan, E-mail: ekamphorst@ukaachen.de [Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstraße 30, D-52074 Aachen (Germany); Stock, Peggy, E-mail: peggy.stock@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Brückner, Sandra, E-mail: sandra.brueckner@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Dollinger, Matthias, E-mail: matthias.dollinger@uniklinik-ulm.de [Department for Internal Medicine I, University Hospital Ulm, Albert-Einstein-Allee 23, D-89081 Ulm (Germany); Weiskirchen, Ralf, E-mail: rweiskirchen@ukaachen.de [Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstraße 30, D-52074 Aachen (Germany); Christ, Bruno, E-mail: bruno.christ@medizin.uni-leipzig.de [Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstraße 21, D-04103 Leipzig (Germany); Translational Centre for Regenerative Medicine (TRM), University of Leipzig, Leipzig (Germany)

    2014-08-15

    Non-alcoholic steatohepatitis (NASH) is a frequent clinical picture characterised by hepatic inflammation, lipid accumulation and fibrosis. When untreated, NASH bears a high risk of developing liver cirrhosis and consecutive hepatocellular carcinoma requiring liver transplantation in its end-stage. However, donor organ scarcity has prompted the search for alternatives, of which hepatocyte or stem cell-derived hepatocyte transplantation are regarded auspicious options of treatment. Mesenchymal stem cells (MSC) are able to differentiate into hepatocyte-like cells and thus may represent an alternative cell source to primary hepatocytes. In addition these cells feature anti-inflammatory and pro-regenerative characteristics, which might favour liver recovery from NASH. The aim of this study was to investigate the potential benefit of hepatocyte-like cells derived from human bone marrow MSC in a mouse model of diet-induced NASH. Seven days post-transplant, human hepatocyte-like cells were found in the mouse liver parenchyma. Triglyceride depositions were lowered in the liver but restored to normal in the blood. Hepatic inflammation was attenuated as verified by decreased expression of the acute phase protein serum amyloid A, inflammation-associated markers (e.g. lipocalin 2), as well as the pro-inflammatory cytokine TNFα. Moreover, the proliferation of host hepatocytes that indicate the regenerative capacity in livers receiving cell transplants was enhanced. Transplantation of MSC-derived human hepatocyte-like cells corrects NASH in mice by restoring triglyceride depositions, reducing inflammation and augmenting the regenerative capacity of the liver. - Highlights: • First time to show NASH in an immune-deficient mouse model. • Human MSC attenuate NASH and improve lipid homeostasis. • MSC act anti-fibrotic and augment liver regeneration by stimulation of proliferation. • Pre-clinical assessment of human MSC for stem cell-based therapy of NASH.

  10. Molecular characterization of the fecal microbiota in patients with nonalcoholic steatohepatitis--a longitudinal study.

    Directory of Open Access Journals (Sweden)

    Vincent Wai-Sun Wong

    Full Text Available The human gut microbiota has profound influence on host metabolism and immunity. This study characterized the fecal microbiota in patients with nonalcoholic steatohepatitis (NASH. The relationship between microbiota changes and changes in hepatic steatosis was also studied.Fecal microbiota of histology-proven NASH patients and healthy controls was analyzed by 16S ribosomal RNA pyrosequencing. NASH patients were from a previously reported randomized trial on probiotic treatment. Proton-magnetic resonance spectroscopy was performed to monitor changes in intrahepatic triglyceride content (IHTG.A total of 420,344 16S sequences with acceptable quality were obtained from 16 NASH patients and 22 controls. NASH patients had lower fecal abundance of Faecalibacterium and Anaerosporobacter but higher abundance of Parabacteroides and Allisonella. Partial least-square discriminant analysis yielded a model of 10 genera that discriminated NASH patients from controls. At month 6, 6 of 7 patients in the probiotic group and 4 of 9 patients in the usual care group had improvement in IHTG (P=0.15. Improvement in IHTG was associated with a reduction in the abundance of Firmicutes (R(2=0.4820, P=0.0028 and increase in Bacteroidetes (R(2=0.4366, P=0.0053. This was accompanied by corresponding changes at the class, order and genus levels. In contrast, bacterial biodiversity did not differ between NASH patients and controls, and did not change with probiotic treatment.NASH patients have fecal dysbiosis, and changes in microbiota correlate with improvement in hepatic steatosis. Further studies are required to investigate the mechanism underlying the interaction between gut microbes and the liver.

  11. Current Concepts and Management Approaches in Nonalcoholic Fatty Liver Disease

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    Bashar M. Attar

    2013-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common cause of liver dysfunction worldwide. NAFLD may progress to nonalcoholic steatohepatitis (NASH and in turn cirrhosis. Importantly, hepatic cancer can occur in NASH in the absence of cirrhosis. The cardinal histologic feature of NAFLD is the presence of an excessive accumulation of triacylglycerols and diacylglycerols in hepatocytes. The presence of obesity and insulin resistance lead to an increased hepatic-free fatty acid (FFA flux creating an environment appropriate for the development of NAFLD. The generation of toxic reactive oxygen species with the production of hepatic injury and inflammation as a consequence of FFA oxidation will ultimately lead to the initiation and progression of fibrosis. Lifestyle modifications specifically weight loss, physical exercise, and cognitive behavior therapy have been recommended as treatments for NASH. Dietary fructose is an independent risk factor for the development of NAFLD. Pioglitazone can be used to treat biopsy-proven NASH; however, its safety risks should be considered carefully. Greater consumption for coffee, independent of its caffeine component, has been associated with a significant reduced risk of advanced fibrosis in NASH. Additional data are needed before recommending bariatric surgery as an established option for the specific treatment of NASH.

  12. Konsep Qath’iy-Zhanniy serta Implikasinya dalam Istinbath Hukum

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    Romli SA

    2015-06-01

    Full Text Available This article is the result of research that reviewing the concept qath'iy and zhanniy. In addition, also discussed how the existence of nash indicated (dilalah by nash word. From the results of this study, the findings obtained are: first, that the concept qath'i and zhanniy as one of the devices in doing istinbath which rests on the principles of language is very useful in order to ensure legal charge indicated by nash word. Second, the concept of qath'iy and zhanniy also a means to ensure the existence of a proposition both in terms of existence of nash and also the dilalah. Knowing the existence (wurud and nash of dilalah in reviewing Islamic law is a necessity. Third, the concept of  qath'iy and zhanniy is a means to distinguish the clear and unclear text, because the nash of qath'iy or zhanniy each has it’s own characteristics that will influence and determine the conclusion of the legal charge indicated by the word. In addition, the concept of qath'iy and zhanniy also serves as a means for the development of Islamic law.

  13. Associations of Fatty Liver Disease with Hypertension, Diabetes, and Dyslipidemia: Comparison between Alcoholic and Nonalcoholic Steatohepatitis

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    Nobuyuki Toshikuni

    2017-01-01

    Full Text Available Alcoholic steatohepatitis (ASH and nonalcoholic steatohepatitis (NASH are representative types of fatty liver disease (FLD and have similar histologic features. In this study, we aimed to compare the associations of the two FLD types with hypertension (HT, diabetes mellitus (DM, and dyslipidemia (DL. A nationwide survey investigating FLD status included 753 Japanese subjects (median age 55 years; male 440, female 313 with biopsy-proven ASH (n=172 or NASH (n=581. We performed a multiple logistic regression analysis to identify the factors associated with HT, DM, or DL. Older age and a higher body mass index were significant factors associated with HT. Older age, female sex, a higher body mass index, advanced liver fibrosis, and the NASH type of FLD (odds ratio 2.77; 95% confidence interval 1.78–4.31; P<0.0001 were significant factors associated with DM. Finally, the NASH type of FLD (odds ratio 4.05; 95% confidence interval 2.63–6.24; P<0.0001 was the only significant factor associated with DL. Thus, the associations of NASH with DM and DL were stronger than those of ASH with DM and DL. In the management of FLD subjects, controlling DM and DL is particularly important for NASH subjects.

  14. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    Science.gov (United States)

    Sumida, Yoshio; Nakajima, Atsushi; Itoh, Yoshito

    2014-01-01

    It is estimated that 30% of the adult population in Japan is affected by nonalcoholic fatty liver disease (NAFLD). Fatty changes of the liver are generally diagnosed using imaging methods such as abdominal ultrasonography (US) and computed tomography (CT), but the sensitivity of these imaging techniques is low in cases of mild steatosis. Alanine aminotransferase levels may be normal in some of these patients, warranting the necessity to establish a set of parameters useful for detecting NAFLD, and the more severe form of the disease, nonalcoholic steatohepatitis (NASH). Although liver biopsy is currently the gold standard for diagnosing progressive NASH, it has many drawbacks, such as sampling error, cost, and risk of complications. Furthermore, it is not realistic to perform liver biopsies on all NAFLD patients. Diagnosis of NASH using various biomarkers, scoring systems and imaging methods, such as elastography, has recently been attempted. The NAFIC score, calculated from the levels of ferritin, fasting insulin, and type IV collagen 7S, is useful for the diagnosis of NASH, while the NAFLD fibrosis score and the FIB-4 index are useful for excluding NASH in cases of advanced fibrosis. This article reviews the limitations and merits of liver biopsy and noninvasive diagnostic tests in the diagnosis of NAFLD/NASH. PMID:24574716

  15. Symmetric Decomposition of Asymmetric Games.

    Science.gov (United States)

    Tuyls, Karl; Pérolat, Julien; Lanctot, Marc; Ostrovski, Georg; Savani, Rahul; Leibo, Joel Z; Ord, Toby; Graepel, Thore; Legg, Shane

    2018-01-17

    We introduce new theoretical insights into two-population asymmetric games allowing for an elegant symmetric decomposition into two single population symmetric games. Specifically, we show how an asymmetric bimatrix game (A,B) can be decomposed into its symmetric counterparts by envisioning and investigating the payoff tables (A and B) that constitute the asymmetric game, as two independent, single population, symmetric games. We reveal several surprising formal relationships between an asymmetric two-population game and its symmetric single population counterparts, which facilitate a convenient analysis of the original asymmetric game due to the dimensionality reduction of the decomposition. The main finding reveals that if (x,y) is a Nash equilibrium of an asymmetric game (A,B), this implies that y is a Nash equilibrium of the symmetric counterpart game determined by payoff table A, and x is a Nash equilibrium of the symmetric counterpart game determined by payoff table B. Also the reverse holds and combinations of Nash equilibria of the counterpart games form Nash equilibria of the asymmetric game. We illustrate how these formal relationships aid in identifying and analysing the Nash structure of asymmetric games, by examining the evolutionary dynamics of the simpler counterpart games in several canonical examples.

  16. Internalization of modified lipids by CD36 and SR-A leads to hepatic inflammation and lysosomal cholesterol storage in Kupffer cells.

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    Veerle Bieghs

    Full Text Available Non-alcoholic steatohepatitis (NASH is characterized by steatosis and inflammation, which can further progress into fibrosis and cirrhosis. Recently, we demonstrated that combined deletion of the two main scavenger receptors, CD36 and macrophage scavenger receptor 1 (MSR1, which are important for modified cholesterol-rich lipoprotein uptake, reduced NASH. The individual contributions of these receptors to NASH and the intracellular mechanisms by which they contribute to inflammation have not been established. We hypothesize that CD36 and MSR1 contribute independently to the onset of inflammation in NASH, by affecting intracellular cholesterol distribution inside Kupffer cells (KCs.Ldlr(-/- mice were transplanted with wild-type (Wt, Cd36(-/- or Msr1(-/- bone marrow and fed a Western diet for 3 months. Cd36(-/-- and Msr1(-/-- transplanted (tp mice showed a similar reduction in hepatic inflammation compared to Wt-tp mice. While the total amount of cholesterol inside KCs was similar in all groups, KCs of Cd36(-/-- and Msr1(-/--tp mice showed increased cytoplasmic cholesterol accumulation, while Wt-tp mice showed increased lysosomal cholesterol accumulation.CD36 and MSR1 contribute similarly and independently to the progression of inflammation in NASH. One possible explanation for the inflammatory response related to expression of these receptors could be abnormal cholesterol trafficking in KCs. These data provide a new basis for prevention and treatment of NASH.

  17. Usefulness of Cytokeratin-18M65 in Diagnosing Non-Alcoholic Steatohepatitis in Japanese Population.

    Science.gov (United States)

    Hasegawa, Yutaka; Kim, Soo Ryang; Hatae, Takashi; Ohta, Mitsuhiro; Fujinami, Aya; Sugimoto, Kayo; Kim, Ke Ih; Imoto, Susumu; Tohyama, Madoka; Kim, Soo Ki; Ikura, Yoshihiro; Kudo, Masatoshi

    2015-10-01

    The aim of this study was to evaluate cytokeratin-18M65 (CK-18M65) for distinguishing between simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) against healthy individuals (HIs) in Japanese population. The serum from 24 HIs, 21 patients with SS and 20 patients with NASH were examined. Serum CK-18M65 was measured by enzyme-linked immunosorbent assay. Aspartate aminotransferase was significantly different between NASH patients and HIs with p fashion in HIs and also in SS and NASH patients. Multivariate logistic regression analysis revealed that NASH could be diagnosed with the use of CK-18M65 alone (p = 0.0285, OR 1.0038, 95% CI 1.0004-1.0073). At the optimal cut-off level of 548 U/l, CK-18M65 had an AUC value of 0.7369, 60.00% sensitivity and 85.70% specificity. In patients with NASH, no significant difference was observed between low fibrosis (Stage 0-1, 794.30 ± 454.41, n = 10) and high fibrosis (Stage 2-3, 809.70 ± 641.43, n = 10; p = 0.5967) and between slight steatosis (Japanese population. © 2015 S. Karger AG, Basel.

  18. Taurine and tea polyphenols combination ameliorate nonalcoholic steatohepatitis in rats.

    Science.gov (United States)

    Zhu, Wenhua; Chen, Siwen; Chen, Ronggui; Peng, Zhiqing; Wan, Jun; Wu, Benyan

    2017-09-08

    Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease, for which there is currently no safe and effective drug for therapy. In this study, we explored the effects of taurine, tea polyphenols (TPs), or a combination thereof, on NASH rats. Rats were divided into a normal group, a high-fat diet induced model group and a treatment group (including taurine, TPs, or taurine + TPs treatment for 8 weeks). Twelve weeks later, all rats were sacrificed, and serum transaminase, lipid and lipopolysaccharide levels and hepatic oxidative stress levels were determined. Histological changes were evaluated. In NASH rats, hepatocyte damage, lipid disturbance, oxidative stress and elevated lipopolysaccharide levels were confirmed. Taurine treatment alleviated hepatocyte damage and oxidative stress. TPs treatment improved lipid metabolism and increased hepatic antioxidant activity. The therapeutic effects of taurine + TPs treatment on hepatocyte damage, lipid disturbance, and oxidative stress were superior to those of taurine and TPs treatment, respectively. Taurine, TPs and their combination all decreased serum lipopolysaccharide levels in NASH rats, but the combination of the compounds caused these levels to decrease more significantly than taurine or TPs treatment alone. Taurine combined with TPs treatment could relieve NASH by alleviating hepatocyte damage, decreasing oxidative stress and improving lipid metabolism and gut flora disturbance partly. Taurine and TPs combination may act as a new effective medicine for treating NASH patients.

  19. Utility of the ELF Test for Detecting Steatohepatitis in Morbid Obese Patients with Suspicion of Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    López, Iria Cebreiros; Aroca, Florentina Guzmán; Bernal, Maria Dolores Frutos; Mompeán, Juan Antonio Luján; Bernal, Águeda Bas; Martínez, Antonio Miguel Hernández; Barba, Enrique Martínez; Velasco, Jose Antonio Noguera; Paricio, Pascual Parilla

    2017-09-01

    Morbid obese patients have a high rate of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). NASH is related to the progression and poor evolution of chronic hepatopathy in NAFLD, so that its detection makes it possible to identify the subjects who are most at risk in order to prioritize treatment. The ELF test (Enhanced Liver Fibrosis test; Siemens Diagnostics, NY, USA) has been assessed for its capacity to detect fibrosis in patients with NAFLD, but its capacity for diagnosing NASH has not been checked. Our objective is to determine the utility of the ELF test for detecting NASH in morbid obese patients with suspected NAFLD. ELF values were determined in a cohort of obese patients who underwent bariatric surgery with suspected NAFLD. Liver biopsy was used as the reference standard. The values of ELF were significantly higher in patients with NASH (p = 0.002) and in those who presented with metabolic syndrome (p = 0.047). An ELF cut-off point of 8.72 allows the detection of patients with NASH with a sensitivity of 71.4% and a specificity of 74.1% (AUC = 0.742, p = 0.002). The ELF test is efficient for the identification of obese patients with NAFLD and early signs of steatohepatitis and fibrosis.

  20. Fatty Acid Elongation in Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma

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    Sonja M. Kessler

    2014-04-01

    Full Text Available Non-alcoholic steatohepatitis (NASH represents a risk factor for the development of hepatocellular carcinoma (HCC and is characterized by quantitative and qualitative changes in hepatic lipids. Since elongation of fatty acids from C16 to C18 has recently been reported to promote both hepatic lipid accumulation and inflammation we aimed to investigate whether a frequently used mouse NASH model reflects this clinically relevant feature and whether C16 to C18 elongation can be observed in HCC development. Feeding mice a methionine and choline deficient diet to model NASH not only increased total hepatic fatty acids and cholesterol, but also distinctly elevated the C18/C16 ratio, which was not changed in a model of simple steatosis (ob/ob mice. Depletion of Kupffer cells abrogated both quantitative and qualitative methionine-and-choline deficient (MCD-induced alterations in hepatic lipids. Interestingly, mimicking inflammatory events in early hepatocarcinogenesis by diethylnitrosamine-induced carcinogenesis (48 h increased hepatic lipids and the C18/C16 ratio. Analyses of human liver samples from patients with NASH or NASH-related HCC showed an elevated expression of the elongase ELOVL6, which is responsible for the elongation of C16 fatty acids. Taken together, our findings suggest a detrimental role of an altered fatty acid pattern in the progression of NASH-related liver disease.