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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. Moskovskije oligarhi predpotshitajut / Tatjana Tridvornova ; interv. Marina Poltavtseva

    Index Scriptorium Estoniae

    Tridvornova, Tatjana

    2005-01-01

    Lilleballi ja Lillekleidi konkursi autori Tatjana Tridvornovaga tema tööst Moskvas. Avas Moskvas kunstistuudio Flowers Vasari. Tema abilisteks on eesti lilleseadjad Heiti Põder, Ahti Lyra ja Eve Aben

  3. 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

  4. 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.

  5. 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

  6. "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. ​

  7. 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 ...

  8. 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...

  9. 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

  10. Strong Nash Equilibria and the Potential Maimizer

    NARCIS (Netherlands)

    van Megen, F.J.C.; Facchini, G.; Borm, P.E.M.; Tijs, S.H.

    1996-01-01

    A class of non cooperative games characterized by a `congestion e ect' is studied, in which there exists a strong Nash equilibrium, and the set of Nash equilibria, the set of strong Nash equilibria and the set of strategy pro les maximizing the potential function coincide.The structure of the class

  11. Computing Nash equilibria through computational intelligence methods

    Science.gov (United States)

    Pavlidis, N. G.; Parsopoulos, K. E.; Vrahatis, M. N.

    2005-03-01

    Nash equilibrium constitutes a central solution concept in game theory. The task of detecting the Nash equilibria of a finite strategic game remains a challenging problem up-to-date. This paper investigates the effectiveness of three computational intelligence techniques, namely, covariance matrix adaptation evolution strategies, particle swarm optimization, as well as, differential evolution, to compute Nash equilibria of finite strategic games, as global minima of a real-valued, nonnegative function. An issue of particular interest is to detect more than one Nash equilibria of a game. The performance of the considered computational intelligence methods on this problem is investigated using multistart and deflection.

  12. A biomarker panel for non-alcoholic steatohepatitis (NASH) and NASH-related fibrosis.

    Science.gov (United States)

    Younossi, Zobair M; Page, Sandra; Rafiq, Nila; Birerdinc, Aybike; Stepanova, Maria; Hossain, Noreen; Afendy, Arian; Younoszai, Zahra; Goodman, Zachary; Baranova, Ancha

    2011-04-01

    Patients with biopsy-proven NASH and especially those with fibrosis are at risk for progressive liver disease, emphasizing the clinical importance of developing non-invasive biomarkers for NASH and NASH-related fibrosis. This study examines the performance of a new biomarker panel for NASH and NASH-related fibrosis with a combination of clinical and laboratory variables. Enrolled patients had biopsy-proven NAFLD. Clinical data, laboratory data, and serum samples were collected at the time of biopsy. Fasting serum was assayed for adiponectin, resistin, glucose, M30, M65, Tissue inhibitor of metalloproteinases-1 (Timp-1), ProCollagen 3 N-terminal peptide (PIIINP), and hyaluronic acid (HA). Regression models predictive of NASH, NASH-related fibrosis, and NASH-related advanced fibrosis were designed and cross-validated. Of the 79 enrolled NAFLD patients, 40 had biopsy-proven NASH and 39 had non-NASH NAFLD. Clinical and laboratory data were from this cohort were used to develop a NAFLD Diagnostic Panel that includes three models (models for NASH, NASH-related fibrosis, and NASH-related advanced fibrosis). The model for predicting NASH includes diabetes, gender, BMI, triglycerides, M30 (apoptosis), and M65-M30 (necrosis) [AUC: 0.81, 95% CI, 0.70-0.89, 300 p value <9E 301 (-06)]. The NASH-related fibrosis prediction model includes the same predictors [AUC: 0.80, 95% CI 0.68-0.88, 307 p value <0.00014]. Finally, the NASH-related advanced fibrosis model includes type 2 diabetes, serum triglycerides, Timp-1, and AST [AUC: 0.81, 95% CI, 0.70-0.89; p value, 0.000062]. This NAFLD Diagnostic Panel based on a clinical and laboratory data has good performance characteristics and is easy to use. This biomarker panel could become useful in the management of patients with NAFLD.

  13. Nash social welfare in multiagent resource allocation

    NARCIS (Netherlands)

    Ramezani, S.; Endriss, U.; David, E.; Gerding, E.; Sarne, D.; Shehory, O.

    2010-01-01

    We 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 fairness

  14. 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.

  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. [Tatjana Niemsch. Reval im 16. Jahrhundert : erfahrungsräumliche Deutungsmuster städtischer Konflikte] / Juhan Kreem

    Index Scriptorium Estoniae

    Kreem, Juhan, 1971-

    2015-01-01

    Arvustus: Niemsch, Tatjana. Reval im 16. Jahrhundert : erfahrungsräumliche Deutungsmuster städtischer Konflikte. (Kieler Werkstücke. Reihe G: Beiträge zur Frühen Neuzeit, 6). Verlag Peter Lang. Frankfurt am Main u.a. 2013

  17. Koolis töötada on ikka veel põnev / Ülo Tikk ; kommenteerivad: Vadim Rõbtsov, Tatjana Antsma, Olga kalju

    Index Scriptorium Estoniae

    Tikk, Ülo, 1941-

    2009-01-01

    Vestlusest Tallinna Mustamäe Reaalgümnaasiumi eesti keele ja kirjanduse õpetajast-metoodiku Olga Ivanovaga. Õpetajast kõnelevad ka vilistlane Vadim Rõbtsov, lapsevanem Tatjana Antsma, reaalgümnaasiumi direktor Olga Kalju

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. Nash equilibria via duality and homological selection

    Indian Academy of Sciences (India)

    1Quantitative Methods and Information Systems Area, Indian Institute ... The original proof of existence of Nash equilibria [13] uses fairly ...... The fiber over a regular point a of the disk Di consists of three inverse images (labeled. A1,A2,A3 in ...

  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. 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...

  5. A unifying approach to existence of Nash equilibria

    NARCIS (Netherlands)

    Balder, E.J.

    1997-01-01

    An approach initiated in [4] is shown to unify results about the existence of (i) Nash equilibria in games with at most countably many players, (ii) Cournot-Nash equilibrium distributions for large, anonymous games, and (iii) Nash equilibria (both mixed and pure) for continuum games. A new, central

  6. 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.

  7. The Optimal Nash Equilibrium Strategies Under Competition

    Institute of Scientific and Technical Information of China (English)

    孟力; 王崇喜; 汪定伟; 张爱玲

    2004-01-01

    This paper presented a game theoretic model to study the competition for a single investment oppertunity under uncertainty. It models the hazard rate of investment as a function of competitors' trigger level. Under uncertainty and different information structure, the option and game theory was applied to researching the optimal Nash equilibrium strategies of one or more firm. By means of Matlab software, the paper simulates a real estate developing project example and illustrates how parameter affects investment strategies. The paper's work will contribute to the present investment practice in China.

  8. Dendritic Cells Limit Fibro-Inflammatory Injury in NASH

    Science.gov (United States)

    Henning, Justin R.; Graffeo, Christopher S.; Rehman, Adeel; Fallon, Nina C.; Zambirinis, Constantinos P.; Ochi, Atsuo; Barilla, Rocky; Jamal, Mohsin; Deutsch, Michael; Greco, Stephanie; Ego-Osuala, Melvin; Saeed, Usama Bin; Rao, Raghavendra S.; Badar, Sana; Quesada, Juan P.; Acehan, Devrim; Miller, George

    2013-01-01

    Non-alcoholic steatohepatitis (NASH) is the most common etiology of chronic liver dysfunction in the United States and can progress to cirrhosis and liver failure. Inflammatory insult resulting from fatty infiltration of the liver is central to disease pathogenesis. Dendritic cells (DC) are antigen presenting cells with an emerging role in hepatic inflammation. We postulated that DC are important in the progression of NASH. We found that intrahepatic DC expand and mature in NASH liver and assume an activated immune-phenotype. However, rather than mitigating the severity of NASH, DC depletion markedly exacerbated intrahepatic fibro-inflammation. Our mechanistic studies support a regulatory role for DC in NASH by limiting sterile inflammation via their role in clearance of apoptotic cells and necrotic debris. We found that DC limit CD8+ T cell expansion and restrict Toll-like receptor expression and cytokine production in innate immune effector cells in NASH, including Kupffer cells, neutrophils, and inflammatory monocytes. Consistent with their regulatory role in NASH, during the recovery phase of disease, ablation of DC populations results in delayed resolution of intrahepatic inflammation and fibroplasia. Conclusion Our findings support a role for DC in modulating NASH. Targeting DC functional properties may hold promise for therapeutic intervention in NASH. PMID:23322710

  9. 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.

  10. 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

  11. 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....

  12. 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

  13. The Nash Equilibrium Revisited: Chaos and Complexity Hidden in Simplicity

    Science.gov (United States)

    Fellman, Philip V.

    The Nash Equilibrium is a much discussed, deceptively complex, method for the analysis of non-cooperative games (McLennan and Berg, 2005). If one reads many of the commonly available definitions the description of the Nash Equilibrium is deceptively simple in appearance. Modern research has discovered a number of new and important complex properties of the Nash Equilibrium, some of which remain as contemporary conundrums of extraordinary difficulty and complexity (Quint and Shubik, 1997). Among the recently discovered features which the Nash Equilibrium exhibits under various conditions are heteroclinic Hamiltonian dynamics, a very complex asymptotic structure in the context of two-player bi-matrix games and a number of computationally complex or computationally intractable features in other settings (Sato, Akiyama and Farmer, 2002). This paper reviews those findings and then suggests how they may inform various market prediction strategies.

  14. 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.

  15. 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.

  16. 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

  17. Controversies in the Diagnosis and Management of NAFLD and NASH.

    Science.gov (United States)

    Rinella, Mary E; Loomba, Rohit; Caldwell, Stephen H; Kowdley, Kris; Charlton, Michael; Tetri, Brent; Harrison, Stephen A

    2014-04-01

    Nonalcoholic fatty liver disease (NAFLD) is recognized as the most common cause of chronic liver disease in the United States. Nonalcoholic steatohepatitis (NASH) occurs in a subset of patients with NAFLD and is characterized by the presence of hepa-tocellular injury, which is progressive in a substantial proportion of cases and can lead to cirrhosis and all of its complications. Although the diagnosis of NAFLD can be made through imaging studies or liver biopsy, the diagnosis of NASH still requires histologic confirmation. Liver biopsy should be performed in the presence of risk factors for advanced disease. Measures aimed at promoting weight loss, a healthier lifestyle, and optimization of metabolic risk factors remain the cornerstone of management of NAFLD. Therapeutic agents that are presently considered the most promising in NAFLD are effective in less than 50% of patients. Among patients with biopsy-proven NASH, treatment with pharmacologic agents should be considered; however, the role of specific agents in NASH still needs further study. Despite a wealth of research over the past 15 years, many controversies remain with respect to the diagnosis and management of NAFLD and NASH as well as the influence of alcohol on liver disease progression in these patients.

  18. Nash Equilibria in Symmetric Graph Games with Partial Observation

    DEFF Research Database (Denmark)

    Bouyer, Patricia; Markey, Nicolas; Vester, Steen

    2017-01-01

    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...... 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....

  19. Nash Equilibria in Symmetric Games with Partial Observation

    DEFF Research Database (Denmark)

    Bouyer, Patricia; Markey, Nicolas; Vester, Steen

    2014-01-01

    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...... 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....

  20. 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

  1. 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

  2. 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

  3. 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.

  4. Nash equilibria in noncooperative predator-prey games

    Czech Academy of Sciences Publication Activity Database

    Ramos, A. M.; Roubíček, Tomáš

    2007-01-01

    Roč. 56, č. 2 (2007), s. 211-241 ISSN 0095-4616 Grant - others:GA ČR(CZ) GA201/03/0934 Institutional research plan: CEZ:AV0Z10750506 Keywords : Reaction-diffusion system * Lotka-Voltera system * Nash equilibrium Subject RIV: BA - General Mathematics Impact factor: 0.873, year: 2007

  5. Nash was a first to axiomatize expected utility

    NARCIS (Netherlands)

    H. Bleichrodt (Han); C. Li (Chen); I. Moscati (Ivan); P.P. Wakker (Peter)

    2016-01-01

    textabstractNash is famous for many inventions, but it is less known that he, simultaneously with Marschak, also was the first to axiomatize expected utility for risk. In particular, these authors were the first to state the independence condition, a condition that should have been but was not

  6. 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

  7. 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...

  8. 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

  9. 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

  10. 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...

  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. 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…

  13. 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.

  14. Implications of Nash Bargaining for Horizontal Industry Integration

    OpenAIRE

    Richard E. Just; Siddhartha Mitra; Sinaia Netanyahu

    2005-01-01

    This article shows how horizontal industry integration can arise from transferable asymmetry of technologies and endowments. The Nash bargaining solution suggests that greater technological diversity among coordinating parties yields greater gains from horizontal integration. The framework fits the case where a firm with a superior technology franchises the technology by horizontal integration. The results appear to fit hog production where integration has been primarily horizontal and, in pa...

  15. DISCRETE FIXED POINT THEOREMS AND THEIR APPLICATION TO NASH EQUILIBRIUM

    OpenAIRE

    Sato, Junichi; Kawasaki, Hidefumi

    2007-01-01

    Fixed point theorems are powerful tools in not only mathematics but also economic. In some economic problems, we need not real-valued but integer-valued equilibriums. However, classical fixed point theorems guarantee only real-valued equilibria. So we need discrete fixed point theorems in order to get discrete equilibria. In this paper, we first provide discrete fixed point theorems, next apply them to a non-cooperative game and prove the existence of a Nash equilibrium of pure strategies.

  16. Uniqueness of Nash equilibria in a quantum Cournot duopoly game

    International Nuclear Information System (INIS)

    Sekiguchi, Yohei; Sakahara, Kiri; Sato, Takashi

    2010-01-01

    A quantum Cournot game whose classical form game has multiple Nash equilibria is examined. Although the classical equilibria fail to be Pareto optimal, the quantum equilibrium exhibits the following two properties: (i) if the measurement of entanglement between strategic variables chosen by the competing firms is sufficiently large, the multiplicity of equilibria vanishes, and (ii) the more strongly the strategic variables are entangled, the more closely the unique equilibrium approaches to the optimal one.

  17. 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...problems and two market models of duopoly ith this type of information structure are extensively analyzed and examined. DO jAN7, 1473 EDIION OF NV SS IS...information 3 structure is employed in both Nash games and optimal coordination problems and two market models of duopoly with this type of information

  18. 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.

  19. 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)

  20. 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

  1. On Nash-Equilibria of Approximation-Stable Games

    Science.gov (United States)

    Awasthi, Pranjal; Balcan, Maria-Florina; Blum, Avrim; Sheffet, Or; Vempala, Santosh

    One reason for wanting to compute an (approximate) Nash equilibrium of a game is to predict how players will play. However, if the game has multiple equilibria that are far apart, or ɛ-equilibria that are far in variation distance from the true Nash equilibrium strategies, then this prediction may not be possible even in principle. Motivated by this consideration, in this paper we define the notion of games that are approximation stable, meaning that all ɛ-approximate equilibria are contained inside a small ball of radius Δ around a true equilibrium, and investigate a number of their properties. Many natural small games such as matching pennies and rock-paper-scissors are indeed approximation stable. We show furthermore there exist 2-player n-by-n approximation-stable games in which the Nash equilibrium and all approximate equilibria have support Ω(log n). On the other hand, we show all (ɛ,Δ) approximation-stable games must have an ɛ-equilibrium of support O(Δ^{2-o(1)}/ɛ2{log n}), yielding an immediate n^{O(Δ^{2-o(1)}/ɛ^2log n)}-time algorithm, improving over the bound of [11] for games satisfying this condition. We in addition give a polynomial-time algorithm for the case that Δ and ɛ are sufficiently close together. We also consider an inverse property, namely that all non-approximate equilibria are far from some true equilibrium, and give an efficient algorithm for games satisfying that condition.

  2. 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.

  3. 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

  4. Enhanced A-FABP expression in visceral fat: potential contributor to the progression of NASH

    Directory of Open Access Journals (Sweden)

    Min Yong Yoon

    2012-09-01

    Full Text Available Background/AimsAdipose tissue is an active endocrine organ that secretes various metabolically important substances including adipokines, which represent a link between insulin resistance and nonalcoholic steatohepatitis (NASH. The factors responsible for the progression from simple steatosis to steatohepatitis remain elusive, but adipokine imbalance may play a pivotal role. We evaluated the expressions of adipokines such as visfatin, adipocyte-fatty-acid-binding protein (A-FABP, and retinol-binding protein-4 (RBP-4 in serum and tissue. The aim was to discover whether these adipokines are potential predictors of NASH.MethodsPolymerase chain reaction, quantification of mRNA, and Western blots encoding A-FABP, RBP-4, and visfatin were used to study tissue samples from the liver, and visceral and subcutaneous adipose tissue. The tissue samples were from biopsy specimens obtained from patients with proven NASH who were undergoing laparoscopic cholecystectomy due to gallbladder polyps.ResultsPatients were classified into two groups: NASH, n=10 and non-NASH, n=20 according to their nonalcoholic fatty liver disease Activity Score. Although serum A-FABP levels did not differ between the two groups, the expressions of A-FABP mRNA and protein in the visceral adipose tissue were significantly higher in NASH group than in non-NASH group (104.34 vs. 97.05, P<0.05, and 190.01 vs. 95.15, P<0.01, respectively. Furthermore, the A-FABP protein expression ratio between visceral adipose tissue and liver was higher in NASH group than in non-NASH group (4.38 vs. 1.64, P<0.05.ConclusionsNASH patients had higher levels of A-FABP expression in their visceral fat compared to non-NASH patients. This differential A-FABP expression may predispose patients to the progressive form of NASH.

  5. Development of a novel diagnostic algorithm to predict NASH in HCV-positive patients.

    Science.gov (United States)

    Gallotta, Andrea; Paneghetti, Laura; Mrázová, Viera; Bednárová, Adriana; Kružlicová, Dáša; Frecer, Vladimir; Miertus, Stanislav; Biasiolo, Alessandra; Martini, Andrea; Pontisso, Patrizia; Fassina, Giorgio

    2018-05-01

    Non-alcoholic steato-hepatitis (NASH) is a severe disease characterised by liver inflammation and progressive hepatic fibrosis, which may progress to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests that in hepatitis C virus patients steatosis and NASH are associated with faster fibrosis progression and hepatocellular carcinoma. A safe and reliable non-invasive diagnostic method to detect NASH at its early stages is still needed to prevent progression of the disease. We prospectively enrolled 91 hepatitis C virus-positive patients with histologically proven chronic liver disease: 77 patients were included in our study; of these, 10 had NASH. For each patient, various clinical and serological variables were collected. Different algorithms combining squamous cell carcinoma antigen-immunoglobulin-M (SCCA-IgM) levels with other common clinical data were created to provide the probability of having NASH. Our analysis revealed a statistically significant correlation between the histological presence of NASH and SCCA-IgM, insulin, homeostasis model assessment, haemoglobin, high-density lipoprotein and ferritin levels, and smoke. Compared to the use of a single marker, algorithms that combined four, six or seven variables identified NASH with higher accuracy. The best diagnostic performance was obtained with the logistic regression combination, which included all seven variables correlated with NASH. The combination of SCCA-IgM with common clinical data shows promising diagnostic performance for the detection of NASH in hepatitis C virus patients.

  6. 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.

  7. 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.

  8. 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.

  9. How hard is it to find extreme Nash equilibria in network congestion games?

    NARCIS (Netherlands)

    Gassner, E.; Hatzl, J.; Krumke, S.O.; Sperber, H.; Woeginger, G.J.; Papadimitriou, C.; Zhang, S.

    2008-01-01

    We study the complexity of finding extreme pure Nash equilibria in symmetric (unweighted) network congestion games. In our context best and worst equilibria are those with minimum respectively maximum makespan. On series-parallel graphs a worst Nash equilibrium can be found by a Greedy approach

  10. 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.

  11. 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...

  12. 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

  13. 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.

  14. 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

  15. 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

  16. Water extract of Vitis coignetiae Pulliat leaves attenuates oxidative stress and inflammation in progressive NASH rats.

    Science.gov (United States)

    Pak, Wing; Takayama, Fusako; Hasegawa, Azusa; Mankura, Mitsumasa; Egashira, Toru; Ueki, Keiji; Nakamoto, Kazuo; Kawasaki, Hiromu; Mori, Akitane

    2012-01-01

    This study aimed to investigate the therapeutic effects of the water extract of leaves of Vitis coignetiae Pulliat (VCPL) on nonalcoholic steatohepatitis (NASH) with advanced fibrosis, as our previous study exhibited its preventive effect on NASH. The NASH animal model [PCT/JP2007/52477] was prepared by loading recurrent and intermittent hypoxemia stress to a rat with fatty liver, which resembled the condition occurring in patients with obstructive sleep apnea (OSA) and fatty liver, who have a high incidence of NASH. Intermittent hypoxemia stress is regarded as a condition similar to warm ischemia followed by re-oxygenation, which induces oxidative stress (OS). The daily 100 or 300 mg/kg VCPL administrations were performed for 3 weeks perorally beginning at the time of detection of advanced liver fibrosis. The therapeutic efficacy of VCPL on NASH was demonstrated by the reduction of the leakage of hepato-biliary enzymes and the amelioration of liver fibrosis. The OS elevation in NASH rats was measured based on the derivation of reactive oxygen species from liver mitochondrial energy metabolism and on the decrease in plasma SOD-like activity. The aggravation of inflammatory responses was demonstrated by the neutrophil infiltration (elevated myeloperoxidase activity) and the progression of fibrosis in the livers of NASH rats. In addition, the NASH rats without VCPL treatment also exhibited activation of nuclear factor-κB, a key factor in the link between oxidative stress and inflammation. All of these changes were reduced dose-dependently by the VCPL administration. These findings indicate that VCPL may improve hepatic fibrosis or at least suppress the progression of NASH, by breaking the crosstalk between OS and inflammation.

  17. 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.

  18. 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.

  19. 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.

  20. 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 ... diagnosis of NASH and its usefulness in correlation with disease severity in Egyptian ... International Business Machines; IR, insulin resistance; LDL, low ..... Logistic Regression Test showing positive prediction of. CK18 in ...

  1. 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.

  2. Non-alcoholic steatohepatitis (NASH) in patients with polycystic ovarian syndrome (PCOS).

    Science.gov (United States)

    Hossain, Noreen; Stepanova, Maria; Afendy, Arian; Nader, Fatema; Younossi, Youssef; Rafiq, Nila; Goodman, Zachary; Younossi, Zobair M

    2011-04-01

    Both non-alcoholic steatohepatitis (NASH) and polycystic ovary syndrome (PCOS) are associated with metabolic syndrome (MS) and insulin resistance (IR). Except for a few case reports, there are no systematic assessments of NASH in PCOS patients. To determine the prevalence of NASH and independent factors associated with NASH in a cohort of patients with documented PCOS. Patients with established diagnosis of PCOS and matched controls (matched for gender, age, and body mass index (BMI)) were included in the study. Causes of other liver diseases were systematically excluded by clinical and laboratory tests. Excessive alcohol use was defined as alcohol consumption of greater than 10 g/day. All liver biopsies were read by a single pathologist blinded to the clinical data. Histologic NASH was defined as steatosis with lobular inflammation and ballooning degeneration of hepatocytes with or without Mallory-Denk bodies or pericellular fibrosis. Univariate and multivariate analyses with logistic regression were performed to compare PCOS to matched controls. Sixty-six patients were included in the study (34 PCOS and 32 matched controls). Of PCOS patients, 73% had a liver biopsy while 78% of the matched controls had a liver biopsy. In comparing PCOS patients to the matched controls, clinical (BMI, waist circumference, type 2 diabetes, MS, or its components, any alcohol consumption in the prior year, ethnic background, age, gender, etc.) and laboratory data (aminotransferases, ferritin, glucose, etc.) were not significantly different (p > 0.05). However, PCOS patients tended to have more histologic NASH on their liver biopsies (44.0% vs. 20.8%, p = 0.08). Independent predictors of histologic NASH in PCOS patients were elevated aspartate aminotransferase (AST), high triglycerides and small amounts of alcohol consumption (p = 0.019, 10-fold cross-validated AUC = 0.80, 95% CI = 0.56-0.94). Although about half of PCOS patients did not report any alcohol consumption, 50% did report

  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. A novel diagnostic biomarker panel for obesity-related nonalcoholic steatohepatitis (NASH).

    Science.gov (United States)

    Younossi, Zobair M; Jarrar, Mohammed; Nugent, Clare; Randhawa, Manpreet; Afendy, Mariam; Stepanova, Maria; Rafiq, Nila; Goodman, Zachary; Chandhoke, Vikas; Baranova, Ancha

    2008-11-01

    Within the spectrum of nonalcoholic fatty liver disease (NAFLD), only patients with nonalcoholic steatohepatitis (NASH) show convincing evidence for progression. To date, liver biopsy remains the gold standard for the diagnosis of NASH; however, liver biopsy is expensive and associated with a small risk, emphasizing the urgent need for noninvasive diagnostic biomarkers. Recent findings suggest a role for apoptosis and adipocytokines in the pathogenesis of NASH. The aim of this study was to develop a noninvasive diagnostic biomarker for NASH. The study included 101 patients with liver biopsies who were tested with enzyme-linked immunosorbent assay (ELISA)-based assays. Of these, 69 were included in the biomarker development set and 32 were included in the biomarker validation set. Clinical data and serum samples were collected at the time of biopsy. Fasting serum samples were assayed for adiponectin, resistin, insulin, glucose, TNF-alpha, IL-6, IL-8, cytokeratin CK-18 (M65 antigen), and caspase-cleaved CK-18 (M30 antigen). Data analysis revealed that the levels of M30 antigen (cleaved CK-18) predicted histological NASH with 70% sensitivity and 83.7% specificity and area under the curve (AUC) = 0.711, p < 10(-4), whereas the predictive value of the levels of intact CK-18 (M65) was higher (63.6% sensitivity and 89.4% specificity and AUC = 0.814, p < 10(-4)). Histological NASH could be predicted by a combination of Cleaved CK-18, a product of the subtraction of Cleaved CK-18 level from intact CK-18 level, serum adiponectin, and serum resistin with a sensitivity of 95.45% sensitivity, specificity of 70.21%, and AUC of 0.908 (p < 10(-4)). Blinded validation of this model confirmed its reliability for separating NASH from simple steatosis. Four ELISA-based tests were combined to form a simple diagnostic biomarker for NASH.

  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. 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.

  7. 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.

  8. STUDY ON NONALCOHOLIC STEATOHEPATITIS (NASH IN PATIENTS OF OBESE, TYPE 2 DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    Uma Shankar Mishra

    2018-02-01

    Full Text Available BACKGROUND Nonalcoholic steatohepatitis (NASH represents only a part of a wide spectrum of non-alcoholic fatty liver disease (NAFLD and its prevalence is only 2-3% in the general population. Diabetes mellitus increases the risk for severe necroinflammation. The diagnosis rests on the hallmark histological features. Liver biopsy is essential for positive diagnosis and prognostication of NASH. The aim of this study was to evaluate the correlation between NASH and risk factor like diabetes, BMI and other risk factors. MATERIALS AND METHODS 36 patients with histologically confirmed NASH with elevated liver aminotransferase and negative markers for other diseases admitted to our institution from Sept-2012 to August-2014, were included in the study, meeting our inclusion & exclusion criteria. Investigations were done & data was collected. Data were pooled & interpreted using standard statistical methods. RESULTS Twenty out of thirty-six patients had diabetes in our study i.e. 55.6% were diabetes. 22 out of 36 patients i.e. 61.1% had BMI >28 kg/m2 . the mean waist circumference in our study was 93.13 Cm. 15 out of 24 female patients i.e. 62.5% females had WC>88 cm and 8 out of 12 male patients i.e. 66.7% males had WC >102 cm., 20 out of 36 patients i.e. 55.6% patients fulfilled at least 3 out of 5 criteria and therefore had insulin resistance syndrome or metabolic syndrome. CONCLUSION Patients with NASH are typically asymptomatic unless cirrhosis develops. 97.22% patients were dyslipidaemics. NASH may be considered an additional features of insulin resistance & metabolic syndrome. Age, gender, waist circumference, BMI, ALT, AST: ALT ratio, serum triglyceride levels, HTN & BAAT score are independent predictors of NASH.

  9. Influence of Sleeve Gastrectomy on NASH and Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    W. K. Karcz

    2011-01-01

    Full Text Available Background. Nonalcoholic fatty liver disease is present in up to 85% of adipose patients and may proceed to nonalcoholic steatohepatitis (NASH. With insulin resistance and obesity being the main risk factors for NASH, the effect of isolated sleeve gastrectomy (ISG on these parameters was examined. Methods. 236 patients underwent ISG with intraoperative liver biopsy from December 2002 to September 2009. Besides demographic data, pre-operative weight/BMI, HbA1c, AST, ALT, triglycerides, HDL and LDL levels were determined. Results. A significant correlation of NASH with higher HbA1c, AST and ALT and lower levels for HDL was observed (P<.05, <.0001, <.0001, <.01, resp.. Overall BMI decreased from 45.0 ± 6.8 to 29.7 ± 6.5 and 31.6 ± 4.4 kg/m2 at 1 and 3 years. An impaired weight loss was demonstrated for patients with NASH and patients with elevated HbA1c (plateau 28.08 kg/m2 versus 29.79 kg/m2 and 32.30 kg/m2 versus 28.79 kg/m2, resp.. Regarding NASH, a significant improvement of AST, ALT, triglyceride and HDL levels was shown (P<.0001 for all. A resolution of elevated HbA1c was observed in 21 of 23 patients. Summary. NASH patients showed a significant loss of body weight and amelioration of NASH status. ISG can be successfully performed in these patients and should be recommended for this subgroup.

  10. Nonalcoholic steatohepatitis (NASH) after pancreaticoduodenectomy: association of pancreatic exocrine deficiency and infection.

    Science.gov (United States)

    Murata, Yasuhiro; Mizuno, Shugo; Kato, Hiroyuki; Kishiwada, Masashi; Ohsawa, Ichiro; Hamada, Takashi; Usui, Masanobu; Sakurai, Hiroyuki; Tabata, Masami; Nishimura, Keisuke; Fukutome, Kazuo; Isaji, Shuji

    2011-08-01

    Previous clinical study has demonstrated that 30-40% of patients undergoing pancreaticoduodenectomy (PD) developed hepatic steatosis. However, nonalcoholic steatohepatitis (NASH) is a little-known complication after PD. Recently we encountered two patients with PD who later developed NASH diagnosed by liver biopsy. Case 1 was a 79-year-old woman who underwent PD for intraductal papillary mucinous neoplasm (IPMN). She had postoperative severe diarrhea due to pseudomembranous enterocolitis. Severe liver dysfunction was observed on the 31st postoperative day. Abdominal computed tomography (CT) on the 32nd day showed remarkably decreased hepatic CT value of 6 HU. Immediate liver biopsy revealed NASH (Brunt criteria: grade 2, stage 2). Case 2 was a 71-year-old woman who underwent PD for IPMN. Liver biopsy on 70th postoperative day, which was performed for assessment of moderate liver dysfunction and decreased hepatic CT value of 44 HU, demonstrated simple steatosis. In the 21st postoperative month, she developed severe urinary tract infection together with marked liver dysfunction. Immediate liver biopsy revealed NASH (Brunt criteria: grade 1, stage 1). For each patient, treatment of infection and high-dose pancreatic enzyme supplements improved liver dysfunction and liver steatosis. Clinical features of our cases seem to support the current leading hypothesis of the pathogenesis of NASH, i.e., the two-hit theory.

  11. 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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Jiawei Li

    Full Text Available 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.

  14. 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

  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. Nash equilibrium in differential games and the construction of the programmed iteration method

    International Nuclear Information System (INIS)

    Averboukh, Yurii V

    2011-01-01

    This work is devoted to the study of nonzero-sum differential games. The set of payoffs in a situation of Nash equilibrium is examined. It is shown that the set of payoffs in a situation of Nash equilibrium coincides with the set of values of consistent functions which are fixed points of the program absorption operator. A condition for functions to be consistent is given in terms of the weak invariance of the graph of the functions under a certain differential inclusion. Bibliography: 18 titles.

  17. 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

  18. 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

  19. Statins improve NASH via inhibition of RhoA and Ras

    DEFF Research Database (Denmark)

    Schierwagen, Robert; Maybüchen, Lara; Hittatiya, Kanishka

    2016-01-01

    . Hepatic steatosis, inflammation, and fibrosis were assessed by histology, Western blot, and RT-PCR measurements of cholesterol and hydroxyproline content. SMV treatment significantly decreased hepatic inflammation and fibrosis, but had no significant effect on steatosis and hepatic cholesterol content...... by statins is responsible for the beneficial hepatic effects in NASH....

  20. 75 FR 41518 - Match-E-Be-Nash-She-Wish (Gun Lake) Tribe Liquor Control Ordinance

    Science.gov (United States)

    2010-07-16

    ... ethyl alcohol, hydrated oxide of ethyl, or spirit of wine, commonly produced by the fermentation or... benefit of the Tribe. (j) ``Tribe'' means the Match-E-Be-Nash-She-Wish Band of Pottawatomi Indians of... and wine shall be purchased from distributors licensed by the Michigan Liquor Control Commission. (f...

  1. 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.

  2. Remediating Language Deficient/Dyslexic College Students: An Interview with Robert Nash.

    Science.gov (United States)

    Lundquist, Arlene J.; Nash, Robert

    1988-01-01

    Robert Nash responds to questions concerning his personal and professional background, the Simultaneous Multisensory Instructional Procedure for Teaching the Complete Sound Structure of the Language, problems associated with dyslexia, the social/emotional impact of learning disabilities, and the University of Wisconsin's Project Success for…

  3. On the Open-Loop Nash Equilibrium in LQ-Games

    NARCIS (Netherlands)

    Engwerda, J.C.

    1996-01-01

    In this paper we consider open-loop Nash equilibria of the linear-quadratic differential game.As well the finite-planning-horizon, the infinite-planning horizon as convergence properties of the finite-planning-horizon equilibrium if the planning horizon is extended to infinity are studied.Particular

  4. Motion – All Patients with NASH Need to Have a Liver Biopsy: Arguments for the Motion

    Directory of Open Access Journals (Sweden)

    Jayant A Talwalkar

    2002-01-01

    Full Text Available Previously regarded as an obscure disorder, nonalcoholic steatohepatitis (NASH has recently emerged as an important chronic liver disease. NASH is within a spectrum of disorders characterized by excessive accumulation of fat in the liver, including simple hepatic steatosis (fatty liver, inflammation and necrosis (steatohepatitis, and fibrosis. Collectively, the disorders are called nonalcoholic fatty liver disease (NAFLD. Estimates of the prevalence of these individual conditions are suspect because liver biopsy is required for definitive diagnosis and is not generally performed. Although these conditions have traditionally been thought of as diseases of obese women, and are frequently associated with diabetes mellitus and hypertriglyceridemia, they have also been identified in lean men. Insulin resistance appears to be a common factor. These conditions are difficult to distinguish from each other clinically, and no biochemical or radiological test reliably establishes the diagnosis. A ratio of serum aspartate to alanine aminotransferase levels of less than one can distinguish NAFLD from alcoholic liver disease, but this is a nonspecific finding. Fatty infiltration imparts a diffuse echogenicity to the liver at ultrasonography, but this test cannot easily distinguish fat from fibrous tissue or identify cases of NASH. Only histological examination can establish the diagnosis of NASH, grade its severity, determine the prognosis and guide treatment.

  5. NASH and atherosclerosis are two aspects of a shared disease : Central role for macrophages

    NARCIS (Netherlands)

    Bieghs, Veerle; Rensen, Patrick C. N.; Hofker, Marten H.; Shiri-Sverdlov, Ronit

    Macrophage infiltration into the atherosclerotic lesion is known to play a central role in the initiation of atherosclerosis. In contrast, the role of macrophages during the etiology of non-alcoholic steatohepatitis (NASH) has been considered to be merely a late consequence of steatosis. However,

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. Optimization, Monotonicity and the Determination of Nash Equilibria — An Algorithmic Analysis

    Science.gov (United States)

    Lozovanu, D.; Pickl, S. W.; Weber, G.-W.

    2004-08-01

    This paper is concerned with the optimization of a nonlinear time-discrete model exploiting the special structure of the underlying cost game and the property of inverse matrices. The costs are interlinked by a system of linear inequalities. It is shown that, if the players cooperate, i.e., minimize the sum of all the costs, they achieve a Nash equilibrium. In order to determine Nash equilibria, the simplex method can be applied with respect to the dual problem. An introduction into the TEM model and its relationship to an economic Joint Implementation program is given. The equivalence problem is presented. The construction of the emission cost game and the allocation problem is explained. The assumption of inverse monotony for the matrices leads to a new result in the area of such allocation problems. A generalization of such problems is presented.

  12. 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

  13. 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 ...

  14. MicroRNA Expression Relating to Dietary-Induced Liver Steatosis and NASH

    Directory of Open Access Journals (Sweden)

    Aida Zarfeshani

    2015-11-01

    Full Text Available Health issues associated with excessive caloric intake and sedentary lifestyle are driving a modern “epidemic” of liver disease. Initially presenting in the clinic as an excessive accumulation of fat within hepatocyte cells (steatosis, the progression to more severe non-alcoholic steatohepatitis (NASH in which liver damage and inflammation are overt features, is becoming increasingly common. Often developing as a sequela of obesity, non-alcoholic fatty liver disease (NAFLD arises in almost one-third of people initially carrying excess hepatic fat and is likely the result of the liver’s limited capacity to cope with the modern-day levels of dietary fatty acids circulating in the blood. While routine imaging can readily assess the presence and level of “extra-hepatic fat”, a proper diagnosis of disease progression to NASH is currently only possible by liver biopsy. A general reluctance to undergo such screening means that the prevalence of NASH is likely to be under reported and, thus, risk assessment for future metabolic syndrome (MetS markedly compromised. The seemingly inevitable progression to overt insulin resistance that characterizes MetS may in part be the consequence of the body’s attempt to cope with NAFLD by driving systemic insulin sensitivity and, thus, fatty acid breakdown. The potential significance of miRNAs in both physiological homeostasis and pathogenesis is increasingly appreciated and in the liver may contribute specifically to the regulation of lipid pathways and NAFLD progression. As such, they may have utility as molecular indicators for the accurate profiling of both initial risk and disease progression from simple steatosis to NASH, and further to fibrosis/cirrhosis.

  15. 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...

  16. 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.

  17. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, David, E-mail: schneide@tandar.cnea.gov.ar [Departamento de Fisica, Comision Nacional de EnergIa Atomica. Av. del Libertador 8250, 1429 Buenos Aires (Argentina)

    2011-03-04

    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.

  19. 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

  20. Serum Oxidative Stress Markers and Lipidomic Profile to Detect NASH Patients Responsive to an Antioxidant Treatment: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Paola Stiuso

    2014-01-01

    Full Text Available Liver steatosis can evolve to steatohepatitis (NASH through a series of biochemical steps related to oxidative stress in hepatocytes. Antioxidants, such as silybin, have been proposed as a treatment of patients with nonalcoholic fatty liver disease (NAFLD and NASH. In this study, we evaluated, in patients with histologically documented NASH, the oxidant/antioxidant status and lipid “fingerprint” in the serum of NASH patients, both in basal conditions and after 12 months of treatment with silybin-based food integrator Realsil (RA. The oxidant/antioxidant status analysis showed the presence of a group of patients with higher basal severity of disease (NAS scores 4.67 ± 2.5 and a second group corresponding to borderline NASH (NAS scores = 3.8 ± 1.5. The chronic treatment with RA changed the NAS score in both groups that reached the statistical significance only in group 2, in which there was also a significant decrease of serum lipid peroxidation. The lipidomic profile showed a lipid composition similar to that of healthy subjects with a restoration of the values of free cholesterol, lysoPC, SM, and PC only in group 2 of patients after treatment with RA. Conclusion. These data suggest that lipidomic and/or oxidative status of serum from patients with NASH could be useful as prognostic markers of response to an antioxidant treatment.

  1. 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

  2. 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

  3. Vozvrashtshenije "Tihhogo Dona" / Tatjana Hartshenko

    Index Scriptorium Estoniae

    Hartshenko, Tatjana

    2006-01-01

    Sergei Bondartshuki teleseriaali "Vaikne Don" (M. Sholohhovi teose järgi) lugu. 10-seerialine epopöa oli maksmata arvete katteks 15 aastat arestituna Itaalia pangas. Seriaali on asunud uuesti monteerima režissööri poeg Fjodor Bondartshuk. Ajalehe "Pjarnuski Ekspress" vahel olev lisaleht on dateeritud 4. aprill 2006, nr. 12

  4. "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

  5. 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.

  6. Iterative algorithms for computing the feedback Nash equilibrium point for positive systems

    Science.gov (United States)

    Ivanov, I.; Imsland, Lars; Bogdanova, B.

    2017-03-01

    The paper studies N-player linear quadratic differential games on an infinite time horizon with deterministic feedback information structure. It introduces two iterative methods (the Newton method as well as its accelerated modification) in order to compute the stabilising solution of a set of generalised algebraic Riccati equations. The latter is related to the Nash equilibrium point of the considered game model. Moreover, we derive the sufficient conditions for convergence of the proposed methods. Finally, we discuss two numerical examples so as to illustrate the performance of both of the algorithms.

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

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Tvede, Mich

    2012-01-01

    In this paper we consider the minimum cost spanning tree model. We assume that a central planner aims at implementing a minimum cost spanning tree not knowing the true link costs. The central planner sets up a game where agents announce link costs, a tree is chosen and costs are allocated according...... 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...

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18.  The product of triglycerides and glucose as biomarker for screening simple steatosis and NASH in asymptomatic women.

    Science.gov (United States)

    Simental-Mendía, Luis E; Simental-Mendía, Esteban; Rodríguez-Hernández, Heriberto; Rodríguez-Morán, Martha; Guerrero-Romero, Fernando

    2016-01-01

     Introduction and aim. Given that early identification of non-alcoholic fatty liver disease (NAFLD) is an important issue for primary prevention of hepatic disease, the objectives of this study were to evaluate the efficacy of the product of triglyceride and glucose levels (TyG) for screening simple steatosis and non-alcoholic steatohepatitis (NASH) in asymptomatic women, and to compare its efficacy vs. other biomarkers for recognizing NAFLD. Asymptomatic women aged 20 to 65 years were enrolled into a cross-sectional study. The optimal values of TyG, for screening simple steatosis and NASH were established on a Receiver Operating Characteristic scatter plot; the sensitivity, specificity, and likelihood ratios of TyG index were estimated versus liver biopsy. According sensitivity and specificity, the efficacy of TyG was compared versus the well-known clinical biomarkers for recognizing NAFLD. A total of 50 asymptomatic women were enrolled. The best cutoff point of TyG for screening simple steatosis was 4.58 (sensitivity 0.94, specificity 0.69); in addition, the best cutoff point of TyG index for screening NASH was 4.59 (sensitivity 0.87, specificity 0.69). The positive and negative likelihood ratios were 3.03 and 0.08 for simple steatosis, and 2.80 and 0.18 for NASH. As compared versus SteatoTest, NashTest, Fatty liver index, and Algorithm, the TyG showed to be the best test for screening. TyG has high sensitivity and low negative likelihood ratio; as compared with other clinical biomarkers, the TyG showed to be the best test for screening simple steatosis and NASH.

  19. 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

  20. 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

  1. 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

  2. 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...

  3. 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)

  4. 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.

  5. 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.

  6. 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)

  7. Development, Testing, and Psychometric Qualities of the Nash Duty to Care Scale for Disaster Response.

    Science.gov (United States)

    Nash, Tracy Jeanne

    2017-08-01

    Although nurses struggle with the decision to report for work during disaster events, there are no instruments to measure nurses' duty to care for disaster situations. The purpose of this study was to describe the development, testing, and psychometric qualities of the Nash Duty to Care Scale. A convenience sample of 409 registered nurses were recruited from 3 universities in the United States. Exploratory factor analysis resulted in a 19-item, 4-factor model explaining 67.34% of the variance. Internal consistency reliability was supported by Cronbach's alpha ranging from .81 to .91 for the 4-factor subscales and .92 for the total scale. The psychometrically sound instrument for measuring nurses' perceived duty to care for disasters is applicable to contemporary nursing practice, institutional disaster management plans, and patient health outcomes worldwide.

  8. Midkine Increases Diagnostic Yield in AFP Negative and NASH-Related Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Roslyn Vongsuvanh

    Full Text Available Robust biomarkers for population-level hepatocellular carcinoma (HCC surveillance are lacking. We compared serum midkine (MDK, dickkopf-1 (DKK1, osteopontin (OPN and AFP for HCC diagnosis in 86 HCC patients matched to 86 cirrhotics, 86 with chronic liver disease (CLD and 86 healthy controls (HC. Based on the performance of each biomarker, we assessed a separate longitudinal cohort of 28 HCC patients, at and before cancer diagnosis. Serum levels of MDK and OPN were higher in HCC patients compared to cirrhosis, CLD and HC groups. DKK1 was not different between cases and controls. More than half of HCC patients had normal AFP. In this AFP-negative HCC cohort, 59.18% (n = 29/49 had elevated MDK, applying the optimal cut-off of 0.44 ng/ml. Using AFP ≥ 20 IU/ml or MDK ≥ 0.44 ng/ml, a significantly greater number (76.7%; n = 66/86 of HCC cases were detected. The area under the receiver operating curve for MDK was superior to AFP and OPN in NASH-HCC diagnosis. In the longitudinal cohort, MDK was elevated in 15/28 (54% of HCC patients at diagnosis, of whom 67% had elevated MDK 6 months prior.AFP and MDK have a complementary role in HCC detection. MDK increases the diagnostic yield in AFP-negative HCC and has greater diagnostic performance than AFP, OPN and DKK-1 in the diagnosis of NASH-HCC. Additionally, MDK has a promising role in the pre-clinical diagnosis of HCC.

  9. 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.

  10. 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.

  11. NAFLD and NASH in HCV Infection: Prevalence and Significance in Hepatic and Extrahepatic Manifestations

    Directory of Open Access Journals (Sweden)

    Luigi Elio Adinolfi

    2016-05-01

    Full Text Available The aim of this paper is to review and up to date the prevalence of hepatitis C virus (HCV-associated non-alcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH and their significance in both accelerating progression of HCV-related liver disease and development of HCV-associated extrahepatic diseases. The reported mean prevalence of HCV-related NAFLD was 55%, whereas NASH was reported in 4%–10% of cases. HCV genotype 3 directly induces fatty liver deposition, namely “viral steatosis” and it is associated with the highest prevalence and degree of severity, whereas, HCV non-3 genotype infection showed lower prevalence of steatosis, which is associated with metabolic factors and insulin resistance. The host’s genetic background predisposes him or her to the development of steatosis. HCV’s impairment of lipid and glucose metabolism causes fatty liver accumulation; this seems to be a viral strategy to optimize its life cycle. Irrespective of insulin resistance, HCV-associated NAFLD, in a degree-dependent manner, contributes towards accelerating the liver fibrosis progression and development of hepatocellular carcinoma by inducing liver inflammation and oxidative stress. Furthermore, NAFLD is associated with the presence of metabolic syndrome, type 2 diabetes, and atherosclerosis. In addition, HCV-related “metabolic steatosis” impairs the response rate to interferon-based treatment, whereas it seems that “viral steatosis” may harm the response rate to new oral direct antiviral agents. In conclusion, a high prevalence of NAFLD occurs in HCV infections, which is, at least in part, induced by the virus, and that NAFLD significantly impacts progression of the liver disease, therapeutic response, and some extrahepatic diseases.

  12. Results from exploratory drill hole UE2ce, Northwest Yucca Flat, Nevada Test Site, near the NASH Event

    International Nuclear Information System (INIS)

    Pawloski, G.A.

    1982-01-01

    Exploratory drill hole UE2ce was drilled in January 1977 to determine geologic and geophysical characteristics of this site. This report presents geophysical logs, lithology, geologic structure, water table measurements, and physical properties for this drill hole. The data are then extrapolated to the NASH site, an event in U2ce, 55.6 m due north of UE2ce

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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".

  18. 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.

  19. Transcriptome analysis to investigate the link between obesity and its metabolic complications : type 2 diabetes and NASH

    NARCIS (Netherlands)

    Wolfs, Marcel Guillaume Maria

    2012-01-01

    Wereldwijd zijn meer dan een half miljard mensen te dik. Dit is een enorm probleem, omdat zwaarlijvigheid vaak leidt tot ernstige ziekten zoals ouderdomssuikerziekte en Niet-Alcoholische SteatoHepatitis (NASH; soort leverontsteking). De oorzaak van de obesitas-epidemie ligt voor een belangrijk deel

  20. 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.

  1. Nash points, Ky Fan inequality and equilibria of abstract economies in Max-Plus and -convexity

    Science.gov (United States)

    Briec, Walter; Horvath, Charles

    2008-05-01

    -convexity was introduced in [W. Briec, C. Horvath, -convexity, Optimization 53 (2004) 103-127]. Separation and Hahn-Banach like theorems can be found in [G. Adilov, A.M. Rubinov, -convex sets and functions, Numer. Funct. Anal. Optim. 27 (2006) 237-257] and [W. Briec, C.D. Horvath, A. Rubinov, Separation in -convexity, Pacific J. Optim. 1 (2005) 13-30]. We show here that all the basic results related to fixed point theorems are available in -convexity. Ky Fan inequality, existence of Nash equilibria and existence of equilibria for abstract economies are established in the framework of -convexity. Monotone analysis, or analysis on Maslov semimodules [V.N. Kolokoltsov, V.P. Maslov, Idempotent Analysis and Its Applications, Math. Appl., volE 401, Kluwer Academic, 1997; V.P. Litvinov, V.P. Maslov, G.B. Shpitz, Idempotent functional analysis: An algebraic approach, Math. Notes 69 (2001) 696-729; V.P. Maslov, S.N. Samborski (Eds.), Idempotent Analysis, Advances in Soviet Mathematics, Amer. Math. Soc., Providence, RI, 1992], is the natural framework for these results. From this point of view Max-Plus convexity and -convexity are isomorphic Maslov semimodules structures over isomorphic semirings. Therefore all the results of this paper hold in the context of Max-Plus convexity.

  2. 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.

  3. The Computation of Nash Equilibrium in Fashion Games via Semi-Tensor Product Method

    Institute of Scientific and Technical Information of China (English)

    GUO Peilian; WANG Yuzhen

    2016-01-01

    Using the semi-tensor product of matrices,this paper investigates the computation of pure-strategy Nash equilibrium (PNE) for fashion games,and presents several new results.First,a formal fashion game model on a social network is given.Second,the utility function of each player is converted into an algebraic form via the semi-tensor product of matrices,based on which the case of two-strategy fashion game is studied and two methods are obtained for the case to verify the existence of PNE.Third,the multi-strategy fashion game model is investigated and an algorithm is established to find all the PNEs for the general case.Finally,two kinds of optimization problems,that is,the so-called social welfare and normalized satisfaction degree optimization problems are investigated and two useful results are given.The study of several illustrative examples shows that the new results obtained in this paper are effective.

  4. 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.

  5. The uptake of uranium from soil to vetiver grass (vetiver zizanioides (L.) nash)

    International Nuclear Information System (INIS)

    Luu Viet Hung; Bui Duy Cam; Dang Duc Nhan

    2012-01-01

    Uranium uptake of vetiver grass (Vetiveria zizanioides (L.) Nash) from Eutric Fluvisols (AK), Albic Acrisols (LP), Dystric Fluvisols (TT) and Ferralic Acrisols (TC) in northern Vietnam is assessed. The soils were mixed with aqueous solution of uranyl nitrate to make soils be contaminated with uranium at 0, 50, 100, 250 mg per 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 soil properties. CEC facilitates the uptake and the increase soil pH could reduce the uptake and translocation of uranium in the plant. Organic matter content as well as ferrous and potassium inhibit the uranium uptake of the grass. It was revealed that the lower fertile soil the higher uranium uptake. The grass could tolerate to the high extent (up to 77%) of uranium in soils and could survive and grow well without fertilization. The translocation of uranium in root for all the soil types studies almost higher than that in its shoot. It seem that vetiver grass potentially be use for the purpose of phytoremediation of soils contaminated with uranium. (author)

  6. Quality and Pricing Decisions in a Two-Echelon Supply Chain with Nash Bargaining Fairness Concerns

    Directory of Open Access Journals (Sweden)

    Ji-cai Li

    2018-01-01

    Full Text Available Product quality and pricing, as the important competitive tools, play a key role in attracting consumers. In a supply chain, the decisions on product quality and pricing are usually interlinked and would influence the cooperation relation between the members, especially when they are fairness-concerned and have different bargaining power. However, linking the quality and pricing decisions to the decision-makers’ behavioral factors such as fairness concern draws a little attention in the literature of supply chain management. This paper incorporates the members’ fairness preference and bargaining power into the product quality and pricing decisions in a two-echelon supply chain, where the supplier offers core components with a certain quality level to the downstream manufacturer, who subsequently sells the final products in the end market. Both the supplier and the manufacturer are assumed to be fairness-concerned by adopting Nash bargaining solutions as their fairness reference points. We use game-theoretic models to analyze the equilibrium product quality and pricing strategies under the setting of integrated and decentralized supply chain, respectively. Detailed comparisons and sensitivity analysis are further conducted to examine the impacts of members’ strengths of fairness concern, bargaining power, and decision structure on their equilibrium product quality and pricing strategies and corresponding payoffs.

  7. Nonalcoholic steatohepatitic (NASH) mice are protected from higher hepatotoxicity of acetaminophen upon induction of PPARα with clofibrate

    International Nuclear Information System (INIS)

    Donthamsetty, Shashikiran; Bhave, Vishakha S.; Mitra, Mayurranjan S.; Latendresse, John R.; Mehendale, Harihara M.

    2008-01-01

    The objective was to investigate if the hepatotoxic sensitivity in nonalcoholic steatohepatitic mice to acetaminophen (APAP) is due to downregulation of nuclear receptor PPARα via lower cell division and tissue repair. Male Swiss Webster mice fed methionine and choline deficient diet for 31 days exhibited NASH. On the 32nd day, a marginally toxic dose of APAP (360 mg/kg, ip) yielded 70% mortality in steatohepatitic mice, while all non steatohepatitic mice receiving the same dose survived. 14 C-APAP covalent binding, CYP2E1 protein, and enzyme activity did not differ from the controls, obviating increased APAP bioactivation as the cause of amplified APAP hepatotoxicity. Liver injury progressed only in steatohepatitic livers between 6 and 24 h. Cell division and tissue repair assessed by 3 H-thymidine incorporation and PCNA were inhibited only in the steatohepatitic mice given APAP suggesting that higher sensitivity of NASH liver to APAP-induced hepatotoxicity was due to lower tissue repair. The hypothesis that impeded liver tissue repair in steatohepatitic mice was due to downregulation of PPARα was tested. PPARα was downregulated in NASH. To investigate whether downregulation of PPARα in NASH is the critical mechanism of compromised liver tissue repair, PPARα was induced in steatohepatitic mice with clofibrate (250 mg/kg for 3 days, ip) before injecting APAP. All clofibrate pretreated steatohepatitic mice receiving APAP exhibited lower liver injury, which did not progress and the mice survived. The protection was not due to lower bioactivation of APAP but due to higher liver tissue repair. These findings suggest that inadequate PPARα expression in steatohepatitic mice sensitizes them to APAP hepatotoxicity

  8. 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 OCA showed a trend towards higher scavenger receptor Class B type I (SR-BI) and lower LDL-receptor hepatic protein expression. OCA reduced NAS score for inflammation (P OCA as observed in humans, and should be useful for evaluating novel drugs targeting NASH. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. 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.

  10. Nash, el último fundador de la teoría de juegos, y la evolución del concepto de equilibrio desde Cournot

    OpenAIRE

    Streb, Jorge M.

    2015-01-01

    Nash recibió el premio Nobel de economía por dos aportes fundamentales: la distinción entre juegos cooperativos y no cooperativos, y el concepto de solución básico para juegos no cooperativos. Myerson indica que este equilibrio es el concepto de solución básico de teoría de juegos dado que, como señala Nash, los juegos cooperativos se pueden reducir a un juego no cooperativo más amplio agregando la negociación previa. El equilibrio de Nash puede verse también como equilibrio de Cournot-Nash p...

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

    Directory of Open Access Journals (Sweden)

    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

  12. 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

  13. 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

  14. 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.

  15. Field geochemical studies of groundwaters in Nash Draw, southeastern New Mexico

    International Nuclear Information System (INIS)

    Lambert, S.J.; Robinson, K.L.

    1984-08-01

    Physiochemical properties of effluents from 15 pump tests in the water-producing horizons intercepted by six holes in Nash Draw east of the WIPP site in southeastern New Mexico were field-measured at intervals of a few hours. These properties were Eh, pH, specific conductance, specific gravity, bicarbonate/carbonate, chloride, divalent cations, calcium, hydrogen sulfide, and total iron. Observations were made over periods of 17 to 184 h, during which the measurements reached varying degrees of steady state, but not necessarily equilibrium. The most useful indicators of steady state were divalent cations, chloride, and in some cases Eh. Typically, bicarbonate changed significantly during a pump test, seldom reaching steady state. This observation and the drilling history have shown that, given the nongeological sources of carbon, radiocarbon results will be difficult to interpret. Heavy-metal contamination from iron pipe in a well was not purged simply by displacing a well-bore volume, but is some complex function of armor-coating of iron by corrosion. This process of armor-coating is, in turn, influenced by pump rate, instantaneous solid-to-liquid ratio, dissolved gases, and aqueous thermodynamic properties. Thus, further determinations of trace constituents associated with heavy metals must be interpreted with care in view of the iron content. Reliable sampling of pumped wells requires a long observation time; detailed documentation of procedures, apparatus, and hole history; and a commitment of human and financial resources that may be much greater than those required for conventional laboratory analyses. 13 references, 15 figures, 19 tables

  16. Epilepsy management in older people: Lessons from National Audit of Seizure management in Hospitals (NASH).

    Science.gov (United States)

    Ziso, B; Dixon, P A; Marson, A G

    2017-08-01

    Epilepsy is the third most common diagnosis in older people, however management in this group remains variable. National Audit of Seizure management in Hospitals (NASH) set out to assess care provided to patients attending hospitals in England following a seizure. 154 Emergency Departments (EDs) across the UK took part. 1256 patients aged 60 years or over were included for analysis (median age 74 years, 54% men). 51% were known to have epilepsy, 17% had history of previous seizure or blackout and 32% presented with a suspected first seizure. 14% of older patients with epilepsy were not on treatment, 59% were on monotherapy. Sodium valproate was the most commonly used antiepileptic, 28%. 35% of patients with epilepsy, aged 60 and over, had a CT during admission compared to only 17% of those under 60. 80% of patients aged 60 and over presenting with a likely first seizure were admitted to hospital, compared to 65% of those under 60. 34% of those with suspected first seizure were referred to a neurologist on discharge compared to 68% of patients under the age of 60. 52% of 60-69year olds with a suspected first seizure were referred to neurology compared to 25% of patients aged 80-89. Older patients presenting with seizures are more likely to be admitted to hospital and have imaging. They are less likely to be referred to specialist services on discharge. There appears to be significant disparity in patient age and rate of referral. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  17. 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

  18. 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.

  19. 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)

  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. 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

  2. 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

  3. 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.

  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. Increased Tim-3 expression alleviates liver injury by regulating macrophage activation in MCD-induced NASH mice.

    Science.gov (United States)

    Du, Xianhong; Wu, Zhuanchang; Xu, Yong; Liu, Yuan; Liu, Wen; Wang, Tixiao; Li, Chunyang; Zhang, Cuijuan; Yi, Fan; Gao, Lifen; Liang, Xiaohong; Ma, Chunhong

    2018-05-07

    As an immune checkpoint, Tim-3 plays roles in the regulation of both adaptive and innate immune cells including macrophages and is greatly involved in chronic liver diseases. However, the precise roles of Tim-3 in nonalcoholic steatohepatitis (NASH) remain unstated. In the current study, we analyzed Tim-3 expression on different subpopulations of liver macrophages and further investigated the potential roles of Tim-3 on hepatic macrophages in methionine and choline-deficient diet (MCD)-induced NASH mice. The results of flow cytometry demonstrated the significantly increased expression of Tim-3 on all detected liver macrophage subsets in MCD mice, including F4/80 + CD11b + , F4/80 + CD68 + , and F4/80 + CD169 + macrophages. Remarkably, Tim-3 knockout (KO) significantly accelerated MCD-induced liver steatosis, displaying higher serum ALT, larger hepatic vacuolation, more liver lipid deposition, and more severe liver fibrosis. Moreover, compared with wild-type C57BL/6 mice, Tim-3 KO MCD mice demonstrated an enhanced expression of NOX2, NLRP3, and caspase-1 p20 together with increased generation of IL-1β and IL-18 in livers. In vitro studies demonstrated that Tim-3 negatively regulated the production of reactive oxygen species (ROS) and related downstream pro-inflammatory cytokine secretion of IL-1β and IL-18 in macrophages. Exogenous administration of N-Acetyl-L-cysteine (NAC), a small molecular inhibitor of ROS, remarkably suppressed caspase-1 p20 expression and IL-1β and IL-18 production in livers of Tim-3 KO mice, thus significantly reducing the severity of steatohepatitis induced by MCD. In conclusion, Tim-3 is a promising protector in MCD-induced steatohepatitis by controlling ROS and the associated pro-inflammatory cytokine production in macrophages.

  6. [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

  7. 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

  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. 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.

  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. Branched-chain amino acids alleviate hepatic steatosis and liver injury in choline-deficient high-fat diet induced NASH mice.

    Science.gov (United States)

    Honda, Takashi; Ishigami, Masatoshi; Luo, Fangqiong; Lingyun, Ma; Ishizu, Yoji; Kuzuya, Teiji; Hayashi, Kazuhiko; Nakano, Isao; Ishikawa, Tetsuya; Feng, Guo-Gang; Katano, Yoshiaki; Kohama, Tomoya; Kitaura, Yasuyuki; Shimomura, Yoshiharu; Goto, Hidemi; Hirooka, Yoshiki

    2017-04-01

    For successful treatment for nonalcoholic steatohepatitis (NASH), it may be important to treat the individual causative factors. At present, however, there is no established treatment for this disease. Branched-chain amino acids (BCAAs) have been used to treat patients with decompensated cirrhosis. In order to elucidate the mechanisms responsible for the effects of BCAAs on hepatic steatosis and disease progression, we investigated the effects of BCAA supplementation in mice fed a choline-deficient high-fat diet (CDHF), which induces NASH. Male mice were divided into four groups that received (1) choline-sufficient high fat (HF) diet (HF-control), (2) HF plus 2% BCAA in drinking water (HF-BCAA), (3) CDHF diet (CDHF-control), or (4) CDHF-BCAA for 8weeks. We monitored liver injury, hepatic steatosis and cholesterol, gene expression related to lipid metabolism, and hepatic fat accumulation. Serum alanine aminotransferase (ALT) levels and hepatic triglyceride (TG) were significantly elevated in CDHF-control relative to HF-control. Liver histopathology revealed severe steatosis, inflammation, and pericellular fibrosis in CDHF-control, confirming the NASH findings. Serum ALT levels and hepatic TG and lipid droplet areas were significantly lower in CDHF-BCAA than in CDHF-control. Gene expression and protein level of fatty acid synthase (FAS), which catalyzes the final step in fatty acid biosynthesis, was significantly decreased in CDHF-BCAA than in CDHF-control (PBCAA was significantly lower than those of CDHF-control. BCAA can alleviate hepatic steatosis and liver injury associated with NASH by suppressing FAS gene expression and protein levels. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. 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

    histology in nondiabetic patients with insulin resistance and NASH. Decrease in BMI through diet and exercise significantly improved HOMA - IR scores, serum...BMI through diet and exercise significantly improved HOMA - IR scores, serum aminotransferases and liver histology. 15. SUBJECT TERMS 16. SECURITY...insulin resistance (or HOMA - IR ) score was calculated using the formula: fasting insulin (mIU/ml) fasting glu- cose (mg/dl)/405 [Matthews et al. 1985

  14. Modulatory role of Co-enzyme Q10 on methionine and choline deficient diet-induced non-alcoholic steatohepatitis (NASH) in albino rats.

    Science.gov (United States)

    Saleh, Dalia O; Ahmed, Rania F; Amin, Mohamed M

    2017-03-01

    The present study aimed to evaluate the hepato-protective and neuro-protective activity of Co-enzyme Q10 (CoQ10) on non-alcoholic steatohepatitis (NASH) in albino rats induced by methionine and choline-deficient (MCD) diet. Rats were fed an MCD diet for 8 weeks to induce non-alcoholic steatohepatitis. CoQ10 (10 mg/(kg·day) -1 ) was orally administered for 2 consecutive weeks. Twenty-four hours after the last dose of the drug, the behavioral test, namely the activity cage test, was performed and the activity counts were recorded. Serum alanine transaminase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, total/direct bilirubin, and albumin were valued to assess liver function. Moreover, hepatic cytokines interleukin-6 as well as its modulator nuclear factor kappa-light-chain-enhancer of activated B cells were determined. In addition, brain biomarkers, viz ammonia, nitric oxide, and brain-derived neurotrophic factor (BDNF), were measured as they are reliable indices to assess brain damage. Histopathological and immunohistochemical examination of brain proliferating cell nuclear antigen in brain and liver tissues were also evaluated. Results revealed that MCD-induced NASH showed impairment in the liver functions with an increase in the liver inflammatory markers. Moreover, NASH resulted in pronounced brain dysfunction as evidenced by hyper-locomotor activity, a decrease in the BDNF level, as well as an increase in the brain nitric oxide and ammonia contents. Oral treatment of MCD-diet-fed rats with CoQ10 for 14 days showed a marked improvement in all the assigned parameters. Finally, it can be concluded that CoQ10 has a hepatoprotective and neuroprotective role in MCD-diet-induced NASH in rats.

  15. Assessment of the impact of a parameter estimation method for the Nash Model on selected parameters of a catchment discharge hydrograph

    Directory of Open Access Journals (Sweden)

    Kołodziejczyk Katarzyna

    2017-01-01

    Full Text Available An analysis of the usefulness of two parameter calculation methods (N and k parameters for the Nash Model was performed to transform effective rainfall into discharge based on two rainfall episodes gauged at the Kostrze gauging station as well as urban development data for the city of Cracow for 2014 and data obtained from a soil and agriculture map. The methods were the Rao et al. method and the Bajkiewicz-Grabowska method for regression relationships between instantaneous unit hydrograph model parameters and the physiographic parameters of a catchment. Effective rainfall was calculated for each rainfall episode using the SCS-CN method. A direct discharge hydrograph was calculated based on an effective rainfall hyetograph and using the Nash Model. Research has found that both studied methods yield comparable results, which indicates that both methods of effective rainfall transformation into discharge are useful. In addition, it has been shown that the impact of the Nash Model parameter estimation method on discharge hydrographs is minimal.

  16. 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.

  17. 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.

  18. 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

  19. 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"

  20. National Audit of Seizure management in Hospitals (NASH): results of the national audit of adult epilepsy in the UK.

    Science.gov (United States)

    Dixon, Peter A; Kirkham, Jamie J; Marson, Anthony G; Pearson, Mike G

    2015-03-31

    About 100,000 people present to hospitals each year in England with an epileptic seizure. How they are managed is unknown; thus, the National Audit of Seizure management in Hospitals (NASH) set out to assess prior care, management of the acute event and follow-up of these patients. This paper describes the data from the second audit conducted in 2013. 154 emergency departments (EDs) across the UK. Data from 4544 attendances (median age of 45 years, 57% men) showed that 61% had a prior diagnosis of epilepsy, 12% other neurological problems and 22% were first seizure cases. Each ED identified 30 consecutive adult cases presenting due to a seizure. Details were recorded of the patient's prior care, management at hospital and onward referral to neurological specialists onto an online database. Descriptive results are reported at national level. Of those with epilepsy, 498 (18%) were on no antiepileptic drug therapy and 1330 (48%) were on monotherapy. Assessments were often incomplete and witness histories were sought in only 759 (75%) of first seizure patients, 58% were seen by a senior doctor and 57% were admitted. For first seizure patients, advice on further seizure management was given to 264 (27%) and only 55% were referred to a neurologist or epilepsy specialist. For each variable, there was wide variability among sites that was not explicable. For the sites who partook in both audits, there was a trend towards better care in 2013, but this was small and dwarfed by the intersite variability. These results have parallels with the Sentinel Audit of Stroke performed a decade earlier. There is wide intersite variability in care covering the entire care pathway, and a need for better organised and accessible care for these patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Nash otvet Tsereteli

    Index Scriptorium Estoniae

    2006-01-01

    Tallinna linnavõimud alustavad tööd Kalevipoja kuju Tallinna lahte püstitamiseks. Skulptuuri autor Tauno Kangro soovitab15 m kõrguse kuju püstitada Lauluväljaku lähedale merre. Insener Paavo Pikandi kommentaarid

  2. 02 Nash 02.pmd

    African Journals Online (AJOL)

    Owner

    2009-06-23

    Jun 23, 2009 ... reisbrief”, “Brown travel letter”); his role in the underground politics of ... Around the time that Breyten Breytenbach became active in ... must be made real by being lived and by transforming the lives of those who uphold them ...

  3. 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.

  4. 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.

  5. 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

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

    International Nuclear Information System (INIS)

    Murphy, Mark B.

    1999-01-01

    The overall objective of this project is to demonstrate that a development program based on advanced reservoir management methods can significantly improve oil recovery at the Nash Draw Pool (NDP). The plan includes developing a control area using standard reservoir management techniques and comparing its performance to an area developed using advanced reservoir management methods. Specific goals are (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 oil and gas producers in the Permian Basin and elsewhere throughout the U.S. oil and gas industry

  7. 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

  8. 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)

  9. Alleviation of insulin resistance and liver damage by oral administration of Imm124-E is mediated by increased Tregs and associated with increased serum GLP-1 and adiponectin: results of a phase I/II clinical trial in NASH

    Directory of Open Access Journals (Sweden)

    Mizrahi M

    2012-12-01

    Full Text Available Meir Mizrahi,1 Yehudit Shabat,1 Ami Ben Ya'acov,1 Gadi Lalazar,1 Tomer Adar,1 Victor Wong,2 Brian Muller,2 Grant Rawlin,2 Yaron Ilan11Liver Unit, Hebrew University-Hadassah Medical Center, Jerusalem, Israel; 2Immuron Limited, North Melbourne, AustraliaBackground: Nonalcoholic steatohepatitis (NASH is considered to be part of the nonalcoholic fatty liver disorders and its incidence is increasing. Imm124-E (Immuron Ltd, Melbourne, Australia, containing hyperimmune bovine colostrum, has been shown to exert an immunomodulatory effect and to alleviate target organ damage in animal models of NASH. The aim of our study was to determine the safety and efficacy of oral administration of Imm124-E to patients with insulin resistance and NASH.Methods: In an open-label trial, ten patients with biopsy-proven NASH and insulin resistance were orally treated with Imm124-E for 30 days.Results: Oral administration of Imm124-E was safe, and no side effects were noted. Alleviation of insulin resistance was reflected by significantly improved hemoglobin A1c (HbA1c values in all ten treated patients. For between five and eight responders, the following effects were noted: a decrease in fasting glucose levels; improved oral glucose tolerance test (OGGT and homeostatic model assessment insulin resistance (HOMA scores; and alleviation in lipid profile. These effects were accompanied by increased serum levels of glucagon-like peptide 1 (GLP-1, adiponectin and T regulatory cells.Conclusion: Hyperimmune colostrum alleviates NASH.Keywords: NASH, anti-LPS, diabetes, adipokines, regulatory T cells

  10. An optimized Nash nonlinear grey Bernoulli model based on particle swarm optimization and its application in prediction for the incidence of Hepatitis B in Xinjiang, China.

    Science.gov (United States)

    Zhang, Liping; Zheng, Yanling; Wang, Kai; Zhang, Xueliang; Zheng, Yujian

    2014-06-01

    In this paper, by using a particle swarm optimization algorithm to solve the optimal parameter estimation problem, an improved Nash nonlinear grey Bernoulli model termed PSO-NNGBM(1,1) is proposed. To test the forecasting performance, the optimized model is applied for forecasting the incidence of hepatitis B in Xinjiang, China. Four models, traditional GM(1,1), grey Verhulst model (GVM), original nonlinear grey Bernoulli model (NGBM(1,1)) and Holt-Winters exponential smoothing method, are also established for comparison with the proposed model under the criteria of mean absolute percentage error and root mean square percent error. The prediction results show that the optimized NNGBM(1,1) model is more accurate and performs better than the traditional GM(1,1), GVM, NGBM(1,1) and Holt-Winters exponential smoothing method. Copyright © 2014. Published by Elsevier Ltd.

  11. MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: Clinical trials to clinical practice

    Science.gov (United States)

    Dulai, Parambir S.; Sirlin, Claude B.; Loomba, Rohit

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) represents one of the most common causes of chronic liver disease, and its prevalence is rising worldwide. The occurrence of nonalcoholic steatohepatitis (NASH) is associated with a substantial increase in disease related morbidity and mortality. Accordingly, there has been a surge of innovation surrounding drug development in an effort to off-set the natural progression and long-term risks of this disease. Disease assessment within clinical trials and clinical practice for NAFLD is currently done with liver biopsies. Liver biopsy-based assessments, however, remain imprecise and are not without cost or risk. This carries significant implications for the feasibility and costs of bringing therapeutic interventions to market. A need therefore arises for reliable and highly accurate surrogate end-points that can be used in phase 2 and 3 clinical trials to reduce trial size requirements and costs, while improving feasibility and ease of implementation in clinical practice. Significant advances have now been made in magnetic resonance technology, and magnetic resonance imaging (MRI) and elastrography (MRE) have been demonstrated to be highly accurate diagnostic tools for the detection of hepatic steatosis and fibrosis. In this review article, we will summarize the currently available evidence regarding the use of MRI and MRE among NAFLD patients, and the evolving role these surrogate biomarkers will play in the rapidly advancing arena of clinical trials in NASH and hepatic fibrosis. Furthermore, we will highlight how these tools can be readily applied to routine clinical practice, where the growing burden of NAFLD will need to be met with enhanced monitoring algorithms. PMID:27312947

  12. 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.

  13. 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

  14. Fracture propagation through a layered shale and limestone sequence at Nash Point, South Wales: Implications on the development of fracture networks in layered sequences

    Science.gov (United States)

    Forbes Inskip, N.; Meredith, P. G.; Gudmundsson, A.

    2017-12-01

    While considerable effort has been expended on the study of fracture propagation in rocks in recent years, our understanding of how fractures propagate through sedimentary rocks composed of layers with different mechanical and elastic properties remains poor. Yet the mechanical layering is a key parameter controlling the propagation of fractures in sedimentary sequences. Here we report measurements of the contrasting properties of the Lower Lias at Nash Point, South Wales, which comprises a sequence of interbedded shale and limestone layers, and how those properties influence fracture propagation. The static Young's modulus (Estat) of both rock types has been measured parallel and normal to bedding. The shale is highly anisotropic, with Estat varying from 2.4 GPa, in the bedding-normal orientation, to 7.9 GPa, in the bedding-parallel orientation, yielding an anisotropy of 107%. By contrast the limestone has a very low anisotropy of 8%, with Estat values varying from 28.5 GPa, in the bedding-normal orientation, to 26.3 GPa in the bedding-parallel orientation. It follows that for a vertical fracture propagating in this sequence the modulus contrast is by a factor of about 12. This is important because the contrast in elastic properties is a key factor in controlling whether fractures arrest, deflect, or propagate across interfaces between layers in a sequence. Preliminary numerical modelling results (using a finite element modelling software) of induced fractures at Nash Point demonstrate a rotation of the maximum principal compressive stress across interfaces but also the concentration of tensile stress within the more competent (high Estat) limestone layers. The tensile strength (σT), using the Brazil-disk technique, and fracture toughness (KIc), using the semi-circular bend methodology, of both rock types have been measured. Measurements were made in the three principal orientations relative to bedding, Arrester, Divider, and Short-Transverse, and also at 15

  15. Derivation of the Euler characteristic and the curvature of Cantorian-fractal spacetime using Nash Euclidean embedding and the universal Menger sponge

    International Nuclear Information System (INIS)

    El Naschie, M.S.

    2009-01-01

    The present work gives an analytical derivation of the curvature K of fractal spacetime at the point of total unification of all fundamental forces which is marked by an inverse coupling constant equal α-bar gs =26.18033989. To do this we need to first find the exact dimensionality of spacetime. This turned out to be n = 4 for the topological dimension and ∼ =4+φ 3 =4.236067977 for the intrinsic Hausdorff dimension. Second we need to find the Euler characteristic of our fractal spacetime manifold. Since E-infinity Cantorian spacetime is accurately modelled by a fuzzy K3 Kaehler manifold, we just need to extend the well known value χ=24 of a crisp K3 to the case of a fuzzy K3. This leads then to χ(fuzzy)=26+k=α-bar gs . The final quite surprising result is that at the point of unification of our resolution dependent fractal-Cantorian spacetime manifold we encounter a Coincidencia Egregreium, namely K=χ=D=α-bar gs =26+k=26.18033989. Finally we look for some indirect experimental evidence for the correctness of our result using the COBE measurement in conjunction with Nash embedding of the universal Menger sponge.

  16. Nevidannoje kino-6 / Igor Glazistov ; interv. Tatjana Lavrova

    Index Scriptorium Estoniae

    Glazistov, Igor

    2006-01-01

    3. ja 4. juunil toimus Maardus ja Tallinnas 6. rahvusvaheline lühifilmide festival "Ennenägematu Film" ("Nevidannoje kino"). Festivali organisaator, noortestuudio "MEKSVIDEO" juht Igor Glazistov festivalist ja tulevikuplaanidest

  17. 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

  18. Po plodam ihh uznajete ihh / Olev Raju ; interv. Tatjana Opekina

    Index Scriptorium Estoniae

    Raju, Olev, 1948-

    2005-01-01

    Ilmunud ka: Pravo i Pravda 30. august lk. 6-7. Tartu ülikooli majandusprofessor õiglusest ühiskonnas, tendentsidest nn kahe Eesti struktuuris, probleemidest Eesti majanduses, uuest riigieelarve projektist, tööpuudusest

  19. 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

  20. Vozmozhen li amerikanskii variant na narvskoi potshve? / Tatjana Gritsenko

    Index Scriptorium Estoniae

    Gritsenko, Tatjana

    2007-01-01

    Narva linnavalitsuse delegatsioon külastas programmi International Visitor Leadership Program raames USA-d. Visiidi eesmärgiks oli tutvuda kohalike omavalitsuste tööga. Ülevaate külaskäigust teeb Narva abilinnapea Sofja Homjakova

  1. 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

  2. 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

  3. Bud tvortsom v muzeje KUMU / Jelena Levtshenkova ; interv. Tatjana Lavrova

    Index Scriptorium Estoniae

    Levtshenkova, Jelena

    2006-01-01

    KUMU integratsiooniprogrammide kuraatoriga muuseumi haridusprojektidest. Muuseum pakub ligi 20 kunstiharidusprogrammi, meistriklasse, kursusi ja õpetust KUMU kunstikoolis. Hariduskeskust juhib Piret Kruusandi, haridusprogrammide kuraator on Anu Lüsi, kunstnik-metoodik Anu Purre ja assistent Kätlin Tischler

  4. 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

  5. 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

  6. Ot Gannibala do "Russkogo bunta" / Tatjana Mühlbeier

    Index Scriptorium Estoniae

    Mühlbeier, Tatjana

    2000-01-01

    Eestis elanud legendaarsest A. Pushkini vaarisast Abram Hannibalist ja temaga seoses ka sama ajastut kujutavast vene režissööri Aleksandr Proshkini uuest ajaloolisest mängufilmist "Vene mäss" ("Russki bunt")

  7. 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

  8. The Creative Genius: John Nash

    Indian Academy of Sciences (India)

    IAS Admin

    ity, and capacity for seeing the inner meaning of an argument, all unrivalled in my ... he started working on David Hilbert's 19th problem, 'Are the solutions of regular ... awarded the Sveriges Riksbank Prize in Economic Sciences in Memory of ...

  9. Nash Shirvindt - babnik! / Oksana Truhhan

    Index Scriptorium Estoniae

    Truhhan, Oksana

    2005-01-01

    Komöödiafilm "Naistemees" ("Babnik") : stsenarist ja režissöör Anatoli Eiramdzhan : osades Aleksandr Shirvindt, Mihhail Derzhavin, Irina Muravjova : NSV Liit 1990. Režissöör ja näitlejad meenutavad filmivõtteid

  10. 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

  11. Nash otvet Tshemberlenu / Igor Dmitrijev

    Index Scriptorium Estoniae

    Dmitrijev, Igor

    2006-01-01

    Vastukaaluks ENPA poolt vastu võetud kommunistlike režiimide inimsusevastaste kuritegude hukkamõistvale resolutsioonile kavandab Venemaa Kommunistlik Partei vastusammuna Moskvas toimuval vasakparteide kongressil liberaalsete kapitalistlike režiimide kuritegusid hukkamõstva memorandumi vastuvõttu

  12. 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 ...

  13. 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

  14. 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

  15. Hvad er din virksomheds Nash-equilibrium?

    DEFF Research Database (Denmark)

    Hendricks, Vincent F.

    2006-01-01

    Wargames fra 1983 med Matthew Broderick og Ally Sheedy i hovedrollerne. Forskellige ”populærkulturelle” game-shows har også elementer af spilteori i deres grundlæggende struktur, herunder Friend or Foe, Survivor og de danske plagiater som Robinson Ekspeditionen, Big Brother, og hvad de andre simulerede...

  16. 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...

  17. 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

  18. 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

  19. 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

  20. Nash tshelovek v "Gazprome" / Virkko Lepassalu

    Index Scriptorium Estoniae

    Lepassalu, Virkko, 1971-

    2006-01-01

    Vene ajaleht Komsomolskaja Pravda avaldas infot, miks Eestile müüdi aastate jooksul jätkuvalt Euroopa tasemega arvestades odavamat gaasi. Ajaleht Vesti Dnja kontrollis Komsomolskaja Pravda andmete paikapidavust. Gaasihinna, põlevkiviõli hinna tõusust Eestis

  1. 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 ...

  2. 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 ...

  3. 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.

  4. Nash buksirovshtshik stanet krupneishim / Artur Tooman

    Index Scriptorium Estoniae

    Tooman, Artur, 1971-

    2008-01-01

    Puksiirettevõtete SIA PKL ja SIA Ostas Flote ühinemisel tekib Läänemere põhjaosa suurim kompanii, millest pool kuulub Eesti firmale PKL Holding AS ja teine pool tuntud Läti ärimehele Oleg Stepanovile

  5. Imidzh - eto nashe vsjo / Eteri Kekelidze

    Index Scriptorium Estoniae

    Kekelidze, Eteri, 1944-

    2006-01-01

    Eesti riiklikud, munitsipaal- ning eraorganisatsioonid, mis tegelevad turismiga, peaksid edasise edu suurendamiseks ja riigi imidzhi parandamiseks kooskõlastatult tegutsema. Tallinnas toimunud rahvusvahelisest messist TOUREST 2006, turismialane statistika

  6. "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

  7. Knut i prjanik v kulture / David Vseviov ; tõlk. Tatjana Nikitina

    Index Scriptorium Estoniae

    Vseviov, David, 1949-

    2006-01-01

    Põhjamaade ja Baltimaade kultuurisituatsioonidest pärast Teist maailmasõda. Piitsa ja prääniku poliitikast kultuuris. Võimalusest, et eestlased seisavad praegu sama valiku ees kui etruskid 2000 aastat tagasi, kuna ohtu osatakse näha ainult piitsas, mitte präänikus

  8. 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

  9. 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

  10. 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

  11. Mari e-raamatukogu / Tatjana Verina ; vene keelest tõlkinud Ene Riet

    Index Scriptorium Estoniae

    Verina, Tatjana

    2011-01-01

    Mari e-raamatukogu loomise aluseks on Mari-Eli Vabariigi etnokultuuriliste ja rahvusvaheliste suhete arendamise projekt, hetkel on elektroonilises raamatukogus 52 täistekstilist teavikut Tšavaini nimelise Mari Rahvusraamatukogu haruldaste raamatute kogust

  12. 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

  13. 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

  14. 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

  15. Odnu detalnuju planirovku v raione Edize Iõhvi prinjal, druguju - provalil / Tatjana Leppik

    Index Scriptorium Estoniae

    Leppik, Tatjana

    2008-01-01

    Jõhvis toimus kahe detailplaneeringu eskiislahenduse avalik arutelu. Projekteerimisfirma BF Projektibüroo esitles Mesinduse katastriüksuse eskiisi, mis nägi ette äripindade rajamist, mille käigus tuleks lammutada ajalooline ehitis. Jõhvi peaarhitekti Andres Toome vastuargumendid. Tartu firma AS Kobras esitatud tulevaste ärihoonete eskiisid katastriüksusele Valge teenisid Jõhvi valla heakskiidu

  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. 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

  18. 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

  19. 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)

  20. 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

  1. 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

  2. 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

  3. Delo o 15 millionah dollarov, ili Istorija s kontrabandoi, krazhami, obmanom i podozrenijem v ubiistve / Tatjana Jurassova

    Index Scriptorium Estoniae

    Jurassova, Tatjana

    1998-01-01

    Nikolai Hardzhijevi (1903-1996) arhiivi saatusest. Arhiivi kunsti-osa moodustasid Malevitshi, Larionovi, Tatlini, Gontsharovi, Lissitski jt. (1355 eks.) tööd. N. Hardzhijev oli teadlane, vene avangardi (kunstnikud, poeedid) parim tundja

  4. "Krasnaja gvozdika - sputnitsa trevog, krasnaja gvozdika - nash tsvetok"

    Index Scriptorium Estoniae

    2001-01-01

    Kommentaarid Mart Laari lillevalikule uue presidendi õnnitlemisel. Pealk. ajalehes Molodjozh Estonii : Subbota (2001/Sep/29) lk. 8: "I gde tolko Laar vzjal eti tsvetõ?". Refereeritud Eve Heinla artiklit "Kust küll Laar need lilled sai?", Õhtuleht (2001/Sep/25)

  5. 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

  6. 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)

  7. 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 ...

  8. 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

  9. Tallinn - eto nash s vami gorod / Leivi Sher

    Index Scriptorium Estoniae

    Šer, Leivi, 1941-

    2007-01-01

    Linnavolikogu valis 5. aprillil Tallinna linnapeaks Keskerakonna esimehe Edgar Savisaare. Rääkides ees ootavatest ülesannetest, loetles E. Savisaar ئ Vabaduse väljaku uuendamine, Kopli liinid, Pae park

  10. 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

  11. Nash put v budushtsheje / Mihhail Stalnuhhin ; interv. Aleksandr Mjassojedov

    Index Scriptorium Estoniae

    Stalnuhhin, Mihhail, 1961-

    2005-01-01

    Narva volikogu esimees Mihhail Stalnuhhin osales Šveitsis toimunud rahvusvahelisel konverentsil "Multikultuurilisus ja 21. sajandi etnopoliitilised mudelid", konverentsil räägitust ning teemadest, mis puudutasid Eestit

  12. Shtirlits sovetski, a Istomin prosto nash! / Jekaterina Saltõkova

    Index Scriptorium Estoniae

    Saltõkova, Jekaterina

    2008-01-01

    Seoses Juri Morozi uue Teist Maailmasõda kujutava seriaaliga "Apostel" arutletakse sõjaseriaalide ja filmide üha kasvava tootmise üle. Režissöörid Sergei Ursuljak ("Likvideerimine") ja Igor Zaitsev ("Diversant") lühidalt oma seriaalidest

  13. 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

  14. 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

  15. Nõukogude Liidu kõige kaunimad näitlejannad : Kümme portreed ja lühikest biograafiat = Самые красивые актрисы Советского Союза : Десять портретов и кратких биографий

    Index Scriptorium Estoniae

    2009-01-01

    Vene näitlejannade Irina Alferova, Anastassia Vertinskaja, Tatjana Doronina, Irina Mirošnitšenko, Ljubov Orlova, Tatjana Samoilova, Anna Samohhina, Svetlana Svetlitšnaja, Margarita Terehhova ja Natalja Fatejeva lühibiograafiad

  16. 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

    the charging time and increases the share of EVs as commuting mode, it results in unintended consequences including electricity peak-load problem, an increase in electricity tariff for household use, and an increase in car use that worsens traffic congestion. For the electricity supplier, workplace charging...... and when the labor tax is high; ii) employers pay less electricity tariff than households do; iii) the employment contract duration is long; iv) recharging electric vehicles (EVs) takes longer time and the value of time is higher. Accessibility of cheaper charging facility at workplace, while saves...... increases the cost of supplying electricity by aggravating the daytime peak-load problem and by increasing the demand variation from the mean. Tax based on yearly travel distance, and restriction on free workplace charging access improves social welfare. The results from this study are relevant in (i...

  17. Nash evolutionary algorithms : Testing problem size in reconstruction problems in frame structures

    OpenAIRE

    Greiner, D.; Periaux, Jacques; Emperador, J.M.; Galván, B.; Winter, G.

    2016-01-01

    The use of evolutionary algorithms has been enhanced in recent years for solving real engineering problems, where the requirements of intense computational calculations are needed, especially when computational engineering simulations are involved (use of finite element method, boundary element method, etc). The coupling of game-theory concepts in evolutionary algorithms has been a recent line of research which could enhance the efficiency of the optimum design procedure and th...

  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. A Probable Case of Burn-out NASH Caused by Panhypopituitarism

    Science.gov (United States)

    Terawaki, Yuichi; Murase, Kunitaka; Motonaga, Ryoko; Tanabe, Makito; Nomiyama, Takashi; Shakado, Satoshi; Mizoguchi, Mikiro; Sakisaka, Shotaro; Yanase, Toshihiko

    2016-03-01

    A 38-year-old man diagnosed with craniopharyngioma at 8 years old underwent repeated surgery and radiation therapy. Complications included panhypopituitarism including growth hormone deficiency and hypogonadism at 13 years old. At 26 years of age, a slight fatty liver was found, which finally developed into liver cirrhosis (LC) at 35 years old. Viral infection or other etiologies causing LC were negative on serum examinations. Liver biopsy suggested a possibility of burn-out non-alcoholic steatohepatitis. This case indicates that a long-standing growth hormone deficiency and hypogonadism may lead to LC as a type of burn-out non-alcoholic steatohepatitis.

  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. 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.

  3. 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.

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

    Science.gov (United States)

    ... and increase your chance of becoming obese. Four types of fats are saturated fats , found in meat, poultry skin, ... of nuts. Omega-3 fatty acids are a type of polyunsaturated fat. Sources include oily fish such as salmon, walnuts, ...

  5. 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

    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....

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

    OpenAIRE

    Sarparandeh, Mohammad Hossein; Ehsan, Mehdi

    2017-01-01

    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 make...

  7. Role of metabolic overload and metabolic inflammation in the development of Nonalcoholic Steatohepatitis (NASH)

    NARCIS (Netherlands)

    Liang, W.

    2015-01-01

    Overload of nutrients can lead to diet-induced inflammation, also called metabolic inflammation, which is thought to play an important role in many metabolic diseases, including the development of nonalcoholic fatty liver disease (NAFLD). NAFLD encompasses a spectrum of pathologies that range from

  8. NASH BARGAINING BASED BANDWIDTH ALLOCATION IN COGNITIVE RADIO FOR DELAY CRITICAL APPLICATIONS

    Directory of Open Access Journals (Sweden)

    Kalyani Kulkarni

    2015-11-01

    Full Text Available In order to effectively regulate the existing resources, dynamic spectrum access in cognitive radio needs to adopt the effective resource allocation strategies. Multimedia applications require large bandwidth and have to meet the delay constraints while maintaining the data quality. Game theory is emerging as an effective analytical tool for the analysis of available resources and its allocation. This paper addresses resource allocation schemes employing bargaining game model for Multi-carrier CDMA based Cognitive Radio. Resource allocation scheme is designed for transmission of video over cognitive radio networks and aim to perform bandwidth allocation for different cognitive users. Utility function based on bargaining model is proposed. Primary user utility function includes the pricing factor and an upbeat factor that can be adjusted by observing the delay constraints of the video. Allocated bandwidth to the secondary user can be adjusted by changing the upbeat factor. Throughput in the proposed scheme is increased by 2% as compared to other reported pricing based resource allocation schemes. The edge PSNR of reconstructed video obtained as 32.6dB resulting to optimum decoding of the video at the receiver. The study also shows upbeat factor can be used to enhanced capacity of the network.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. Eti roskoshnõje tsvetotshnõje platja! / Jelena Saar

    Index Scriptorium Estoniae

    Saar, Jelena

    2006-01-01

    Tatjana Tridvornova korraldatud Lilleballi raames toimunud konkursist "Lillekleit" Tallinnas. Võitis Regina Gurjanova töö "Sambo Vila Izabel", teise koha sai Janne Lumi ja kolmanda Jevgeni Bulahtin

  15. Kuumav disain / Kristjan Arunurm

    Index Scriptorium Estoniae

    Arunurm, Kristjan

    2008-01-01

    Eestis pakutavatest disainradiaatoritest, soovitusi radiaatori ostjatele. Kommenteerivad Zehnder esindaja Eestis Anneli Saal, Tatjana Mihhailova Radiaatorikeskusest, Meelis Saal firmast Vikingland ja Aivar Kahr firmast Airmate

  16. "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

  17. 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

  18. 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

  19. 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

  20. The possible role of hydroxylation in the detoxification of atrazine in mature vetiver (Chrysopogon zizanioides Nash) grown in hydroponics.

    Science.gov (United States)

    Marcacci, Sylvie; Raventon, Muriel; Ravanel, Patrick; Schwitzguébel, Jean-Paul

    2005-01-01

    The resistance mechanism of vetiver (Chrysopogon zizanioides) to atrazine was investigated to evaluate its potential for phytoremediation of environment contaminated with the herbicide. Plants known to metabolise atrazine rely on hydroxylation mediated by benzoxazinones, conjugation catalyzed by glutathione-S-transferases and dealkylation probably mediated by cytochromes P450. All three possibilities were explored in mature vetiver grown in hydroponics during this research project. Here we report on the chemical role of benzoxazinones in the transformation of atrazine. Fresh vetiver roots and leaves were cut to extract and study their content in benzoxazinones known to hydroxylate atrazine, such as 2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one (DIBOA), 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA) and their mono- and di-glucosylated forms. Identification of benzoxazinones was performed by thin layer chromatography (TLC) and comparison of retention factors (Rf) and UV spectra with standards: although some products exhibited the same Rf as standards, UV spectra were different. Furthermore, in vitro hydroxylation of atrazine could not be detected in the presence of vetiver extracts. Finally, vetiver organs exposed to [14C]-atrazine did not produce any significant amount of hydroxylated products, such as hydroxyatrazine (HATR), hydroxy-deethylatrazine (HDEA), and hydroxy-deisopropylatrazine (HDIA). Altogether, these metabolic features suggest that hydroxylation was not a major metabolic pathway of atrazine in vetiver.

  1. How does ANWR exploration affect OPEC behavior? - A simulation study of an open-loop cournot-nash game

    International Nuclear Information System (INIS)

    Yang, Zili

    2008-01-01

    Exploring petroleum reserves in the Alaskan Arctic National Wildlife Refuge (ANWR) has been proposed to reduce the dependence on foreign oil and to ease the energy shortage in the United States. To investigate the impacts of the ANWR exploration on strategic behavior of OPEC members, a calibrated dynamic model of oligopolistic competition and cartel collusion in the U.S. petroleum market is built in this paper. Numerical simulations on an open-loop game are used here to examine the scope and magnitude of strategic interactions between OPEC's decisions and ANWR exploration. The simulation results show that OPEC's strategic postures have much stronger effects on the U.S. petroleum market than the ANWR exploration. The simulations in this paper indicate that preventing cartel collusion by OPEC is more effective than the ANWR exploration in alleviating short petroleum supplies of the United States in the near future. (author)

  2. 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.

  3. 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...

  4. The Mathematics of Aggregation, Interdependence, Organizations and Systems of Nash Equilibria (NE): A Replacement for Game Theory

    Science.gov (United States)

    2011-06-01

    Some organizations are dark on purpose (e.g., gangs, terrorists, undercover teams); however, their purposeful darkness “leaks” information. 2...there a free-market economist in the House?, American Journal of Economics and Sociology, 66(2): 309-334. Jasny, B. R., Zahn, L.M., & Marshall, E

  5. 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

  6. 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

  7. Lennart Meri pühendusüritus tõi taas kokku kõlavad esinejad / Vahur Koorits

    Index Scriptorium Estoniae

    Koorits, Vahur, 1981-

    2008-01-01

    Tallinnas toimuvast president Lennart Meri nimelisest konverentsist teemal "Tabamata Euroopa". Esinejate seas on Euroopa Komisjoni asepresident Siim Kallas, president Toomas Hendrik Ilves, Venemaa presidendi Vladimir Putini majandusnõunik Andrei Illarionov ning ajakirja Economist Ida-Euroopa korrespondent Edward Lucas. Aruteluteemasid tutvustab konverentsi korraldava Rahvusvahelise Kaitseuuringute Keskuse juhataja Kadri Liik. Vt. samas: Euroopa sotsiaaldemokraadid peavad Eestis konverentsi. Tallinnas Reval Hotel Olümpia konverentsisaalis toimuva konverentsi "Sotsiaaldemokraatia perspektiivid 21. sajandi Euroopas" tervitussõnavõtu peab president Toomas Hendrik Ilves

  8. 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...

  9. 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

  10. Tretjakova, Alavainu ja Johanson tuuritavad Ida-Virumaal

    Index Scriptorium Estoniae

    2004-01-01

    5. apr. alustavad turneed Ida-Virumaal Ave Alavainu ja Tatjana Tretjakova, et esitleda oma luuleraamatut "2keelsed = 2jazõtshnõje" (Kärdla : A. Alavainu, 2004). Jaak Johanson laulab laule nimetatud autorite tekstidele

  11. Shahmatistõ otpravilis na Olimpiadu / interv. Gennadi Medvedjev

    Index Scriptorium Estoniae

    1996-01-01

    Eesti maletajad osalevad maleolümpial Jerevanis. Intervjuu Eesti Maleliidu presidendi Ülo Pärnitsaga ja maletajate Jaan Ehlvesti, Tatjana Fomina, Mihhail Rõtshagoviga ning FIDE kohtuniku Lembit Vahesaarega

  12. Leila Pärtelpoeg / Leila Pärtelpoeg ; interv. Ene Ammer

    Index Scriptorium Estoniae

    Pärtelpoeg, Leila, 1927-

    1998-01-01

    Leila pärtelpoeg oma elust, arengust ja loomingust. Õpingutest Tallinna Riiklikus Tarbekunstiinstituudis, õppejõududest. Stazheerimisest Ermitaazhis NSVL mööblitundja Tatjana Mihhailovna Sokolova juures

  13. 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"

  14. 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

  15. 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

  16. Podarok fotografov k 8 Marta / A. Shurina

    Index Scriptorium Estoniae

    Shurina, A.

    1999-01-01

    Naistepäevaeelsest fotonäitusest 'Objektiiv kui elu peegel' Narva kindluses. Enamik autoreid ja fotografeerituid on naised. Osalevad Tatjana Novikova, Irina Ivanen, Irina Kivimäe, Galina Bannikova, Sergei Andrejev, Valeri Boltushin jt.

  17. Investor goda narushajet stroitelnõje zakonõ / Tanel Mazur

    Index Scriptorium Estoniae

    Mazur, Tanel, 1971-

    2004-01-01

    Narva hotell-restorani "King" ebaseaduslikust ümberehitamisest. Projekti koostajad on OÜ Narva ehitusprojekti projekteerijad Tatjana Zhuravljova ja Olga Medvedjeva. Linnaarhitekti kohusetäitja Anne Halliku kommentaare

  18. 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"

  19. 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)

  20. 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

  1. Estonskije juvelirõ udivili idavirustsev / Irina Kiviselg

    Index Scriptorium Estoniae

    Kiviselg, Irina, 1961-

    1999-01-01

    Eesti Proovikoja tegevusest ja selle korraldatud juveliiride konkursist, mille töid eksponeeriti Kohtla-Järve kaupluses 'Miss Lora'. Konkursi võitjate Kristo Pacheli ja Tatjana Tsõuntshiku töödest

  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. Vaprad lucky loser'id / Jüri Aarma ; kommenteerinud Tanja Muravskaja

    Index Scriptorium Estoniae

    Aarma, Jüri, 1951-

    2009-01-01

    Tanja Muravskaja isikunäitus "Lucky Losers" Tallinna Linnagaleriis. Eksponeeritud videoportreed vene rahvusest Eesti kodanikest Dimitri Klenskist, Adolf Käisist, Anna Levandist, Tatjana Muravjovast, Mihhail Stalnuhhinist, Eduard Tomanist ja Boris Tuchist

  4. 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

  5. Krasota vetshna! / Olga Solovjova

    Index Scriptorium Estoniae

    Solovjova, Olga

    2006-01-01

    Tallinna Lilleballist ja rahvusvahelisest konkursist "Lillekleit". Võitis Regina Gurjanova töö "Sambo Vila Izabel", teise koha sai Janne Lumi ja kolmanda Jevgeni Bulahtini töö. Kommenteerib projekti autor Tatjana Tridvornova

  6. 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

  7. 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

  8. 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

  9. 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"

  10. Nash Game Model for Optimizing Market Strategies, Configuration of Platform Products in a Vendor Managed Inventory (VMI) Supply Chain for a Product Family

    NARCIS (Netherlands)

    Y. Yu (Yugang); G.Q. Huang (George)

    2009-01-01

    textabstractThis paper discusses how a manufacturer and its retailers interact with each other to optimize their product marketing strategies, platform product configuration and inventory policies in a VMI (Vendor Managed Inventory) supply chain. The manufacturer procures raw materials from multiple

  11. 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.

  12. A Study on the Effect of the Macmillan Tutorial System on the Reading Achievement of Selected First Graders in Nash County.

    Science.gov (United States)

    Smith, Ruth Suessmuth

    The purpose of this study was to determine the effect of the Macmillan Tutorial System when used as a supplement to regular classroom instruction in beginning reading. The experimental subjects were first grade children who ranked in the lower third of the distribution scores on the Macmillan Reading Readiness Test or who, in the opinion of their…

  13. Genetic Nrf2 Overactivation Inhibits the Deleterious Effects Induced by Hepatocyte-Specific c-met Deletion during the Progression of NASH

    Directory of Open Access Journals (Sweden)

    Pierluigi Ramadori

    2017-01-01

    Full Text Available We have recently shown that hepatocyte-specific c-met deficiency accelerates the progression of nonalcoholic steatohepatitis in experimental murine models resulting in augmented production of reactive oxygen species and accelerated development of fibrosis. The aim of this study focuses on the elucidation of the underlying cellular mechanisms driven by Nrf2 overactivation in hepatocytes lacking c-met receptor characterized by a severe unbalance between pro-oxidant and antioxidant functions. Control mice (c-metfx/fx, single c-met knockouts (c-metΔhepa, and double c-met/Keap1 knockouts (met/Keap1Δhepa were then fed a chow or a methionine-choline-deficient (MCD diet, respectively, for 4 weeks to reproduce the features of nonalcoholic steatohepatitis. Upon MCD feeding, met/Keap1Δhepa mice displayed increased liver mass albeit decreased triglyceride accumulation. The marked increase of oxidative stress observed in c-metΔhepa was restored in the double mutants as assessed by 4-HNE immunostaining and by the expression of genes responsible for the generation of free radicals. Moreover, double knockout mice presented a reduced amount of liver-infiltrating cells and the exacerbation of fibrosis progression observed in c-metΔhepa livers was significantly inhibited in met/Keap1Δhepa. Therefore, genetic activation of the antioxidant transcription factor Nrf2 improves liver damage and repair in hepatocyte-specific c-met-deficient mice mainly through restoring a balance in the cellular redox homeostasis.

  14. 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.

  15. 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"

  16. 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

  17. 2016 Quantum Science Gordon Research Conference

    Science.gov (United States)

    2018-01-10

    Poster Presenter Registered Barik , Sabyasachi IREAP Attendee Registered Beck, Mark Whitman College Poster Presenter Registered Béguin, Jean...Innsbruck Speaker Registered Bollinger, John J National Institute of Standards and Technology Speaker Registered Bondar, Denys I Princeton...Tatjana AFOSR Attendee Registered Dauphinais, Guillaume Université de Sherbrooke Poster Presenter Registered Davis, Emily J Stanford University

  18. 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

  19. "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

  20. 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"

  1. MMi pronksimehed Jaanson-Endrekson sõuaksid meeleldi koos Pekingi olümpialgi / Marko Paloveer

    Index Scriptorium Estoniae

    Paloveer, Marko

    2007-01-01

    Vt. ka Postimees : na russkom jazõke 3. sept., lk. 13. Treener Tatjana Jaansoni käe all harjutavad sõudjad Jüri Jaanson ja Tõnu Endrekson üritavad tänavuse kogemuse najal ajastada tippvormi vähem kui aasta pärast algavateks Pekingi olümpiamängudeks

  2. 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

  3. 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

  4. 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

  5. South African Journal of Education - Vol 37, No 2 (2017)

    African Journals Online (AJOL)

    Inclusive values in the planning of Mathematical issues at an early age · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Veselin Mićanović, Tatjana Novović, Biljana Maslovarić. http://dx.doi.org/10.15700/saje.v37n2a1267 ...

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Eesti kullassepad üllatasid idavirulasi / Irina Kiviselg

    Index Scriptorium Estoniae

    Kiviselg, Irina, 1961-

    1999-01-01

    Vestlus Eesti Proovikoja direktori Tõnu Tõnniste ja tema korraldatud juveliiride konkursi võitja Kristo Pacheliga (teiseks jäi Tatjana Tshõuntshik) eesti juveelikunstist ja proovikoja tegevusest; konkursi töid eksponeeriti nädal aega Kohtla-Järve kaupluses "Miss Lora"

  13. 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

  14. 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

  15. 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.

  16. Modelli tabamas / Andri Ksenofontov

    Index Scriptorium Estoniae

    Ksenofontov, Andri, 1962-

    2009-01-01

    Tallinna Linnagaleriis 3. maini avatud Tanja Muravskaja isikunäitus "Lucky Losers" ("Õnnelikud kaotajad") esitab seitsme vene rahvusest Eestis tuntud inimese videoportreed. Portreteeritavad on Dimitri Klenski, Adolf Käis, Anna Levandi, Tatjana Muravjova, Mihhail Stalnuhhin, Eduard Toman ja Boris Tuch

  17. Volodimir Makarenko / Volodimir Makarenko ; interv. Reet Varblane

    Index Scriptorium Estoniae

    Makarenko, Volodimir

    2002-01-01

    Eestist 1981. a. Pariisi läinud kunstnik V. Makarenko, kelle tööd on väljas Vene t. avatud Magnoni galerii (galerist Tatjana Mangus) avanäitusel, erootilise kunsti väljapanekul "Art-delikatess, kevad 2002", läbilöögivõimalusest Pariisis kunstnikuna, sidemetest Eestiga, ajakirjast "kunst.ee"

  18. Kak gotovjatsja art-delikatesõ / Galina Balashova

    Index Scriptorium Estoniae

    Balashova, Galina

    2002-01-01

    Uue galerii MAGNON avamisest Tallinnas Vene tänaval (galerist Tatjana Mangus) erootikateemalise näitusega "Art-delikatess". Vladimir Makarenko, Slava Semerikovi, Vladimir Baciu, Igor Balashovi, Anatoli Strahhovi, skulptorite Mihhail Duhhomjonoki, Simsoni Seakülast jt. töödest näitusel

  19. Osnovnoi instinkt / Boris Tuch

    Index Scriptorium Estoniae

    Tuch, Boris, 1946-

    2002-01-01

    Erootilise kunsti näitusest "Art-delikatess" uues galeriis "Magnon" Tallinnas, Vene tän. 19. Galerii perenaine ja näituse organiseerija on Tatjana Mangus. Osalejad loetletud (19) - maalikunstnikud, skulptorid. Näituse avamisest ja eksponeeritud töödest

  20. "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)

  1. 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)

  2. 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

  3. 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

  4. 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

  5. Музыкальная "Пышка" вызвала разные эмоции / Ирина Кивисельг ; комментировал Андрей Лобанов

    Index Scriptorium Estoniae

    Кивисельг, Ирина, 1961-

    2009-01-01

    Jõhvi Kontserdimajas etendunud Guy de Maupassant'i novelli "Rasvarull" ainetel Peterburi Riiklikus Draamateatris Liteinõil lavastatud muusikalist "Пышка". Lavastaja Vladislav Pazi, peaosas Tatjana Tuzova. Arvamust avaldavad teatri direktor Andrei Lobanov ja etenduse külastajad

  6. 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

  7. Кино на все времена! / Элла Аграновская

    Index Scriptorium Estoniae

    Аграновская, Элла, 1950-

    2009-01-01

    Vene filmirežissöör Igor Minajev, kes elab ja töötab Prantsusmaal, sai valmis teose "Kaugel Sunset-Boulevard'ist". Rollides ka Lembit Ulfsak ja vene kino legend Tatjana Samoilova. Filmi saab näha 31. märtsil Vene Kultuurikeskuse filmiklubis

  8. 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

  9. Uudised

    Index Scriptorium Estoniae

    2008-01-01

    Laulja Mati Turi kontserdist 19. apr. Kadrioru lossis. Vene viiuldaja Tatjana Grindenko ja ansambli Opus Post kontserdist 19. apr. Tallinnas dominiiklaste kloostri Katariina kirikus. USA bändi Creedence Clearwater Revival laulja John Fogerty kontserdist 26. mail Helsingi Hartwall Arenal

  10. "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

  11. 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.

  12. 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.

  13. Learning to Play Efficient Coarse Correlated Equilibria

    KAUST Repository

    Borowski, Holly P.; Marden, Jason R.; Shamma, Jeff S.

    2018-01-01

    The majority of the distributed learning literature focuses on convergence to Nash equilibria. Coarse correlated equilibria, on the other hand, can often characterize more efficient collective behavior than even the best Nash equilibrium. However

  14. 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.

  15. Special Section: Colorectal Cancer Symptoms, Diagnosis and Treatment

    Science.gov (United States)

    ... What are my risk factors for colon cancer? What can I do to reduce my risk of getting colon cancer? Photos: David Nash Former Globetrotter Star Recommends Early Screening Former Harlem Globetrotter David Nash, ...

  16. Non alcoholic steatohepatitis - Introduction

    NARCIS (Netherlands)

    Jansen, Peter L. M.

    2004-01-01

    Non-alcoholic steatohepatitis (NASH) is an underdiagnosed liver disease characterized by steatosis, necroinflammation and fibrosis. This disease may eventually develop into cirrhosis and hepatocellular carcinoma. NASH is highly prevalent among obese individuals and among patients with diabetes

  17. Nonalcoholic steatohepatitis

    NARCIS (Netherlands)

    Jansen, P. L. M.

    2004-01-01

    Nonalcoholic steatohepatitis (NASH) is an underdiagnosed liver disease characterised by steatosis, necroinflammation and fibrosis. This disease may eventually develop into cirrhosis and hepatocellular carcinoma. NASH is highly prevalent among obese individuals and among patients with diabetes

  18. 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...

  19. 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

  20. 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.

  1. 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 ...

  2. 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

  3. 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".

  4. 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

  5. Золотова: Мой отец отказал Ленину / Татьяна Золотова ; интервьюировал Андрей Бабин

    Index Scriptorium Estoniae

    Золотова, Татьяна, 1909-2010

    2009-01-01

    100. sünnipäeva tähistab 1914. aastast tallinlane Tatjana Zolotova, sünd. Kašneva, kasutas seda ka kirjanikunimena. Kirjastus Aleksandra andis sel puhul välja tema mälestusteraamatu "Земная коротка наша память..." kordustrüki (1. tr. ilmus 1993. a.)

  6. Saadikud annavad aru, kas ja kuidas nende palga kallale minna

    Index Scriptorium Estoniae

    2008-01-01

    Ilmunud ka: Postimees : na russkom jazõke 12. märts lk. 2. Riigikogu liikmete vastused küsimustele palga suuruse ja palgasüsteemi muutmise kohta. Lisa: Seisukohti jaganud riigikogulased. Postimees : na russkom jazõke küsimustele vastavad: Villu Reiljan, Jürgen Ligi, Imre Sooäär, Tatjana Muravjova, Evelyn Sepp, Olga Sõtnik, Vladimir Vellman, Jüri Tamm, Peeter Kreitzberg, Aleksei Lotman, Toomas Tõniste, Mart Nutt

  7. 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

  8. 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

  9. 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

  10. De Novo and Recurrence of Nonalcoholic Steatohepatitis After Liver Transplantation.

    Science.gov (United States)

    Kappus, Matthew; Abdelmalek, Manal

    2017-05-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developing countries. Approximately 25% of patients with NAFLD develop nonalcoholic steatohepatitis (NASH). NASH-related cirrhosis is now a leading listing indication for liver transplantation in the United States. Although posttransplant survival for NASH-related cirrhosis is comparable with that of other liver diseases, many patients have features of metabolic syndrome, which can contribute to a recurrence of NAFLD or NASH. This article reviews the epidemiology, pathophysiology, and treatment of de novo and recurrence of NASH after liver transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. 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

  12. Hyperthyroidism Improves the Pathological Condition of Nonalcoholic Steatohepatitis: A Case of Nonalcoholic Steatohepatitis with Graves' Disease.

    Science.gov (United States)

    Miyake, Teruki; Matsuura, Bunzo; Furukawa, Shinya; Todo, Yasuhiko; Yamamoto, Shin; Yoshida, Osamu; Imai, Yusuke; Watanabe, Takao; Yamamoto, Yasunori; Hirooka, Masashi; Tokumoto, Yoshio; Kumagi, Teru; Abe, Masanori; Seike, Hirotaka; Miyauchi, Shozo; Hiasa, Yoichi

    2016-01-01

    3,5,3'-triiodo-L-thyronine regulates the glucose metabolism, lipid metabolism, and hepatic steatosis. Several groups have shown the relationships between hypothyroidism and nonalcoholic fatty liver and hypothyroidism and nonalcoholic steatohepatitis (NASH). However, the effect of hyperthyroidism on NASH has not yet been investigated. We herein report effects of thyroid hormone on the pathological condition of NASH in a patient with NASH complicated by Graves' disease. In our case, the liver enzyme level improved with the increasing thyroid hormone level; however, the liver enzyme level was aggravated with the improving thyroid hormone level. Therefore, hyperthyroidism may improve the pathological condition of NASH.

  13. Questionnaire survey on lifestyle of patients with nonalcoholic steatohepatitis.

    Science.gov (United States)

    Noto, Haruka; Tokushige, Katsutoshi; Hashimoto, Etsuko; Taniai, Makiko; Shiratori, Keiko

    2014-11-01

    Lack of exercise and excessive food intake are known to be the important causes of nonalcoholic steatohepatitis (NASH). To elucidate the relationship between lifestyle and NASH, we surveyed exercise and dietary habits, comparing them among 171 biopsy-proven NASH patients, 29 nonalcoholic fatty liver (NAFL) patients and 49 normal subjects. Dietary habits including the duration of dinner time, amount of rice at dinner, and weekly frequencies of meat, fries, Chinese noodles, sweets, and instant food consumption were significantly different in male NASH patients compared to normal male subjects. In women, differences were seen in the amount of rice at dinner, frequency of eating out, and proclivity for sweets. In male NASH patients, the frequency of physical exercise was significantly lower. The lifestyle tendencies of NASH were almost similar to those of NAFL. In the comparison between obese NASH and non-obese NASH, no clear lifestyle differences were found. In conclusion, the most striking result of this survey was that the lifestyle of males contributed significantly to the development of NASH. These results point to treatment of NASH in males. In female NASH patients, lifestyle differences were minimal, and the effects of other factors such as genetic background will need to be investigated.

  14. Histological Remission during Corticosteroid Therapy of Overlapping Nonalcoholic Steatohepatitis and Autoimmune Hepatitis: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Shinichiroh Fukuda

    2011-09-01

    Full Text Available Concurrence of nonalcoholic steatohepatitis (NASH with autoimmune hepatitis (AIH is a rare condition that is challenging to diagnosis, due to the relatively high prevalence of autoantibodies in NASH. It is also difficult to determine the most effective treatment as corticosteroids are likely to worsen NASH despite being effective in the treatment of AIH. In this case report, we present a female diagnosed with NASH-AIH overlap with accompanying diabetes mellitus, who successfully achieved normalization of serum alanine aminotransferase levels following prednisolone therapy and weight loss. A follow-up liver biopsy performed 40 months after the initial diagnosis showed only minimal inflammatory infiltrates in the portal area without any NASH histology. Resolution of NASH, in conjunction with a reduction in hepatic fibrosis, might suggest that prednisolone itself does not aggravate steatohepatitis, but rather prevents disease progression. Appropriate immunosuppressive treatment may therefore be an important component of the optimum therapy for NASH-AIH overlap.

  15. 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

  16. Expression of cytokine signaling genes in morbidly obese patients with non-alcoholic steatohepatitis and hepatic fibrosis.

    Science.gov (United States)

    Estep, J Michael; Baranova, Ancha; Hossain, Noreen; Elariny, Hazem; Ankrah, Kathy; Afendy, Arian; Chandhoke, Vikas; Younossi, Zobair M

    2009-05-01

    White adipose tissue (WAT) from visceral adiposity plays an important role in the pathogenesis of non-alcoholic steatohepatitis (NASH). Development of NASH and its progression to fibrosis is partially due to cytokines and adipokines produced by WAT. The aim of this study was to assess the association of hepatic fibrosis and NASH by evaluating the intrinsic differences in the inflammatory cytokine signaling in the visceral adipose tissue obtained from morbidly obese patients. We used targeted microarrays representing human genes involved in the inflammatory and fibrogenic reactions to profile visceral adipose samples of 15 well-matched NASH patients with and without fibrosis. Additionally, visceral adipose samples were subjected to real-time polymerase chain reaction profiling of 84 inflammations related genes. Eight genes (CCL2, CCL4, CCL18, CCR1, IL10RB, IL15RA, and LTB) were differentially expressed in NASH with fibrosis. Additionally, an overlapping but distinct list of the differentially expressed genes were found in NASH with type II diabetes (DM; IL8, BLR1, IL2RA, CD40LG, IL1RN, IL15RA, and CCL4) as compared to NASH without DM. Inflammatory cytokines are differentially expressed in the adipose tissue of NASH with fibrosis, as well in NASH with DM. These findings point at the interaction of adipose inflammatory cytokines, DM, hepatic fibrosis in NASH, and its progression to cirrhosis and end-stage liver disease.

  17. 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.

  18. 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

  19. The 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.......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...... are not yet clarified, and clinical results on NAFLD are ambiguous. Thus, we aimed to compare the RSV-mediated preventive and therapeutic effects on experimental NAFL and NASH. METHODS: We used a high-fat (HF) diet to generate a rat NAFL model and a high-fat, high-cholesterol (HFC) diet to generate a rat NASH...

  20. 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)

  1. Partial Cooperative Equilibria: Existence and Characterization

    Directory of Open Access Journals (Sweden)

    Amandine Ghintran

    2010-09-01

    Full Text Available We study the solution concepts of partial cooperative Cournot-Nash equilibria and partial cooperative Stackelberg equilibria. The partial cooperative Cournot-Nash equilibrium is axiomatically characterized by using notions of rationality, consistency and converse consistency with regard to reduced games. We also establish sufficient conditions for which partial cooperative Cournot-Nash equilibria and partial cooperative Stackelberg equilibria exist in supermodular games. Finally, we provide an application to strategic network formation where such solution concepts may be useful.

  2. 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...

  3. Questionnaire survey on lifestyle of patients with nonalcoholic steatohepatitis

    OpenAIRE

    Noto, Haruka; Tokushige, Katsutoshi; Hashimoto, Etsuko; Taniai, Makiko; Shiratori, Keiko

    2014-01-01

    Lack of exercise and excessive food intake are known to be the important causes of nonalcoholic steatohepatitis (NASH). To elucidate the relationship between lifestyle and NASH, we surveyed exercise and dietary habits, comparing them among 171 biopsy-proven NASH patients, 29 nonalcoholic fatty liver (NAFL) patients and 49 normal subjects. Dietary habits including the duration of dinner time, amount of rice at dinner, and weekly frequencies of meat, fries, Chinese noodles, sweets, and instant ...

  4. 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 number of patients with NASH and assess the prognosis associated with the condition in a large Danish referral centre for liver disease....

  5. Dendritic cells limit fibroinflammatory injury in nonalcoholic steatohepatitis in mice.

    Science.gov (United States)

    Henning, Justin R; Graffeo, Christopher S; Rehman, Adeel; Fallon, Nina C; Zambirinis, Constantinos P; Ochi, Atsuo; Barilla, Rocky; Jamal, Mohsin; Deutsch, Michael; Greco, Stephanie; Ego-Osuala, Melvin; Bin-Saeed, Usama; Rao, Raghavendra S; Badar, Sana; Quesada, Juan P; Acehan, Devrim; Miller, George

    2013-08-01

    Nonalcoholic steatohepatitis (NASH) is the most common etiology of chronic liver dysfunction in the United States and can progress to cirrhosis and liver failure. Inflammatory insult resulting from fatty infiltration of the liver is central to disease pathogenesis. Dendritic cells (DCs) are antigen-presenting cells with an emerging role in hepatic inflammation. We postulated that DCs are important in the progression of NASH. We found that intrahepatic DCs expand and mature in NASH liver and assume an activated immune phenotype. However, rather than mitigating the severity of NASH, DC depletion markedly exacerbated intrahepatic fibroinflammation. Our mechanistic studies support a regulatory role for DCs in NASH by limiting sterile inflammation through their role in the clearance of apoptotic cells and necrotic debris. We found that DCs limit CD8(+) T-cell expansion and restrict Toll-like receptor expression and cytokine production in innate immune effector cells in NASH, including Kupffer cells, neutrophils, and inflammatory monocytes. Consistent with their regulatory role in NASH, during the recovery phase of disease, ablation of DC populations results in delayed resolution of intrahepatic inflammation and fibroplasia. Our findings support a role for DCs in modulating NASH. Targeting DC functional properties may hold promise for therapeutic intervention in NASH. Copyright © 2013 American Association for the Study of Liver Diseases.

  6. Combined Adiponectin Deficiency and Resistance in Obese Patients: Can It Solve Part of the Puzzle in Nonalcoholic Steatohepatitis.

    Science.gov (United States)

    Salman, Ahmed; Hegazy, Mona; AbdElfadl, Soheir

    2015-06-15

    Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease, nonalcoholic steatohepatitis (NASH) and fibrosis in obese patients identifies the risk group with increased incidence of liver-related deaths. To clarify the role of serum adiponectin and its receptor liver gene expression in the progression of liver damage in NAFLD. Fifty four (54) obese patients with NAFLD preliminary diagnosed by liver ultra-sound were recruited. Full medical history, anthropometric measurement, biochemical studies, serum adiponectin level, liver biopsy for histological examination and NAS score to identify NASH patients, and assessment of adiponectin receptor gene expression by RT-PCR, were conducted for each patients. Fifteen ages matched average weight healthy adult had been chosen as a control for serum adiponectin level. According to NAS score, patients were divided into non- NASH (8 patients), and NASH (46 patients). Serum adiponectin level was significantly lower in NAFLD patients compared to normal participants (p < 0.004). Serum adiponectin level was lower in NASH patients (4.437 ± 2.569 ng/dl in NASH vs. 5.138 ± 2.841 ng/dl in non-NASH). Adiponectin receptor liver gene expression was lower in NASH patients (0.8459 ± 0.4671 vs. 1.0688 ± 0.3965 in non-NASH). Both adiponectin deficiency and resistance had a role in progression of simple liver steatosis to severe injury in obese patients.

  7. 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.

  8. Liver injury and fibrosis induced by dietary challenge in the Ossabaw miniature Swine.

    Science.gov (United States)

    Liang, Tiebing; Alloosh, Mouhamad; Bell, Lauren N; Fullenkamp, Allison; Saxena, Romil; Van Alstine, William; Bybee, Phelan; Werling, Klára; Sturek, Michael; Chalasani, Naga; Masuoka, Howard C

    2015-01-01

    Ossabaw miniature swine when fed a diet high in fructose, saturated fat and cholesterol (NASH diet) develop metabolic syndrome and nonalcoholic steatohepatitis (NASH) characterized by liver injury and fibrosis. This study was conducted to further characterize the development of NASH in this large animal model. Ossabaw swine were fed standard chow (control group; n = 6) or NASH diet (n = 6) for 24 weeks. Blood and liver tissue were collected and liver histology were characterized at 0, 8, 16 and 24 weeks of dietary intervention. Hepatic apoptosis and lipid levels were assessed at week 24. The NASH diet group developed metabolic syndrome and progressive histologic features of NASH including: (a) hepatocyte ballooning at 8 weeks which progressed to extensive ballooning (>90% hepatocytes), (b) hepatic fibrosis at week 16, which progressed to moderate fibrosis, and (c) Kupffer cell accumulation with vacuolization at 8 weeks which progressed through week 24. The NASH diet group showed increased hepatocyte apoptosis that correlated with hepatic total and free cholesterol and free fatty acids, but not esterified cholesterol or triglycerides. This report further characterizes the progression of diet-induced NASH in the Ossabaw swine model. In Ossabaw swine fed the NASH diet: (a) hepatocyte injury and fibrosis can occur without macrovesicular steatosis or excess triglyceride accumulation; (b) hepatocyte ballooning generally precedes the development of fibrosis; (c) there is increased hepatocyte apoptosis, and it is correlated more significantly with hepatic free cholesterol than hepatic free fatty acids and had no correlation with hepatic triglycerides.

  9. Liver injury and fibrosis induced by dietary challenge in the Ossabaw miniature Swine.

    Directory of Open Access Journals (Sweden)

    Tiebing Liang

    Full Text Available Ossabaw miniature swine when fed a diet high in fructose, saturated fat and cholesterol (NASH diet develop metabolic syndrome and nonalcoholic steatohepatitis (NASH characterized by liver injury and fibrosis. This study was conducted to further characterize the development of NASH in this large animal model.Ossabaw swine were fed standard chow (control group; n = 6 or NASH diet (n = 6 for 24 weeks. Blood and liver tissue were collected and liver histology were characterized at 0, 8, 16 and 24 weeks of dietary intervention. Hepatic apoptosis and lipid levels were assessed at week 24.The NASH diet group developed metabolic syndrome and progressive histologic features of NASH including: (a hepatocyte ballooning at 8 weeks which progressed to extensive ballooning (>90% hepatocytes, (b hepatic fibrosis at week 16, which progressed to moderate fibrosis, and (c Kupffer cell accumulation with vacuolization at 8 weeks which progressed through week 24. The NASH diet group showed increased hepatocyte apoptosis that correlated with hepatic total and free cholesterol and free fatty acids, but not esterified cholesterol or triglycerides.This report further characterizes the progression of diet-induced NASH in the Ossabaw swine model. In Ossabaw swine fed the NASH diet: (a hepatocyte injury and fibrosis can occur without macrovesicular steatosis or excess triglyceride accumulation; (b hepatocyte ballooning generally precedes the development of fibrosis; (c there is increased hepatocyte apoptosis, and it is correlated more significantly with hepatic free cholesterol than hepatic free fatty acids and had no correlation with hepatic triglycerides.

  10. 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)

  11. 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

  12. Kommunikatsioon eeldab keeleoskust / Reet Varblane

    Index Scriptorium Estoniae

    Varblane, Reet, 1952-

    2008-01-01

    Religiooni ja demokraatia suhteid käsitlevast rahvusvahelisest näitusest "Obscurum per obscurius" Tallinna Kunstihoones. Avatud kuni 06.07.2008. Kuraatorid Ilja Sundelevitsh ja Reet Varblane, kujundaja Liina Siib. 28 osalejat loetletud. Eestist osalevad: Anu Juurak, Leonhard Lapin, Peeter Laurits, Raul Meel, Tatjana Muravskaja, Jüri Ojaver, Terje Ojaver, Anne-Daniela Rodgers & Paul Rodgers, Liina Siib, Jaan Toomik. 28. V toimunud seminarist, kus pikemate ettekannetega esinesid Toomas Paul ja Linnar Priimägi, ning ümarlaua arutelust

  13. 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

  14. 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

  15. Low-dimensionality and predictability of solar wind and global magnetosphere during magnetic storms

    OpenAIRE

    Zivkovic, Tatjana; Rypdal, Kristoffer

    2011-01-01

    This article is part of Tatjana Živkovics' doctoral thesis. Available in Munin at http://hdl.handle.net/10037/3231 The storm index SYM-H, the solar wind velocity v, and interplanetary magnetic field Bz show no signatures of low-dimensional dynamics in quiet periods, but tests for determinism in the time series indicate that SYM-H exhibits a significant low-dimensional component during storm time, suggesting that self-organization takes place during magnetic storms. Even though our analysis...

  16. 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)

  17. 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

  18. [Prevalence of non-alcoholic fatty liver disease in a population with elevated transaminases and level of accuracy of the diagnosis in Primary Care].

    Science.gov (United States)

    Samperio-González, María Amelia; Selvi-Blasco, Marta; Manzano-Montero, Mónica; Méndez-Gómez, Judit; Gil-Prades, Montserrat; Azagra, Rafael

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated transaminases in adults. Determine the prevalence of NASH in patients with sustained hypertransaminasemia, and Know the adequacy of the registered in Primary Care (AP) diagnosis. 1) Cross-sectional study with a random sample of patients with elevated alanine aminotransferase (ALT) held (ALT> 32 for ≥6 months), ruling out other causes of liver disease, according to clinical, laboratory and ultrasound scan criteria in AP and 2) cross-sectional description of all cases diagnosed with NASH recorded (K76 - ICD10) with diagnostic adequacy analysis according to standard criteria. 290 patients were analyzed: 76 were diagnosed as NASH (26.1%), 44 women (57.9%). Multivariate analysis adjusted for age and sex showed no association between NASH and male gender (OR: 0.5; CI95%: 0.3-0.9), diabetes mellitus (DM) (OR: 2.42; CI95%: 1.2-4.9) and hypertension blood pressure (HBP) (OR: 3.07; CI 95% 1.6-5.6). Of the 209 diagnosed with NASH record: 51 (24.4%) met the criteria for NASH. The rest had insufficient records. 53.1% lacked sustained hypertransaminasemia; 48% of viral serology; 11% supported and 53.1% abdominal ultrasound registration of alcohol. Severe NASH is frequent among patients with sustained hypertransaminasemia. The DM and hypertension significantly increase the risk of NASH. The diagnosis of NASH is recorded without considering all criteria and mainly NASH made by ultrasonography. They should unify diagnostic criteria in the register of NASH. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. Governance and matching

    NARCIS (Netherlands)

    Klos, Tomas B.

    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

  5. 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.

  6. 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

  7. What does the data say about wage setting and job search?

    NARCIS (Netherlands)

    Gottfries, A.; Teulings, C.

    2015-01-01

    Do current wages depend on past labour market conditions? Wage posting models suggest so, Nash bargaining models do not, Bertrand competition between employers is somewhere in between. Recent evidence suggests Nash bargaining to be an adequate description of the data. We re-evaluate this evidence,

  8. Intervention with a caspase-1 inhibitor reduces obesity-associated hyperinsulinemia, non-alcoholic steatohepatitis and hepatic fibrosis in LDLR-/-.Leiden mice

    NARCIS (Netherlands)

    Morrison, M. C.; Mulder, P.; Salic, K.; Verheij, J.; Liang, W.; van Duyvenvoorde, W.; Menke, A.; Kooistra, T.; Kleemann, R.; Wielinga, P. Y.

    BACKGROUND/OBJECTIVES: Non-alcoholic steatohepatitis (NASH) is a serious liver condition, closely associated with obesity and insulin resistance. Recent studies have suggested an important role for inflammasome/caspase-1 in the development of NASH, but the potential therapeutic value of caspase-1

  9. Promising therapies for treatment of nonalcoholic steatohepatitis

    Science.gov (United States)

    Noureddin, Mazen; Zhang, Alice; Loomba, Rohit

    2018-01-01

    Introduction Non-alcoholic fatty liver disease (NAFLD) has become the most common etiology for abnormal aminotransferase levels and chronic liver disease. Its growing prevalence is largely linked to the presence of metabolic syndrome, particularly diabetes and insulin resistance. It is estimated that 60–80% of the type 2 diabetic population has NAFLD. NAFLD encompasses a range of conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). A subset of patients with hepatic steatosis progress to NASH, while 15–20% of patients with NASH develop cirrhosis. This progression is thought to be multifactorial, and there are currently no FDA-approved medications for the treatment of NASH. Areas covered We review drugs currently in Phase II and III clinical trials for treatment of NAFLD and NASH, including their mechanisms of action, relationship to the pathophysiology of NASH, and rationale for their development. Expert opinion The treatment of NASH is complex and necessitates targeting a number of different pathways. Combination therapy, preferably tailored toward the disease stage and severity, will be needed to achieve maximum therapeutic effect. With multiple agents currently being developed, there may soon be an ability to effectively slow or even reverse the disease process in many NAFLD/NASH patients. PMID:27501374

  10. Trapping of oxidized LDL in lysosomes of Kupffer cells is a trigger for hepatic inflammation

    NARCIS (Netherlands)

    Bieghs, Veerle; Walenbergh, Sofie M. A.; Hendrikx, Tim; van Gorp, Patrick J.; Verheyen, Fons; Olde Damink, Steven W.; Masclee, Ad A.; Koek, Ger H.; Hofker, Marten H.; Binder, Christoph J.; Shiri-Sverdlov, Ronit

    Background & Aims: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis and inflammation. The transition from steatosis towards NASH represents a key step in pathogenesis, as it will set the stage for further severe liver damage. Under normal conditions, lipoproteins that are

  11. 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

  12. 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.

  13. 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.

  14. 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…

  15. 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

  16. 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...

  17. 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......%) 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...... 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...

  18. Disease Progression in a Patient with Nonalcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Ping-Huei Tseng

    2008-10-01

    Full Text Available Nonalcoholic steatohepatitis (NASH is a severe form of nonalcoholic fatty liver disease (NAFLD. The prevalence and clinical significance of NAFLD/NASH have been increasingly recognized in Western countries but much less known in Asian countries, including Taiwan. Here, we report the case of a 43-year-old man who had abnormal liver tests for 18 years. Retrospective evaluation of his initial clinical, laboratory and histologic findings indicated that the hepatic disorder was compatible with the diagnosis of NASH. Although his liver biochemical tests improved after taking lipid-lowering agents, a liver biopsy 17 years later demonstrated histologic progression of intralobular necroinflammation and perivenular fibrosis. These facts suggest that NASH, albeit mild and slowly progressive, indeed exists in Taiwan. After the control of chronic hepatitis B and C and westernization of the lifestyle in Taiwan, an increasing burden of NAFLD/NASH is anticipated and active prophylactic measures should be implemented.

  19. Noninvasive clinical model for the diagnosis of nonalcoholic steatohepatitis in overweight and morbidly obese patients undergoing bariatric surgery.

    Science.gov (United States)

    Pirvulescu, I; Gheorghe, L; Csiki, I; Becheanu, G; Dumbravă, M; Fica, S; Martin, S; Sarbu, A; Gheorghe, C; Diculescu, M; Copăescu, C

    2012-01-01

    Liver biopsy, an invasive method, is the gold standard for differentiate nonalcoholic steatohepatitis (NASH) from other stages of fatty liver disease. A noninvasive test to diagnose NASH and disease severity before surgery and also for monitoring disease status after bariatric surgery (BS) will be an important medical challenge. To create a noninvasive biomarkers model for the diagnosis of NASH in overweight, obese and morbidly obese patients (MOP). Sixty patients (mean BMI= 47.81kg/m2) were admitted after exclusion of other causes of liver disease. Liver biopsies were obtained at the time of the bariatric surgery or by percutaneous liver biopsy and graded using Kleiner score. Continuous variables were compared using Wilcoxon rank sum test and for prediction of NASH we used logistic regression. Logistic regression analysis showed that BMI, ALT, AST, alkaline phosphatase (ALP), HOMA-R, hs-CRP, M30, M65, leptine and adiponectine levels remained independent predictors for NASH (p less than 0.02). Using AUC analysis, we established the following cutoff levels being indicative of NASH: BMI ė 47 kg/m2, ALT ė 32 IU/mL, AST ė 25 IU/mL, ALP ė 85 IU/mL, HOMA-IR ė 4, M65 ė 389 U/L. Adiponectine less than 13.5 mg/L. A NASH-score, calculated as the sum of these 7 parameters, at a cutoff level of 4 points, can accurately predict NASH (sensitivity of 90%, specificity of 93.94% and AUC of 0.9576). We propose a noninvasive model for NASH diagnosis in MOP that should be validated prospectively. Using this noninvasive score, NASH would be predicted without the risks of liver biopsy. Celsius.

  20. 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.

  1. 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.

  2. Phosphoproteomic biomarkers predicting histologic nonalcoholic steatohepatitis and fibrosis.

    Science.gov (United States)

    Younossi, Zobair M; Baranova, Ancha; Stepanova, Maria; Page, Sandra; Calvert, Valerie S; Afendy, Arian; Goodman, Zachary; Chandhoke, Vikas; Liotta, Lance; Petricoin, Emanuel

    2010-06-04

    The progression of nonalcoholic fatty liver disease (NAFLD) has been linked to deregulated exchange of the endocrine signaling between adipose and liver tissue. Proteomic assays for the phosphorylation events that characterize the activated or deactivated state of the kinase-driven signaling cascades in visceral adipose tissue (VAT) could shed light on the pathogenesis of nonalcoholic steatohepatitis (NASH) and related fibrosis. Reverse-phase protein microarrays (RPMA) were used to develop biomarkers for NASH and fibrosis using VAT collected from 167 NAFLD patients (training cohort, N = 117; testing cohort, N = 50). Three types of models were developed for NASH and advanced fibrosis: clinical models, proteomics models, and combination models. NASH was predicted by a model that included measurements of two components of the insulin signaling pathway: AKT kinase and insulin receptor substrate 1 (IRS1). The models for fibrosis were less reliable when predictions were based on phosphoproteomic, clinical, or the combination data. The best performing model relied on levels of the phosphorylation of GSK3 as well as on two subunits of cyclic AMP regulated protein kinase A (PKA). Phosphoproteomics technology could potentially be used to provide pathogenic information about NASH and NASH-related fibrosis. This information can lead to a clinically relevant diagnostic/prognostic biomarker for NASH.

  3. Multiagent Reinforcement Learning with Regret Matching for Robot Soccer

    Directory of Open Access Journals (Sweden)

    Qiang Liu

    2013-01-01

    Full Text Available This paper proposes a novel multiagent reinforcement learning (MARL algorithm Nash- learning with regret matching, in which regret matching is used to speed up the well-known MARL algorithm Nash- learning. It is critical that choosing a suitable strategy for action selection to harmonize the relation between exploration and exploitation to enhance the ability of online learning for Nash- learning. In Markov Game the joint action of agents adopting regret matching algorithm can converge to a group of points of no-regret that can be viewed as coarse correlated equilibrium which includes Nash equilibrium in essence. It is can be inferred that regret matching can guide exploration of the state-action space so that the rate of convergence of Nash- learning algorithm can be increased. Simulation results on robot soccer validate that compared to original Nash- learning algorithm, the use of regret matching during the learning phase of Nash- learning has excellent ability of online learning and results in significant performance in terms of scores, average reward and policy convergence.

  4. Teucrium polium reversed the MCD diet-induced liver injury in rats.

    Science.gov (United States)

    Amini, Rahim; Yazdanparast, Razieh; Aghazadeh, Safiyeh; Ghaffari, Seyed H

    2011-09-01

    In the present study, we evaluated the ability of Teucrium polium ethyl acetate fraction, with high antioxidant activity, in the treatment of nonalcoholic steatohepatitis (NASH) in rats and its possible effect on factors involved in pathogenesis of the disease. To induce NASH, a methionine and choline deficient (MCD) diet was given to N-Mary rats for 8 weeks. After NASH development, MCD-fed rats were divided into 2 groups: NASH group that received MCD diet and NASH + T group which was fed MCD diet plus ethyl acetate fraction of T. polium orally for 3 weeks. Histopathological evaluations revealed that treatment with the extract has abated the severity of NASH among the MCD-fed rats. In addition, the fraction reduced the elevated levels of hepatic tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) gene expression and also the elevated level of malondialdehyde (MDA). In addition, the extract increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and enhanced the level of hepatic glutathione (GSH). Moreover, the fraction treatments lowered caspase-3 level and the phosphorylated form of C-Jun N-terminal kinase (JNK) and augmented the phosphorylated level of extracellular regulated kinase1/2 (ERK1/2). These results indicate that the ethyl acetate fraction of T. poium effectively reversed NASH, mainly due to its strong antioxidant and anti-inflammatory properties.

  5. 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.

  6. 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.

  7. Rising Rates of Hepatocellular Carcinoma Leading to Liver Transplantation in Baby Boomer Generation with Chronic Hepatitis C, Alcohol Liver Disease, and Nonalcoholic Steatohepatitis-Related Liver Disease.

    Science.gov (United States)

    Cholankeril, George; Yoo, Eric R; Perumpail, Ryan B; Liu, Andy; Sandhu, Jeevin S; Nair, Satheesh; Hu, Menghan; Ahmed, Aijaz

    2017-09-26

    We aim to study the impact of the baby boomer (BB) generation, a birth-specific cohort (born 1945-1965) on hepatocellular carcinoma (HCC)-related liver transplantation (LT) in patients with chronic hepatitis C virus (HCV), alcoholic liver disease (ALD), and non-alcoholic steatohepatitis (NASH). We performed a retrospective analysis using the United Network for Organ Sharing (UNOS)/Organ Procurement Transplant Network (OPTN) database from 2003 to 2014 to compare HCC-related liver transplant surgery trends between two cohorts-the BB and non-BB-with a secondary diagnosis of HCV, ALD, or NASH. From 2003-2014, there were a total of 8313 liver transplant recipients for the indication of HCC secondary to HCV, ALD, or NASH. Of the total, 6658 (80.1%) HCC-related liver transplant recipients were BB. The number of liver transplant surgeries for the indication of HCC increased significantly in NASH (+1327%), HCV (+382%), and ALD (+286%) during the study period. The proportion of BB who underwent LT for HCC was the highest in HCV (84.7%), followed by NASH (70.3%) and ALD (64.7%). The recommendations for birth-cohort specific HCV screening stemmed from a greater understanding of the high prevalence of chronic HCV and HCV-related HCC within BB. The rising number of HCC-related LT among BB with ALD and NASH suggests the need for increased awareness and improved preventative screening/surveillance measures within NASH and ALD cohorts as well.

  8. Noninvasive Differentiation between Hepatic Steatosis and Steatohepatitis with MR Imaging Enhanced with USPIOs in Patients with Nonalcoholic Fatty Liver Disease: A Proof-of-Concept Study.

    Science.gov (United States)

    Smits, Loek P; Coolen, Bram F; Panno, Maria D; Runge, Jurgen H; Nijhof, Wouter H; Verheij, Joanne; Nieuwdorp, Max; Stoker, Jaap; Beuers, Ulrich H; Nederveen, Aart J; Stroes, Erik S

    2016-03-01

    To (a) study the optimal timing and dosing for ultrasmall superparamagnetic iron oxide particle (USPIO)-enhanced magnetic resonance (MR) imaging of the liver in nonalcoholic fatty liver disease, (b) evaluate whether hepatic USPIO uptake is decreased in nonalcoholic steatohepatitis (NASH), and (c) study the diagnostic accuracy of USPIO-enhanced MR imaging to distinguish between NASH and simple steatosis. This prospective study was approved by the local institutional review board, and informed consent was obtained from all patients. Quantitative R2* MR imaging of the liver was performed at baseline and 72 hours after USPIO administration in patients with biopsy-proven NASH (n = 13), hepatic steatosis without NASH (n = 11), and healthy control subjects (n = 9). The hepatic USPIO uptake in the liver was quantified by the difference in R2* (ΔR2*) between the contrast material-enhanced images and baseline images. Between-group differences in mean ΔR2* were tested with the Student t test, and diagnostic accuracy was tested by calculating the area under the receiver operating characteristic curve. Patients with NASH had a significantly lower ΔR2* 72 hours after USPIO administration when compared with patients who had simple steatosis and healthy control subjects (mean ± standard deviation for patients with NASH, 37.0 sec(-1) ± 16.1; patients with simple steatosis, 61.0 sec(-1) ± 17.3; and healthy control subjects, 72.2 sec(-1) ± 22.0; P = .006 for NASH vs simple steatosis; P steatosis was 0.87 (95% confidence interval: 0.72, 1.00). This proof-of-concept study provides clues that hepatic USPIO uptake in patients with NASH is decreased and that USPIO MR imaging can be used to differentiate NASH from simple steatosis.

  9. 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

  10. 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)

  11. Role of peroxisome proliferators-activated receptors in the pathogenesis and treatment of nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Eric R Kallwitz; Alan McLachlan; Scott J Cotler

    2008-01-01

    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 peroxisorne 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 PPARα and PPARγ to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH.

  12. Resolution of non-alcoholic steatohepatitis after growth hormone replacement in a pediatric liver transplant patient with panhypopituitarism

    DEFF Research Database (Denmark)

    Gilliland, Thomas; Dufour, Sylvie; Shulman, Gerald I.

    2016-01-01

    NAFLD is a common condition linked to obesity, type 2 diabetes, and metabolic syndrome. Simple hepatic steatosis is a risk factor for inflammatory reactions in the liver (NASH), which may lead to cirrhosis. While the mechanism is unclear, NAFLD and NASH are associated with panhypopituitarism, which...... case of NASH secondary to panhypopituitarism from craniopharyngioma, which recurred by 11 months after LDLT. Despite low-dose GH replacement, the patient remained GH deficient. Pubertal dosed GH therapy led to rapid and complete resolution of hepatic steatosis, which we tracked using serial (1) H MRS...

  13. 77 FR 17458 - Marine Mammals; File No. 17159

    Science.gov (United States)

    2012-03-26

    ... Simon Nash, Parthenon Entertainment Ltd, 34 Whiteladies Road, Bristol, BS8 2LG, United Kingdom, has... Animal Planet in the U.S. and elsewhere internationally. The initial filming period is scheduled for two...

  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. Risk-taking behaviour of Cape Peninsula high-school students .

    African Journals Online (AJOL)

    three major education departments, of whom ... something to avoid pregnancy. The most fre- ... is still relatively low,',9"o their sexual behaviour has direct relevance for RIV ..... Nash E. Teenage pregnancy - need a child bear a child? S Afr Med.

  16. 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 ...

  17. APPROACHES FOR SOLVING BIMATRIX INFORMATIONAL EXTENDED GAMES

    Directory of Open Access Journals (Sweden)

    Boris HÂNCU

    2015-12-01

    Full Text Available Different ways of solving bimatrix games in complete and perfect information (or over the set of informational extended strategies are studied in the present paper. The Nash and Bayes-Nash solutions for informational extended games are discussed.MODALITĂŢI DE SOLUŢIONARE A JOCURILOR BIMATRICEALE INFORMAŢIONAL EXTINSEÎn acest articol sunt analizate diferite moduri de soluţionare a jocurilor bimatriceale în informaţie completă a şi perfectă. Informaţia perfectă permite jucătorilor să utilizeze strategii informaţional extinse. Se analizează asoluţii de tip Nash şi Bayes-Nash pentru jocuri în strategii informaţional extinse.

  18. Increased accumulation of 4-hydroxynonenal adducts in female GSTA4/PPAR alpha double knockout mice enhance steatosis and inflammation in a model of pediatric nonalcoholic fatty liver disease

    Science.gov (United States)

    Hepatocellular injury resulting from increased lipid peroxidation products and oxidative stress is considered a potential mechanism driving the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitsis (NASH). To test the significance of lipid peroxidation and protein...

  19. 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...

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

    African Journals Online (AJOL)

    Cholesterol (LDL-c) , Triglycerides (TG) and BMI were significantly decreased in group (A), ... iponectin and High Density Lipoprotein Cholesterol (HDL-c) were significantly increased, ... NASH6 and a strong positive correlation exists between.

  1. 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.

  2. 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"

  3. Noncompact Equilibrium Points and Applications

    Directory of Open Access Journals (Sweden)

    Zahra Al-Rumaih

    2012-01-01

    Full Text Available We prove an equilibrium existence result for vector functions defined on noncompact domain and we give some applications in optimization and Nash equilibrium in noncooperative game.

  4. 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

  5. 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).

  6. 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.

  7. 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,

  8. 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,

  9. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Disease (NAFLD) & Non-alcoholic Steatohepatitis (NASH) Autoimmune Hepatitis Bile duct disease such as Primary Biliary Cirrhosis (PBC) ... spleen (splenomegaly) Stone-like particles in gallbladder and bile duct (gallstones) Liver cancer (hepatocellular carcinoma) Chronic liver ...

  10. The North Atlantic Treaty Organization and the European Union’s Common Security and Defense Policy: Intersecting Trajectories

    Science.gov (United States)

    2011-07-01

    Lieutenant General, Canadian Forces, Canadian Military Repre- sentative to NATO Elizabeth Race, Deputy Defence Policy Advisor, Canadian Joint...Ruehle, Head, Energy Security Section, Emerging Security Challenges Division, NATO ( Brus - sels) Patrick Nash, Lieutenant General, Irish Army, for- mer

  11. 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...

  12. Giardia infection

    Science.gov (United States)

    ... eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 283. Haines CF, Sears CL. ... Gastrointestinal and Liver Disease . 10th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 110. Nash TE, Hill DR. ...

  13. Fulltext PDF

    Indian Academy of Sciences (India)

    IAS Admin

    When the two compa- nies produce the same product, they have equal market ..... be thought of as simultaneously choosing their strate- gies from the ..... Roger Bruce Myerson, Nash equilibrium and the history of economic theory, Journal of ...

  14. 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"

  15. Incentive Compatibility

    OpenAIRE

    Ledyard, John O.

    1987-01-01

    Incentive compatibility is described and discussed. A summary of the current state of understanding is provided. Key words are: incentive compatibility, game theory, implementation, mechanism, Bayes, Nash, and revelation.

  16. 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

  17. Nonalcoholic fatty liver disease: Update on pathogenesis, diagnosis, treatment and the role of S-adenosylmethionine

    Science.gov (United States)

    Mato, José M; Lu, Shelly C

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease worldwide affecting over one-third of the population in the U.S. It has been associated with obesity, type 2 diabetes, hyperlipidemia, and insulin resistance and is initiated by the accumulation of triglycerides in hepatocytes. Isolated hepatic steatosis (IHS) remains a benign process, while a subset develops superimposed inflammatory activity and progression to nonalcoholic steatohepatitis (NASH) with or without fibrosis. However, the molecular mechanisms underlying NAFLD progression are not completely understood. Liver biopsy is still required to differentiate IHS from NASH as easily accessible noninvasive biomarkers are lacking. In terms of treatments for NASH, pioglitazone, vitamin E, and obeticholic acid have shown some benefit. All of these agents have potential complications associated with long-term use. Nowadays, a complex hypothesis suggests that multiple parallel hits are involved in NASH development. However, the ‘key switch’ between IHS and NASH remains to be discovered. We have recently shown that knocking out enzymes involved in S-adenosylmethionine (SAMe) metabolism, the main biological methyl donor in humans that is abundant in the liver, will lead to NASH development in mice. This could be due to the fact that a normal SAMe level is required to establish the proper ratio of phosphatidylethanolamine to phosphatidylcholine that has been found to be important in NAFLD progression. New data from humans have also suggested that these enzymes play a role in the pathogenesis of NAFLD and that some of SAMe cycle metabolites may serve as noninvasive biomarkers of NASH. In this review, we discuss the evidence of the role of SAMe in animal models and humans with NAFLD and how studying this area may lead to the discovery of new noninvasive biomarkers and possibly personalized treatment for NASH. PMID:25873078

  18. Emergence of scale-free characteristics in socio-ecological systems with bounded rationality

    OpenAIRE

    Kasthurirathna, Dharshana; Piraveenan, Mahendra

    2015-01-01

    Socio?ecological systems are increasingly modelled by games played on complex networks. While the concept of Nash equilibrium assumes perfect rationality, in reality players display heterogeneous bounded rationality. Here we present a topological model of bounded rationality in socio-ecological systems, using the rationality parameter of the Quantal Response Equilibrium. We argue that system rationality could be measured by the average Kullback?-Leibler divergence between Nash and Quantal Res...

  19. 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.

  20. 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...

  1. 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

  2. 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

  3. Applying Gödel's Dialectica Interpretation to Obtain a Constructive Proof of Higman's Lemma

    Directory of Open Access Journals (Sweden)

    Thomas Powell

    2012-10-01

    Full Text Available We use Gödel's Dialectica interpretation to analyse Nash-Williams' elegant but non-constructive "minimal bad sequence" proof of Higman's Lemma. The result is a concise constructive proof of the lemma (for arbitrary decidable well-quasi-orders in which Nash-Williams' combinatorial idea is clearly present, along with an explicit program for finding an embedded pair in sequences of words.

  4. Comparison of clinical, biochemical and histological features of alcoholic steatohepatitis and non-alcoholic steatohepatitis in Asian Indian patients

    Directory of Open Access Journals (Sweden)

    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. 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.

  6. 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...... 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...

  7. 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...... 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....

  8. Influence of gut microbiota on the development and progression of nonalcoholic steatohepatitis.

    Science.gov (United States)

    de Faria Ghetti, Fabiana; Oliveira, Daiane Gonçalves; de Oliveira, Juliano Machado; de Castro Ferreira, Lincoln Eduardo Villela Vieira; Cesar, Dionéia Evangelista; Moreira, Ana Paula Boroni

    2018-04-01

    Nonalcoholic steatohepatitis (NASH) is characterized by the presence of steatosis, inflammation, and ballooning degeneration of hepatocytes, with or without fibrosis. The prevalence of NASH has increased with the obesity epidemic, but its etiology is multifactorial. The current studies suggest the role of gut microbiota in the development and progression of NASH. The aim is to review the studies that investigate the relationship between gut microbiota and NASH. These review also discusses the pathophysiological mechanisms and the influence of diet on the gut-liver axis. The available literature has proposed mechanisms for an association between gut microbiota and NASH, such as: modification energy homeostasis, lipopolysaccharides (LPS)-endotoxemia, increased endogenous production of ethanol, and alteration in the metabolism of bile acid and choline. There is evidence to suggest that NASH patients have a higher prevalence of bacterial overgrowth in the small intestine and changes in the composition of the gut microbiota. However, there is still a controversy regarding the microbiome profile in this population. The abundance of Bacteroidetes phylum may be increased, decreased, or unaltered in NASH patients. There is an increase in the Escherichia and Bacteroides genus. There is depletion of certain taxa, such as Prevotella and Faecalibacterium. Although few studies have evaluated the composition of the gut microbiota in patients with NASH, it is observed that these individuals have a distinct gut microbiota, compared to the control groups, which explains, at least in part, the genesis and progression of the disease through multiple mechanisms. Modulation of the gut microbiota through diet control offers new challenges for future studies.

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

    OpenAIRE

    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...

  11. A preliminary study of inflammatory markers in non-alcoholic steatohepatitis patients

    Directory of Open Access Journals (Sweden)

    Manopriya T. Priya

    2010-03-01

    Full Text Available It was reported that C-reactive protein (CRP levels increase in parallel with the progression of chronic liver diseases, such as chronic hepatitis and liver cirrhosis. Inflammatory markers, such as high sensitive C-reactive protein (hsCRP, ferritin, transferrin, albumin, alpha-1 acid glycoprotein (AAG, alpha-2 macroglobulin (AMG, alpha-1 anti-trypsin (AAT and lipoprotein a [Lp(a] were measured in coronary artery disease patients (CAD and CAD patients with non-alcoholic steatohepatitis (NASH. 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 serum AMG and ceruloplasmin (CP were also increased (p<0.01. The CAD patients with NASH had a higher proportion of diabetes, hypertension and dyslipidaemia compared to CAD patients. But how this difference contributes to the elevation in acute inflammatory markers particularly AMG and CP levels in CAD patients with NASH cannot be explained. This study shows that a substantial number of CAD patients may be associated with NASH. Non-invasive simple parameters that reflect the degree of inflammation and fibrosis of the liver in patients with NASH would facilitate improved understanding and treatment of the disease. Further studies may be necessary to evaluate the percentage of NASH patients progressing to CAD.

  12. Rising Rate of Liver Transplantation in the Baby Boomer Generation with Non-alcoholic Steatohepatitis in the United States.

    Science.gov (United States)

    Siddique, Osama; Joseph-Talreja, Mairin; Yoo, Eric R; Perumpail, Ryan B; Cholankeril, George; Harrison, Stephen A; Younossi, Zobair M; Wong, Robert J; Ahmed, Aijaz

    2017-09-28

    Background and Aims: Nonalcoholic steatohepatitis (NASH) is the most rapidly growing indication for liver transplantation (LT) in the United States and is on a trajectory to become the leading indication for LT in the next decade. We aimed to study the trends in NASH-related LT among persons born between 1945 and 1965, the baby boomer (BB) generation. Methods: We performed a retrospective cohort analysis using population-based data from the United Network for Organ Sharing/Organ Procurement and Transplantation Network registry from 2004-2015 to evaluate the birth cohort-specific trends in liver transplant waitlist registrations and liver transplant surgeries in patients with NASH. We stratified our study population into three birth cohorts: 1) birth before 1945, 2) birth between 1945 and 1965, and 3) birth after 1965. Results: The overall rates of NASH-related waitlist registrations and liver transplant surgeries steadily increased from 2004 to 2015 and were reflective of a sharp rise noted in the NASH BB sub-group. From 2004 to 2015, the proportion of BB patients with NASH added to LT waitlist demonstrated an incremental growth, 60.6% in 2004 versus 83.2% in 2015 ( p < 0.01). Among the liver transplant recipients with NASH, the proportion represented by the BB cohort increased from 56.3% in 2004 to 80.0% in 2015 ( p < 0.01). Conclusions: We report rising rates of waitlist registration and LT for the indication of NASH. More importantly, the BB sub-cohort was mainly responsible for these alarming trends.

  13. 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

  14. 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.

  15. 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

  16. 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)

  17. A review of a scientific work A SCHOOL TO MATCH ANY CHILD A MANUAL FOR WORKING WITH PUPILS WITH DEVELOPMENTAL DIFICULTIES IN REGULAR SCHOOLS

    Directory of Open Access Journals (Sweden)

    Sofija АRNAUDOVA

    2005-12-01

    Full Text Available The presented text is a review of the scientific work A school to match any child, a manual to work with children of regular schools with physical disabilities. The author and the editor of this work is Sulejman Hrnjica, in cooperation with Vera Rajovikj, Tatjana Cholin, Ksenija Krtikj and Dijana Dopunovikj. The manual is a part of the project Inclusion of students with physical disabilities in regular primary education, which was approved and financed by the Ministry of education and sport of the Republic of Serbia, and published by the Institute of Psychology at the Faculty of Philosophy in Belgrade, with the assistance of the foundation "Save the Children" from Great Britain, the office in Belgrade, 2004. This work can hardly be found in bookshops through the country, but it can be found in the library of the Faculty of Philosophy, and certainly at the Book Fair, held every year in Skopje.

  18. Metabolomics Profiling to Investigate the Pharmacologic Mechanisms of Berberine for the Treatment of High-Fat Diet-Induced Nonalcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Jian Li

    2015-01-01

    Full Text Available Objective. Berberine has been used to treat nonalcoholic steatohepatitis (NASH, which has been addressed in many studies. In this study, we investigated the molecular pharmacology mechanisms of berberine using metabolomic techniques. Methods. Sprague-Dawley rats were randomly divided into three groups (10 rats in each group: (i normal control group; (ii high-fat diet- (HFD- induced NASH model group; and (iii HFD berberine-treated group (i.d. 200 mg/kg. The handling procedure lasted eight weeks. Then, UPLC-Q-TOF/MS techniques coupled with histopathology and biochemical analyses were adopted to explore the mechanisms of berberine on the protective effects against NASH. Key Findings. (i According to conventional test results, berberine treatment plays a fighting role in HFD-induced NASH due to its beneficial effects against insulin resistance, inflammation, and lipid metabolism. (ii Based on UPLC-Q-TOF/MS techniques, metabolic profiles that involved sphingomyelin (SM, phosphatidylcholine (PC, lysophosphatidylcholine (LysoPC, 13-hydroperoxy-9, 11-octadecadienoic acid (13-HpODE, eicosatrienoic acid, docosatrienoic acid, and eicosenoic acid could provide potential metabolic biomarkers to address the pharmacological mechanisms of berberine. Conclusions. The parts of molecular pharmacological mechanisms of berberine for NASH treatment are related to the regulation of metabolic disruption involving phospholipid and unsaturated fatty acids in rats with NASH.

  19. [Metabolic parameters in patients with steatosis non alcoholic liver and controlled diabetes type 2 versus uncontrolled diabetes type 2].

    Science.gov (United States)

    Miranda Manrique, Gonzalo

    2016-01-01

    Non-alcoholic fatty liver (NASH) is widely distributed around the world and is more common in subjects with dyslipidemia, metabolic syndrome obese and DM2 (34-74%). However, the prevalence of cirrhosis by NASH in general population is unknown which is still subject of research. To determine if there are significant differences between metabolic parameters of non-alcoholic fatty liver in controlled versus uncontrolled diabetes type 2 of recent diagnosis. retrospective case-control study, performed in the Hospital Guillermo Almenara Irigoyen, Lima, Peru from November 2014 to February 2015.This study included 231 patients: 147 patients (NASH with DM2 of recent diagnosis and poor control) and 84 patients (NASH with DM2 ofrecent diagnosis and adequate control). Levene test for evaluating homogeneity of variances intra groups and parametric test for independent samples. After applying Levene test of homogeneity and student test, significant metabolic parameters were the triglycerides, HbA1C level, metformin dose and gender. It is important in diabetic patients to diagnose NASH early for a tighter control, not only of glucose but other metabolic parameters mainly triglycerides which strongly supports existing concept of "multiple hits" which considers NASH affects glucose homeostasis, and it could be the starting point of new research to improve interventions for decreasing progression from to cirrhosis in diabetic patients and also to delay progression of diabetes mellitus in patients with non alcoholic steatohepatitis.

  20. Pathogenesis of Nonalcoholic Steatohepatitis: Interactions between Liver Parenchymal and Nonparenchymal Cells

    Directory of Open Access Journals (Sweden)

    Nancy Magee

    2016-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common type of chronic liver disease in the Western countries, affecting up to 25% of the general population and becoming a major health concern in both adults and children. NAFLD encompasses the entire spectrum of fatty liver disease in individuals without significant alcohol consumption, ranging from nonalcoholic fatty liver (NAFL to nonalcoholic steatohepatitis (NASH and cirrhosis. NASH is a manifestation of the metabolic syndrome and hepatic disorders with the presence of steatosis, hepatocyte injury (ballooning, inflammation, and, in some patients, progressive fibrosis leading to cirrhosis. The pathogenesis of NASH is a complex process and implicates cell interactions between liver parenchymal and nonparenchymal cells as well as crosstalk between various immune cell populations in liver. Lipotoxicity appears to be the central driver of hepatic cellular injury via oxidative stress and endoplasmic reticulum (ER stress. This review focuses on the contributions of hepatocytes and nonparenchymal cells to NASH, assessing their potential applications to the development of novel therapeutic agents. Currently, there are limited pharmacological treatments for NASH; therefore, an increased understanding of NASH pathogenesis is pertinent to improve disease interventions in the future.