WorldWideScience

Sample records for adprt1 akr1b1 rage

  1. Expression of the Aldo-Keto Reductases AKR1B1 and AKR1B10 in Human Cancers.

    Directory of Open Access Journals (Sweden)

    BrianLaffin

    2012-06-01

    Full Text Available The American Cancer Society estimates that there will be more than 1.5 million new cases of cancer in 2011, underscoring the need for identification of new therapeutic targets and development of novel cancer therapies. Previous studies have implicated the human aldo-keto reductases AKR1B1 and AKR1B10 in cancer, and therefore we examined AKR1B1 and AKR1B10 expression across all major human cancer types using the Oncomine cancer gene expression database (Compendia Biosciences, www.oncomine.com. Using this database, we found that expression of of AKR1B1 and AKR1B10 varies greatly by cancer type and tissue of origin, including agreement with previous reports that AKR1B10 is significantly over-expressed in cancers of the lungs and liver. AKR1B1 is more broadly over-expressed in human cancers than AKR1B10, albeit at a generally lower magnitude. AKR1B1 over-expression was found to be associated with shortened patient survival in acute myelogenous leukemias and multiple myelomas. High AKR1B10 expression tends to predict less aggressive clinical course generally, notably within lung cancers, where it tends to be highly over-expressed compared to normal tissue. These findings suggest that AKR1B1 inhibitors in particular hold great potential as novel cancer therapeutics.

  2. The Rage of Gifted Students.

    Science.gov (United States)

    Cross, Tracy L.

    2001-01-01

    This article discusses the rage gifted students feel because of the treatment they receive in the school. It argues that the mixed messages they receive, along with normal developmental issues and the repetitious images of adolescents engaging in homicides, suicide, and other undesirable behavior, all contribute to the rage. (Contains references.)…

  3. "Uproar, bulk, rage, suffocation, effort unceasing, frenzied and vain": Beckett's Transports of Rage.

    Science.gov (United States)

    Smith, Russell

    2016-06-01

    In a 1961 interview, Beckett warded off philosophical interpretations of his work: 'I'm no intellectual. All I am is feeling'. Despite the emotional intensity of Beckett's post-war writing, Beckett criticism has tended to ignore this claim, preferring the kinds of philosophical readings that Beckett here rejects. In particular, Beckett criticism underestimates the element of rage in his work. This paper argues that Beckett's post-war breakthrough is enabled by a radical reconsideration of the nature of feeling and of rage in particular. It involves the rejection of the idea of rage as pathological and the embrace of a positive conception of rage as drive or compulsion, a locus of energy and even pleasure.This paper reads the 'Moran' section of Molloy as a kind of 'rage fable', drawing on the ancient Greek concept of thymos, of anger as a virtue. It draws on Alfred Adler's theory of the 'masculine protest', with which Beckett was familiar from his extensive note-taking on Adler in 1934-5, and Sianne Ngai's discussion of the distinction between irritation and rage. According to this reading, Moran's report charts a narrative of thymotic liberation from the irritations of servitude, prefiguring the Unnamable's abandonment to impersonal affective intensities. It ends by suggesting that the prose of the Trilogy might be better understood, not as a 'syntax of weakness' but as a 'syntax of rage', a stylistic correlative of the imperious drive of thymos. We might then begin to understand the Trilogy as the epic of a heroic, impersonal, implacable and liberated rage. PMID:26696308

  4. xRage Equation of State

    Energy Technology Data Exchange (ETDEWEB)

    Grove, John W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-16

    The xRage code supports a variety of hydrodynamic equation of state (EOS) models. In practice these are generally accessed in the executing code via a pressure-temperature based table look up. This document will describe the various models supported by these codes and provide details on the algorithms used to evaluate the equation of state.

  5. RAGE regulates immune cell infiltration and angiogenesis in choroidal neovascularization.

    Directory of Open Access Journals (Sweden)

    Mei Chen

    Full Text Available PURPOSE: RAGE regulates pro-inflammatory responses in diverse cells and tissues. This study has investigated if RAGE plays a role in immune cell mobilization and choroidal neovascular pathology that is associated with the neovascular form of age-related macular degeneration (nvAMD. METHODS: RAGE null (RAGE-/- mice and age-matched wild type (WT control mice underwent laser photocoagulation to generate choroidal neovascularization (CNV lesions which were then analyzed for morphology, S100B immunoreactivity and inflammatory cell infiltration. The chemotactic ability of bone marrow derived macrophages (BMDMs towards S100B was investigated. RESULTS: RAGE expression was significantly increased in the retina during CNV of WT mice (p<0.001. RAGE-/- mice exhibited significantly reduced CNV lesion size when compared to WT controls (p<0.05. S100B mRNA was upregulated in the lasered WT retina but not RAGE-/- retina and S100B immunoreactivity was present within CNV lesions although levels were less when RAGE-/- mice were compared to WT controls. Activated microglia in lesions were considerably less abundant in RAGE-/- mice when compared to WT counterparts (p<0.001. A dose dependent chemotactic migration was observed in BMDMs from WT mice (p<0.05-0.01 but this was not apparent in cells isolated from RAGE-/- mice. CONCLUSIONS: RAGE-S100B interactions appear to play an important role in CNV lesion formation by regulating pro-inflammatory and angiogenic responses. This study highlights the role of RAGE in inflammation-mediated outer retinal pathology.

  6. A Many-Body RAGE Theorem

    Science.gov (United States)

    Lampart, Jonas; Lewin, Mathieu

    2015-12-01

    We prove a generalized version of the RAGE theorem for N-body quantum systems. The result states that only bound states of systems with {0 ≤slant n ≤slant N} particles persist in the long time average. The limit is formulated by means of an appropriate weak topology for many-body systems, which was introduced by the second author in a previous work, and is based on reduced density matrices. This topology is connected to the weak-* topology of states on the algebras of canonical commutation or anti-commutation relations, and we give a formulation of our main result in this setting.

  7. Cultural Causes of Rage and Violence in Children and Youth.

    Science.gov (United States)

    Manno, Carla J.; Bantz, Jeanmarie; Kauffman, James M.

    2000-01-01

    Examines differences between rage and violence. States that attitudes towards violence are influenced by: family, peer group, the media, weapons, school structure, and community. Strategies for preventing rage and aggression include: (1) communicating clear behavioral expectations; (2) giving frequent praise and other forms of recognition; and (3)…

  8. The Rejection-Rage Contingency in Borderline Personality Disorder

    Science.gov (United States)

    Berenson, Kathy R.; Downey, Geraldine; Rafaeli, Eshkol; Coifman, Karin; Leventhal, Nina

    2011-01-01

    Though longstanding clinical observation reflected in the DSM-IV suggests that the rage characteristic of borderline personality disorder (BPD) often appears in response to perceived rejection, the role of perceived rejection in triggering rage in BPD has never been empirically tested. Extending basic personality research on rejection sensitivity to a clinical sample, a priming-pronunciation experiment and a 21-day experience-sampling diary examined the contingent relationship between perceived rejection and rage in participants diagnosed with BPD compared to healthy controls. Despite the differences in these two assessment methods, the indices of rejection-contingent rage that they produced were both elevated in the BPD group, and were strongly interrelated. They provide corroborating evidence that reactions to perceived rejection significantly explain the rage seen in BPD. PMID:21500875

  9. xRage: HE initiation models

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Laboratory; Scovel, Christina A. [Los Alamos National Laboratory

    2012-06-01

    The xRage code contains three HE ignition models: Forest Fire, Cerro Grande and Ignition and Growth. After describing these models we present results of verification and validation (V and V) tests. These include simulations to determine the Pop-plot for each model and comparision with embedded velocity gauge data for shock-to-detonation transition (SDT) experiments. The data for the SDT experiments on PBX 9502 is taken from the recently developed high explosive database (HED). The HED data files contains additional meta-data with the key experimental parameters. This enables the use of scripts to automate testing: generating xRage input file, running simulation and generating comparison plots with experimental and simulated data. The simulations show that the models are robust. But there is a mesh dependence with the time for transition-to-detonation varying by several tenths of microseconds. After the transition to a detonation wave, the detonation speed and pressure may vary by a few per cent.

  10. RNAi-Assisted Genome Evolution (RAGE) in Saccharomyces cerevisiae.

    Science.gov (United States)

    Si, Tong; Zhao, Huimin

    2016-01-01

    RNA interference (RNAi)-assisted genome evolution (RAGE) applies directed evolution principles to engineer Saccharomyces cerevisiae genomes. Here, we use acetic acid tolerance as a target trait to describe the key steps of RAGE. Briefly, iterative cycles of RNAi screening are performed to accumulate multiplex knockdown modifications, enabling directed evolution of the yeast genome and continuous improvement of a target phenotype. Detailed protocols are provided on the reconstitution of RNAi machinery, creation of genome-wide RNAi libraries, identification and integration of beneficial knockdown cassettes, and repeated RAGE cycles. PMID:27581294

  11. The S100B/RAGE Axis in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Estelle Leclerc

    2010-01-01

    Full Text Available Increasing evidence suggests that the small EF-hand calcium-binding protein S100B plays an important role in Alzheimer's disease. Among other evidences are the increased levels of both S100B and its receptor, the Receptor for Advanced Glycation Endproducts (RAGEs in the AD diseased brain. The regulation of RAGE signaling by S100B is complex and probably involves other ligands including the amyloid beta peptide (A, the Advanced Glycation Endproducts (AGEs, or transtheyretin. In this paper we discuss the current literature regarding the role of S100B/RAGE activation in Alzheimer's disease.

  12. The RAGE radiation-hydrodynamic code

    Energy Technology Data Exchange (ETDEWEB)

    Gittings, Michael; Clover, Michael; Betlach, Thomas; Byrne, Nelson; Ranta, Dale [Science Applications International Corp. MS A-1, 10260 Campus Point Drive, San Diego, CA 92121 (United States); Weaver, Robert; Coker, Robert; Dendy, Edward; Hueckstaedt, Robert; New, Kim; Oakes, W Rob [Los Alamos National Laboratory, MS T087, PO Box 1663, Los Alamos, NM 87545 (United States); Stefan, Ryan [TaylorMade-adidas Golf, 5545 Fermi Court, Carlsbad, CA 92008-7324 (United States)], E-mail: michael.r.clover@saic.com

    2008-10-01

    We describe RAGE, the 'radiation adaptive grid Eulerian' radiation-hydrodynamics code, including its data structures, its parallelization strategy and performance, its hydrodynamic algorithm(s), its (gray) radiation diffusion algorithm, and some of the considerable amount of verification and validation efforts. The hydrodynamics is a basic Godunov solver, to which we have made significant improvements to increase the advection algorithm's robustness and to converge stiffnesses in the equation of state. Similarly, the radiation transport is a basic gray diffusion, but our treatment of the radiation-material coupling, wherein we converge nonlinearities in a novel manner to allow larger timesteps and more robust behavior, can be applied to any multi-group transport algorithm.

  13. The RAGE radiation-hydrodynamic code

    International Nuclear Information System (INIS)

    We describe RAGE, the 'radiation adaptive grid Eulerian' radiation-hydrodynamics code, including its data structures, its parallelization strategy and performance, its hydrodynamic algorithm(s), its (gray) radiation diffusion algorithm, and some of the considerable amount of verification and validation efforts. The hydrodynamics is a basic Godunov solver, to which we have made significant improvements to increase the advection algorithm's robustness and to converge stiffnesses in the equation of state. Similarly, the radiation transport is a basic gray diffusion, but our treatment of the radiation-material coupling, wherein we converge nonlinearities in a novel manner to allow larger timesteps and more robust behavior, can be applied to any multi-group transport algorithm

  14. Pentamidine blocks the interaction between mutant S100A5 and RAGE V domain and inhibits the RAGE signaling pathway.

    Science.gov (United States)

    Cho, Ching Chang; Chou, Ruey Hwang; Yu, Chin

    2016-08-19

    The human S100 protein family contains small, dimeric and acidic proteins that contain two EF-hand motifs and bind calcium. When S100A5 binds calcium, its conformation changes and promotes interaction with the target protein. The extracellular domain of RAGE (Receptor of Advanced Glycation End products) contain three domains: C1, C2 and V. The RAGE V domain is the target protein of S100A5 that promotes cell survival, growth and differentiation by activating several signaling pathways. Pentamidine is an apoptotic and antiparasitic drug that is used to treat or prevent pneumonia. Here, we found that pentamidine interacts with S100A5 using HSQC titration. We elucidated the interactions of S100A5 with RAGE V domain and pentamidine using fluorescence and NMR spectroscopy. We generated two binary models-the S100A5-RAGE V domain and S100A5-Pentamidine complex-and then observed that the pentamidine and RAGE V domain share a similar binding region in mS100A5. We also used the WST-1 assay to investigate the bioactivity of S100A5, RAGE V domain and pentamidine. These results indicated that pentamidine blocks the binding between S100A5 and RAGE V domain. This finding is useful for the development of new anti-proliferation drugs. PMID:27297108

  15. LARGE SCALE ISOLATION AND PURIFICATION OF SOLUBLE RAGE FROM LUNG TISSUE

    OpenAIRE

    Englert, Judson M; Ramsgaard, Lasse; Valnickova, Zuzana; Enghild, Jan J.; Oury, Tim D.

    2008-01-01

    The receptor for advanced glycation end-products (RAGE) has been implicated in numerous disease processes including: atherosclerosis, diabetic nephropathy, impaired wound healing, and neuropathy to name a few. Treatment of animals with a soluble isoform of the receptor (sRAGE) has been shown to prevent and even reverse many disease processes. Isolating large quantities of pure sRAGE for in vitro and in vivo studies has hindered its development as a therapeutic strategy in other RAGE mediated ...

  16. Radical Roles for RAGE in the Pathogenesis of Oxidative Stress in Cardiovascular Diseases and Beyond

    OpenAIRE

    Radha Ananthakrishnan; Ravichandran Ramasamy; Karen M O'Shea; Carmen Hurtado del Pozo; Gurdip Daffu; Ann Marie Schmidt

    2013-01-01

    Oxidative stress is a central mechanism by which the receptor for advanced glycation endproducts (RAGE) mediates its pathological effects. Multiple experimental inquiries in RAGE-expressing cultured cells have demonstrated that ligand-RAGE interaction mediates generation of reactive oxygen species (ROS) and consequent downstream signal transduction and regulation of gene expression. The primary mechanism by which RAGE generates oxidative stress is via activation of NADPH oxidase; amplificatio...

  17. Blockade of RAGE in Zucker obese rats with experimental periodontitis

    DEFF Research Database (Denmark)

    Grauballe, M B; Østergaard, J A; Schou, S;

    2016-01-01

    interrelationship between periodontitis and T2D in a rat model of both diseases. MATERIAL AND METHODS: Zucker obese rats (HsdHlr:ZUCKER-Lepr (fa/fa) ) and their lean littermates were divided into five treatment groups, with and without periodontitis. Monoclonal anti-RAGE IgG3 were injected into the rats three times......, treatment with anti-RAGE IgG3 resulted in improved glucose tolerance and attenuated renal complications. However, no effect was observed on the diabetes-associated periodontitis in Zucker obese rats. Furthermore, periodontitis had no effect on diabetic markers or renal complications. Therefore, activation...

  18. RAGE Architecture for Reusable Serious Gaming Technology Components

    Directory of Open Access Journals (Sweden)

    Wim van der Vegt

    2016-01-01

    Full Text Available For seizing the potential of serious games, the RAGE project—funded by the Horizon-2020 Programme of the European Commission—will make available an interoperable set of advanced technology components (software assets that support game studios at serious game development. This paper describes the overall software architecture and design conditions that are needed for the easy integration and reuse of such software assets in existing game platforms. Based on the component-based software engineering paradigm the RAGE architecture takes into account the portability of assets to different operating systems, different programming languages, and different game engines. It avoids dependencies on external software frameworks and minimises code that may hinder integration with game engine code. Furthermore it relies on a limited set of standard software patterns and well-established coding practices. The RAGE architecture has been successfully validated by implementing and testing basic software assets in four major programming languages (C#, C++, Java, and TypeScript/JavaScript, resp.. Demonstrator implementation of asset integration with an existing game engine was created and validated. The presented RAGE architecture paves the way for large scale development and application of cross-engine reusable software assets for enhancing the quality and diversity of serious gaming.

  19. RAGE Architecture for Reusable Serious Gaming Technology Components

    NARCIS (Netherlands)

    Van der Vegt, Wim; Westera, Wim; Nyamsuren, Enkhbold; Georgiev, Atanas; Martinez Ortiz, Ivan

    2016-01-01

    For seizing the potential of serious games, the RAGE project - funded by the Horizon-2020 Programme of the European Commission - will make available an interoperable set of advanced technology components (software assets) that support game studios at serious game development. This paper describes th

  20. Physical and situational inequality on airplanes predicts air rage.

    Science.gov (United States)

    DeCelles, Katherine A; Norton, Michael I

    2016-05-17

    We posit that the modern airplane is a social microcosm of class-based society, and that the increasing incidence of "air rage" can be understood through the lens of inequality. Research on inequality typically examines the effects of relatively fixed, macrostructural forms of inequality, such as socioeconomic status; we examine how temporary exposure to both physical and situational inequality, induced by the design of environments, can foster antisocial behavior. We use a complete set of all onboard air rage incidents over several years from a large, international airline to test our predictions. Physical inequality on airplanes-that is, the presence of a first class cabin-is associated with more frequent air rage incidents in economy class. Situational inequality-boarding from the front (requiring walking through the first class cabin) versus the middle of the plane-also significantly increases the odds of air rage in both economy and first class. We show that physical design that highlights inequality can trigger antisocial behavior on airplanes. More broadly, these results point to the importance of considering the design of environments-from airplanes to office layouts to stadium seating-in understanding both the form and emergence of antisocial behavior. PMID:27140642

  1. Controlled Rage: An Overlooked Cause of Remediation Failure.

    Science.gov (United States)

    Ungerleider, Dorothy

    Experiences of an individual working with illiterate delinquents are related. It is suggested that controlled rage as a concomitant to learning failure is a potential source of school difficulty as well as social violence. A case of a ninth-grader with reading problems whose IQ had steadily decreased with age is cited. The schools' unsuccessful…

  2. Radical Roles for RAGE in the Pathogenesis of Oxidative Stress in Cardiovascular Diseases and Beyond

    Directory of Open Access Journals (Sweden)

    Radha Ananthakrishnan

    2013-10-01

    Full Text Available Oxidative stress is a central mechanism by which the receptor for advanced glycation endproducts (RAGE mediates its pathological effects. Multiple experimental inquiries in RAGE-expressing cultured cells have demonstrated that ligand-RAGE interaction mediates generation of reactive oxygen species (ROS and consequent downstream signal transduction and regulation of gene expression. The primary mechanism by which RAGE generates oxidative stress is via activation of NADPH oxidase; amplification mechanisms in the mitochondria may further drive ROS production. Recent studies indicating that the cytoplasmic domain of RAGE binds to the formin mDia1 provide further support for the critical roles of this pathway in oxidative stress; mDia1 was required for activation of rac1 and NADPH oxidase in primary murine aortic smooth muscle cells treated with RAGE ligand S100B. In vivo, in multiple distinct disease models in animals, RAGE action generates oxidative stress and modulates cellular/tissue fate in range of disorders, such as in myocardial ischemia, atherosclerosis, and aneurysm formation. Blockade or genetic deletion of RAGE was shown to be protective in these settings. Indeed, beyond cardiovascular disease, evidence is accruing in human subjects linking levels of RAGE ligands and soluble RAGE to oxidative stress in disorders such as doxorubicin toxicity, acetaminophen toxicity, neurodegeneration, hyperlipidemia, diabetes, preeclampsia, rheumatoid arthritis and pulmonary fibrosis. Blockade of RAGE signal transduction may be a key strategy for the prevention of the deleterious consequences of oxidative stress, particularly in chronic disease.

  3. Receptor for Advanced Glycation End Products (RAGE Serves a Protective Role during Klebsiella pneumoniae - Induced Pneumonia.

    Directory of Open Access Journals (Sweden)

    Ahmed Achouiti

    Full Text Available Klebsiella species is the second most commonly isolated gram-negative organism in sepsis and a frequent causative pathogen in pneumonia. The receptor for advanced glycation end products (RAGE is expressed on different cell types and plays a key role in diverse inflammatory responses. We here aimed to investigate the role of RAGE in the host response to Klebsiella (K. pneumoniae pneumonia and intransally inoculated rage gene deficient (RAGE-/- and normal wild-type (Wt mice with K. pneumoniae. Klebsiella pneumonia resulted in an increased pulmonary expression of RAGE. Furthermore, the high-affinity RAGE ligand high mobility group box-1 was upregulated during K. pneumoniae pneumonia. RAGE deficiency impaired host defense as reflected by a worsened survival, increased bacterial outgrowth and dissemination in RAGE-/- mice. RAGE-/- neutrophils showed a diminished phagocytosing capacity of live K. pneumoniae in vitro. Relative to Wt mice, RAGE-/- mice demonstrated similar lung inflammation, and slightly elevated-if any-cytokine and chemokine levels and unchanged hepatocellular injury. In addition, RAGE-/- mice displayed an unaltered response to intranasally instilled Klebsiella lipopolysaccharide (LPS with respect to pulmonary cell recruitment and local release of cytokines and chemokines. These data suggest that (endogenous RAGE protects against K. pneumoniae pneumonia. Also, they demonstrate that RAGE contributes to an effective antibacterial defense during K. pneumoniae pneumonia, at least partly via its participation in the phagocytic properties of professional granulocytes. Additionally, our results indicate that RAGE is not essential for the induction of a local and systemic inflammatory response to either intact Klebsiella or Klebsiella LPS.

  4. Receptor for Advanced Glycation End Products (RAGE) Serves a Protective Role during Klebsiella pneumoniae - Induced Pneumonia.

    Science.gov (United States)

    Achouiti, Ahmed; de Vos, Alex F; van 't Veer, Cornelis; Florquin, Sandrine; Tanck, Michael W; Nawroth, Peter P; Bierhaus, Angelika; van der Poll, Tom; van Zoelen, Marieke A D

    2016-01-01

    Klebsiella species is the second most commonly isolated gram-negative organism in sepsis and a frequent causative pathogen in pneumonia. The receptor for advanced glycation end products (RAGE) is expressed on different cell types and plays a key role in diverse inflammatory responses. We here aimed to investigate the role of RAGE in the host response to Klebsiella (K.) pneumoniae pneumonia and intransally inoculated rage gene deficient (RAGE-/-) and normal wild-type (Wt) mice with K. pneumoniae. Klebsiella pneumonia resulted in an increased pulmonary expression of RAGE. Furthermore, the high-affinity RAGE ligand high mobility group box-1 was upregulated during K. pneumoniae pneumonia. RAGE deficiency impaired host defense as reflected by a worsened survival, increased bacterial outgrowth and dissemination in RAGE-/- mice. RAGE-/- neutrophils showed a diminished phagocytosing capacity of live K. pneumoniae in vitro. Relative to Wt mice, RAGE-/- mice demonstrated similar lung inflammation, and slightly elevated-if any-cytokine and chemokine levels and unchanged hepatocellular injury. In addition, RAGE-/- mice displayed an unaltered response to intranasally instilled Klebsiella lipopolysaccharide (LPS) with respect to pulmonary cell recruitment and local release of cytokines and chemokines. These data suggest that (endogenous) RAGE protects against K. pneumoniae pneumonia. Also, they demonstrate that RAGE contributes to an effective antibacterial defense during K. pneumoniae pneumonia, at least partly via its participation in the phagocytic properties of professional granulocytes. Additionally, our results indicate that RAGE is not essential for the induction of a local and systemic inflammatory response to either intact Klebsiella or Klebsiella LPS. PMID:26824892

  5. Regulation of Receptor for Advanced Glycation End Products (RAGE) Ectodomain Shedding and Its Role in Cell Function.

    Science.gov (United States)

    Braley, Alex; Kwak, Taekyoung; Jules, Joel; Harja, Evis; Landgraf, Ralf; Hudson, Barry I

    2016-06-01

    The receptor for advanced glycation end products (RAGE) is a multiligand transmembrane receptor that can undergo proteolysis at the cell surface to release a soluble ectodomain. Here we observed that ectodomain shedding of RAGE is critical for its role in regulating signaling and cellular function. Ectodomain shedding of both human and mouse RAGE was dependent on ADAM10 activity and induced with chemical activators of shedding (ionomycin, phorbol 12-myristate 13-acetate, and 4-aminophenylmercuric acetate) and endogenous stimuli (serum and RAGE ligands). Ectopic expression of the splice variant of RAGE (RAGE splice variant 4), which is resistant to ectodomain shedding, inhibited RAGE ligand dependent cell signaling, actin cytoskeleton reorganization, cell spreading, and cell migration. We found that blockade of RAGE ligand signaling with soluble RAGE or inhibitors of MAPK or PI3K blocked RAGE-dependent cell migration but did not affect RAGE splice variant 4 cell migration. We finally demonstrated that RAGE function is dependent on secretase activity as ADAM10 and γ-secretase inhibitors blocked RAGE ligand-mediated cell migration. Together, our data suggest that proteolysis of RAGE is critical to mediate signaling and cell function and may therefore emerge as a novel therapeutic target for RAGE-dependent disease states. PMID:27022018

  6. RAGE Architecture for Reusable Serious Gaming Technology Components

    OpenAIRE

    Wim van der Vegt; Wim Westera; Enkhbold Nyamsuren; Atanas Georgiev; Iván Martínez Ortiz

    2016-01-01

    For seizing the potential of serious games, the RAGE project - funded by the Horizon-2020 Programme of the European Commission - will make available an interoperable set of advanced technology components (software assets) that support game studios at serious game development. This paper describes the overall software architecture and design conditions that are needed for the easy integration and reuse of such software assets in existing game platforms. Based on the component-based software en...

  7. Thalamus segmentation from MP2RAGE: a comparative study

    DEFF Research Database (Denmark)

    Eskildsen, Simon Fristed; Næss-Schmidt, Erhard; Blicher, Jakob;

    RAGE sequence on a Siemens Magnetom Skyra 3T MRI system with a 32 channel head coil. Parameters were TR=5 s, TI1=0.7 s, TI2=2.5 s, α1=4°, α2=5° and acquired at a nominal, isotropic, resolution of 1mm (acquisition matrix: 240x256, 176 sagittal slices). An experienced neuro-radiologist manually traced...

  8. Diabetes and cancer: Looking at the multiligand/RAGE axis

    OpenAIRE

    2011-01-01

    The association between diabetes and hyperglycemia and the associated increased risk of several solid and hematologic malignancies has been the subject of investigation for many years. Although the association is not fully understood, current knowledge clearly indicates that diabetes may influence malignant cell transformation by several mechanisms, including hyperinsulinemia, hyperglycemia and chronic inflammation. In this context, the receptor for advanced glycation end-products (RAGE) has ...

  9. Peripheral and central mediators of lipopolysaccharide (LPS) induced suppression of defensive rage behavior in the cat

    OpenAIRE

    Bhatt, Suresh; Bhatt, Rekha S; Zalcman, Steven S; Siegel, Allan

    2009-01-01

    Based upon recent findings in our laboratory that cytokines microinjected into the medial hypothalamus or periaqueductal gray (PAG) powerfully modulate defensive rage behavior in cat, the present study determined the effects of peripherally released cytokines following lipopolysaccharide LPS challenge upon defensive rage. The study involved initial identification of the effects of peripheral administration of LPS upon defensive rage by electrical stimulation from PAG and subsequent determinat...

  10. Women's Experiences of Rage towards their Intimate Partners: Diverse Voices within the Criminal Justice System

    OpenAIRE

    Flemke, Kimberly Renee

    2003-01-01

    "Women's Experiences of Rage towards their Intimate Partners: Diverse Voices within the Criminal Justice System" By: Kimberly R. Flemke Abstract A multi-method study investigating incarcerated womenâ s experiences of rage towards their intimate partners was conducted. The sample was drawn from a Philadelphia prisonâ s recovery unit for women. Phenomenological and feminist critical theory perspectives guided the study; these combined approaches captured the essence of rage, while a...

  11. Soluble RAGE Treatment Delays Progression of Amyotrophic Lateral Sclerosis in SOD1 Mice

    Science.gov (United States)

    Juranek, Judyta K.; Daffu, Gurdip K.; Geddis, Matthew S.; Li, Huilin; Rosario, Rosa; Kaplan, Benjamin J.; Kelly, Lauren; Schmidt, Ann Marie

    2016-01-01

    The etiology of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disorder characterized by progressive muscle weakness and spasticity, remains largely unknown. Approximately 5–10% of cases are familial, and of those, 15–20% are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). Mutations of the SOD1 gene interrupt cellular homeostasis and contribute to cellular toxicity evoked by the presence of altered SOD1, along with other toxic species, such as advanced glycation end products (AGEs). AGEs trigger activation of their chief cell surface receptor, RAGE (receptor for advanced glycation end products), and induce RAGE-dependent cellular stress and inflammation in neurons, thereby affecting their function and leading to apoptosis. Here, we show for the first time that the expression of RAGE is higher in the SOD1 transgenic mouse model of ALS vs. wild-type mouse spinal cord. We tested whether pharmacological blockade of RAGE may delay the onset and progression of disease in this mouse model. Our findings reveal that treatment of SOD1 transgenic mice with soluble RAGE (sRAGE), a natural competitor of RAGE that sequesters RAGE ligands and blocks their interaction with cell surface RAGE, significantly delays the progression of ALS and prolongs life span compared to vehicle treatment. We demonstrate that in sRAGE-treated SOD1 transgenic animals at the final stage of the disease, a significantly higher number of neurons and lower number of astrocytes is detectable in the spinal cord. We conclude that RAGE antagonism may provide a novel therapeutic strategy for ALS intervention.

  12. Knockdown of RAGE inhibits growth and invasion of gastric cancer cells

    Directory of Open Access Journals (Sweden)

    X.C. Xu

    2013-11-01

    Full Text Available The receptor for advanced glycation endproducts (RAGE is an oncogenic trans-membranous receptor, which is overexpressed in multiple human cancers. However, the role of RAGE in gastric cancer is still elusive. In this study, we investigated the expression and molecular mechanisms of RAGE in gastric cancer cells. Forty cases of gastric cancer and corresponding adjacent non-cancerous tissues (ANCT were collected, and the expression of RAGE was assessed using immunohistochemistry (IHC in biopsy samples. Furthermore, RAGE signaling was blocked by constructed recombinant small hairpin RNA lentiviral vector (Lv-shRAGE used to transfect into human gastric cancer SGC-7901 cells. The expression of AKT, proliferating cell nuclear antigen (PCNA and matrix metallopeptidase-2 (MMP-2 was detected by Real-time PCR and Western blot assays. Cell proliferative activities and invasive capability were respectively determined by MTT and Transwell assays. Cell apoptosis and cycle distribution were analyzed by flow cytometry. As a consequence, RAGE was found highly expressed in cancer tissues compared with the ANCT (70.0% vs 45.0%, P=0.039, and correlated with lymph node metastases (P=0.026. Knockdown of RAGE reduced cell proliferation and invasion of gastric cancer with decreased expression of AKT, PCNA and MMP-2, and induced cell apoptosis and cycle arrest. Altogether, upregulation of RAGE expression is associated with lymph node metastases of gastric cancer, and blockade of RAGE signaling suppresses growth and invasion of gastric cancer cells through AKT pathway, suggesting that RAGE may represent a potential therapeutic target for this aggressive malignancy.

  13. Images en mouvement stockage, repérage, indexation

    CERN Document Server

    Turner, James

    1998-01-01

    L'avènement puis la fusion des nouveaux modes de communication que sont l'informatique, les télécommunications et l'audiovisuel ont mis à la portée de tous une grande quantité d'images fixes et en mouvement dont la conservation et le repérage risquent de prendre des proportions démesurées. Le présent ouvrage veut offrir aux responsables de collection des repères pour aborder la problématique de l'indexation des images et faciliter l'accès des usagers à ces images.

  14. Rage Attacks in Pediatric Obsessive-Compulsive Disorder: Phenomenology and Clinical Correlates

    Science.gov (United States)

    Storch, Eric A.; Jones, Anna M.; Lack, Caleb W.; Ale, Chelsea M.; Sulkowski, Michael L.; Lewin, Adam B.; De Nadai, Alessandro S.; Murphy, Tanya K.

    2012-01-01

    Objective: Rage attacks have been documented in youth with varied psychiatric disorders, but few data have been reported on the clinical characteristics and correlates of rage attacks among children with obsessive-compulsive disorder (OCD). Method: Participants were 86 children (ages 6-16 years) with a primary diagnosis of OCD. Patients and their…

  15. Decreased Neointimal Extracellular Matrix Formation in RAGE-Knockout Mice After Microvascular Denudation

    International Nuclear Information System (INIS)

    Purpose: To evaluate in vivo the role of RAGE (receptor for advanced glycated end products) in the development of restenosis and neointimal proliferation in RAGE-deficient knockout (KO) mice compared with wild-type (WT) mice in an animal model. Materials and Methods: Sixteen WT and 15 RAGE-deficient mice underwent microvascular denudation of the common femoral artery under general anaesthesia. Contralateral arteries underwent a sham operation and served as controls. Four weeks after the intervention, all animals were killed, and paraformaldehyde-fixed specimens of the femoral artery were analysed with different stains (hematoxylin and eosin and Elastica van Gieson) and several different types of immunostaining (proliferating cell nuclear antigen, α-actin, collagen, von Willebrand factor, RAGE). Luminal area, area of the neointima, and area of the media were measured in all specimens. In addition, colony-formation assays were performed, and collagen production by WT smooth muscle cells (SMCs) and RAGE-KO SMCs was determined. For statistical analysis, P 2 [n = 15) in the WT group compared with only 8.4 (*1000 μm2 [n = 16]) in the RAGE-KO group. RAGE-KO SMCs showed significantly decreased proliferation activity and production of extracellular matrix protein. Conclusion: RAGE may be shown to play a considerable role in the formation of neointima leading to restenosis after vascular injury.

  16. A Molecular Dynamics Study on RAGE-Aβ42 Interaction and the Influence of G82S RAGE Polymorphism on Aβ Interaction

    Directory of Open Access Journals (Sweden)

    Sreeram Krishnan

    2015-12-01

    Full Text Available Interaction of amyloid peptides (Aβ with receptor for advanced glycation end products (RAGE elicits an inflammatory response and augments Alzheimer's disease (AD pathology. The present study was aimed to analyse the interactions of different forms of Aβ42 peptide with ligand binding domain of normal and G82S RAGE and their possible consequences in AD pathology. The structures of RAGE ectodomain (3CJJ, monomeric forms of Aβ42 - 1IYT (apolar and 1Z0Q (polar and fibrillar (2BEG were obtained from PDB. The structure of G82 and S82 RAGE was generated using SWISS MODEL. SIFT and PolyPhen analysis was performed to predict the phenotypic and functional effect of the amino acid substitution. The G82 and S82 variant structures were simulated in GROMACS and the 10 lowest energy structures were docked with different forms of Aβ42 using CLUSPRO in antibody mode. The lowest energy docked structure was further simulated for 5 ns. The structures corresponding to 0-5 ns were taken and the amino acid interactions were generated using PDBSUM. SIFT analysis indicated that G82S SNP had a tolerating effect on the structure of protein but polyphen predicted a probable damaging effect. Highest binding score was obtained with 2BEG docked with both G82 RAGE (-375.84 ± 7.425 Kcal/mol and G82S variant (-391.09 ± 13.391 Kcal/mol indicating that the fibrillar form showed better interaction. Compared to G82 RAGE, the S82 variant showed better interaction to all three forms of Aβ42. The results of study indicate that RAGE interacted better with fibrillar form of Aβ42 peptide and G82S mutation enhanced the binding affinity of RAGE towards amyloid peptides leading to enhanced inflammatory response.

  17. The receptor for advanced glycation end products (RAGE) and the lung.

    LENUS (Irish Health Repository)

    Buckley, Stephen T

    2010-01-01

    The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface molecules. As a pattern-recognition receptor capable of binding a diverse range of ligands, it is typically expressed at low levels under normal physiological conditions in the majority of tissues. In contrast, the lung exhibits high basal level expression of RAGE localised primarily in alveolar type I (ATI) cells, suggesting a potentially important role for the receptor in maintaining lung homeostasis. Indeed, disruption of RAGE levels has been implicated in the pathogenesis of a variety of pulmonary disorders including cancer and fibrosis. Furthermore, its soluble isoforms, sRAGE, which act as decoy receptors, have been shown to be a useful marker of ATI cell injury. Whilst RAGE undoubtedly plays an important role in the biology of the lung, it remains unclear as to the exact nature of this contribution under both physiological and pathological conditions.

  18. MR imaging in epilepsy with use of 3D MP-RAGE

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Akio; Ohno, Sigeru; Sei, Tetsuro; Kanazawa, Susumu; Yasui, Koutaro; Kuroda, Masahiro; Hiraki, Yoshio; Oka, Eiji [Okayama Univ. (Japan). School of Medicine

    1996-06-01

    The patients were 40 males and 33 females; their ages ranged from 1 month to 39 years (mean: 15.7 years). The patients underwent MR imaging, including spin-echo T{sub 1}-weighted, turbo spin-echo proton density/T{sub 2}-weighted, and 3D magnetization-prepared rapid gradient-echo (3D MP-RAGE) images. These examinations disclosed 39 focal abnormalities. On visual evaluation, the boundary of abnormal gray matter in the neuronal migration disorder (NMD) cases was most clealy shown on 3D MP-RAGE images as compared to the other images. This is considered to be due to the higher spatial resolution and the better contrast of the 3D MP-RAGE images than those of the other techniques. The relative contrast difference between abnormal gray matter and the adjacent white matter was also assessed. The results revealed that the contrast differences on the 3D MP-RAGE images were larger than those on the other images; this was statistically significant. Although the sensitivity of 3D MP-RAGE for NMD was not specifically evaluated in this study, the possibility of this disorder, in cases suspected on other images, could be ruled out. Thus, it appears that the specificity with respect to NMD was at least increased with us of 3D MP-RAGE. 3D MP-RAGE also enabled us to build three-dimensional surface models that were helpful in understanding the three-dimensional anatomy. Furthermore. 3D MP-RAGE was considered to be the best technique for evaluating hippocampus atrophy in patients with MTS. On the other hand, the sensitivity in the signal change of the hippocampus was higher on T{sub 2}-weighted images. In addition, demonstration of cortical tubers of tuberous sclerosis in neurocutaneous syndrome was superior on T{sub 2}-weighted images than on 3D MP-RAGE images. (K.H.)

  19. Decreased Neointimal Extracellular Matrix Formation in RAGE-Knockout Mice After Microvascular Denudation

    Energy Technology Data Exchange (ETDEWEB)

    Groezinger, Gerd, E-mail: gerd.groezinger@med.uni-tuebingen.de; Schmehl, Joerg, E-mail: joerg.schmehl@med.uni-tuebingen.de; Bantleon, Ruediger, E-mail: ruediger.bantleon@med.uni-tuebingen.de; Kehlbach, Rainer, E-mail: rainer.kehlbach@uni-tuebingen.de [University of Tuebingen, Department of Diagnostic and Interventional Radiology (Germany); Mehra, Tarun, E-mail: tarun.mehra@med.uni-tuebingen.de [University of Tuebingen, Department of Dermatology (Germany); Claussen, Claus, E-mail: gerd.groezinger@med.uni-tuebingen.de; Wiesinger, Benjamin, E-mail: benjamin.wiesinger@med.uni-tuebingen.de [University of Tuebingen, Department of Diagnostic and Interventional Radiology (Germany)

    2012-12-15

    Purpose: To evaluate in vivo the role of RAGE (receptor for advanced glycated end products) in the development of restenosis and neointimal proliferation in RAGE-deficient knockout (KO) mice compared with wild-type (WT) mice in an animal model. Materials and Methods: Sixteen WT and 15 RAGE-deficient mice underwent microvascular denudation of the common femoral artery under general anaesthesia. Contralateral arteries underwent a sham operation and served as controls. Four weeks after the intervention, all animals were killed, and paraformaldehyde-fixed specimens of the femoral artery were analysed with different stains (hematoxylin and eosin and Elastica van Gieson) and several different types of immunostaining (proliferating cell nuclear antigen, {alpha}-actin, collagen, von Willebrand factor, RAGE). Luminal area, area of the neointima, and area of the media were measured in all specimens. In addition, colony-formation assays were performed, and collagen production by WT smooth muscle cells (SMCs) and RAGE-KO SMCs was determined. For statistical analysis, P < 0.05 was considered statistically significant. Results: Four weeks after denudation, WT mice showed a 49.6% loss of luminal area compared with 14.9% loss of luminal area in RAGE-deficient mice (sham = 0% loss) (P < 0.001). The neointima was 18.2 (*1000 {mu}m{sup 2} [n = 15) in the WT group compared with only 8.4 (*1000 {mu}m{sup 2} [n = 16]) in the RAGE-KO group. RAGE-KO SMCs showed significantly decreased proliferation activity and production of extracellular matrix protein. Conclusion: RAGE may be shown to play a considerable role in the formation of neointima leading to restenosis after vascular injury.

  20. MR imaging in epilepsy with use of 3D MP-RAGE

    International Nuclear Information System (INIS)

    The patients were 40 males and 33 females; their ages ranged from 1 month to 39 years (mean: 15.7 years). The patients underwent MR imaging, including spin-echo T1-weighted, turbo spin-echo proton density/T2-weighted, and 3D magnetization-prepared rapid gradient-echo (3D MP-RAGE) images. These examinations disclosed 39 focal abnormalities. On visual evaluation, the boundary of abnormal gray matter in the neuronal migration disorder (NMD) cases was most clealy shown on 3D MP-RAGE images as compared to the other images. This is considered to be due to the higher spatial resolution and the better contrast of the 3D MP-RAGE images than those of the other techniques. The relative contrast difference between abnormal gray matter and the adjacent white matter was also assessed. The results revealed that the contrast differences on the 3D MP-RAGE images were larger than those on the other images; this was statistically significant. Although the sensitivity of 3D MP-RAGE for NMD was not specifically evaluated in this study, the possibility of this disorder, in cases suspected on other images, could be ruled out. Thus, it appears that the specificity with respect to NMD was at least increased with us of 3D MP-RAGE. 3D MP-RAGE also enabled us to build three-dimensional surface models that were helpful in understanding the three-dimensional anatomy. Furthermore. 3D MP-RAGE was considered to be the best technique for evaluating hippocampus atrophy in patients with MTS. On the other hand, the sensitivity in the signal change of the hippocampus was higher on T2-weighted images. In addition, demonstration of cortical tubers of tuberous sclerosis in neurocutaneous syndrome was superior on T2-weighted images than on 3D MP-RAGE images. (K.H.)

  1. Pyrazole-5-carboxamides, novel inhibitors of receptor for advanced glycation end products (RAGE).

    Science.gov (United States)

    Han, Young Taek; Kim, Kyeojin; Choi, Gyeong-In; An, Hongchan; Son, Dohyun; Kim, Hee; Ha, Hee-Jin; Son, Jun-Hyeng; Chung, Suk-Jae; Park, Hyun-Ju; Lee, Jeewoo; Suh, Young-Ger

    2014-05-22

    In an effort to develop novel inhibitors of receptor for advanced glycation end products (RAGE) for the treatment of Alzheimer's disease, a series of pyrazole-5-carboxamides were designed, synthesized and biologically evaluated. Analyses of the extensive structure-activity relationship (SAR) led us to identify a 4-fluorophenoxy analog (40) that exhibited improved in vitro RAGE inhibitory activity and more favorable aqueous solubility than the parent 2-aminopyrimidine, 1. Surface plasmon resonance (SPR) and molecular docking study strongly supported the RAGE inhibitory activity of pyrazole-5-carboxamides. The brain Aβ-lowering effect of 40 is also described. PMID:24727489

  2. MK615 decreases RAGE expression and inhibits TAGE-induced proliferation in hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Yuhki; Sakuraoka; Tokihiko; Sawada; Toshie; Okada; Takayuki; Shiraki; Yoshikazu; Miura; Katsuya; Hiraishi; Tatsushi; Ohsawa; Masakazu; Adachi; Jun-ichi; Takino; Masayoshi; Takeuchi; Keiichi; Kubota

    2010-01-01

    AIM:To investigate the proliferative effect of advanced glycation end-products(AGEs) and the role of their cellular receptor(RAGE) on hepatocellular carcinoma(HCC) cells,and the inhibitory effects of MK615,an extract from Japanese apricot,against AGEs were also evaluated.METHODS:Two HCC cell lines,HuH7 and HepG2,were used.Expression of RAGE was investigated by poly-merase chain reaction,Western blotting,and flow cytemetry(FACS).The effect of MK615 on RAGE expression was also evaluated by FACS.The proliferat...

  3. Expression of RAGE and HMGB1 in thymic epithelial tumors, thymic hyperplasia and regular thymic morphology.

    Directory of Open Access Journals (Sweden)

    Bernhard Moser

    Full Text Available Recently, a role of the receptor for advanced glycation endproducts (RAGE in myasthenia gravis was described. RAGE and its ligand high mobility group box 1 (HMGB1 play key roles in autoimmunity and cancer. To test whether these molecules are involved in patients with thymic abnormalities we applied immunohistochemical analysis in 33 cases of thymic epithelial tumors, comprising 27 thymomas and 6 thymic carcinomas, and 21 nonneoplastic thymuses. Both molecules were detected in neoplastic epithelial cells: RAGE staining was most intense in WHO type B2 thymomas and thymic carcinomas (pB3>thymic carcinoma (p<0.001. Conversely, HMGB1 cytoplasmic staining intensities were as follows: A and AB (none, B1 (strong, B2 (moderate, B3 and thymic carcinoma (weak; (p<0.001. Fetal thymic tissue showed a distinct expression of RAGE and HMGB1 in subcapsular cortical epithelial cells which was found in 50% of myasthenic patients. Furthermore RAGE and HMGB1 were expressed in thymocytes, macrophages, Hassall's corpuscles, thymic medulla, and germinal center cells in myasthenic patients. Immunohistochemistry results were complemented by systemic measurements (immunosorbent assay: serum levels of soluble RAGE were significantly reduced in patients with epithelial tumors (p = 0.008; and in invasive tumors (p = 0.008. Whereas RAGE was equally reduced in thymic hyperplasia and epithelial tumors (p = 0.003, HMGB1 was only elevated in malignancies (p = 0.036. Results were most pronounced in thymic carcinomas. Thus, RAGE and HMGB1 are involved in the (patho-physiology of thymus, as evidenced by differentiated thymic and systemic expression patterns that may act as diagnostic or therapeutic targets in autoimmune disease and cancer.

  4. Dynamic changes in sRAGE levels and relationship with cardiac function in STEMI patients

    DEFF Research Database (Denmark)

    Jensen, Louise J N; Lindberg, Søren; Hoffmann, Søren;

    2015-01-01

    early phase of AMI; sRAGE levels significantly increased after pPCI compared with sRAGE before pPCI (median ratio: 1.25, 95% CI: 1.15-1.35, P<0.001), and the increase was observed prior to Troponin I (TnI). sRAGE levels decreased notably the first day after pPCI (median ratio: 0.34, 95% CI: 0.30-0.39, P...... dynamic changes in sRAGE levels during AMI and relationship with cardiac dysfunction. DESIGN AND METHODS: We prospectively included 80 patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). sRAGE concentrations were measured before pPCI......, immediately after pPCI and again on the first and second following days. Left ventricular ejection fraction (LVEF) was evaluated 1-3 days after the pPCI and again at a median of 7months by echocardiography, and infarct size was measured by cardiac magnetic resonance. RESULTS: sRAGE levels were high in the...

  5. Expression and Clinical Significance of HMGB1 and RAGE in Cervical Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To study the expression level and clinical significance of HMGB1 and RAGE in cervical squamous epithelial carcinoma.METHODS Real time quantitative polymerase chain reaction (qRT-PCR)was employed to examine the expression of HMGB1 (high mobility group box protein1), and RAGE (receptor for advanced glycation endproducts)in 60 cervical squamous epithelial carcinomas (CSEC), their paraneoplastic tissues (PS) and 30 normal cervix tissues (NCS).RESULTS The expression of HMGB1 in the CSEC samples and PS was similar (P>0.05), but higher compared to NCS (P<0.05). Overexpression of HMGB1 in the CESC tissues was significantly correlated with the tumor (P<0.05), and the presence of metastasis (P<0.01), but not correlated with the tumor diameter or tumor grade. RAGE expression was not significantly different among these tissue types, and showed no significant correlation with the the tumor stage, diameter or grade. But there was a significant positive correlation between RAGE expression and CSEC metastasis.CONCLUSION The results suggest that HMGB1 may be related to the proliferation, progression and metastasis of CSEC. The relationship of HMGB1/RAGE may be of importance for CSEC metastasis. HMGB1 presents a new potential gene target for prevention and treatment of CSEC.Study of HMGB1/RAGE expression will offer an experimental foundation for understanding the pathogenesis of CSES.

  6. Serum soluble RAGE levels and carotid atherosclerosis: the Northern Manhattan Study (NOMAS)

    Science.gov (United States)

    Hudson, Barry I; Gardener, Hannah; Liu-Mares, Wen; Dong, Chuanhui; Cheung, Ken; Elkind, Mitchell SV; Wright, Clinton B; Sacco, Ralph L; Rundek, Tatjana

    2016-01-01

    Background Recent cohort studies suggested that serum levels of soluble Receptor for Advanced Glycation End-products (sRAGE) are associated with the risk of cardiovascular disease. We hypothesized that sRAGE levels are associated with subclinical atherosclerosis in a racially and ethnically diverse population. Methods and results 828 stroke-free participants from the Northern Manhattan Study (mean age 71.1±8.7yrs; 64% Hispanic, 19% black, and 17% white) underwent high-resolution carotid B-mode ultrasound to measure carotid plaque (present in 62% of subjects) and intima-media thickness (IMT) (mean Total= 0.96±0.10 mm). Serum sRAGE was measured by ELISA and associations tested between sRAGE with IMT and plaque presence. Soluble RAGE levels were not associated with plaque presence or IMT after adjusting for sociodemographic, vascular risk factors and medication use. Stratification by race-ethnicity did not reveal any associations with carotid IMT or plaque. Conclusion In the present study, sRAGE levels were not associated with carotid atherosclerosis. PMID:25744702

  7. Soluble Levels of Receptor for Advanced Glycation Endproducts (RAGE) and Progression of Atherosclerosis in Individuals Infected with Human Immunodeficiency Virus: ACTG NWCS 332.

    Science.gov (United States)

    Danoff, Ann; Kendall, Michelle A; Currier, Judith S; Kelesidis, Theodoros; Schmidt, Ann Marie; Aberg, Judith A

    2016-08-01

    Identification of biomarkers and/or mediators of cardiovascular disease (CVD) associated with HIV infection would be of diagnostic and therapeutic value. As soluble receptor for advanced glycation endproducts (sRAGE) and endogenous secretory (esRAGE) have been implicated in vascular complications in other settings, we investigated whether either soluble form of RAGE was associated with changes in carotid intima-media thickness (CIMT) in HIV-infected patients and HIV-uninfected controls. We found no differences in sRAGE, esRAGE, or CIMT among groups at study entry, or in yearly rates of change in sRAGE, esRAGE, or CIMT by HIV-serostatus (all p > 0.10). However, yearly rates of change in sRAGE (p = 0.07) and esRAGE (p mediator of CVD in HIV-infected persons. PMID:27216802

  8. Road Rage: Prevalence Pattern and Web Based Survey Feasibility

    Directory of Open Access Journals (Sweden)

    Shaily Mina

    2014-01-01

    Full Text Available Introduction. Incidents of road rage are on a rise in India, but the literature is lacking in the aspect. There is an increasing realization of possibility of effective web based interventions to deliver public health related messages. Objective. The aim was to quantitatively evaluate risk factors among motor vehicle drivers using an internet based survey. Methods. Facebook users were evaluated using Life Orientation Test-Revised (LOT-R and Driving Anger Scale (DAS. Results. An adequate response rate of 65.9% and satisfactory reliability with sizable correlation were obtained for both scales. Age was found to be positively correlated to LOT-R scores (r=0.21; P=0.02 and negatively correlated to DAS scores (r=-0.19; P=0.03. Years of education were correlated to LOT-R scores (r=0.26; P=0.005 but not DAS scores (r=-0.14; P=0.11. LOT-R scores did not correlate to DAS scores. Conclusion. There is high prevalence of anger amongst drivers in India particularly among younger males. A short web survey formatted in easy to use question language can result in a feasible conduction of an online survey.

  9. Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway

    International Nuclear Information System (INIS)

    An abnormal high mobility group box 1 (HMGB1) activation and a decrease in receptor for advanced glycation end-product (RAGE) play a key role in the pathogenesis of pulmonary fibrosis. Protocatechuic aldehyde (PA) is a naturally occurring compound, which is extracted from the degradation of phenolic acids. However, whether PA has anti-fibrotic functions is unknown. In this study, the effects of PA on the transforming growth factor-β1 (TGF-β1)-mediated epithelial–mesenchymal transition (EMT) in A549 cells, on the apoptosis of human type I alveolar epithelial cells (AT I), on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis in vivo were investigated. PA treatment resulted in a reduction of EMT in A549 cells with a decrease in vimentin and HMGB, an increase of E-cadherin and RAGE, a reduction of HLF-1 proliferation with a decrease of fibroblast growth factor 2 (FGF-2) and platelet-derived growth factor (PDGF). Apoptosis of AT I was attenuated with an increase of RAGE. PA ameliorated BLM-induced pulmonary fibrosis in rats with a reduction of histopathological scores and collagen deposition, and a lower FGF-2, PDGF, α-smooth muscle actin (α-SMA) and HMGB1 expression, whereas higher RAGE was found in BLM-instilled lungs. Through the decrease of HGMB1 and the regulation of RAGE, PA reversed the EMT, inhibited HLF-1 proliferation as well as reduced apoptosis in AT I, and prevented pulmonary fibrosis in vivo. Collectively, our results demonstrate that PA prevents experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway. - Highlights: • PA prevents EMT, reduces the apoptosis of AT1 in vitro. • PA decreases proliferation of HLF-1, reduces PDGF and FGF expression in vitro. • PA prevents experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway

  10. Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Liang, E-mail: countryspring@sina.com; Ji, Yunxia, E-mail: 413499057@qq.com; Kang, Zechun, E-mail: davidjiangwl@163.com; Lv, Changjun, E-mail: Lucky_lcj@sina.com; Jiang, Wanglin, E-mail: jwl518@163.com

    2015-02-15

    An abnormal high mobility group box 1 (HMGB1) activation and a decrease in receptor for advanced glycation end-product (RAGE) play a key role in the pathogenesis of pulmonary fibrosis. Protocatechuic aldehyde (PA) is a naturally occurring compound, which is extracted from the degradation of phenolic acids. However, whether PA has anti-fibrotic functions is unknown. In this study, the effects of PA on the transforming growth factor-β1 (TGF-β1)-mediated epithelial–mesenchymal transition (EMT) in A549 cells, on the apoptosis of human type I alveolar epithelial cells (AT I), on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis in vivo were investigated. PA treatment resulted in a reduction of EMT in A549 cells with a decrease in vimentin and HMGB, an increase of E-cadherin and RAGE, a reduction of HLF-1 proliferation with a decrease of fibroblast growth factor 2 (FGF-2) and platelet-derived growth factor (PDGF). Apoptosis of AT I was attenuated with an increase of RAGE. PA ameliorated BLM-induced pulmonary fibrosis in rats with a reduction of histopathological scores and collagen deposition, and a lower FGF-2, PDGF, α-smooth muscle actin (α-SMA) and HMGB1 expression, whereas higher RAGE was found in BLM-instilled lungs. Through the decrease of HGMB1 and the regulation of RAGE, PA reversed the EMT, inhibited HLF-1 proliferation as well as reduced apoptosis in AT I, and prevented pulmonary fibrosis in vivo. Collectively, our results demonstrate that PA prevents experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway. - Highlights: • PA prevents EMT, reduces the apoptosis of AT1 in vitro. • PA decreases proliferation of HLF-1, reduces PDGF and FGF expression in vitro. • PA prevents experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.

  11. Periodontal disease and the oral-systemic connection: "is it all the RAGE?".

    Science.gov (United States)

    Katz, Joseph; Wallet, Shannon; Cha, Seunghee

    2010-03-01

    Ample studies have reported on the association between periodontal diseases, a persistent inflammatory process, and other chronic ailments such as cardiovascular diseases, diabetes mellitus, Alzheimer disease, and cancer. Other conditions such as low birth weight and premature delivery due to chorioamnionitis are also known to be linked to poor periodontal health. Although much epidemiologic data support these associations, a cause-and-effect relationship has not been established. The receptor for advanced glycation end products (RAGE) is a multiligand receptor expressed on various cell membranes, including immune, endothelial, and epithelial, and cells of the central nervous system. This receptor, which is frequently associated with proinflammatory responses, has been shown to be activated by various ligands such as high mobility group box-1 (HMGB1/amphoterin), amyloid fibrils, transthyrein, Mac-1 (Integrin Mac-1), as well as advanced glycation end products (AGEs). Recent studies indicate that signaling through RAGE has been implicated as an underlying condition in diverse pathologies including periodontal disease, cardiovascular diseases, diabetes mellitus, Alzheimer disease, cancer, and neurologic conditions. Review of the literature supports the hypothesis that activation of RAGE by ligands in a variety of cell types and tissues may play a role in oral systemic associations. In addition, the ligand cell source and timing of RAGE stimulation may determine the disease produced by this axis. Understanding the distribution and functions of RAGE and its ligands would enhance clinicians' knowledge on pathogenesis of the oral-systemic connection. PMID:20213024

  12. Donnees Serologiques sur la rage Vulpine Etudiee en Iran

    Directory of Open Access Journals (Sweden)

    Y. KARIMI

    1975-01-01

    Full Text Available During the epidemiological research of zoonoses, the authors have studied the rabies of wild animals : fox. For the scro lo-uical tests. the blood . was taken by heart puncture of foxes. 193 specimens were tested and 26 (13. 5% o r the foxes had neut ralizing antibody in their blood. This study confirms that during the rabies epizooty. the Vulpin population, may contract a non-fatal disease and produce the neutralizing antibody. Thus, the fox has a real place in the epidemiology of rabies in Iran."n* * *"nA la sui te des etudes effectuees par nous-merne (8, nous rapportons ici, les resultats scrologiques, des travaux acheves dans Ie but d'enrichir et  de completer les donnees precedentcs, Le present travail, ainsi que notre etude prcliminairc, ont etc realises dans la meme region, ccntree par le village d'AGH BOULAGH MORCHED, dans Ie Kurdistan, i186 Km au Nord-Ouest de HAMADAN (Ca rte N° I . Le role primordial du Renard, dans Ie processus de la Rage naturelle a deja fait l'objet de plusieurs articles (4, (5, (7, (17, (14, Cependant l'existence chez les animaux sauvages danticorps antirabiques n'est que rarement mentionnee dans ccs travaux. Les donnees experimentales ne peuvent pas toujours expliquer ce qui se passe dans les conditions naturelles de l'enzootie rabique, au point de vue de la reponse serologique chez Ie renard. C'est pourquoi nous nous sommes attaches a completer la recherche d'anticorps neutralisants antirabiques, chez Ie renard, dans son milieu nature!

  13. AGE-RAGE interaction in the TGFβ2-mediated epithelial to mesenchymal transition of human lens epithelial cells.

    Science.gov (United States)

    Raghavan, Cibin T; Nagaraj, Ram H

    2016-08-01

    Basement membrane (BM) proteins accumulate chemical modifications with age. One such modification is glycation, which results in the formation of advanced glycation endproducts (AGEs). In a previous study, we reported that AGEs in the human lens capsule (BM) promote the TGFβ2-mediated epithelial-to-mesenchymal transition (EMT) of lens epithelial cells, which we proposed as a mechanism for posterior capsule opacification (PCO) or secondary cataract formation. In this study, we investigated the role of a receptor for AGEs (RAGE) in the TGFβ2-mediated EMT in a human lens epithelial cell line (FHL124). RAGE was present in FHL124 cells, and its levels were unaltered in cells cultured on either native or AGE-modified BM or upon treatment with TGFβ2. RAGE overexpression significantly enhanced the TGFβ2-mediated EMT responses in cells cultured on AGE-modified BM compared with the unmodified matrix. In contrast, treatment of cells with a RAGE antibody or EN-RAGE (an endogenous ligand for RAGE) resulted in a significant reduction in the TGFβ2-mediated EMT response. This was accompanied by a reduction in TGFβ2-mediated Smad signaling and ROS generation. These results imply that the interaction of matrix AGEs with RAGE plays a role in the TGFβ2-mediated EMT of lens epithelial cells and suggest that the blockade of RAGE could be a strategy to prevent PCO and other age-associated fibrosis. PMID:27263094

  14. Structural insights into calcium-bound S100P and the V domain of the RAGE complex.

    Directory of Open Access Journals (Sweden)

    Srinivasa R Penumutchu

    Full Text Available The S100P protein is a member of the S100 family of calcium-binding proteins and possesses both intracellular and extracellular functions. Extracellular S100P binds to the cell surface receptor for advanced glycation end products (RAGE and activates its downstream signaling cascade to meditate tumor growth, drug resistance and metastasis. Preventing the formation of this S100P-RAGE complex is an effective strategy to treat various disease conditions. Despite its importance, the detailed structural characterization of the S100P-RAGE complex has not yet been reported. In this study, we report that S100P preferentially binds to the V domain of RAGE. Furthermore, we characterized the interactions between the RAGE V domain and Ca(2+-bound S100P using various biophysical techniques, including isothermal titration calorimetry (ITC, fluorescence spectroscopy, multidimensional NMR spectroscopy, functional assays and site-directed mutagenesis. The entropy-driven binding between the V domain of RAGE and Ca(+2-bound S100P was found to lie in the micromolar range (Kd of ∼ 6 µM. NMR data-driven HADDOCK modeling revealed the putative sites that interact to yield a proposed heterotetrameric model of the S100P-RAGE V domain complex. Our study on the spatial structural information of the proposed protein-protein complex has pharmaceutical relevance and will significantly contribute toward drug development for the prevention of RAGE-related multifarious diseases.

  15. Can Targeting the Incretin Pathway Dampen RAGE-Mediated Events in Diabetic Nephropathy?

    Science.gov (United States)

    Sourris, Karly C; Yao, Henry; Jerums, George; Cooper, Mark E; Ekinci, Elif I; Coughlan, Melinda T

    2016-01-01

    Diabetic nephropathy is the major cause of end-stage renal disease in Western societies. To date, interruption of the Renin-Angiotensin System is the most effective intervention for diabetic nephropathy, however these agents only slow progression of the disease. Thus, there is a major unmet need for new therapeutic targets. Aberrant activation of the receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of diabetic nephropathy via binding to a variety of ligands and inciting reactive oxygen species (ROS) production, inflammation and fibrosis. In recent years there have been considerable efforts in the development of effective RAGE antagonists, however, direct RAGE targeting may be problematic. Glucagon like peptide-1 (GLP-1) is an incretin hormone released by the L-cells of the small intestine to mediate glucose-dependent insulin release from pancreatic islets. The incretin-based therapies, GLP-1 receptor agonists and dipeptidylpeptidase-4 (DPP4) inhibitors, are novel glucose-lowering agents used in type 2 diabetes. However, the extra pancreatic functions of GLP-1 have gained attention, including putative anti-apoptotic and anti-inflammatory properties. In rodent models of diabetes, incretin-based therapies are renoprotective. Interestingly, GLP-1 has been shown to interfere with the signalling and expression of RAGE. The current review aims to give an overview of the interactions between the RAGE and incretin pathways and to discuss the utility of targeting the GLP-1/incretin pathway in DN. It is possible that indirect targeting of RAGE through GLP-1 agonism will be of clinical benefit to patients with diabetic nephropathy. PMID:26201485

  16. Experiments at Scale with In-Situ Visualization Using ParaView/Catalyst in RAGE

    Energy Technology Data Exchange (ETDEWEB)

    Kares, Robert John [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-10-31

    In this paper I describe some numerical experiments performed using the ParaView/Catalyst in-situ visualization infrastructure deployed in the Los Alamos RAGE radiation-hydrodynamics code to produce images from a running large scale 3D ICF simulation on the Cielo supercomputer at Los Alamos. The detailed procedures for the creation of the visualizations using ParaView/Catalyst are discussed and several images sequences from the ICF simulation problem produced with the in-situ method are presented. My impressions and conclusions concerning the use of the in-situ visualization method in RAGE are discussed.

  17. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

    International Nuclear Information System (INIS)

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction

  18. RAGE genetic polymorphisms are associated with risk, chemotherapy response and prognosis in patients with advanced NSCLC.

    Directory of Open Access Journals (Sweden)

    Xiang Wang

    Full Text Available AIM: To explore the association between genetic polymorphisms of the receptor for advanced glycation end-products (RAGE and susceptibility, chemotherapy response rate and prognosis of non-small cell lung cancer (NSCLC. METHOD: This is a prospective study in which 562 patients with NSCLC and 764 healthy controls were enrolled. Three RAGE genetic polymorphisms, namely, -429T/C, -374T/A and 82G/S were genotyped. Platinum-based chemotherapy was given to 432 subjects with advanced inoperable NSCLC and their responses to chemotherapy were evaluated. RESULTS: All the polymorphic genotypes of RAGE polymorphisms were associated with susceptibility for NSCLC. Only the 82G/S polymorphisms denoted a significant difference between responders and non-responders to chemotherapy. The 82SS genotype and 82S allele distribution not only increased the NSCLC risk, but also was associated with a lower chemotherapy response rate and poor prognosis, indicated by overall survival and progression free survival. CONCLUSION: The 82G/S genetic polymorphism of RAGE gene might be used as a genetic marker to screen for patients sensitive to thermotherapy and to predict the prognosis of NSCLC.

  19. RAGE Reusable Game Software Components and Their Integration into Serious Game Engines

    NARCIS (Netherlands)

    VanderVegt, Wim; Nyamsuren, Enkhbold; Westera, Wim

    2016-01-01

    This paper presents and validates a methodology for integrating reusable software components in diverse game engines. While conforming to the RAGE com-ponent-based architecture described elsewhere, the paper explains how the interac-tions and data exchange processes between a reusable software compo

  20. Thinking through Moments of Sexual Refusal in "Looking for Alibrandi" and "The Rage in Placid Lake"

    Science.gov (United States)

    Clarke, Kyra

    2016-01-01

    This paper explores two scenarios in which young women refuse the sexual advances of young men in the films "Looking for Alibrandi" and "The Rage in Placid Lake." The paper highlights the heteronormative nature of education around refusing sex, which reinstates gendered stereotypes of masculine as active and feminine as…

  1. Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Li, D.X.; Deng, T.Z.; Lv, J.; Ke, J. [Department of Stomatology, Air Force General Hospital PLA, Haidian District, Beijing (China)

    2014-09-19

    Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction.

  2. Explaining seemingly paradoxical consumer experiences: conjoining weekly road rage and church attendance.

    Science.gov (United States)

    Gau, Li-Shiue; Woodside, Arch G; Martin, Drew

    2015-02-01

    The purposes of the current study are threefold: Provide evidence that an extreme paradoxical group exists-people frequently attending church and exhibiting road rage, profile this group, and frame possible explanations for the seemingly paradoxical behaviors. This study employs data from a national (USA) lifestyle survey conducted by Market Facts with 3,350 American respondents. The major questions asked about church participation and road-rage behavior ("giving a finger" and "flashing headlights"). Nomologically, relevant activities include 3 items for church goers and 3 items for road-rage givers. Additionally, 14 items profiled the lifestyles of the unique paradoxical behavior segment. Utilizing cross-tabulation tables, property space analyses identify the double extreme (XX) group (18 people) and other 6 groups with a significant chi-square test, confirming the extreme group exists. Analyses of variance test results show that comparing nomologically relevant activities among the seven groups is all statistically significant, indicating the nomological validity is met. Overall, the XX group tends to have more males, be younger, and have a higher proportion of people working in sales. The profile of lifestyle analyses shows the XX group members have both high ambitions and expectations, might be very frustrated individuals, and equip with the adventurous and masculine traits related to aggression. The XX behavior group's demographic and psychographic characteristics portray similar lifestyles that differ from other groups. Case-based analyses provide further contextual information of nuances to XX segment individuals. The limited energy theory, the Eagleman's theory of unconscious mind, and justification theory help to explain why people conjointly go to church and commit road rage. Addressing chronic paradoxical behaviors provides implications for social de-marketing to reduce aggressive anti-social behavior such as road rage. Frequent church attendance may

  3. Plasma levels of sRAGE, loss of aeration and weaning failure in ICU patients: a prospective observational multicenter study.

    Directory of Open Access Journals (Sweden)

    Matthieu Jabaudon

    Full Text Available RATIONALE: Postextubation distress after a successful spontaneous breathing trial (SBT is associated with increased morbidity and mortality. Lung ultrasound determination of changes in lung aeration predicts weaning failure. It remains unknown whether this derecruitment is related to alveolar epithelial dysfunction or not. OBJECTIVE: To verify whether lung alveolar type I epithelial cell injury marker sRAGE (soluble form of the receptor for advanced glycation end-products is predictive of postextubation distress and weaning failure or not, and to verify whether plasma sRAGE levels can be related to lung derecruitment during the process of weaning from mechanical ventilation or not. INTERVENTIONS MEASUREMENTS: 88 patients from 2 intensive care units were included in this observational prospective study. Plasma sRAGE levels were measured in duplicate by ELISA before, at the end of a 60-minute SBT, and 4 hours after extubation. To quantify lung aeration, a lung ultrasound score was calculated. MAIN RESULTS: 34% of extubated patients experienced postextubation distress. Patients with or without postextubation distress had comparable sRAGE levels before SBT, after SBT, and 4 hours after extubation. In patients with postextubation distress, sRAGE levels were not predictive of the need for mechanical ventilation. sRAGE levels were not associated with lung aeration as assessed by echography. Patients who succeeded SBT (86% and those who failed (14% had no differences in sRAGE levels, before (median 1111 vs 1021 pg/mL, p = 0,87 and at the end of SBT (1165 vs 1038 pg/mL, p = 0.74. CONCLUSIONS: Plasma levels of sRAGE do not predict postextubation distress or SBT failure/success in patients weaning from mechanical ventilation. Lung aeration loss during a successful weaning trial predicts postextubation distress, but may not be evaluable by plasma levels of sRAGE, a marker of alveolar type I epithelial cell injury. TRIAL REGISTRATION: Clinical

  4. Beneficial Effect of Glucose Control on Atherosclerosis Progression in Diabetic ApoE−/− Mice: Shown by Rage Directed Imaging

    OpenAIRE

    Yared Tekabe; Maria Kollaros; Qing Li; Geping Zhang; Chong Li; Ann Marie Schmidt; Johnson, Lynne L.

    2014-01-01

    Objective. Receptor for advanced glycated endproducts (RAGE) plays an important role in atherogenesis in diabetes. We imaged RAGE to investigate the effect of glucose control to suppress RAGE and reduce atherosclerosis in apolipoprotein E null (apoE−/−) diabetic mice. Methods and Results. Thirty-three apoE−/− mice received streptozotocin and 6 weeks later 15 began treatment with insulin implants. Blood glucose measurements during study averaged: 140 ± 23 mg/dL (treated) and 354 ± 14 mg/dL (un...

  5. GeneOptimizer program-assisted cDNA reengineering enhances sRAGE autologous expression in Chinese hamster ovary cells.

    Science.gov (United States)

    Wei, Wen; Kim, Ji Min; Medina, Danny; Lakatta, Edward G; Lin, Li

    2014-03-01

    Soluble receptor for advanced glycation end products (sRAGE) is a secreted mammalian protein that functions as a decoy to counter-react RAGE signaling-resultant pathological conditions, and has high therapeutic potentials. Our prior studies showed that recombinant human sRAGE expressed in Chinese hamster, Ceanothus griseus, ovary (CHO) cells is modified by specific N-glycosylation, and exhibits higher bioactivity than that expressed in other host systems including insect Spodoptera frugiperda cells. Here, we show that GeneOptimizer software program-assisted, reengineered sRAGE cDNA enhances the recombinant protein expression in CHO cells. The cDNA sequence encoding human sRAGE was optimized for RNA structure, stability, and codon usages in CHO cells. We found that such optimization augmented sRAGE expression over 2 folds of its wild-type counterpart. We also studied how individual parameter impacted sRAGE autologous expression in CHO cells, and whether sRAGE bioactivity was compromised. We found that the enhanced expression appeared not to affect sRAGE N-glycosylation and bioactivity. Optimization of sRAGE expression provides a basis for future large-scale production of this protein to meet medical needs. PMID:24373844

  6. Study on the serum level of esRAGE and other related factors in patients with type 2 diabetes

    International Nuclear Information System (INIS)

    Objective: To study the serum level of endogenous secretory receptor for advanced glycation end products (esRAGE) in type 2 diabetes (T2DM) and its relationship with other related factors. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum esRAGE level in 60 T2DM 30 of which bad carotid atherosclerosis and 28 normal controls, other clinical index was also tested. Results: Serum esRAGE level was significantly lower in T2DM with carotid atherosclerosis than in T2DM without carotid atherosclerosis and in the normal controls(P<0.01). T2DM without carotid atherosclerosis was also significantly lower than that in the normal controls (P<0.05). Pearson correlation analysis showed serum esRAGE was inversely correlated with age and components of the metabolic syndrome including glycosylated hemoglobin Alc, total cholesterol, low density lipoprotein, systolic blood pressure and body mass index (P<0.01). Multiple linear regression analyses showed that age, total cholesterol, glycosylated hemoglobin Alc and body index were independently associated with esRAGE (P<0.05). Conclusion: esRAGE is probably a potential protective factor for diabetes with atherosclerosis and metabolic syndrome. (authors)

  7. Effects of methanolic extracts of edible plants on RAGE in high-glucose-induced human endothelial cells.

    Science.gov (United States)

    Okada, Mizue; Okada, Yoshinori

    2015-01-01

    Advanced glycation end products' (AGEs) engagement of a cell-surface receptor for AGEs (RAGE) has been causally implicated in the pathogenesis of vascular complications in diabetic patients. Methanolic extracts from edible plants (MEEP) are naturally occurring phenolic compounds. The phenolic compounds have been reported to possess potent radical-scavenging properties. We investigated whether MEEP could inhibit high glucose-induced RAGE production through interference with reactive oxygen species generation in endothelial cells (ECs). ECs were incubated with 4.5 g/l of glucose in culture medium treated with 21 MEEP. Determination of RAGE production in the culture supernatants was performed by colorimetric ELISA. DNA damage was determined by using the 8-hydroxydeoxyguanosine ELISA kit. Because peroxynitrite radicals with stronger toxicity were produced by nitric oxide radical (NO), the NO scavenging activity of MEEP was assessed as nitrite generation. Peroxynitrite radical-dependent oxidation inhibition by MEEP was estimated by the Crow method. The results showed that four extracts reduced RAGE production. The extract from onion peel showed the highest RAGE production inhibition activity, followed by that of onion rhizome, cow pea and burdock. The results showed that RAGE production is correlated with the above-mentioned indicators. This study supports the utilization of four extracts for improved treatment of diabetic complications. PMID:26407112

  8. HMGB1 Regulates RANKL-Induced Osteoclastogenesis in a Manner Dependent on RAGE

    OpenAIRE

    Zhou, Zheng; Han, Jun-Yan; Xi, Cai-Xia; Xie, Jian-Xin; FENG, XU; Wang, Cong-Yi; Mei, Lin; Xiong, Wen-Cheng

    2008-01-01

    High-mobility group box 1 (HMGB1), a nonhistone nuclear protein, is released by macrophages into the extracellular milieu consequent to cellular activation. Extracellular HMGB1 has properties of a pro-inflammatory cytokine through its interaction with receptor for advanced glycation endproducts (RAGE) and/or toll-like receptors (TLR2 and TLR4). Although HMGB1 is highly expressed in macrophages and differentiating osteoclasts, its role in osteoclastogenesis remains largely unknown. In this rep...

  9. Nuclear DAMP complex-mediated RAGE-dependent macrophage cell death

    International Nuclear Information System (INIS)

    High mobility group box 1 (HMGB1), histone, and DNA are essential nuclear components involved in the regulation of chromosome structure and function. In addition to their nuclear function, these molecules act as damage-associated molecular patterns (DAMPs) alone or together when released extracellularly. The synergistic effect of these nuclear DNA-HMGB1-histone complexes as DAMP complexes (nDCs) on immune cells remains largely unexplored. Here, we demonstrate that nDCs limit survival of macrophages (e.g., RAW264.7 and peritoneal macrophages) but not cancer cells (e.g., HCT116, HepG2 and Hepa1-6). nDCs promote production of inflammatory tumor necrosis factor α (TNFα) release, triggering reactive oxygen species-dependent apoptosis and necrosis. Moreover, the receptor for advanced glycation end products (RAGE), but not toll-like receptor (TLR)-4 and TLR-2, was required for Akt-dependent TNFα release and subsequent cell death following treatment with nDCs. Genetic depletion of RAGE by RNAi, antioxidant N-Acetyl-L-cysteine, and TNFα neutralizing antibody significantly attenuated nDC-induced cell death. These findings provide evidence supporting novel signaling mechanisms linking nDCs and inflammation in macrophage cell death. - Highlights: • Nuclear DAMP complexes (nDCs) selectively induce cell death in macrophages, but not cancer cells. • TNFα-mediated oxidative stress is required for nDC-induced death. • RAGE-mediated Akt activation is required for nDC-induced TNFα release. • Blocking RAGE and TNFα inhibits nDC-induced macrophage cell death

  10. Nuclear DAMP complex-mediated RAGE-dependent macrophage cell death

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ruochan [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Department of Infectious Diseases and State Key Lab of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China); Fu, Sha; Fan, Xue-Gong [Department of Infectious Diseases and State Key Lab of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China); Lotze, Michael T.; Zeh, Herbert J. [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Tang, Daolin, E-mail: tangd2@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Kang, Rui, E-mail: kangr@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States)

    2015-03-13

    High mobility group box 1 (HMGB1), histone, and DNA are essential nuclear components involved in the regulation of chromosome structure and function. In addition to their nuclear function, these molecules act as damage-associated molecular patterns (DAMPs) alone or together when released extracellularly. The synergistic effect of these nuclear DNA-HMGB1-histone complexes as DAMP complexes (nDCs) on immune cells remains largely unexplored. Here, we demonstrate that nDCs limit survival of macrophages (e.g., RAW264.7 and peritoneal macrophages) but not cancer cells (e.g., HCT116, HepG2 and Hepa1-6). nDCs promote production of inflammatory tumor necrosis factor α (TNFα) release, triggering reactive oxygen species-dependent apoptosis and necrosis. Moreover, the receptor for advanced glycation end products (RAGE), but not toll-like receptor (TLR)-4 and TLR-2, was required for Akt-dependent TNFα release and subsequent cell death following treatment with nDCs. Genetic depletion of RAGE by RNAi, antioxidant N-Acetyl-L-cysteine, and TNFα neutralizing antibody significantly attenuated nDC-induced cell death. These findings provide evidence supporting novel signaling mechanisms linking nDCs and inflammation in macrophage cell death. - Highlights: • Nuclear DAMP complexes (nDCs) selectively induce cell death in macrophages, but not cancer cells. • TNFα-mediated oxidative stress is required for nDC-induced death. • RAGE-mediated Akt activation is required for nDC-induced TNFα release. • Blocking RAGE and TNFα inhibits nDC-induced macrophage cell death.

  11. Role of IL-1β and 5-HT2 Receptors in Midbrain Periaqueductal Gray (PAG) in Potentiating Defensive Rage Behavior in Cat

    OpenAIRE

    Bhatt, Suresh; Bhatt, Rekha; Zalcman, Steven S; Siegel, Allan

    2007-01-01

    Feline defensive rage, a form of aggressive behavior that occurs in response to a threat can be elicited by electrical stimulation of the medial hypothalamus or midbrain periaqueductal gray (PAG). Our laboratory has recently begun a systematic examination of the role of cytokines in the regulation of rage and aggressive behavior. It was shown that the cytokine, interleukin-2 (IL-2), differentially modulates defensive rage when microinjected into the medial hypothalamus and PAG by acting throu...

  12. Beneficial Effect of Glucose Control on Atherosclerosis Progression in Diabetic ApoE−/− Mice: Shown by Rage Directed Imaging

    Directory of Open Access Journals (Sweden)

    Yared Tekabe

    2014-01-01

    Full Text Available Objective. Receptor for advanced glycated endproducts (RAGE plays an important role in atherogenesis in diabetes. We imaged RAGE to investigate the effect of glucose control to suppress RAGE and reduce atherosclerosis in apolipoprotein E null (apoE−/− diabetic mice. Methods and Results. Thirty-three apoE−/− mice received streptozotocin and 6 weeks later 15 began treatment with insulin implants. Blood glucose measurements during study averaged: 140 ± 23 mg/dL (treated and 354 ± 14 mg/dL (untreated. After 15 wk 30 mice were injected with Tc99m-anti-RAGE F(ab′2, 3 with Tc99m-nonimmune IgG F(ab′2, and all with CT contrast agent and underwent SPECT/CT imaging. At necropsy, the proximal aorta was weighed, counted, and sectioned and the % injected dose per gram (%ID/g was calculated. From the merged SPECT/CT scans, tracer uptake localized to arteries was lower in the treated mice: 3.15±1.82×10-3 versus 8.69±4.58×10-3%ID (P=0.001. Percent cross-sectional lesion area was smaller in the treated (14.3±7.8% versus 29.5±10.9% (P=0.03. RAGE uptake on scans (%ID correlated with quantitative RAGE staining in the atheroma and with %ID/g (R=0.6887; P=0.01. Lesion size as percent cross-sectional area was smaller in the treated (14.3±7.8% versus 29.5±10.9% (P=0.03. RAGE uptake on scans (%ID correlated with quantitative RAGE staining in the atheroma and with %ID/g (R=0.6887; P=0.01. Conclusions. These results support the importance of suppressing RAGE to reduce atherosclerotic complications of diabetes and value of molecular imaging to assess treatment effect.

  13. Therapeutic effects of antigen affinity-purified polyclonal anti-receptor of advanced glycation end-product (RAGE) antibodies on cholestasis-induced liver injury in rats.

    Science.gov (United States)

    Xia, Peng; Deng, Qing; Gao, Jin; Yu, Xiaolan; Zhang, Yang; Li, Jingjing; Guan, Wen; Hu, Jianjun; Tan, Quanhui; Zhou, Liang; Han, Wei; Yuan, Yunsheng; Yu, Yan

    2016-05-15

    Cholestasis leads to acute hepatic injury, fibrosis/cirrhosis, inflammation, and duct proliferation. We investigated whether blocking receptor of advanced glycation end-products (RAGE) with polyclonal anti-RAGE antibodies (anti-RAGE) could regulate acute liver injury and fibrosis in a rat bile duct ligation (BDL) model. Male Wister rats received 0.5mg/kg rabbit anti-RAGE or an equal amount of rabbit IgG by subcutaneous injection twice a week after BDL. Samples of liver tissue and peripheral blood were collected at 14 days after BDL. Serum biochemistry and histology were used to analyze the degree of liver injury. Quantitative real-time PCR (qPCR) and immunohistochemical staining were used to further analyze liver injury. Anti-RAGE improved the gross appearance of the liver and the rat survival rate. Liver tissue histology and relevant serum biochemistry indicated that anti-RAGE attenuated liver necrosis, inflammation, liver fibrosis, and duct proliferation in the BDL model. qPCR and western blotting showed significant reductions in interleukin-1β expression levels in the liver by treatment with anti-RAGE. Anti-RAGE also significantly reduced the mRNA levels of α1(1) collagen (Col1α1) and cholesterol 7α-hydroxylase, and the ratio of tissue inhibitor of matrix metalloproteinase-1 to matrix metalloproteinases (MMPs) in the liver. In addition, anti-RAGE regulated the transcriptional level of Col1α1 and MMP-9 in transforming growth factor-β-induced activated LX-2 cells in vitro. Anti-RAGE was found to inhibit hepatic stellate cell proliferation in vivo and in vitro. Therefore, anti-RAGE can protect the liver from injury induced by BDL in rats. PMID:26970185

  14. Sleep Now in the Fire: An Analysis of A Song By Rage Against the Machine using Marxism

    Directory of Open Access Journals (Sweden)

    Abdul Aziz Turhan Kariko

    2011-09-01

    Full Text Available Rage against the Machine is known for their politics as well as their music, which the later helped creating an aggressive-heavy rock-rap genre. Article presents a song by Rage against the Machine band related to ideological movement in America, titled Sleep Now in the Fire. This effort brings an understanding of ideology that is embraced by the band. The method is through literature study. Presentation begins with a short biography of the band, theoretical concepts, and analysis of the song as well its music video. It is concluded that the song represents ideological criticism toward capitalism using Marxism. Both of these lyric and music video represents Marxism as it shares the same movement to fight capitalism which in this case, Rage against the Machine is using their music, lyric, and video to fight the crime against humanity and cultural imperialism.

  15. Expression and purification of the soluble isoform of human receptor for advanced glycation end products (sRAGE) from Pichia pastoris.

    Science.gov (United States)

    Ostendorp, Thorsten; Weibel, Mirjam; Leclerc, Estelle; Kleinert, Peter; Kroneck, Peter M H; Heizmann, Claus W; Fritz, Günter

    2006-08-18

    RAGE is a multi-ligand receptor involved in various human diseases including diabetes, cancer or Alzheimer's disease. Engagement of RAGE by its ligands triggers activation of key cellular signalling pathways such as the MAP kinase and NF-kappaB pathways. Whereas the main isoform of RAGE is a transmembrane receptor with both extra- and intracellular domains, a secreted soluble isoform (sRAGE), corresponding to the extracellular part only, has the ability to block RAGE signalling and suppress cellular activation. Administration of sRAGE to animal models of cancer or multiple sclerosis blocked successfully tumour growth and the course of the autoimmune disease. These findings demonstrate that sRAGE may have a potential as therapeutic. We present here a fast and simple purification protocol of sRAGE from the yeast Pichia pastoris. The identity of the protein was confirmed by mass spectrometry and Western blot. The protein was N-glycosylated and 95-98% pure as judged by SDS-PAGE. PMID:16806067

  16. Interpersonal violence in road rage. Cases from the Medico-Legal Center for Victims of Violence in Hamburg.

    Science.gov (United States)

    Pfeiffer, Joost-Levin; Pueschel, Klaus; Seifert, Dragana

    2016-04-01

    Aggressive behavior in traffic is a widespread phenomenon. Up to 90% of the population are involved in mild forms such as shouting or gesturing. More dramatic cases with injury to individuals affect at least 1100 people in the US annually. Certain factors such as a male sex, a young age and an urban residency have been identified to contribute to the likelihood of road rage. Central to this analysis is the determination of specific features regarding the conflicting parties, the crime scene and the injury pattern in violent offenses related to traffic. In a retrospective study spanning 10 years, cases of road rage-linked injuries were identified amongst patients at the Medico-Legal Center of the Institute of Legal Medicine in Hamburg, Germany. The data were digitized and then analyzed using descriptive statistics via SPSS. There are disproportionately large numbers of males (85.7%) and motorists (61.2%) amongst road rage perpetrators. Usually the conflicting parties have no prior relationship (89.7%). In 68.1% of the cases, the violence applied was exclusively physical. Objects were utilized in 31.0% of all cases, and in more than half (55.6%) of these cases the vehicle was used as a weapon. The resulting trauma in road rage is mostly blunt and applied to the face and the extremities. There are characteristic features regarding the demographics, time and place of incident, as well as severity and pattern of injury in road rage associated offenses. Identifying these factors may lead to appropriate measures in the reduction of road rage. PMID:26817969

  17. Perindopril Attenuates Lipopolysaccharide-Induced Amyloidogenesis and Memory Impairment by Suppression of Oxidative Stress and RAGE Activation.

    Science.gov (United States)

    Goel, Ruby; Bhat, Shahnawaz Ali; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

    2016-02-17

    Clinical and preclinical studies account hypertension as a risk factor for dementia. We reported earlier that angiotensin-converting enzyme (ACE) inhibition attenuated the increased vulnerability to neurodegeneration in hypertension and prevented lipopolysaccharide (LPS)-induced memory impairment in normotensive wistar rats (NWRs) and spontaneously hypertensive rats (SHRs). Recently, a receptor for advanced glycation end products (RAGE) has been reported to induce amyloid beta (Aβ1-42) deposition and memory impairment in hypertensive animals. However, the involvement of ACE in RAGE activation and amyloidogenesis in the hypertensive state is still unexplored. Therefore, in this study, we investigated the role of ACE on RAGE activation and amyloidogenesis in memory-impaired NWRs and SHRs. Memory impairment was induced by repeated (on days 1, 4, 7, and 10) intracerebroventricular (ICV) injections of LPS in SHRs (25 μg) and NWRs (50 μg). Our data showed that SHRs exhibited increased oxidative stress (increased gp91-phox/NOX-2 expression and ROS generation), RAGE, and β-secretase (BACE) expression without Aβ1-42 deposition. LPS (25 μg, ICV) further amplified oxidative stress, RAGE, and BACE activation, culminating in Aβ1-42 deposition and memory impairment in SHRs. Similar changes were observed at the higher dose of LPS (50 μg, ICV) in NWRs. Further, LPS-induced oxidative stress was associated with endothelial dysfunction and reduction in cerebral blood flow (CBF), more prominently in SHRs than in NWRs. Finally, we showed that perindopril (0.1 mg/kg, 15 days) prevented memory impairment by reducing oxidative stress, RAGE activation, amyloidogenesis, and improved CBF in both SHRs and NWRs. These findings suggest that perindopril might be used as a therapeutic strategy for the early stage of dementia. PMID:26689453

  18. Atorvastatin inhibits the expression of RAGE induced by advanced glycation end products on aortas in healthy Sprague–Dawley rats

    OpenAIRE

    Xu, Lei; Zang, Panpan; Feng, Bo; Qian, Qiaohui

    2014-01-01

    Background Atorvastatin can downregulate the expression of receptor for advanced glycation end products (RAGE) in the aortas of diabetic rats. However, its effect on healthy rats remains unclear. The aim of this study was to observe the direct impact of atorvastatin on advanced glycation end products- (AGEs) induced RAGE expression in healthy Sprague Dawley (SD) rats. Methods SD rats received AGE-BSA (20 mg/kg/day or 40 mg/kg/day), dual treatment (AGE-BSA 40 mg/kg/day and atorvastatin 20 mg/k...

  19. Sleep Now in the Fire: An Analysis of A Song By Rage Against the Machine using Marxism

    OpenAIRE

    Abdul Aziz Turhan Kariko

    2011-01-01

    Rage against the Machine is known for their politics as well as their music, which the later helped creating an aggressive-heavy rock-rap genre. Article presents a song by Rage against the Machine band related to ideological movement in America, titled Sleep Now in the Fire. This effort brings an understanding of ideology that is embraced by the band. The method is through literature study. Presentation begins with a short biography of the band, theoretical concepts, and analysis of the song ...

  20. The HMGB1/RAGE axis triggers neutrophil-mediated injury amplification following necrosis.

    Science.gov (United States)

    Huebener, Peter; Pradere, Jean-Philippe; Hernandez, Celine; Gwak, Geum-Youn; Caviglia, Jorge Matias; Mu, Xueru; Loike, John D; Jenkins, Rosalind E; Antoine, Daniel J; Schwabe, Robert F

    2015-02-01

    In contrast to microbially triggered inflammation, mechanisms promoting sterile inflammation remain poorly understood. Damage-associated molecular patterns (DAMPs) are considered key inducers of sterile inflammation following cell death, but the relative contribution of specific DAMPs, including high-mobility group box 1 (HMGB1), is ill defined. Due to the postnatal lethality of Hmgb1-knockout mice, the role of HMGB1 in sterile inflammation and disease processes in vivo remains controversial. Here, using conditional ablation strategies, we have demonstrated that epithelial, but not bone marrow-derived, HMGB1 is required for sterile inflammation following injury. Epithelial HMGB1, through its receptor RAGE, triggered recruitment of neutrophils, but not macrophages, toward necrosis. In clinically relevant models of necrosis, HMGB1/RAGE-induced neutrophil recruitment mediated subsequent amplification of injury, depending on the presence of neutrophil elastase. Notably, hepatocyte-specific HMGB1 ablation resulted in 100% survival following lethal acetaminophen intoxication. In contrast to necrosis, HMGB1 ablation did not alter inflammation or mortality in response to TNF- or FAS-mediated apoptosis. In LPS-induced shock, in which HMGB1 was considered a key mediator, HMGB1 ablation did not ameliorate inflammation or lethality, despite efficient reduction of HMGB1 serum levels. Our study establishes HMGB1 as a bona fide and targetable DAMP that selectively triggers a neutrophil-mediated injury amplification loop in the setting of necrosis. PMID:25562324

  1. Agresividad vial en la población general Road-rage in the general population

    Directory of Open Access Journals (Sweden)

    Inmaculada Fierro

    2010-10-01

    Full Text Available Objetivos: Analizar la prevalencia y los factores sociodemográficos asociados con la agresividad vial en la población. Métodos: Se han realizado 2.500 entrevistas a la población de Castilla y León de entre 14 y 70 años de edad. Se evaluó la agresividad vial en el año previo a la realización de la encuesta utilizando un test de ocho preguntas. Resultados: El 31,1% refirió haber vivido alguna situación de agresividad vial en el último año, y el 26,8% en más de una ocasión. El 2,6% fueron agresores viales «graves». Entre los conductores, la probabilidad de experimentar agresividad vial aumenta a medida que aumentan los miles de kilómetros conducidos a la semana (odds ratio [OR]=1,52, es menor cuanto mayor es la edad del entrevistado (OR=0,975 y es mayor en los hombres (OR=1,287, en los que tienen estudios universitarios (OR=1,408 y en los que viven en localidades de más de 10.000 habitantes (OR=1,25. Conclusiones: Los datos del presente estudio muestran que la agresividad vial afecta a casi un tercio de la población general de Castilla y León, lo que justificaría la adopción de medidas para su prevención y reducción.Objective: To analyze the prevalence of road rage in the general population and the sociodemographic factors associated with this phenomenon. Methods: A total of 2,500 interviews were carried out in the population of Castile and Leon aged 14-70 years. Road rage was evaluated in the year prior to the survey using a test with eight questions. Results: One-third (31.1% of the interviewees reported they had experienced a situation involving road rage during the previous 12 months (26.8% on more than one occasion. Among these episodes, 2.6% involved "serious" aggressors. In drivers, the probability of experiencing road rage increased in line with the number of kilometers driven per week (odds ratio [OR]=1.52, decreased as the age of the driver increased (OR=0.975, and was highest in men (OR=1.287, university

  2. Using SMS as a Harm Reduction Strategy: An Evaluation of the RAGE (Register and Get Educated) Project

    Science.gov (United States)

    Crockett, Belinda; Keleher, Helen; Rudd, Annette; Klein, Ruth; Locke, Beth; Roussy, Véronique

    2013-01-01

    The RAGE (Register And Get Educated) project explored the feasibility of SMS (Short Messaging Service) as a means for communicating harm reduction messages in relation to alcohol and other drugs to young people residing in the City of Knox, Victoria. Almost 700 young people aged 12-26 years registered their mobile phone numbers to receive a series…

  3. Puerarin enhances superoxide dismutase activity and inhibits RAGE and VEGF expression in retinas of STZ-induced early diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Fang Chen; Hong-Quan Zhang; Jun Zhu; Kai-Yang Liu; Hong Cheng; Guo-Li Li; Shan Xu; Wei-Hong Lv; Zheng-Gao Xie

    2012-01-01

    Objective:To investigate the effects of puerarin on the activity of superoxide dismutase (SOD), and expressions of advanced glycation end-product (AGE) receptor (RAGE) and vascular endothelial growth factor (VEGF) in retinas of streptozotocin (STZ)-induced early diabetic rats. Methods: Diabetic rat models were established by inducing diabetes via intra-peritoneal injection of STZ. Rats were randomly divided into normal (control), diabetic (DM), and DM+puerarin groups. After intra-gastric administration of puerarin (500 mg/kg/day for 4 weeks), levels of SOD and malondialdehyde (MDA) were determined in serum and retina. mRNA and protein expression levels of RAGE and VEGF in retinas were determined by real-time polymerase chain reaction (RT-PCR) (mRNA) and Western blot analysis (protein levels). Results:There was significantly lower SOD activity and significantly higher MDA in serum and retinas of the DM group compared with the two other groups (P<0.05). After treatment with puerarin, SOD activity increased and MDA content decreased in this group (P<0.05). mRNA and protein expression levels of RAGE and VEGF in the DM group were significantly higher than those of the other groups (P<0.05), and decreased after puerarin treatment (P<0.05). Conclusions: Puerarin is able to enhance SOD activity, and inhibit RAGE and VEGF expressions in retinas of STZ-induced early diabetic rats.

  4. AGE-RAGE signal generates a specific NF-κB RelA "barcode" that directs collagen I expression.

    Science.gov (United States)

    Peng, Yunqian; Kim, Ji-Min; Park, Hal-Sol; Yang, Annie; Islam, Celia; Lakatta, Edward G; Lin, Li

    2016-01-01

    Advanced glycation end products (AGEs) are sugar-modified biomolecules that accumulate in the body with advancing age, and are implicated in the development of multiple age-associated structural and functional abnormities and diseases. It has been well documented that AGEs signal via their receptor RAGE to activate several cellular programs including NF-κB, leading to inflammation. A large number of stimuli can activate NF-κB; yet different stimuli, or the same stimulus for NF-κB in different cellular settings, produce a very different transcriptional landscape and physiological outcome. The NF-κB barcode hypothesis posits that cellular network dynamics generate signal-specific post-translational modifications, or a "barcode" to NF-κB, and that a signature "barcode" mediates a specific gene expression pattern. In the current study, we established that AGE-RAGE signaling results in NF-κB activation that directs collagen Ia1 and Ia2 expression. We further demonstrated that AGE-RAGE signal induces phosphorylation of RelA at three specific residues, T254, S311, and S536. These modifications are required for transcription of collagen I genes and are a consequence of cellular network dynamics. The increase of collagen content is a hallmark of arterial aging, and our work provides a potential mechanistic link between RAGE signaling, NF-κB activation, and aging-associated arterial alterations in structure and function. PMID:26729520

  5. AB044. AGE/RAGE/Akt pathway contributes to prostate cancer cell proliferation by promoting Rb phosphorylation and degradation

    Science.gov (United States)

    Bao, Jiming; Bao, Yawei; Zhao, Shanchao; He, Minyi; Luo, Haihua; Ren, Zhonglu; Lv, Yongjie; Hong, Yingqia

    2016-01-01

    Objective Metabolomic research has revealed that metabolites play an important role in prostate cancer development and progression. Previous studies have suggested that prostate cancer cell proliferation is induced by advanced glycation end products (AGEs) exposure, but the mechanism of this induction remains unknown. This study aim to investigate the molecular mechanisms underlying the proliferative response of prostate cancer cell to the interaction of AGEs and the receptor for advanced glycation end products (RAGE). Methods To investigate this mechanism, we used Western blotting to evaluate the responses of the retinoblastoma (Rb), p-Rb and PI3K/Akt pathway to AGEs stimulation. We also examined the effect of knocking down Rb and blocking the PI3K/Akt pathway on AGEs induced PC-3 cell proliferation. Results Our results indicated that AGE-RAGE interaction enhanced Rb phosphorylation and subsequently decreased total Rb levels. Bioinformatics analysis further indicated a negative correlation between RAGE and RB1 expression in prostate cancer tissue. Furthermore, we observed that AGEs stimulation activated the PI3K/Akt signaling pathway and that blocking PI3K/Akt signaling abrogated AGEs-induced cell proliferation. Conclusions We report, for the first time, that AGE-RAGE interaction enhances prostate cancer cell proliferation by phosphorylation of Rb via the PI3K/Akt signaling pathway.

  6. AGEs-RAGE Signaling Pathway in Diabetic Refractory Wounds%AGEs-RAGE 信号通路与糖尿病难愈合创面

    Institute of Scientific and Technical Information of China (English)

    王丽; 李杰辉

    2015-01-01

    糖尿病难愈合创面是糖尿病比较严重的并发症和致残原因,故国内外学者对它的研究越来越多。创面愈合是炎性细胞、修复细胞及细胞因子等多种因素共同调控的复杂过程,其中晚期糖基化终末产物( Advanced Glycationend Products, AGEs)及其受体协同的AGEs-RAGE信号通路是目前研究的热点,本文就其进行概述。%Diabetic refractory wound is a serious complication of diabetes and also a cause of disability and thus studies on it are increasing both at home and abroad.Would healing is a complicated process regulated jointly by multiple factors such as inflammatory cells, repairing cells, cytokines and etc.Of the factors, advanced glycation end products ( AGEs) and its synergetic receptor-AGEs-RAGE signaling pathway are the focus of current studies, on which we carried out the review.

  7. HMGB1 induces an inflammatory response in endothelial cells via the RAGE-dependent endoplasmic reticulum stress pathway

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Ying [Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha 410078 (China); Li, Shu-Jun [Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410078 (China); Yang, Jian [Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha 410078 (China); Qiu, Yuan-Zhen [Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha 410078 (China); Chen, Fang-Ping, E-mail: xychenfp@163.com [Department of Hematology, Xiangya Hospital, Central South University, Changsha 410078 (China)

    2013-09-06

    Highlights: •Mechanisms of inflammatory response induced by HMGB1 are incompletely understood. •We found that endoplasmic reticulum stress mediate the inflammatory response induced by HMGB1. •RAGE-mediated ERS pathways are involved in those processes. •We reported a new mechanism for HMGB1 induced inflammatory response. -- Abstract: The high mobility group 1B protein (HMGB1) mediates chronic inflammatory responses in endothelial cells, which play a critical role in atherosclerosis. However, the underlying mechanism is unknown. The goal of our study was to identify the effects of HMGB1 on the RAGE-induced inflammatory response in endothelial cells and test the possible involvement of the endoplasmic reticulum stress pathway. Our results showed that incubation of endothelial cells with HMGB1 (0.01–1 μg/ml) for 24 h induced a dose-dependent activation of endoplasmic reticulum stress transducers, as assessed by PERK and IRE1 protein expression. Moreover, HMGB1 also promoted nuclear translocation of ATF6. HMGB1-mediated ICAM-1 and P-selectin production was dramatically suppressed by PERK siRNA or IRE1 siRNA. However, non-targeting siRNA had no such effects. HMGB1-induced increases in ICAM-1 and P-selectin expression were also inhibited by a specific eIF2α inhibitor (salubrinal) and a specific JNK inhibitor (SP600125). Importantly, a blocking antibody specifically targeted against RAGE (anti-RAGE antibody) decreased ICAM-1, P-selectin and endoplasmic reticulum stress molecule (PERK, eIF2α, IRE1 and JNK) protein expression levels. Collectively, these novel findings suggest that HMGB1 promotes an inflammatory response by inducing the expression of ICAM-1 and P-selectin via RAGE-mediated stimulation of the endoplasmic reticulum stress pathway.

  8. Analysis of xRAGE and flag high explosive burn models with PBX 9404 cylinder tests

    Energy Technology Data Exchange (ETDEWEB)

    Harrier, Danielle [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Andersen, Kyle Richard [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-05

    High explosives are energetic materials that release their chemical energy in a short interval of time. They are able to generate extreme heat and pressure by a shock driven chemical decomposition reaction, which makes them valuable tools that must be understood. This study investigated the accuracy and performance of two Los Alamos National Laboratory hydrodynamic codes, which are used to determine the behavior of explosives within a variety of systems: xRAGE which utilizes an Eulerian mesh, and FLAG with utilizes a Lagrangian mesh. Various programmed and reactive burn models within both codes were tested using a copper cylinder expansion test. The test was based on a recent experimental setup which contained the plastic bonded explosive PBX 9404. Detonation velocity versus time curves for this explosive were obtained using Photon Doppler Velocimetry (PDV). The modeled results from each of the burn models tested were then compared to one another and to the experimental results. This study validate

  9. ANGER IS A GIFT: propaganda, performance e documentário nos Rage Against The Machine

    Directory of Open Access Journals (Sweden)

    Luís Nogueira

    2012-08-01

    Full Text Available About 20 years ago, and during the 1990s, Rage Against the Machinedid not change the world, but endeavored to cause small aesthetic (at the level of musicmakingand ethical quakes (at the level of civic intervention. The visual production that accompanied their music had become equally bold and unusual: videoclips based on foundfootage and live performances, concert films that sought to capture the visceral energy of live performance and a strong propaganda permeating both music and the images that accompany, seem to us aspects of note and worthy of reflection. This article is concernedwith the intersection between documentary and music never seen before in the entertainment industry and culture in contemporary music.

  10. Inhibitory effect of receptor for advanced glycation end products (RAGE) on the TGF-β-induced alveolar epithelial to mesenchymal transition

    OpenAIRE

    Song, Jeong Sup; Kang, Chun Mi; Park, Chan Kwon; Yoon, Hyung Kyu; Lee, Sook Young; Ahn, Joong Hyun; Moon, Hwa-Sik

    2011-01-01

    Idiopathic pulmonary fibrosis (IPF) is a lethal parenchymal lung disease characterized by myofibroblast proliferation. Alveolar epithelial cells (AECs) are thought to produce myofibroblasts through the epithelial to mesenchymal transition (EMT). Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptors whose activation is associated with renal fibrosis during diabetes and liver fibrosis. RAGE is expressed at low basal levels in...

  11. Assessment of Myo‌inositol and Crocin Effects on RAGE and TGF? Gene Expression in the Kidney of Streptozotocin Induced Diabetic Rats

    OpenAIRE

    S. Sadat Heidary; F BAHMANI; Z. Bathaei; Gh. Moshtaghi Kashanian

    2014-01-01

    Introduction & Objective: Diabetic nephropathy is one of the micro vascular complications of uncontrolled diabetes. Chronic hyperglycemia results in the formation of glycated proteins and activation of pathways leading to diabetic nephropathy. Increasing RAGE and TGF? production in the kidney tissue is a major pathway involved in diabetic complications. In this survey, the effect of myoinositol and Crocin on RAGE and TGF? expression in the kidney of diabetic rats was studied. Materials & Meth...

  12. Genetically-Determined Hyperfunction of the S100B/RAGE Axis Is a Risk Factor for Aspergillosis in Stem Cell Transplant Recipients

    OpenAIRE

    Cunha, Cristina; Giovannini, Gloria; Pierini, Antonio; Alain S Bell; Sorci, Guglielmo; Riuzzi, Francesca; Donato, Rosario; Rodrigues, Fernando; Velardi, Andrea; Aversa, Franco; Romani, Luigina; Carvalho, Agostinho

    2011-01-01

    Invasive aspergillosis (IA) is a major threat to the successful outcome of hematopoietic stem cell transplantation (HSCT), although individual risk varies considerably. Recent evidence has established a pivotal role for a danger sensing mechanism implicating the S100B/receptor for advanced glycation end products (RAGE) axis in antifungal immunity. The association of selected genetic variants in the S100B/RAGE axis with susceptibility to IA was investigated in 223 consecutive patients undergoi...

  13. The Association of -429T>C and -374T>A Polymorphisms in the RAGE Gene with Polycystic Ovary Syndrome

    Science.gov (United States)

    Park, Jung-Hyun; Li, Lan; Choi, Jin-Woo; Baek, Kwang-Hyun

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a complex disorder characterized by hyperandrogenism and insulin resistance. In addition, a number of females with PCOS have ovaries with multiple cysts, an irregular or no menstrual cycle, and an imbalance of female hormones compared to those of normal controls. A variety of genetic factors have been involved in the pathogenesis of PCOS. Among these genetic factors, the receptor for advanced glycation end products (RAGE) that is associated with diabetes and involved in the complications of PCOS, was selected. We aimed to assess the relationship between -429T>C and -374T>A single nucleotide polymorphisms (SNPs) of RAGE gene with the susceptibility to PCOS.128 controls and 265 PCOS patients were used for -374T>A polymorphism and 141 controls and 290 PCOS patients were used for -429T>C polymorphism, respectively. Genotyping of two polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and statistical analysis was performed. P values for both alleles were higher than 0.05. Frequencies of genotype and allele of two polymorphisms in RAGE gene showed no significant differences between controls and PCOS patients. The initial study on the correlation between RAGE gene and PCOS indicates that the two polymorphisms of RAGE are not associated with the pathogenesis of PCOS. However, further studies regarding the association between RAGE gene and PCOS patients in different ethnic groups are required. PMID:27279795

  14. EARLY AFFECT-CONFUSION: THE BORDERLINE BETWEEN DESPAIR AND RAGE - PART 1 OF A CASE STUDY TRILOGY

    OpenAIRE

    Richard G. Erskine

    2012-01-01

    This three part case study illustrates the principles, theoretical concepts, and relational methods of Integrative Psychotherapy in the treatment of a client who continually experienced early affect-confusion and lived on a “borderline” between intense neediness and rage, despair and self-reliance, impulsivity and manipulation. Part 1 describes the behavioral dynamics of a 38 year old female client who required a two-part treatment approach that emphasized an inter-subjective relationship, co...

  15. Glycer-AGEs-RAGE signaling enhances the angiogenic potential of hepatocellular carcinoma by upregulating VEGF expression

    Institute of Scientific and Technical Information of China (English)

    Junichi Takino; Shoichi Yamagishi; Masayoshi Takeuchi

    2012-01-01

    AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products (Glycer-AGEs)on hepatocellular carcinoma (HCC) cells.METHODS:Two HCC cell lines (Hep3B and HepG2cells) and human umbilical vein endothelial cells (HUVEC) were used.Cell viability was determined using the WST-8 assay.Western blotting,enzyme linked immunosorbent assay,and real-time reverse transcriptionpolymerase chain reactions were used to detect protein and mRNA.Angiogenesis was evaluated by assessing the proliferation,migration,and tube formation of HUVEC.RESULTS:The receptor for AGEs (RAGE) protein was detected in Hep3B and HepG2 cells.HepG2 cells were not affected by the addition of Glycer-AGEs.GlycerAGEs markedly increased vascular endothelial growth factor (VEGF) mRNA and protein expression,which is one of the most potent angiogenic factors.Compared with the control unglycated bovine serum albumin (BSA)treatment,VEGF mRNA expression levels induced by the Glycer-AGEs treatment were 1.00 ± 0.10 vs 1.92± 0.09 (P < 0.01).Similarly,protein expression levels induced by the Glycer-AGEs treatment were 1.63 ± 0.04ng/mL vs 2.28 ± 0.17 ng/mL for the 24 h treatment and 3.36 ± 0.10 ng/mL vs 4.79 ± 0.31 ng/mL for the 48 h treatment,respectively (P < 0.01).Furthermore,compared with the effect of the control unglycated BSA-treated conditioned medium,the Glycer-AGEstreated conditioned medium significantly increased the proliferation,migration,and tube formation of HUVEC,with values of 122.4% ± 9.0% vs 144.5% ± 11.3% for cell viability,4.29 ± 1.53 vs 6.78 ± 1.84 for migration indices,and 71.0 ± 7.5 vs 112.4 ± 8.0 for the number of branching points,respectively (P < 0.01).CONCLUSION:These results suggest that Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.

  16. Plasma miR-185 is decreased in patients with esophageal squamous cell carcinoma and might suppress tumor migration and invasion by targeting RAGE.

    Science.gov (United States)

    Jing, Rongrong; Chen, Wen; Wang, Huimin; Ju, Shaoqing; Cong, Hui; Sun, Baolan; Jin, Qin; Chu, Shaopeng; Xu, Lili; Cui, Ming

    2015-11-01

    The receptor for advanced-glycation end products (RAGE) is upregulated in various cancers and has been associated with tumor progression, but little is known about its expression and regulation by microRNAs (miRNAs) in esophageal squamous cell carcinoma (ESCC). Here, we describe miR-185, which represses RAGE expression, and investigate the biological role of miR-185 in ESCC. In this study, we found that the high level of RAGE expression in 29 pairs of paraffin-embedded ESCC tissues was correlated positively with the depth of invasion by immunohistochemistry, suggesting that RAGE was involved in ESCC. We used bioinformatics searches and luciferase reporter assays to investigate the prediction that RAGE was regulated directly by miR-185. Besides, overexpression of miR-185 in ESCC cells was accompanied by 27% (TE-11) and 49% (Eca-109) reduced RAGE expression. The effect was further confirmed in RAGE protein by immunofluorescence in both cell lines. The effects were reversed following cotransfection with miR-185 and high-level expression of the RAGE vector. Furthermore, the biological role of miR-185 in ESCC cell lines was investigated using assays of cell viability, Ki-67 staining, and cell migration and invasion, as well as in a xenograft model. We found that overexpression of miR-185 inhibited migration and invasion by ESCC cells in vitro and reduced their capacity to develop distal pulmonary metastases in vivo partly through the RAGE/heat shock protein 27 pathway. Interestingly, in clinical specimens, the level of plasma miR-185 expression was decreased significantly (P = 0.002) in patients with ESCC [0.500; 95% confidence interval (CI) 0.248-1.676] compared with healthy controls (2.410; 95% CI 0.612-5.671). The value of the area under the receiver-operating characteristic curve was 0.73 (95% CI 0.604-0.855). In conclusion, our findings shed novel light on the role of miR-185/RAGE in ESCC metastasis, and plasma miR-185 has potential as a novel diagnostic biomarker

  17. In-Situ Visualization Experiments with ParaView Cinema in RAGE

    Energy Technology Data Exchange (ETDEWEB)

    Kares, Robert John [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-10-15

    A previous paper described some numerical experiments performed using the ParaView/Catalyst in-situ visualization infrastructure deployed in the Los Alamos RAGE radiation-hydrodynamics code to produce images from a running large scale 3D ICF simulation. One challenge of the in-situ approach apparent in these experiments was the difficulty of choosing parameters likes isosurface values for the visualizations to be produced from the running simulation without the benefit of prior knowledge of the simulation results and the resultant cost of recomputing in-situ generated images when parameters are chosen suboptimally. A proposed method of addressing this difficulty is to simply render multiple images at runtime with a range of possible parameter values to produce a large database of images and to provide the user with a tool for managing the resulting database of imagery. Recently, ParaView/Catalyst has been extended to include such a capability via the so-called Cinema framework. Here I describe some initial experiments with the first delivery of Cinema and make some recommendations for future extensions of Cinema’s capabilities.

  18. Verification Test of the SURF and SURFplus Models in xRage: Part II

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-06-20

    The previous study used an underdriven detonation wave (steady ZND reaction zone profile followed by a scale invariant rarefaction wave) for PBX 9502 as a validation test of the implementation of the SURF and SURFplus models in the xRage code. Even with a fairly fine uniform mesh (12,800 cells for 100mm) the detonation wave profile had limited resolution due to the thin reaction zone width (0.18mm) for the fast SURF burn rate. Here we study the effect of finer resolution by comparing results of simulations with cell sizes of 8, 2 and 1 μm, which corresponds to 25, 100 and 200 points within the reaction zone. With finer resolution the lead shock pressure is closer to the von Neumann spike pressure, and there is less noise in the rarefaction wave due to fluctuations within the reaction zone. As a result the average error decreases. The pointwise error is still dominated by the smearing the pressure kink in the vicinity of the sonic point which occurs at the end of the reaction zone.

  19. Verification test of the SURF and SURFplus models in xRage

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-05-18

    As a verification test of the SURF and SURFplus models in the xRage code we use a propagating underdriven detonation wave in 1-D. This is about the only test cases for which an accurate solution can be determined based on the theoretical structure of the solution. The solution consists of a steady ZND reaction zone profile joined with a scale invariant rarefaction or Taylor wave and followed by a constant state. The end of the reaction profile and the head of the rarefaction coincide with the sonic CJ state of the detonation wave. The constant state is required to match a rigid wall boundary condition. For a test case, we use PBX 9502 with the same EOS and burn rate as previously used to test the shock detector algorithm utilized by the SURF model. The detonation wave is propagated for 10 μs (slightly under 80mm). As expected, the pointwise errors are largest in the neighborhood of discontinuities; pressure discontinuity at the lead shock front and pressure derivative discontinuities at the head and tail of the rarefaction. As a quantitative measure of the overall accuracy, the L2 norm of the difference of the numerical pressure and the exact solution is used. Results are presented for simulations using both a uniform grid and an adaptive grid that refines the reaction zone.

  20. Genetically-determined hyperfunction of the S100B/RAGE axis is a risk factor for aspergillosis in stem cell transplant recipients.

    Directory of Open Access Journals (Sweden)

    Cristina Cunha

    Full Text Available Invasive aspergillosis (IA is a major threat to the successful outcome of hematopoietic stem cell transplantation (HSCT, although individual risk varies considerably. Recent evidence has established a pivotal role for a danger sensing mechanism implicating the S100B/receptor for advanced glycation end products (RAGE axis in antifungal immunity. The association of selected genetic variants in the S100B/RAGE axis with susceptibility to IA was investigated in 223 consecutive patients undergoing HSCT. Furthermore, studies addressing the functional consequences of these variants were performed. Susceptibility to IA was significantly associated with two distinct polymorphisms in RAGE (-374T/A and S100B (+427C/T genes, the relative contribution of each depended on their presence in both transplantation counterparts [patient SNP(RAGE, adjusted hazard ratio (HR, 1.97; P = 0.042 and donor SNP(RAGE, HR, 2.03; P = 0.047] or in donors (SNP(S100B, HR, 3.15; P = 7.8e-(4 only, respectively. Functional assays demonstrated a gain-of-function phenotype of both variants, as shown by the enhanced expression of inflammatory cytokines in RAGE polymorphic cells and increased S100B secretion in vitro and in vivo in the presence of the S100B polymorphism. These findings point to a relevant role of the danger sensing signaling in human antifungal immunity and highlight a possible contribution of a genetically-determined hyperfunction of the S100B/RAGE axis to susceptibility to IA in the HSCT setting.

  1. Genetically-determined hyperfunction of the S100B/RAGE axis is a risk factor for aspergillosis in stem cell transplant recipients.

    Science.gov (United States)

    Cunha, Cristina; Giovannini, Gloria; Pierini, Antonio; Bell, Alain S; Sorci, Guglielmo; Riuzzi, Francesca; Donato, Rosario; Rodrigues, Fernando; Velardi, Andrea; Aversa, Franco; Romani, Luigina; Carvalho, Agostinho

    2011-01-01

    Invasive aspergillosis (IA) is a major threat to the successful outcome of hematopoietic stem cell transplantation (HSCT), although individual risk varies considerably. Recent evidence has established a pivotal role for a danger sensing mechanism implicating the S100B/receptor for advanced glycation end products (RAGE) axis in antifungal immunity. The association of selected genetic variants in the S100B/RAGE axis with susceptibility to IA was investigated in 223 consecutive patients undergoing HSCT. Furthermore, studies addressing the functional consequences of these variants were performed. Susceptibility to IA was significantly associated with two distinct polymorphisms in RAGE (-374T/A) and S100B (+427C/T) genes, the relative contribution of each depended on their presence in both transplantation counterparts [patient SNP(RAGE), adjusted hazard ratio (HR), 1.97; P = 0.042 and donor SNP(RAGE), HR, 2.03; P = 0.047] or in donors (SNP(S100B), HR, 3.15; P = 7.8e-(4)) only, respectively. Functional assays demonstrated a gain-of-function phenotype of both variants, as shown by the enhanced expression of inflammatory cytokines in RAGE polymorphic cells and increased S100B secretion in vitro and in vivo in the presence of the S100B polymorphism. These findings point to a relevant role of the danger sensing signaling in human antifungal immunity and highlight a possible contribution of a genetically-determined hyperfunction of the S100B/RAGE axis to susceptibility to IA in the HSCT setting. PMID:22114731

  2. Voltammetric Detection of S100B Protein Using His-Tagged Receptor Domains for Advanced Glycation End Products (RAGE Immobilized onto a Gold Electrode Surface

    Directory of Open Access Journals (Sweden)

    Edyta Mikuła

    2014-06-01

    Full Text Available In this work we report on an electrochemical biosensor for the determination of the S100B protein. The His-tagged VC1 domains of Receptors for Advanced Glycation End (RAGE products used as analytically active molecules were covalently immobilized on a monolayer of a thiol derivative of pentetic acid (DPTA complex with Cu(II deposited on a gold electrode surface. The recognition processes between the RAGE VC1 domain and the S100B protein results in changes in the redox activity of the DPTA-Cu(II centres which were measured by Osteryoung square-wave voltammetry (OSWV. In order to verify whether the observed analytical signal originates from the recognition process between the His6–RAGE VC1 domains and the S100B protein, the electrode modified with the His6–RAGE C2 and His6–RAGE VC1 deleted domains which have no ability to bind S100B peptides were applied. The proposed biosensor was quite sensitive, with a detection limit of 0.52 pM recorded in the buffer solution. The presence of diluted human plasma and 10 nM Aβ1-40 have no influence on the biosensor performance.

  3. Microalbuminuria and sRAGE in High-Risk Hypertensive Patients Treated with Nifedipine/Telmisartan Combination Treatment: A Substudy of TALENT

    Directory of Open Access Journals (Sweden)

    Colomba Falcone

    2012-01-01

    Full Text Available Some antihypertensive drugs have also renoprotective and anti-inflammatory properties that go beyond their effect on blood pressure. It has been suggested that microalbuminuria and glomerular filtration rate (GFR are associated with circulating levels of the soluble form of the receptor, sRAGE (soluble receptor for advanced glycation ends-products. In the present analysis, we used data from the TALENT study to evaluate soluble receptor for advanced glycation end-products (sRAGE plasma levels in patients with hypertension and high-cardiovascular risk-treated nifedipine and telmisartan in combination. Treatment with nifedipine-telmisartan significantly decreased mean systolic and diastolic ambulatory blood pressure and resulted in a significant increase in sRAGE plasma concentrations after 24 weeks of therapy. We concluded that in hypertensive patients with early-stage renal disease, sRAGE concentrations are not influenced by either microalbuminuria or GFR. Long-term treatment with a combination of nifedipine-telmisartan may have a beneficial effect increasing sRAGE plasma levels, thus exerting an atheroprotective and anti-inflammatory activity.

  4. Microalbuminuria and sRAGE in High-Risk Hypertensive Patients Treated with Nifedipine/Telmisartan Combination Treatment: A Substudy of TALENT

    Science.gov (United States)

    Falcone, Colomba; Buzzi, Maria Paola; Bozzini, Sara; Boiocchi, Chiara; D'Angelo, Angela; Schirinzi, Sandra; Esposito, Ciro; Torreggiani, Massimo; Choi, Jasmine; Ochan Kilama, Michael; Mancia, Giuseppe

    2012-01-01

    Some antihypertensive drugs have also renoprotective and anti-inflammatory properties that go beyond their effect on blood pressure. It has been suggested that microalbuminuria and glomerular filtration rate (GFR) are associated with circulating levels of the soluble form of the receptor, sRAGE (soluble receptor for advanced glycation ends-products). In the present analysis, we used data from the TALENT study to evaluate soluble receptor for advanced glycation end-products (sRAGE) plasma levels in patients with hypertension and high-cardiovascular risk-treated nifedipine and telmisartan in combination. Treatment with nifedipine-telmisartan significantly decreased mean systolic and diastolic ambulatory blood pressure and resulted in a significant increase in sRAGE plasma concentrations after 24 weeks of therapy. We concluded that in hypertensive patients with early-stage renal disease, sRAGE concentrations are not influenced by either microalbuminuria or GFR. Long-term treatment with a combination of nifedipine-telmisartan may have a beneficial effect increasing sRAGE plasma levels, thus exerting an atheroprotective and anti-inflammatory activity. PMID:22474401

  5. Effects of RAGE-Specific Inhibitor FPS-ZM1 on Amyloid-β Metabolism and AGEs-Induced Inflammation and Oxidative Stress in Rat Hippocampus.

    Science.gov (United States)

    Hong, Yan; Shen, Chao; Yin, Qingqing; Sun, Menghan; Ma, Yingjuan; Liu, Xueping

    2016-05-01

    An increased level of advanced glycation end products (AGEs) is observed in brains of patients with Alzheimer's disease (AD). AGEs and receptor for AGEs (RAGE) play important roles in the pathogenesis of AD. FPS-ZM1 is a high-affinity RAGE-specific blocker that inhibits amyloid-β binding to RAGE, neurological damage and inflammation in the APP(sw/0) transgenic mouse model of AD. FPS-ZM1 is not toxic to mice and can easily cross the blood-brain barrier. In this study, an AGEs-RAGE-activated rat model were established by intrahippocampal injection of AGEs, then these rats were treated with intraperitoneal administration of FPS-ZM1 and the possible neuroprotective effects were investigated. We found that AGEs administration induced an-regulation of Abeta production, inflammation, and oxidative stress, and an increased escape latency of rats in the Morris water maze test, all of these are significantly reduced by FPS-ZM1 treatment. Our results suggest that the AGEs-RAGE pathway is responsible for cognitive deficits, and therefore may be a potential treatment target. FPS-ZM1 might be a novel therapeutic agent to treat AD patients. PMID:26738988

  6. EARLY AFFECT-CONFUSION: THE BORDERLINE BETWEEN DESPAIR AND RAGE - PART 1 OF A CASE STUDY TRILOGY

    Directory of Open Access Journals (Sweden)

    Richard G. Erskine

    2012-12-01

    Full Text Available This three part case study illustrates the principles, theoretical concepts, and relational methods of Integrative Psychotherapy in the treatment of a client who continually experienced early affect-confusion and lived on a “borderline” between intense neediness and rage, despair and self-reliance, impulsivity and manipulation. Part 1 describes the behavioral dynamics of a 38 year old female client who required a two-part treatment approach that emphasized an inter-subjective relationship, consistency, and respect while helping her to acknowledge and value her relational-needs and to engage in a relationally contactful form of anger.

  7. Scott Wilson, Great Satan’s Rage: American Negativity and Rap/Metal in the Age of Supercapitalism

    OpenAIRE

    Barron, Lee

    2015-01-01

    Although Great Satan’s Rage begins in territory befitting a narrative concerning heavy metal music – a discussion of Satan as the wrath-filled, revenge-seeking enemy of God in the context of John Milton’s 1667 epic poem, Paradise Lost – from there it goes on a varied and unexpected journey. With metal and rap music as the reference points, Scott Wilson’s book explores major incidents in the post-Cold War period that range from the analysis of the USSR and its fall and the Gulf War, to the Col...

  8. Nifedipine inhibits advanced glycation end products (AGEs) and their receptor (RAGE) interaction-mediated proximal tubular cell injury via peroxisome proliferator-activated receptor-gamma activation

    International Nuclear Information System (INIS)

    Research highlights: → Nifedipine inhibited the AGE-induced up-regulation of RAGE mRNA levels in tubular cells, which was prevented by GW9662, an inhibitor of peroxisome proliferator-activated receptor-γ. → GW9662 treatment alone increased RAGE mRNA levels in tubular cells. → Nifedipine inhibited the AGE-induced reactive oxygen species generation, NF-κB activation and increases in intercellular adhesion molecule-1 and transforming growth factor-β gene expression in tubular cells, all of which were blocked by GW9662. -- Abstract: There is a growing body of evidence that advanced glycation end products (AGEs) and their receptor (RAGE) interaction evokes oxidative stress generation and subsequently elicits inflammatory and fibrogenic reactions, thereby contributing to the development and progression of diabetic nephropathy. We have previously found that nifedipine, a calcium-channel blocker (CCB), inhibits the AGE-induced mesangial cell damage in vitro. However, effects of nifedipine on proximal tubular cell injury remain unknown. We examined here whether and how nifedipine blocked the AGE-induced tubular cell damage. Nifedipine, but not amlodipine, a control CCB, inhibited the AGE-induced up-regulation of RAGE mRNA levels in tubular cells, which was prevented by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-γ (PPARγ). GW9662 treatment alone was found to increase RAGE mRNA levels in tubular cells. Further, nifedipine inhibited the AGE-induced reactive oxygen species generation, NF-κB activation and increases in intercellular adhesion molecule-1 and transforming growth factor-beta gene expression in tubular cells, all of which were blocked by GW9662. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-oxidative and anti-inflammatory agent against AGEs in tubular cells by suppressing RAGE expression via PPARγ activation.

  9. Tranilast Blocks the Interaction between the Protein S100A11 and Receptor for Advanced Glycation End Products (RAGE) V Domain and Inhibits Cell Proliferation.

    Science.gov (United States)

    Huang, Yen-Kai; Chou, Ruey-Hwang; Yu, Chin

    2016-07-01

    The human S100 calcium-binding protein A11 (S100A11) is a member of the S100 protein family. Once S100A11 proteins bind to calcium ions at EF-hand motifs, S100A11 changes its conformation, promoting interaction with target proteins. The receptor for advanced glycation end products (RAGE) consists of three extracellular domains, including the V domain, C1 domain, and C2 domain. In this case, the V domain is the target for mutant S100A11 (mS100A11) binding. RAGE binds to the ligands, resulting in cell proliferation, cell growth, and several signal transduction cascades. We used NMR and fluorescence spectroscopy to demonstrate the interactions between mS100A11and RAGE V domain. The tranilast molecule is a drug used for treating allergic disorders. We discovered that the RAGE V domain and tranilast would interact with mS100A11 by using (1)H-(15)N HSQC NMR titrations. According to the results, we obtained two binary complex models from the HADDOCK program, S100A11-RAGE V domain and S100A11-tranilast, respectively. We overlapped two binary complex models with the same orientation of S100A11 homodimer and demonstrated that tranilast would block the binding site between S100A11 and the RAGE V domain. We further utilized a water-soluble tetrazolium-1 assay to confirm this result. We think that the results will be potentially useful in the development of new anti-cancer drugs. PMID:27226584

  10. Nifedipine inhibits advanced glycation end products (AGEs) and their receptor (RAGE) interaction-mediated proximal tubular cell injury via peroxisome proliferator-activated receptor-gamma activation

    Energy Technology Data Exchange (ETDEWEB)

    Matsui, Takanori [Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume (Japan); Yamagishi, Sho-ichi, E-mail: shoichi@med.kurume-u.ac.jp [Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume (Japan); Takeuchi, Masayoshi [Department of Pathophysiological Science, Faculty of Pharmaceutical Science, Hokuriku University, Kanazawa (Japan); Ueda, Seiji; Fukami, Kei; Okuda, Seiya [Department of Medicine, Kurume University School of Medicine, Kurume (Japan)

    2010-07-23

    Research highlights: {yields} Nifedipine inhibited the AGE-induced up-regulation of RAGE mRNA levels in tubular cells, which was prevented by GW9662, an inhibitor of peroxisome proliferator-activated receptor-{gamma}. {yields} GW9662 treatment alone increased RAGE mRNA levels in tubular cells. {yields} Nifedipine inhibited the AGE-induced reactive oxygen species generation, NF-{kappa}B activation and increases in intercellular adhesion molecule-1 and transforming growth factor-{beta} gene expression in tubular cells, all of which were blocked by GW9662. -- Abstract: There is a growing body of evidence that advanced glycation end products (AGEs) and their receptor (RAGE) interaction evokes oxidative stress generation and subsequently elicits inflammatory and fibrogenic reactions, thereby contributing to the development and progression of diabetic nephropathy. We have previously found that nifedipine, a calcium-channel blocker (CCB), inhibits the AGE-induced mesangial cell damage in vitro. However, effects of nifedipine on proximal tubular cell injury remain unknown. We examined here whether and how nifedipine blocked the AGE-induced tubular cell damage. Nifedipine, but not amlodipine, a control CCB, inhibited the AGE-induced up-regulation of RAGE mRNA levels in tubular cells, which was prevented by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}). GW9662 treatment alone was found to increase RAGE mRNA levels in tubular cells. Further, nifedipine inhibited the AGE-induced reactive oxygen species generation, NF-{kappa}B activation and increases in intercellular adhesion molecule-1 and transforming growth factor-beta gene expression in tubular cells, all of which were blocked by GW9662. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-oxidative and anti-inflammatory agent against AGEs in tubular cells by suppressing RAGE expression

  11. Higher plasma soluble Receptor for Advanced Glycation End Products (sRAGE) levels are associated with incident cardiovascular disease and all-cause mortality in type 1 diabetes

    DEFF Research Database (Denmark)

    Nin, Johanna W M; Jorsal, Anders; Ferreira, Isabel;

    2010-01-01

    To investigate the associations of plasma levels of soluble receptor for advanced glycation end products (sRAGE) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes and the extent to which any such associations could be explained by endothelial and renal dysfunct......To investigate the associations of plasma levels of soluble receptor for advanced glycation end products (sRAGE) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes and the extent to which any such associations could be explained by endothelial and renal...

  12. Novel sulfated polysaccharides disrupt cathelicidins, inhibit RAGE and reduce cutaneous inflammation in a mouse model of rosacea.

    Directory of Open Access Journals (Sweden)

    Jianxing Zhang

    Full Text Available BACKGROUND: Rosacea is a common disfiguring skin disease of primarily Caucasians characterized by central erythema of the face, with telangiectatic blood vessels, papules and pustules, and can produce skin thickening, especially on the nose of men, creating rhinophyma. Rosacea can also produce dry, itchy eyes with irritation of the lids, keratitis and corneal scarring. The cause of rosacea has been proposed as over-production of the cationic cathelicidin peptide LL-37. METHODOLOGY/PRINCIPAL FINDINGS: We tested a new class of non-anticoagulant sulfated anionic polysaccharides, semi-synthetic glycosaminoglycan ethers (SAGEs on key elements of the pathogenic pathway leading to rosacea. SAGEs were anti-inflammatory at ng/ml, including inhibition of polymorphonuclear leukocyte (PMN proteases, P-selectin, and interaction of the receptor for advanced glycation end-products (RAGE with four representative ligands. SAGEs bound LL-37 and inhibited interleukin-8 production induced by LL-37 in cultured human keratinocytes. When mixed with LL-37 before injection, SAGEs prevented the erythema and PMN infiltration produced by direct intradermal injection of LL-37 into mouse skin. Topical application of a 1% (w/w SAGE emollient to overlying injected skin also reduced erythema and PMN infiltration from intradermal LL-37. CONCLUSIONS: Anionic polysaccharides, exemplified by SAGEs, offer potential as novel mechanism-based therapies for rosacea and by extension other LL-37-mediated and RAGE-ligand driven skin diseases.

  13. Morphological Changes and Immunohistochemical Expression of RAGE and its Ligands in the Sciatic Nerve of Hyperglycemic Pig (Sus Scrofa

    Directory of Open Access Journals (Sweden)

    Judyta K. Juranek

    2010-09-01

    Full Text Available The aim of our project was to study the effect of streptozotocin (STZ—induced hyperglycemia on sciatic nerve morphology, blood plasma markers and immunohistochemical expression of RAGE (the Receptor for Advanced Glycation End-products, and its ligands—S100B and Carboxymethyl Lysine (CML-advanced glycation endproduct (AGE in the laboratory pig. Six months after STZ—injections, blood plasma measurements, morphometric analysis of sciatic nerve fiber density, immunofluorescent distribution of potential molecular neuropathy contributors, ELISA measurement of plasma AGE level and HPLC analysis of sciatic nerve levels of one of the pre-AGE and the glycolysis intermediate products—methyl-glyoxal (MG were performed. The results of our study revealed that STZ—injected animals displayed elevated levels of plasma glucose, gamma glutamyl transferase (GGT and triglycerides. The sciatic nerve of STZ-injected pigs revealed significantly lower numbers of small-diameter myelinated fibers, higher immunoreactivity for RAGE and S100B and increased levels of MG as compared to control animals. Our results correspond to clinical findings in human patients with hyperglycemia/diabetes-evoked peripheral neuropathy and suggest that the domestic pig may be a suitable large animal model for the study of mechanisms underlying hyperglycemia-induced neurological complications in the peripheral nerve and may serve as a relevant model for the pre-clinical assessment of candidate drugs in neuropathy.

  14. AGE-RAGE signal generates a specific NF-κB RelA “barcode” that directs collagen I expression

    Science.gov (United States)

    Peng, Yunqian; Kim, Ji-Min; Park, Hal-Sol; Yang, Annie; Islam, Celia; Lakatta, Edward G.; Lin, Li

    2016-01-01

    Advanced glycation end products (AGEs) are sugar-modified biomolecules that accumulate in the body with advancing age, and are implicated in the development of multiple age-associated structural and functional abnormities and diseases. It has been well documented that AGEs signal via their receptor RAGE to activate several cellular programs including NF-κB, leading to inflammation. A large number of stimuli can activate NF-κB; yet different stimuli, or the same stimulus for NF-κB in different cellular settings, produce a very different transcriptional landscape and physiological outcome. The NF-κB barcode hypothesis posits that cellular network dynamics generate signal-specific post-translational modifications, or a “barcode” to NF-κB, and that a signature “barcode” mediates a specific gene expression pattern. In the current study, we established that AGE-RAGE signaling results in NF-κB activation that directs collagen Ia1 and Ia2 expression. We further demonstrated that AGE-RAGE signal induces phosphorylation of RelA at three specific residues, T254, S311, and S536. These modifications are required for transcription of collagen I genes and are a consequence of cellular network dynamics. The increase of collagen content is a hallmark of arterial aging, and our work provides a potential mechanistic link between RAGE signaling, NF-κB activation, and aging-associated arterial alterations in structure and function. PMID:26729520

  15. Morphological adaptation of muscle collagen and receptor of advanced glycation end product (RAGE) in osteoarthritis patients with 12 weeks of resistance training

    DEFF Research Database (Denmark)

    Mattiello-Sverzut, Ana Claudia; Petersen, Susanne G; Kjaer, Michael;

    2013-01-01

    The aim of this study was to investigate the effect of 12-week resistance training on morphological presence of collagen and RAGE (receptor for advanced glycation end products) in skeletal muscle of patients with knee osteoarthritis (OA). Little is known about the influence of exercise on the...

  16. The Proinflammatory RAGE/NF-κB Pathway Is Involved in Neuronal Damage and Reactive Gliosis in a Model of Sleep Apnea by Intermittent Hypoxia

    Science.gov (United States)

    Angelo, Maria Florencia; Aguirre, Alejandra; Avilés Reyes, Rolando X.; Villarreal, Alejandro; Lukin, Jerónimo; Melendez, Matías; Vanasco, Virginia; Barker, Phil; Alvarez, Silvia; Epstein, Alberto; Jerusalinsky, Diana; Ramos, Alberto Javier

    2014-01-01

    Sleep apnea (SA) causes long-lasting changes in neuronal circuitry, which persist even in patients successfully treated for the acute effects of the disease. Evidence obtained from the intermittent hypoxia (IH) experimental model of SA has shown neuronal death, impairment in learning and memory and reactive gliosis that may account for cognitive and structural alterations observed in human patients. However, little is known about the mechanism controlling these deleterious effects that may be useful as therapeutic targets in SA. The Receptor for Advanced Glycation End products (RAGE) and its downstream effector Nuclear Factor Kappa B (NF-κB) have been related to neuronal death and astroglial conversion to the pro-inflammatory neurodegenerative phenotype. RAGE expression and its ligand S100B were shown to be increased in experimental models of SA. We here used dissociated mixed hippocampal cell cultures and male Wistar rats exposed to IH cycles and observed that NF-κB is activated in glial cells and neurons after IH. To disclose the relative contribution of the S100B/RAGE/NF-κB pathway to neuronal damage and reactive gliosis after IH we performed sequential loss of function studies using RAGE or S100B neutralizing antibodies, a herpes simplex virus (HSV)-derived amplicon vector that induces the expression of RAGEΔcyto (dominant negative RAGE) and a chemical blocker of NF-κB. Our results show that NF-κB activation peaks 3 days after IH exposure, and that RAGE or NF-κB blockage during this critical period significantly improves neuronal survival and reduces reactive gliosis. Both in vitro and in vivo, S100B blockage altered reactive gliosis but did not have significant effects on neuronal survival. We conclude that both RAGE and downstream NF-κB signaling are centrally involved in the neuronal alterations found in SA models, and that blockage of these pathways is a tempting strategy for preventing neuronal degeneration and reactive gliosis in SA. PMID:25265561

  17. A Correlational Study of How Airline Customer Service and Consumer Perception of Airline Customer Service Affect the Air Rage Phenomenon

    Science.gov (United States)

    Hunter, Joyce A.

    2007-01-01

    Between 1995 and 2000, customer service declined throughout the airline industry, as reported in February 2001 by the U.S. Department of Transportation (2001). One of the biggest problems today within the airline industry is the constant complaining from customers regarding the deterioraton of service (McCollough, Berry, & Yadav, 2000). Since 1995, unfortunately no airline has been immune from service deterioration, as reported by the Airline Quality Rating, an annual report by two airline industry experts who analyzed Department of Transportation statistics (Harrison & Kleinsasser, 1999). The airline' refusal to recognize the issue of customer service has perpetuated an environment that has become dangerous and detrimental to the traveling public as well as to airline employees, which in turn has fueled a new phenomenon, now referred to as "air rage".

  18. Verification Test of the SURF and SURFplus Models in xRage: Part III Affect of Mesh Alignment

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-15

    The previous studies used an underdriven detonation wave in 1-dimension (steady ZND reaction zone profile followed by a scale-invariant rarefaction wave) for PBX 9502 as a verification test of the implementation of the SURF and SURFplus models in the xRage code. Since the SURF rate is a function of the lead shock pressure, the question arises as to the effect on accuracy of variations in the detected shock pressure due to the alignment of the shock front with the mesh. To study the effect of mesh alignment we simulate a cylindrically diverging detonation wave using a planar 2-D mesh. The leading issue is the magnitude of azimuthal asymmetries in the numerical solution. The 2-D test case does not have an exact analytic solution. To quantify the accuracy, the 2-D solution along rays through the origin are compared to a highly resolved 1-D simulation in cylindrical geometry.

  19. Repérage d’Images Ordinaires : Analyse des Requêtes des Chercheurs d’Images

    Directory of Open Access Journals (Sweden)

    Elaine Ménard

    2009-06-01

    also emphasizes the pressing necessity to optimize the methods used for image processing, in order to facilitate image retrieval and dissemination in multilingual environments. Résumé Depuis quelques années, le web est devenu un média incontournable pour la diffusion de ressources multilingues. Cependant, les différences linguistiques constituent souvent un obstacle majeur aux échanges de documents scientifiques, culturels, pédagogiques et commerciaux. En plus de cette diversité linguistique, on constate le développement croissant de bases de données et de collections composées de différents types de documents textuels ou multimédias, ce qui complexifie également le processus de repérage documentaire. Par exemple, les collections d’images numériques sont aussi nombreuses que diversifiées. Le besoin de repérer une image spécifique dans diverses collections est devenu une préoccupation partagée par plusieurs communautés. La croissance du web a mis en relief le besoin pressant de se doter d’outils propres à la description des images dans le but de faciliter leur repérage, puisque l’on retrouve celles-ci dans la plupart des ressources disponibles. Cette recherche compare le repérage d’images dans deux contextes linguistiques différents : un contexte monolingue, c’est-à-dire que la langue de la requête (français est la même que la langue d’indexation (français; et un contexte multilingue où la langue de la requête (français est différente de la langue d’indexation (anglais. Cet article présente les résultats de l’analyse des requêtes formulées par les participants pour repérer un ensemble d’images ordinaires représentant des objets de la vie quotidienne, en contexte de repérage multilingue. L’examen des termes contenus dans les requêtes des chercheurs d’images révèle les tendances observées sur le plan terminologique, perceptuel et structurel. Les participants emploient généralement des requêtes simples

  20. Modulation of cell proliferation, survival and gene expression by RAGE and TLR signaling in cells of the innate and adaptive immune response: role of p38 MAPK and NF-KB

    Science.gov (United States)

    de MEDEIROS, Marcell Costa; FRASNELLI, Sabrina Cruz Tfaile; BASTOS, Alliny de Souza; ORRICO, Silvana Regina Perez; ROSSA JUNIOR, Carlos

    2014-01-01

    Objective The aim of this study was to evaluate a possible synergism between AGE-RAGE and TLR4 signaling and the role of p38 MAPK and NF-kB signaling pathways on the modulation of the expression of inflammatory cytokines and proliferation of cells from the innate and adaptive immune response. Material and Methods T lymphocyte (JM) and monocyte (U937) cell lines were stimulated with LPS and AGE-BSA independently and associated, both in the presence and absence of p38 MAPK and NF-kB inhibitors. Proliferation was assessed by direct counting and viability was assessed by a biochemical assay of mitochondrial function. Cytokine gene expression for RAGe, CCL3, CCR5, IL-6 and TNF-α was studied by RT-PCR and RT-qPCR. Results RAGE mRNA expression was detected in both cell lines. LPS and AGE-BSA did not influence cell proliferation and viability of either cell line up to 72 hours. LPS and LPS associated with AGE induced expression of IL-6 and TNF-α in monocytes and T cells, respectively. Conclusions There is no synergistic effect between RAGE and TLR signaling on the expression of IL-6, TNF-α , RAGE, CCR5 and CCL3 by monocytes and lymphocytes. Activation of RAGE associated or not with TLR signaling also had no effect on cell proliferation and survival of these cell types. PMID:25025559

  1. The Association of -429T>C and -374T>A Polymorphisms in the RAGE Gene with Polycystic Ovary Syndrome

    OpenAIRE

    Park, Jung-Hyun; Li, Lan; Choi, Jin-Woo; Baek, Kwang-Hyun

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a complex disorder characterized by hyperandrogenism and insulin resistance. In addition, a number of females with PCOS have ovaries with multiple cysts, an irregular or no menstrual cycle, and an imbalance of female hormones compared to those of normal controls. A variety of genetic factors have been involved in the pathogenesis of PCOS. Among these genetic factors, the receptor for advanced glycation end products (RAGE) that is associated with diabetes an...

  2. Ethyl pyruvate inhibits proliferation and induces apoptosis of hepatocellular carcinoma via regulation of the HMGB1–RAGE and AKT pathways

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Ping; Dai, Weiqi; Wang, Fan; Lu, Jie; Shen, Miao; Chen, Kan; Li, Jingjing; Zhang, Yan; Wang, Chengfen; Yang, Jing; Zhu, Rong; Zhang, Huawei; Zheng, Yuanyuan; Guo, Chuan-Yong, E-mail: guochuanyong@hotmail.com; Xu, Ling, E-mail: xuling606@sina.com

    2014-01-24

    Highlights: • Ethyl pyruvate inhibits liver cancer. • Promotes apoptosis. • Decreased the expression of HMGB1, p-Akt. - Abstract: Ethyl pyruvate (EP) was recently identified as a stable lipophilic derivative of pyruvic acid with significant antineoplastic activities. The high mobility group box-B1 (HMGB1)–receptor for advanced glycation end-products (RAGE) and the protein kinase B (Akt) pathways play a crucial role in tumorigenesis and development of many malignant tumors. We tried to observe the effects of ethyl pyruvate on liver cancer growth and explored its effects in hepatocellular carcinoma model. In this study, three hepatocellular carcinoma cell lines were treated with ethyl pyruvate. An MTT colorimetric assay was used to assess the effects of EP on cell proliferation. Flow cytometry and TUNEL assays were used to analyze apoptosis. Real-time PCR, Western blotting and immunofluorescence demonstrated ethyl pyruvate reduced the HMGB1–RAGE and AKT pathways. The results of hepatoma orthotopic tumor model verified the antitumor effects of ethyl pyruvate in vivo. EP could induce apoptosis and slow the growth of liver cancer. Moreover, EP decreased the expression of HMGB1, RAGE, p-AKT and matrix metallopeptidase-9 (MMP9) and increased the Bax/Bcl-2 ratio. In conclusion, this study demonstrates that ethyl pyruvate induces apoptosis and cell-cycle arrest in G phase in hepatocellular carcinoma cells, plays a critical role in the treatment of cancer.

  3. Relationship between RAGE and hepatic ischemia/reperfusion injury%RAGE与肝缺血再灌注损伤间的关系

    Institute of Scientific and Technical Information of China (English)

    何超; 支军

    2011-01-01

    晚期糖化终末产物受体(reptor for advanccd glycation end product,RAGE)是一种单穿膜受体,同时也是一种多配体受体,属于免疫球蛋白超家族的成员.其配体包括高速泳动族框1蛋白质(high mobilily group box1,HMGB1)、晚期糖化终末产物(advanced glycalion end product,AGE),S100/钙粒蛋白(calgranulin)及β淀粉样肽等.在肝脏中,RAGE主要表达于巨噬细胞与树突状细胞.RAGE一旦被激活,就会通过一系列的信号传导,诱导这些细胞释放出多种促炎症的物质,并引起中性粒细胞沉积,产生瀑布式的炎症反应链.肝脏的缺血再灌注(ischemia/reperfusion,I/R)损伤作用机制繁多.其中RAGE作为一个关键的调节点,各种外来和内在的因素都可以通过作用于RAGE从而影响炎症反应.现就肝脏I/R损伤与RAGE之间关系做一综述.%Receptor for advanced glycation end products (SAGE), as one kind of single transmembrane receptor as well as multi-ligand receptor, belongs to the immunoglobulin super family. Its ligands include high mobility group boxl (HMGB1), advanced glycation end products (AGEs), S100/calgranulins, and amyloid-β peptides, etc. In the liver, RAGE is mainly expressed on macrophages and dendritic cells. These cells induced by activated RAGE can release a great variety of pro-inflammatory substances by a series of signal transduction, leading to neutrophil deposition and causing inflammatory cascade chain. There are diverse mechanisms in the process of hepatic ischemia/reperfusion (I/R) injury. RAGE, as a key regulator of this process, can be affected by various external and internal factors. This paper reviews the research progress of the relationship between RAGE and hepatic I/R injury.

  4. Effects of psychotropic drugs on the rage responses induced by electrical stimulation of the medial hypothalamus in cats.

    Science.gov (United States)

    Fukuda, T; Tsumagari, T

    1983-08-01

    Effects of psychotropic drugs on the rage responses induced by electrical stimulation were investigated in cats with electrodes chronically implanted in the medial hypothalamus. Diazepam produced marked elevation in the threshold for directed attack and slight elevation in that for hissing. The inhibitory effect of etizolam on hissing was about 6 times as potent as that of diazepam. Anti-anxiety drugs such as diazepam, nitrazepam, lorazepam, clotiazepam and etizolam produced marked elevation in the directed attack threshold dose-dependently. The effect of chlorpromazine on directed attack was far less potent than that of anti-anxiety drugs. The anti-anxiety drugs used in this experiment had anti-pentetrazol activity in mice as well as muscle relaxant activity in cats. There were close correlations between the directed attack inhibition produced by the anti-anxiety drugs and both anti-pentetrazol activity and muscle relaxant activity. These results indicate that the above anti-anxiety drugs have a more potent inhibitory effect on the function of the medial hypothalamus than neuroleptic drugs. The inhibitory effect of anti-anxiety drugs on directed attack may be considered to correlate with clinical anti-anxiety effects. PMID:6632385

  5. De la rage à l'enthousiasme : le parcours d'un jeune électeur saoudien

    Directory of Open Access Journals (Sweden)

    Pascal Ménoret

    2004-12-01

    Full Text Available Comment apprend-on le métier d'électeur dans une société autoritairement dépolitisée ? Cet entretien approfondi, réalisé avec un jeune électeur saoudien au lendemain de la victoire du courant religieux modéré aux élections municipale de février 2005 à Riyad, permet d'avancer quelques éléments de réponse. On verra ainsi que des dispositions politiques susceptibles d'être réinvesties dans l'activisme électoral ont pu être puisées par les plus fervents partisans du processus électoral dans les schèmes de pensée et d'acion propres aux groupes islamiques des écoles, aux cercles coraniques des mosquées et aux centres d'été du ministère des Affaires islamiques. L'activisme islamique n'est pas foncièrement incompatible avec un processus de démocratisation ; encore faut-il que la « rage » contractée au spectacle de la dictature et des injustices occidentales puisse se transformer en « enthousiasme » politique et électoral.

  6. β-Caryophyllene alleviates D-galactosamine and lipopolysaccharide-induced hepatic injury through suppression of the TLR4 and RAGE signaling pathways.

    Science.gov (United States)

    Cho, Hong-Ik; Hong, Jeong-Min; Choi, Joo-Wan; Choi, Hyo-Sun; Kwak, Jong Hwan; Lee, Dong-Ung; Kook Lee, Sang; Lee, Sun-Mee

    2015-10-01

    Agastache rugosa (A. rugosa, Labiatae), a perennial herb spread throughout Korean fields, is widely consumed as a wild edible vegetable and is used in folk medicine. This study examined the hepatoprotective mechanisms of β-caryophyllene (BCP), a major bicyclic sesquiterpene of A. rugosa, against D-galactosamine (GalN) and lipopolysaccharide (LPS)-induced hepatic failure. Mice were given an intraperitoneal injection of BCP (50, 100 and 200 mg/kg) 1 h before GalN (800 mg/kg)/LPS (40 μg/kg) injection and were killed 1 h or 6 h after GalN/LPS injection. GalN/LPS markedly increased mortality and serum aminotransferase activity, both of which were attenuated by BCP. BCP also attenuated increases in serum tumor necrosis factor-α, interleukin 6, and high-mobility group protein B1 levels by GalN/LPS. GalN/LPS significantly increased toll-like receptor (TLR) 4 and receptor for advanced glycation end products (RAGE) protein expression, extracellular signal-related kinase, p38 and c-Jun N-terminal kinase phosphorylation, nuclear factor κB (NF-κB), early growth response protein-1, and macrophage inflammatory protein-2 protein expression. These increases were attenuated by BCP. Furthermore, BCP suppressed increased TLR4 and RAGE protein expression and proinflammatory cytokines production in LPS-treated isolated Kupffer cells. Our findings suggest that BCP protects against GalN/LPS-induced liver injury through down-regulation of the TLR4 and RAGE signaling. PMID:26254779

  7. Chrysin, a PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation.

    Science.gov (United States)

    Rani, Neha; Bharti, Saurabh; Bhatia, Jagriti; Nag, T C; Ray, Ruma; Arya, Dharamvir Singh

    2016-04-25

    AGE-RAGE interaction mediated oxidative stress and inflammation is the key mechanism involved in the pathogenesis of cardiovascular disease in diabetes. Inhibition of AGE-RAGE axis by several PPAR-γ agonists has shown positive results in ameliorating cardio-metabolic disease conditions. Chrysin, a natural flavonoid has shown to possess PPAR-γ agonist activity along with antioxidant and anti-inflammatory effect. Therefore, the present study was designed to evaluate the effect of chrysin in isoproterenol-induced myocardial injury in diabetic rats. In male albino Wistar rats, diabetes was induced by single injection of streptozotocin (70 mg/kg, i.p.). After confirmation of the diabetes, rats were treated with vehicle (1.5 mL/kg, p.o.), chrysin (60 mg/kg, p.o.) or PPAR-γ antagonist GW9662 (1 mg/kg, i.p.) for 28 days. Simultaneously, on 27th and 28th day myocardial injury was induced by isoproterenol (85 mg/kg, s.c.). Chrysin significantly ameliorated cardiac dysfunction as reflected by improved MAP, ±LVdP/dtmax and LVEDP in diabetic rats. This improvement was associated with increased PPAR-γ expression and reduced RAGE expression in diabetic rats. Chrysin significantly decreased inflammation through inhibiting NF-κBp65/IKK-β expression and TNF-α level. Additionally, chrysin significantly reduced apoptosis as indicated by augmented Bcl-2 expression and decreased Bax and caspase-3 expressions. Furthermore, chrysin inhibited nitro-oxidative stress by normalizing the alteration in 8-OHdG, GSH, TBARS, NO and CAT levels and Nox4, MnSOD, eNOS and NT expressions. Co-administration of GW9662 significantly blunted the chrysin mediated cardioprotective effect as there was increase in oxidative stress, inflammation and apoptosis markers. Chrysin significantly ameliorated isoproterenol-induced myocardial injury in diabetic rats via PPAR-γ activation and inhibition of AGE-RAGE mediated oxidative stress and inflammation. PMID:26972669

  8. Hyperoside Downregulates the Receptor for Advanced Glycation End Products (RAGE and Promotes Proliferation in ECV304 Cells via the c-Jun N-Terminal Kinases (JNK Pathway Following Stimulation by Advanced Glycation End-Products In Vitro

    Directory of Open Access Journals (Sweden)

    Zhengyu Zhang

    2013-11-01

    Full Text Available Hyperoside is a major active constituent in many medicinal plants which are traditionally used in Chinese medicines for their neuroprotective, anti-inflammatory and antioxidative effects. The molecular mechanisms underlying these effects are unknown. In this study, quiescent ECV304 cells were treated in vitro with advanced glycation end products (AGEs in the presence or absence of hyperoside. The results demonstrated that AGEs induced c-Jun N-terminal kinases (JNK activation and apoptosis in ECV304 cells. Hyperoside inhibited these effects and promoted ECV304 cell proliferation. Furthermore, hyperoside significantly inhibited RAGE expression in AGE-stimulated ECV304 cells, whereas knockdown of RAGE inhibited AGE-induced JNK activation. These results suggested that AGEs may promote JNK activation, leading to viability inhibition of ECV304 cells via the RAGE signaling pathway. These effects could be inhibited by hyperoside. Our findings suggest a novel role for hyperoside in the treatment and prevention of diabetes.

  9. Hyperoside Downregulates the Receptor for Advanced Glycation End Products (RAGE) and Promotes Proliferation in ECV304 Cells via the c-Jun N-Terminal Kinases (JNK) Pathway Following Stimulation by Advanced Glycation End-Products In Vitro

    Science.gov (United States)

    Zhang, Zhengyu; Sethiel, Mosha Silas; Shen, Weizhi; Liao, Sentai; Zou, Yuxiao

    2013-01-01

    Hyperoside is a major active constituent in many medicinal plants which are traditionally used in Chinese medicines for their neuroprotective, anti-inflammatory and antioxidative effects. The molecular mechanisms underlying these effects are unknown. In this study, quiescent ECV304 cells were treated in vitro with advanced glycation end products (AGEs) in the presence or absence of hyperoside. The results demonstrated that AGEs induced c-Jun N-terminal kinases (JNK) activation and apoptosis in ECV304 cells. Hyperoside inhibited these effects and promoted ECV304 cell proliferation. Furthermore, hyperoside significantly inhibited RAGE expression in AGE-stimulated ECV304 cells, whereas knockdown of RAGE inhibited AGE-induced JNK activation. These results suggested that AGEs may promote JNK activation, leading to viability inhibition of ECV304 cells via the RAGE signaling pathway. These effects could be inhibited by hyperoside. Our findings suggest a novel role for hyperoside in the treatment and prevention of diabetes. PMID:24252909

  10. Generation of Soluble Advanced Glycation End Products Receptor (sRAGE)-Binding Ligands during Extensive Heat Treatment of Whey Protein/Lactose Mixtures Is Dependent on Glycation and Aggregation.

    Science.gov (United States)

    Liu, Fahui; Teodorowicz, Małgorzata; Wichers, Harry J; van Boekel, Martinus A J S; Hettinga, Kasper A

    2016-08-24

    Heating of protein- and sugar-containing materials is considered the primary factor affecting the formation of advanced glycation end products (AGEs). This study aimed to investigate the influence of heating conditions, digestion, and aggregation on the binding capacity of AGEs to the soluble AGE receptor (sRAGE). Samples consisting of mixtures of whey protein and lactose were heated at 130 °C. An in vitro infant digestion model was used to study the influence of heat treatment on the digestibility of whey proteins. The amount of sRAGE-binding ligands before and after digestion was measured by an ELISA-based sRAGE-binding assay. Water activity did not significantly affect the extent of digestibility of whey proteins dry heated at pH 5 (ranging from 3.3 ± 0.2 to 3.6 ± 0.1% for gastric digestion and from 53.5 ± 1.5 to 64.7 ± 1.1% for duodenal digestion), but there were differences in cleavage patterns of peptides among the samples heated at different pH values. Formation of sRAGE-binding ligands depended on the formation of aggregates and was limited in the samples heated at pH 5. Moreover, the sRAGE-binding activity of digested sample was changed by protease degradation and correlated with the digestibility of samples. In conclusion, generation of sRAGE-binding ligands during extensive heat treatment of whey protein/lactose mixtures is limited in acidic heating condition and dependent on glycation and aggregation. PMID:27460534

  11. Cardioprotective effect of pioglitazone in diabetic and non-diabetic rats subjected to acute myocardial infarction involves suppression of AGE-RAGE axis and inhibition of apoptosis.

    Science.gov (United States)

    Khodeer, Dina M; Zaitone, Sawsan A; Farag, Noha E; Moustafa, Yasser M

    2016-05-01

    Insulin resistance increases risk of cardiovascular diseases. This work investigated the protective effect of pioglitazone on myocardial infarction (MI) in non-diabetic and diabetic rats, focusing on its role on advanced glycated endproducts (AGEs) and cardiac apoptotic machinery. Male rats were divided into 2 experiments: experiment I and II (non-diabetic and diabetic rats) were assigned as saline, MI (isoproterenol, 85 mg/kg, daily), and MI+pioglitazone (5, 10, and 20 mg/kg). Injection of isoproterenol in diabetic rats produced greater ECG disturbances compared to non-diabetic rats. Treatment with pioglitazone (5 mg/kg) reduced the infarct size and improved some ECG findings. Pioglitazone (10 mg/kg) enhanced ECG findings, improved the histopathological picture and downregulated apoptosis in cardiac tissues. Whereas the higher dose of pioglitazone (20 mg/kg) did not improve most of the measured parameters but rather worsened some of them, such as proapoptotic markers. Importantly, a positive correlation was found between serum AGEs and cardiac AGE receptors (RAGEs) versus caspase 3 expression in the two experiments. Therefore, the current effect of pioglitazone was, at least in part, mediated through downregulation of AGE-RAGE axis and inhibition of apoptosis. Consequently, these data suggest that pioglitazone, at optimized doses, may have utility in protection from acute MI. PMID:27119311

  12. Soluble HMGB1 is a novel adipokine stimulating IL-6 secretion through RAGE receptor in SW872 preadipocyte cell line: contribution to chronic inflammation in fat tissue.

    Directory of Open Access Journals (Sweden)

    Brice Nativel

    Full Text Available Low-grade inflammation (LGI is a central phenomenon in the genesis of obesity and insulin-resistance characterized by IL-6 in human serum. Whereas this LGI was initially thought to be mainly attributed to macrophage activation, it is now known that pre-adipocytes and adipocytes secrete several adipokines including IL-6 and participate to LGI and associated pathologies. In macrophages, HMGB1 is a nuclear yet secreted protein and acts as a cytokine to drive the production of inflammatory molecules through RAGE and TLR2/4. In this paper we tested the secretion of HMGB1 and the auto- and paracrine contribution to fat inflammation using the human preadipocyte cell line SW872 as a model. We showed that 1 human SW872 secreted actively HMGB1, 2 IL-6 production was positively linked to high levels of secreted HMGB1, 3 recombinant HMGB1 boosted IL-6 expression and this effect was mediated by the receptor RAGE and did not involve TLR2 or TLR4. These results suggest that HMGB1 is a major adipokine contributing to LGI implementation and maintenance, and can be considered as a target to develop news therapeutics in LGI associated pathologies such as obesity and type II diabetes.

  13. [Electrophysiological and behavioral features of septal seizures in cats--experimental sham-rage seizures induced by injection of kainic acid].

    Science.gov (United States)

    Hashizume, K; Tanaka, T; Yonemasu, Y

    1994-07-01

    The septal nucleus has close connections with the hippocampus and amygdala and is known to be involved in emotional behavior. We analyzed the electrophysiological and behavioral features of seizures induced by an injection of kainic acid into the lateral septal nucleus of the cat. Stereotactic surgery was performed to implant a cannula into the lateral septal nucleus to make the injection, and deep electrodes were implanted into the hippocampus and amygdala bilaterally. Seven days post operatively kainic acid, 0.5 microgram/0.5 microliter, was injected via the cannula, and three to five minutes later the cats began to exhibit head turning to the contralateral side. The seizures subsequently progressed limbic seizure status. The electroencephalogram revealed that the spike discharges started in the lateral septal nucleus, extended to the ipsilateral hippocampus and amygdala, then propagated to the contralateral side. Spontaneous sham-rage seizures occurred more than seven days after the injection. These seizure were characterized by sudden onset of aggressive and violent behavior which included hissing, biting and scratching. The electroencephalogram showed synchronization of rhythmic spikes in the ipsilateral septal nucleus, hippocampus and amygdala during such seizures. Further study of this model is important not only to understand the relationship between the septal nucleus and the hippocampus and amygdala but to understand the mechanism of sham-rage seizures. In addition, this model may be useful in understanding the emotional features of intractable complex partial seizures in man. PMID:7946621

  14. Mild exposure of RIN-5F β-cells to human islet amyloid polypeptide aggregates upregulates antioxidant enzymes via NADPH oxidase-RAGE: An hormetic stimulus

    Directory of Open Access Journals (Sweden)

    Elisabetta Borchi

    2014-01-01

    Full Text Available The presence of amyloid aggregates of human islet amyloid polypeptide (hIAPP, a hallmark of type 2 diabetes, contributes to pancreatic β-cell impairment, where oxidative stress plays a key role. A contribution of NADPH oxidase to reactive oxygen species (ROS generation after cell exposure to micromolar concentrations of hIAPP aggregates has been suggested. However, little is known about β-cells exposure to lower amounts of hIAPP aggregates, similar to those found in human pancreas. Thus, we aimed to investigate the events resulting from RIN-5F cells exposure to nanomolar concentrations of toxic hIAPP aggregates. We found an early and transient rise of NADPH oxidase activity resulting from increased Nox1 expression following the engagement of receptor for advanced glycation end-products (RAGE by hIAPP aggregates. Unexpectedly, NADPH oxidase activation was not accompanied by a significant ROS increase and the lipoperoxidation level was significantly reduced. Indeed, cell exposure to hIAPP aggregates affected the antioxidant defences, inducing a significant increase of the expression and activity of catalase and glutathione peroxidase. We conclude that exposure of pancreatic β-cells to nanomolar concentrations of hIAPP aggregates for a short time induces an hormetic response via the RAGE-Nox1 axis; the latter stimulates the enzymatic antioxidant defences that preserve the cells against oxidative stress damage.

  15. Neuroprotective effect of Amaranthus lividus and Amaranthus tricolor and their effects on gene expression of RAGE during oxidative stress in SH-SY5Y cells.

    Science.gov (United States)

    Amornrit, W; Santiyanont, R

    2016-01-01

    Amaranthus plants, or spinach, are used as food sources worldwide. Amaranthus leaves are rich in antioxidant compounds, which act as free radical scavengers. Oxidative stress caused by the aberrant production of reactive oxygen species (ROS) represents an important mechanism for neuronal dysfunction and cell loss in different neurodegenerative disorders. The neuroprotective effects of antioxidant-containing plants have been extensively demonstrated in different models of neurotoxicity. However, few studies have investigated the antioxidant properties of Amaranthus extracts and their effect on the nervous system. In the present study, the leaves of Amaranthus lividus and Amaranthus tricolor were extracted using petroleum ether, dichloromethane, and methanol. Results indicated that antioxidant activities were the highest in methanol extracts from both kinds of Amaranthus leaves. In addition, oxidative stress was induced in human neuroblastoma cell lines (SH-SY5Y) by using H2O2. Intracellular oxidative stress, cytotoxicity, and gene expression of RAGE were then determined. In vitro results demonstrated that pretreatment with A. lividus and A. tricolor extracts can significantly decrease cell toxicity and intracellular ROS production in SH-SY5Y cells. Interestingly, the extracts also significantly downregulated the expression of oxidative stress genes such as HMOX-1, RAGE, and RelA/ NF-κB. Our results suggested that Amaranthus leaves may be useful for reducing oxidative stress and may be beneficial for age-related diseases and neurodegenerative disorders. PMID:27173239

  16. Higher plasma soluble Receptor for Advanced Glycation End Products (sRAGE) levels are associated with incident cardiovascular disease and all-cause mortality in type 1 diabetes: a 12-year follow-up study

    DEFF Research Database (Denmark)

    Nin, Johanna W M; Jorsal, Anders; Merces Ferreira, Isabel Maria; Schalkwijk, Casper G; Prins, Martin H; Parving, Hans-Henrik; Tarnow, Lise; Rossing, Peter; Stehouwer, Coen D A

    2010-01-01

    To investigate the associations of plasma levels of soluble receptor for advanced glycation end products (sRAGE) with incident cardiovascular disease (CVD) and all-cause mortality in type 1 diabetes and the extent to which any such associations could be explained by endothelial and renal dysfunct...

  17. Predictive value of AGEs and their receptor RAGE and sRAGE for perinatal outcome of gestational diabetes%血清中晚期糖基化终产物及其受体对妊娠期糖尿病围产儿结局的预测价值

    Institute of Scientific and Technical Information of China (English)

    汤栩文; 林斯; 谢晓斌

    2012-01-01

    目的 探讨妊娠期糖尿病孕妇(GDM)血清中晚期糖基化终产物(AGEs) -晚期糖基化终产物受体(RAGE)轴所介导的氧化应激反应与国产儿结局间的关系.方法 选择2011年1月至12月在广州市妇女儿童医疗中心产科检查,孕24~28周产前检查被诊断患有GDM的孕妇100例为研究对象(GDM组),另选择同期、相应年龄的正常妊娠妇女50例作为正常对照组.抽取两组孕妇的血样,测量空腹血糖、糖化血红蛋白(HbA1c)和AGEs、可溶性RAGE(sRAGE)水平.分娩后收集胎盘,分析组织中RAGE蛋白的表达.并收集母婴临床信息,根据围产儿结局异常与否分为GDM正常围产儿结局组和GDM不良围产儿结局组.结果 GDM组治疗前孕妇血清AGEs 水平(50.44±16.21) ng/L,明显高于正常对照组(32.69±10.13)ng/L (P<0.01).GDM组经干预治疗后其空腹血糖和HbA1c水平与正常对照组比较,差异无统计学意义(P>0.05);但血清AGEs水平仍然高于正常对照组(P<0.01).GDM组孕母血清AGEs与sRAGE水平呈负相关(r=-0.582,P< 0.01).GDM不良围产儿结局组孕妇血清AGEs水平(67.39 ±14.75) ng/L明显高于GDM正常围产儿结局组(41.59±12.26)ng/L (P <0.05).Logistic回归分析显示高AGEs水平是GDM不良围产儿结局的危险因子(OR =6.197,P<0.01,95% CI 2.514 ~15.453);低sRAGE水平也是GDM不良围产儿结局的危险因子(OR =0.498,P<0.05,95% CI 0.217~0.925).GDM不良围产儿结局组(0.993±0.085)高于GDM正常围产儿结局组(0.611±0.047)和正常对照组(0.247±0.018)(P均<0.01).结论 血清高AGEs水平是GDM围产儿结局的一个不利因素,高AGEs水平可作为GDM 不良围产儿结局的预测指标.血循环中sRAGE可通过竞争结合方式中和AGEs,抑制其下游信号的传递,血清低sRAGE水平可作为GDM病变中AGEs-RAGE轴过度活跃的生物标记.%Objective Explore the relationship between gestational diabetes during pregnancy (GDM) in serum advanced glycation

  18. Repérage et typage d'expressions temporelles pour l'annotation sémantique automatique de pages Web - Application au e-tourisme

    OpenAIRE

    Weiser, Stéphanie

    2010-01-01

    Cette thèse présente Adetoa, système dédié au repérage et à l'annotation sémantique automatique d'expressions temporelles dans des pages Web pour une application de e-tourisme. Une étude linguistique détaillée a permis de mettre en avant les caractéristiques et la complexité de l'expression de la temporalité dans les pages Web touristiques. Une étude sémiotique de ce type de pages a montré que les données y étaient organisées de manière fort variée, ne présentant aucune régularité, ce qui ren...

  19. Pinocembrin protects against β-amyloid-induced toxicity in neurons through inhibiting receptor for advanced glycation end products (RAGE-independent signaling pathways and regulating mitochondrion-mediated apoptosis

    Directory of Open Access Journals (Sweden)

    Liu Rui

    2012-09-01

    Full Text Available Abstract Background It is known that amyloid-β peptide (Aβ plays a pivotal role in the pathogenesis of Alzheimer's disease (AD. Interaction between Aβ and the receptor for advanced glycation end products (RAGE has been implicated in neuronal degeneration associated with this disease. Pinocembrin, a flavonoid abundant in propolis, has been reported to possess numerous biological activities beneficial to health. Our previous studies have demonstrated that pinocembrin has neuroprotective effects on ischemic and vascular dementia in animal models. It has been approved by the State Food and Drug Administration of China for clinical use in stroke patients. Against this background, we investigated the effects of pinocembrin on cognitive function and neuronal protection against Aβ-induced toxicity and explored its potential mechanism. Methods Mice received an intracerebroventricular fusion of Aβ25-35. Pinocembrin was administrated orally at 20 mg/kg/day and 40 mg/kg/day for 8 days. Behavioral performance, cerebral cortex neuropil ultrastructure, neuronal degeneration and RAGE expression were assessed. Further, a RAGE-overexpressing cell model and an AD cell model were used for investigating the mechanisms of pinocembrin. The mechanisms underlying the efficacy of pinocembrin were conducted on target action, mitochondrial function and potential signal transduction using fluorescence-based multiparametric technologies on a high-content analysis platform. Results Our results showed that oral administration of pinocembrin improved cognitive function, preserved the ultrastructural neuropil and decreased neurodegeneration of the cerebral cortex in Aβ25-35-treated mice. Pinocembrin did not have a significant effect on inhibiting Aβ1-42 production and scavenging intracellular reactive oxygen species (ROS. However, pinocembrin significantly inhibited the upregulation of RAGE transcripts and protein expression both in vivo and in vitro, and also markedly

  20. Comparison of contrast-enhanced modified T1-weighted 3D TSE black-blood and 3D MP-RAGE sequences for the detection of cerebral metastases and brain tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kammer, N.N.; Coppenrath, E.; Treitl, K.M.; Saam, T. [Ludwig-Maximilians-University Hospital Munich, Institute for Clinical Radiology, Munich (Germany); Kooijman, H. [Philips Healthcare, Hamburg (Germany); Dietrich, O. [Ludwig-Maximilians-University Hospital Munich, Josef Lissner Laboratory for Biomedical Imaging, Institute for Clinical Radiology, Munich (Germany)

    2016-06-15

    To compare a modified T1-weighted 3D TSE black-blood sequence with sub-millimetre resolution (T1-mVISTA) with a magnetization-prepared rapid gradient echo (MP-RAGE) sequence for the diagnosis of cerebral malignomas. Forty-six patients with known or suspected intracranial tumours and 15 control patients were included in this retrospective study. All patients underwent T1-mVISTA (0.75-mm isotropic resolution, 4:43 min) and MP-RAGE (0.8-mm isotropic resolution, 4:46 minutes) at 3-Tesla in random order after application of contrast agent. Two experienced radiologists determined the number of lesions. Maximum diameter, diagnostic confidence (DC), visual assessment of contrast enhancement (VCE) and CNR{sub lesion/parenchyma} were assessed for each lesion. Significantly more lesions were detected with T1-mVISTA compared to the MP-RAGE (61 vs. 36; p < 0.05). Further, DC and VCE was rated significantly higher in the T1-mVISTA (p < 0.05 and p < 0.001). Mean CNR{sub lesion/parenchyma} was twofold higher for T1-mVISTA (24.2 ± 17.5 vs. 12.7 ± 11.5, p < 0.001). The 25 lesions detected only in T1-mVISTA were significantly smaller than those detected in both sequences (4.3 ± 3.7 mm vs. 11.3 ± 10.7 mm; p < 0.01). T1-mVISTA increases the contrast of lesions significantly compared to MP-RAGE and might therefore improve detection rates of small lesions in early stages of disease. (orig.)

  1. Comparison of contrast-enhanced modified T1-weighted 3D TSE black-blood and 3D MP-RAGE sequences for the detection of cerebral metastases and brain tumours

    International Nuclear Information System (INIS)

    To compare a modified T1-weighted 3D TSE black-blood sequence with sub-millimetre resolution (T1-mVISTA) with a magnetization-prepared rapid gradient echo (MP-RAGE) sequence for the diagnosis of cerebral malignomas. Forty-six patients with known or suspected intracranial tumours and 15 control patients were included in this retrospective study. All patients underwent T1-mVISTA (0.75-mm isotropic resolution, 4:43 min) and MP-RAGE (0.8-mm isotropic resolution, 4:46 minutes) at 3-Tesla in random order after application of contrast agent. Two experienced radiologists determined the number of lesions. Maximum diameter, diagnostic confidence (DC), visual assessment of contrast enhancement (VCE) and CNRlesion/parenchyma were assessed for each lesion. Significantly more lesions were detected with T1-mVISTA compared to the MP-RAGE (61 vs. 36; p < 0.05). Further, DC and VCE was rated significantly higher in the T1-mVISTA (p < 0.05 and p < 0.001). Mean CNRlesion/parenchyma was twofold higher for T1-mVISTA (24.2 ± 17.5 vs. 12.7 ± 11.5, p < 0.001). The 25 lesions detected only in T1-mVISTA were significantly smaller than those detected in both sequences (4.3 ± 3.7 mm vs. 11.3 ± 10.7 mm; p < 0.01). T1-mVISTA increases the contrast of lesions significantly compared to MP-RAGE and might therefore improve detection rates of small lesions in early stages of disease. (orig.)

  2. Nifedipine, a calcium channel blocker, inhibits advanced glycation end product (AGE)-elicited mesangial cell damage by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-gamma activation

    International Nuclear Information System (INIS)

    The interaction between advanced glycation end products (AGE) and their receptor RAGE mediates the progressive alteration in renal architecture and loss of renal function in diabetic nephropathy. Oxidative stress generation and inflammation also play a central role in diabetic nephropathy. This study investigated whether and how nifedipine, a calcium channel blocker (CCB), blocked the AGE-elicited mesangial cell damage in vitro. Nifedipine, but not amlodipine, a control CCB, down-regulated RAGE mRNA levels and subsequently reduced reactive oxygen species (ROS) generation in AGE-exposed mesangial cells. AGE increased mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and induced monocyte chemoattractant protein-1 (MCP-1) production in mesangial cells, both of which were prevented by the treatment with nifedipine, but not amlodipine. The beneficial effects of nifedipine on AGE-exposed mesangial cells were blocked by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-γ (PPAR-γ). Although nifedipine did not affect expression levels of PPAR-γ, it increased the PPAR-γ transcriptional activity in mesangial cells. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-inflammatory agent against AGE by suppressing RAGE expression in cultured mesangial cells via PPAR-γ activation.

  3. Nifedipine, a calcium channel blocker, inhibits advanced glycation end product (AGE)-elicited mesangial cell damage by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-gamma activation

    Energy Technology Data Exchange (ETDEWEB)

    Matsui, Takanori [Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011 (Japan); Yamagishi, Sho-ichi, E-mail: shoichi@med.kurume-u.ac.jp [Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011 (Japan); Takeuchi, Masayoshi [Department of Pathophysiological Science, Faculty of Pharmaceutical Science, Hokuriku University, Kanazawa (Japan); Ueda, Seiji; Fukami, Kei; Okuda, Seiya [Department of Medicine, Kurume University School of Medicine, Kurume (Japan)

    2009-07-24

    The interaction between advanced glycation end products (AGE) and their receptor RAGE mediates the progressive alteration in renal architecture and loss of renal function in diabetic nephropathy. Oxidative stress generation and inflammation also play a central role in diabetic nephropathy. This study investigated whether and how nifedipine, a calcium channel blocker (CCB), blocked the AGE-elicited mesangial cell damage in vitro. Nifedipine, but not amlodipine, a control CCB, down-regulated RAGE mRNA levels and subsequently reduced reactive oxygen species (ROS) generation in AGE-exposed mesangial cells. AGE increased mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and induced monocyte chemoattractant protein-1 (MCP-1) production in mesangial cells, both of which were prevented by the treatment with nifedipine, but not amlodipine. The beneficial effects of nifedipine on AGE-exposed mesangial cells were blocked by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}). Although nifedipine did not affect expression levels of PPAR-{gamma}, it increased the PPAR-{gamma} transcriptional activity in mesangial cells. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-inflammatory agent against AGE by suppressing RAGE expression in cultured mesangial cells via PPAR-{gamma} activation.

  4. A diffusive radiation hydrodynamics code, xRage, is implemented to compare radiation flow with experimental data from the Omega laser facility

    Science.gov (United States)

    Vandervort, Robert; Elgin, Laura; Farag, Ebraheem; Mussack, Katie; Baumgaertel, Jessica Ann; Keiter, Paul; Klein, Sallee; Orban, Christopher; Drake, R. Paul

    2015-11-01

    A sound speed discrepancy between solar models and data collected using helioseismology exists. The sound speed discrepancy is the most pronounced at the base of the convective zone (CZ) for otherwise consistent solar models. One potential solution is that the opacity models for important elements such as carbon, nitrogen and oxygen are incomplete. At these high energy-density conditions few relevant opacity measurements exist to compare to the models. Only relatively recently have user facilities been able to reach the temperatures and densities that resemble the convective zone base. It is our long term goal to determine the opacities of carbon, nitrogen and oxygen at the relevant conditions. Preliminary testing has occurred at the Omega Laser Facility in Rochester, New York. Presented are the results of the shots taken on April 22, 2015. A half hohlraum was used to drive a supersonic radiation front through a dominantly carbon, CRF, foam. These results are compared to diffusive xRage simulations. (LA-UR-15-25495)

  5. Epigallocatechin-3-gallate combined with alpha lipoic acid attenuates high glucose-induced receptor for advanced glycation end products (RAGE expression in human embryonic kidney cells

    Directory of Open Access Journals (Sweden)

    Jyh-Gang Leu

    Full Text Available The anti-oxidant effects of epigallocatechin gallate (EGCG and alpha lipoic acid (ALA have been demonstrated in previous studies. The kidney protection effects of EGCG and ALA in patients with kidney injury are still under investigation. The purpose of this study is to investigate the anti-inflammatory and anti-oxidant effects of EGCG and ALA on high glucose-induced human kidney cell damage. EGCG inhibited high glucose(HG-induced TNF-α and IL-6 production in human embryonic kidney (HEK cells. Both EGCG and ALA decreased HG-induced receptor of advanced glycation end products (RAGE mRNA and protein expressions in HEK cells. EGCG and ALA also recovered HG-inhibited superoxide dismutase production and decreased ROS expressions in HEK cells. The synergism of EGCG and ALA was also studied. The effect of EGCG combined with ALA is greater than the effect of EGCG alone in all anti-inflammation and anti-oxidant experiments. Our studies provide a potential therapeutic application of EGCG and ALA in preventing progression of diabetic nephropathy.Os efeitos antioxidantes de galato de epigalocatequina (EGCG e ácido alfa lipóico (ALA foram demonstrados em estudos anteriores. Os efeitos renais da proteção de EGCG e ALA em pacientes com lesão renal ainda estão sob investigação. A finalidade deste estudo é investigar os efeitos anti-inflamatórios e antioxidantes de EGCG e ALA em lesão de células de rim humano induzida pela alta glicose. EGCG inibiu a produção de TNF-α e IL-6 induzida por HG em células de rim embrionário humano (HEK. Ambos EGCG e ALA diminuíram o mRNA do receptor de produtos finais de glicação avançada (RAGE induzida por HG e a expressão de proteínas em células HEK. EGCG e ALA também recuperaram a produção de superóxido dismutase inibida por HG e diminuíram a expressão de ROS em células HEK. O sinergismo de EGCG e ALA também foi estudado. O efeito de EGCG combinado com ALA é maior do que o efeito de EGCG sozinho

  6. The decrease in the IgG-binding capacity of intensively dry heated whey proteins is associated with intense Maillard reaction, structural changes of the proteins and formation of RAGE-ligands.

    Science.gov (United States)

    Liu, Fahui; Teodorowicz, Małgorzata; van Boekel, Martinus A J S; Wichers, Harry J; Hettinga, Kasper A

    2016-01-01

    Heat treatment is the most common way of milk processing, inducing structural changes as well as chemical modifications in milk proteins. These modifications influence the immune-reactivity and allergenicity of milk proteins. This study shows the influence of dry heating on the solubility, particle size, loss of accessible thiol and amino groups, degree of Maillard reaction, IgG-binding capacity and binding to the receptor for advanced glycation end products (RAGE) of thermally treated and glycated whey proteins. A mixture of whey proteins and lactose was dry heated at 130 °C up to 20 min to mimic the baking process in two different water activities, 0.23 to mimic the heating in the dry state and 0.59 for the semi-dry state. The dry heating was accompanied by a loss of soluble proteins and an increase in the size of dissolved aggregates. Most of the Maillard reaction sites were found to be located in the reported conformational epitope area on whey proteins. Therefore the structural changes, including exposure of the SH group, SH-SS exchange, covalent cross-links and the loss of available lysine, subsequently resulted in a decreased IgG-binding capacity (up to 33%). The binding of glycation products to RAGE increased with the heating time, which was correlated with the stage of the Maillard reaction and the decrease in the IgG-binding capacity. The RAGE-binding capacity was higher in samples with a lower water activity (0.23). These results indicate that the intensive dry heating of whey proteins as it occurs during baking may be of importance to the immunological properties of allergens in cow's milk, both due to chemical modifications of the allergens and formation of AGEs. PMID:26524422

  7. 1,25-Dihydroxyvitamin D3 regulates expression of LRP1 and RAGE in vitro and in vivo, enhancing Aβ1-40 brain-to-blood efflux and peripheral uptake transport.

    Science.gov (United States)

    Guo, Y-X; He, L-Y; Zhang, M; Wang, F; Liu, F; Peng, W-X

    2016-05-13

    Alzheimer's disease (AD) is characterized by the accumulation and deposition of plaques of amyloid-β (Aβ) peptide in the brain. Growing epidemiological and experimental studies have shown that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) exerts neuroprotection against AD. However, the underlying mechanisms of the action remain unclear. Since Aβ clearance plays a crucial role in Aβ balance in the brain, the aim of the present study was to investigate potential effects of 1,25(OH)2D3 on Aβ1-40, the major soluble oligomeric form of Aβ, clearance via transport across blood-brain barrier (BBB) mediated by low-density lipoprotein receptor-related protein 1 (LRP1) (efflux) and receptor for advanced glycation end products (RAGE) (influx) and peripheral uptake by liver mediated by LRP1. We identified colocalization of LRP1 and RAGE at BBB of mice, established an in vitro BBB model by culturing monolayer mouse brain microvascular endothelial cell line (bEnd.3) cells under hypoxia and observed that 1,25(OH)2D3 treatment enhanced Aβ1-40 efflux across the BBB model and uptake by HepG2 cells. After 1,25(OH)2D3 exposure, LRP1 expression was increased significantly both in vivo and in vitro, and RAGE expression was reduced in the in vitro BBB model but not in microvascular endothelial cells of mice hippocampus. Additionally, we explored the correlation between the corresponding effects of 1,25(OH)2D3 and its nuclear hormone receptor vitamin D receptor (VDR) level. We found that VDR expression was upregulated after 1,25(OH)2D3 treatment both in vivo and in vitro. Collectively, our finding that 1,25(OH)2D3 reduces cerebral Aβ1-40 level by increasing Aβ1-40 brain-to-blood efflux and peripheral uptake through regulating LRP1 and RAGE could shed light on the mechanism of 1,25(OH)2D3 neuroprotection against AD. And the action of 1,25(OH)2D3 might be associated with the VDR pathway. PMID:26820600

  8. 生物心理社会医学模式视角下的"路怒症"剖析%Analysis of Road Rage from the Perspective of Bio-psycho-social Medical Model

    Institute of Scientific and Technical Information of China (English)

    骞宪忠; 郑建中

    2011-01-01

    Road rage has become a serious concern in many countries, and some of scholars have conducted the studies about the relationships between driving safety, stress reacting and psychiatric diseases. We thought that it's necessary to study this phenomenon as a kind of health problems from the perspective of Bio-psycho-social medical model; integrate efforts were made to position it scientifically, to find the reasons and to give some advices to help the drivers who intend to perform road rage recover and maintain good physical and mental well-being.%随着汽车作为代步工具逐渐走人家庭,"路怒症"成了一种新的常见汽车综合征.国内外学者从交通安全、应激反应、精神疾患等方面对其作了一定研究,随着研究的深入,这一现象应置于生物心理社会医学模式视角下进行多方位剖析,对其进行科学定位、综合研究,并找出相应的对策,帮助有"路怒症"倾向的驾驶人恢复良好的身心健康状态.

  9. Repérages bibliographiques

    OpenAIRE

    Mommolin, Sabrina

    2016-01-01

    Développement durable – Sustainable development APAK S., ATAY E. (2015), “Global Competitiveness in the EU through Green Innovation Technologies and Knowledge Production”, Procedia - Social and Behavioral Sciences, vol. 181, pp. 207-217. BORSDORF A., BENDER O., BRAUN F., HALLER A. (2015), Web-based instruments for strengthening sustainable regional development in the Alps, Geografski Zbornik / Acta Geographica Slovenica, vol. 55, N° 1, pp. 174-182. SIRSIKAR S.V., KAREMORE P. (2015), Design an...

  10. Repérages bibliographiques

    Directory of Open Access Journals (Sweden)

    Sabrina Mommolin

    2013-04-01

    Full Text Available Gouvernance – Governance AYANSO A., CHATTERJEE D., CHO D. I. (2011, “E-Government readiness index: A methodology and analysis”, Government Information Quarterly, vol. 28, n° 4, pp. 522-532. CHEN Y.-C., CHU P.-Y. (2011, Electronic Governance and Cross-Boundary Collaboration: Innovations and Advancing Tools, Hershey, PA: IGI Global, 422 p. ISBN: 9781609607548 CONCHA G., ASTUDILLO H., PORRÚA M. (et al. (2011, “E-Government procurement observatory, maturity model and early measurements”, Gove...

  11. Repérages bibliographiques

    OpenAIRE

    Mommolin, Sabrina

    2015-01-01

    Commerce électronique - E-commerce AYDIN, E., SAVRUL, B. K. (2014), "The Relationship between Globalization and E-commerce: Turkish Case", Procedia - Social and Behavioral Sciences, vol. 150, pp. 1267-1276. BASTARD, I., BOURREAU, M., MOREAU, F. (2014), "L’impact du piratage sur l’achat et le téléchargement légal: Une comparaison de quatre filières culturelles", Revue économique, vol. 65, n°3, pp. 573-599. FEIZOLLAHI, S., SHIRMOHAMMADI, A., KAHREH, Z. S., et al. (2014), "Investigation the Effe...

  12. Repérages bibliographiques

    OpenAIRE

    Mommolin, Sabrina

    2015-01-01

    Commerce électronique - E-commerce BURKHALTER J. N., WOOD N. T., (Eds.) (2015), Maximizing Commerce and Marketing Strategies through Micro-Blogging, Hershey, PA, USA: IGI Global. 354 p. ISBN: 978-1-4666-8408-9 KHOSROW-POUR M. (Ed.) (2015), Strategic E-Commerce Systems and Tools for Competing in the Digital Marketplace, Hershey, PA, USA: IGI Global, 263 p. ISBN: 978-1-4666-8133-0 LTIFI M., GHARBI J. (2015), « Impact de la qualité perçue du site web marchand sur le bonheur du cyberconsommateur ...

  13. Repérages bibliographiques

    Directory of Open Access Journals (Sweden)

    Sabrina Mommolin

    2016-05-01

    Full Text Available Développement durable – Sustainable development APAK S., ATAY E. (2015, “Global Competitiveness in the EU through Green Innovation Technologies and Knowledge Production”, Procedia - Social and Behavioral Sciences, vol. 181, pp. 207-217. BORSDORF A., BENDER O., BRAUN F., HALLER A. (2015, Web-based instruments for strengthening sustainable regional development in the Alps, Geografski Zbornik / Acta Geographica Slovenica, vol. 55, N° 1, pp. 174-182. SIRSIKAR S.V., KAREMORE P. (2015, Design an...

  14. Repérages bibliographiques

    Directory of Open Access Journals (Sweden)

    Sabrina Mommolin

    2015-10-01

    Full Text Available Commerce électronique - E-commerce AYDIN, E., SAVRUL, B. K. (2014, "The Relationship between Globalization and E-commerce: Turkish Case", Procedia - Social and Behavioral Sciences, vol. 150, pp. 1267-1276. BASTARD, I., BOURREAU, M., MOREAU, F. (2014, "L’impact du piratage sur l’achat et le téléchargement légal: Une comparaison de quatre filières culturelles", Revue économique, vol. 65, n°3, pp. 573-599. FEIZOLLAHI, S., SHIRMOHAMMADI, A., KAHREH, Z. S., et al. (2014, "Investigation the Effe...

  15. Potential of birds to serve as a pathology-free model of type 2 diabetes, Part 1: Is the apparent absence of the rage gene a factor in the resistance of avian organisms to chronic hyperglycemia?

    Science.gov (United States)

    Szwergold, Benjamin S; Miller, Craig B

    2014-02-01

    Diabetes mellitus is a global pandemic that accounts for ever-increasing rates of morbidity and mortality and consumes a growing share of national health care budgets. In spite of concerted efforts, a solution to this problem has not yet been found. One reason for this situation is lack of good animal models. Such models have been used successfully in many areas of biomedical research, but they have proven less than satisfactory in studies on diabetic complications. In this article, we propose to supplement traditional animal models of diabetes that use longitudinal, prospective studies of sick animals (mammals) with retrospective/comparative investigations of healthy animals (birds). Avians are promising models for such studies because they live healthy lives with chronic hyperglycemia that would be fatal to humans. We outline the advantages of the new perspective and show how, by implementing this approach, we observed that birds appear to be missing an important gene linked to diabetic complications. The protein encoded by this gene is a receptor for advanced glycation end products (RAGEs). Although the absence of RAGEs from birds has yet to be confirmed at the protein level, other differences between humans and birds may also be important in accounting for the ability of birds to live with chronic hyperglycemia. Two such additional such characteristics are currently being explored, and it is probable that more will emerge in time. We believe that the proposed perspective may improve the understanding of diabetes mellitus and may help in developing new means for controlling and preventing diabetic complications. PMID:24313337

  16. 白藜芦醇改善糖尿病血管炎症反应及其与RAGE信号的相关性%Resveratrol protecting the aorta against inflammation reaction associated with RAGE signal in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    刘涛; 巩增锋; 尹洁; 景玉宏

    2012-01-01

    Objective To study the protective effect and underlying mechanism of resveratrol treatment on vasculature injury in diabetic rats. Methods Diabetic animal models were established by single injection of STZ(40 mg/kg) through femoral vein together with high fat diet. Blood fructosamine was measured by using reaction of enzyme-substrate for four months. Lipid plaques were tested by using Oil red staining in intact aorta. Levels of TNF-α and 1L-6 in aorta tissue were analyzed by using semi-quantitative RT-PCR technique. Also, expression of RAGE in aorta was tested by Western blot method. Results Resveratrol treatment attenuated the amount of blood fructosamine, suppressed the expression of TNF-α and IL-6, and decreased the expression of RAGE in aorta as well as ameliorated the deposition of lipid plaques in inner wall of aorta in diabetic rats. Conclusion Resveratrol treatment can protect the vasculature injured by diabetes. This protective effect may relate with its functions in attenuation of accumulation of advanced glycation end product, inhibition of the RAGE signal, amelioration of the vasculature inflammatory reaction, and reduction of deposition of lipid plaques in diabetic rats.%目的 在糖尿病动物模型上研究白藜芦醇(RSV)对糖尿病血管损伤的保护效应及可能机制. 方法 STZ单次低剂量(40 mg/kg)经股静脉注射,联合高脂饮食,建立糖尿病模型.利用酶底物分析技术检测血液中糖化血清蛋白的含量,在整体主动脉组织上利用Oil Red检测血管内壁脂肪斑块沉积.利用半定量RT-PCR技术检测主动脉组织中TNF-α及IL-6的水平.利用Western blotting技术检测主动脉组织中RAGE表达水平. 结果 RSV持续给药可以减轻糖尿病大鼠血液中糖化血清蛋白的含量,抑制主动脉组织中TNF-α及IL-6的水平,同时抑制RAGE的高表达.RSV也显著减少了糖尿病所致的主动脉内壁脂肪斑块沉积. 结论 RSV可以保护糖尿病导致的血管损伤,这

  17. Relationship between the advanced glycation end products content and expressions of RAGE,ICAM-1 in vascular tissue of diabetic rats%糖尿病大鼠血管糖基化终产物含量与其受体和ICAM-1表达的关系

    Institute of Scientific and Technical Information of China (English)

    张建伟; 孙仁宇

    2001-01-01

    In this study,the relationship between the advanced glycation end products(AGEs) and the expressions of receptor for AGEs(RAGE),intercellular cell adhesion molecule-1(ICAM-1) was investigated.The diabetic rat model was reconstructed and the fluorescence method,RT-PCR and in-situ hybridization techniques were used to detect AGEs content and the expressions of RAGE and ICAM-1 gene in the aorta and cardiac tissues.The results showed that AGEs content in aortic and cardiac tissues increased(P<0.01) in diabetic rats; The expressions of RAGE and ICAM-1 enhanced (P<0.05~0.01) and were positively correlated with the quantity of AGEs accumulation(P<0.01) in the aorta and cardiac tissue.These parameters change in the diabetic rats can be improved with aminoglumine(AG) treatment.Suggesting that AGEs might induce RAGE and ICAM-1 expression.It's postulated that AGEs binding to RAGE play an important role to result in diabetic endothelial cells dysfunction and lesion.%探讨糖尿病大鼠血管组织糖基化终产物(AGEs)含量与其受体(RAGE)和细胞间粘附因子-1(ICAM-1)表达的关系。复制糖尿病大鼠模型,采用荧光法、RT-PCR及原位杂交方法检测主动脉及心肌组织的AGEs含量以及RAGE和ICAM-1基因的表达。发现糖尿病大鼠主动脉和心肌组织AGEs含量升高(P<0.01);RAGE和ICAM-1基因表达增强(P<0.05~0.01);AGEs含量与RAGE及ICAM-1呈明显正相关(P<0.01);氨基胍治疗可缓解上述指标的变化。提示AGEs可诱导RAGE和ICAM-1的表达。推测AGEs -RAGE相互作用是引起糖尿病血管内皮细胞功能紊乱和损伤的关键环节。

  18. 2型糖尿病患者糖耐量正常的一级亲属血浆sRAGE水平及相关因素的分析%Study of the plasma level of sRAGE and other related factors in first-degree relatives with normal glucose tolerance of Type 2 Diabetes

    Institute of Scientific and Technical Information of China (English)

    康乐; 王静; 王霞; 张娜; 任建民

    2012-01-01

    目的 探讨2型糖尿病患者糖耐量正常的一级亲属血浆sRAGE水平及其与各代谢性疾病危险因素之间的相关性.方法 应用酶联免疫法测定51例2型糖尿病糖耐量正常一级亲属及48例正常对照者血浆sRAGE水平,测量腰围(WC)、臀围(WC)、体质量、收缩压(SBP)、舒张压(DBP),并检测甘油三酯(TG)、胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、空腹胰岛素(FINS),计算腰臀比(WHR)、体质量指数[ BMI=体质量(kg)/身高(m2)]和胰岛素抵抗指数[HOMA-IR=(FBG×FINS)/22.5]等相关指标,运用两样本t检验比较两组人群上述指标间的差异,运用Pearson相关分析和多元线性逐步回归分析观察组血浆sRAGE水平同SBP、DBP、WC、HC、BMI、TG、TC、HDL-C、LDL-C、HOMA-IR之间的关系,探索观察组人群特点.以BMI=25为切点,将观察组分为体质量指数正常组和超重肥胖组,并对血浆sRAGE水平进行比较,进一步验证BMI与sRAGE的关系.结果 与对照组相比,观察组TG、FINS、HOMA-IR水平显著升高(P<0.05),HDL-C、sRAGE水平明显降低(P<0.05);血浆sRAGE水平与BMI、WC、HC、WHR、FBG呈明显负相关(P<0.05);BMI是血浆sRAGE的独立相关因素(复相关系数R2=0.145).超重肥胖组的sRAGE水平明显低于体质量指数正常组(P<0.05).结论 2型糖尿病患者糖耐量正常一级亲属血浆sRAGE水平较正常人群降低,BMI的升高是其下降的独立危险因素.%objective To investigate the association between plasma levels of the soluble form of RAGE ( sRAGE) and cardiometabolic risk factors in first-degree relatives of Type 2 Diabetes with normal glucose tolerance. Methods Plasma levels of sRAGE were detected by ELISA in 51 first-degree relatives of type 2 diabetes patients with normal glucose tolerance and 48 normal controls. The WC, HC, body mass, SBP and DBP were measured. In addition, other clinical indexes,including TG, TC, HDL-C, LDL-C, and FINS

  19. 银杏叶提取物、α-硫辛酸对糖尿病大鼠肾组织中糖基化终产物及其受体RAGE表达的影响%Extract of Ginkgo biloba and α-lipoic Acid Attenuate Advanced Glycation End Products Accumulation and RAGE Expression in Diabetic Nephropathy Rats

    Institute of Scientific and Technical Information of China (English)

    李雪竹; 严海东; 王俊; 江薇

    2011-01-01

    Objective To investigate the accumulation of advanced glycation end products (AGEs) and expression of receptor for AGEs (RAGE) in streptozocin (STZ)-induced diabetic nephropathy in rats, and the role of antioxidants on the AGEs-RAGE signaling.Methods Diabetic rats were induced by once intraperitoneal injection of STZ at the dose of 60 mg/kg, and randomly divided into the DN group (n=12, treated with normal saline by intraperitoneal injection, once daily), the extract of Ginkgo biloba (EGb) group ( n =14, treated with EGb 300 mg/kg by oral administration, once every other day), and the α-lipoic add (ALA) group ( n =12, treated with ALA at the dose of 35 mg/kg by intraperitoneal injection, once every other day).Rats of the normal control group (n=10) were given vehicle dtrate buffer at the dose of 60 mg/kg.Rats were sacrificed at the 12th week and the 20th week of this study.The four groups were compared in terms of body weight, blood glucose, renal function, 24-h urine protein.Renal pathological changes were observed by PAS staining.Oxidative stress indices were detected using spectrophotometry.The concentrations of AGEs were measured using fluorospectrophotometry, and the expressions of RAGE were detected by Real-time PCR and Western blot.Results Compared with the normal control group, the 24-h urine protein quantitation was higher and the glomerular filtration rate increased in rats at the 12th week and the 20th week.The pathological tissue staining showed dilated glomerular mesangium, proliferated glomerular matrix, vacuolar degeneration of the renal tubular epithelium.Malonaldehyde (MDA) levels and 8-hydroxide radical guanine deoxyriboside (8-OHdG) levels increased, and catalase (CAT) and reduced glutathione hormone (GSH) levels decreased.The AGEs contents in serum and renal tissue homogenate increased.The expressions of RAGE mRNA and protein increased in the DN group at the 12th and the 20th week.The 24-h udne protein quantitation was reduced in the EGb group

  20. PTW modeling in xRage

    Energy Technology Data Exchange (ETDEWEB)

    Long, Christopher Curtis [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Rauenzahn, Rick M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-05-01

    Preston-Tonks-Wallace Model (PTW), is a viscoplastic material model for very high strain rates (~1011/s) and uses a Voce work hardening model. Strain rates above 109/s uses Wallace’s model of overdriven shocks in metals. PTW is applicable for broad range of strain rates (10-3) -1012).

  1. GHB acid: A rage or reprive

    Directory of Open Access Journals (Sweden)

    Prakhar Kapoor

    2013-01-01

    Full Text Available Gamma-hydroxybutyric acid (GHB is a naturally occurring analog of gamma-aminobutyric acid (GABA that has been used in research and clinical medicine for many years. GHB was used clinically as an anesthetic in the 1960s but was withdrawn due to side effects that included seizures and coma. GHB has been implicated in a number of crime types; most notably in drug-facilitated sexual assault. GHB is abused by three main groups of users: Body builders who use the substance believing that it stimulated the release of growth hormone; sexual predators who covertly administer the drug for its sedative and amnesic effects and club-goers (rave parties who take the drug for its euphoric effects. The short-lived hypnotic effects, relative safety and widespread availability of the drug have made it particularly well suited to this role. The drug has an addictive potential if used for long term. The primary effects of GHB use are those of a CNS depressant and therefore range from relaxation, to euphoria, confusion, amnesia, hallucinations, and coma. Despite the increased regulation, GHB remains widely available through the Internet where one can easily purchase the necessary reagents as well as recipes for home production. There are reports of patients being unresponsive to painful stimuli and cases of oral self-mutilations linked to the abuse of GHB, though quiet rare. Such cases should remind odontologists that intra-oral lesions may be the result of self-mutilation either due to mental illness or altered states caused by the use of prescription or non-prescription drugs.

  2. RAGE阻断剂FPS-ZM1对糖基化终末产物所致大鼠脑部炎症反应的影响及机制%Effects of RAGE inhibitor FPS-ZM1 on inflammatory reaction in the brain of rats induced by advanced glycation end products

    Institute of Scientific and Technical Information of China (English)

    孙梦晗; 洪艳; 候训尧; 马莹娟; 申超; 罗鼎真; 刘雪平

    2014-01-01

    目的:探讨RAGE受体特异性阻断剂FPS-ZM1对糖基化终末产物( AGEs)所致大鼠脑部炎症反应及认知功能的影响。方法将40只大鼠随机分为四组:生理盐水组( NC组) FPS-ZM1对照组、AGEs组和FPS-ZM1组,采用脑立体定位技术,向AGEs组及FPS-ZM1组大鼠两侧海马注射AGEs 5μl,以制造动物损伤模型,用同样方法向 NC组及 FPS-ZM1对照组注射等量生理盐水,以制造模型对照;造模前1 w以1 mg · kg-1· d-1 FPS-ZM1向FPS-ZM1组和FPS-ZM1对照组大鼠进行腹腔注射,并连续4 w给药,AGEs组、NC组则同时注射相同体积生理盐水,造模3 w后对各组大鼠进行Morris水迷宫实验,检测各组大鼠逃逸潜伏期( EL);用 Elisa 检测各组大鼠海马区 Aβ1~40, Aβ1~42的水平;用 Western 印迹检测各组大鼠RAGE,p-NF-κB和肿瘤坏死因子( TNF)-α蛋白的表达;用免疫组织化学法检测各组大鼠海马区TNF-α蛋白的表达强度。结果 AGEs组与其他各组相比,EL显著延长(P<0.01),且 Aβ1~40、Aβ1~42浓度均显著升高(P<0.01);同时 AGEs 组 RAGE、p-NF-κB 和 TNF-α的蛋白表达明显增强(P<0.01);FPS-ZM1干预后上述各指标均明显低于AGEs组。结论 FPS-ZM1作为RAGE受体特异性阻断剂,能作用中枢系统减少Aβ1~40,生成从而提高AGEs脑损伤大鼠的智能,并通过抑制脑组织 p-NF-κB上调,减轻脑AGEs损伤引起的炎性反应。该药因能透过血脑屏障有望成为抑制阿尔茨海默样病变的有效措施。%Objective To explore the effects of RAGE inhibitor FPS-ZM1 on inhibiting inflammatory reaction in the brain of rats and cognition induced by advanced glycation end products.Methods Fourty Wistar rats were randomly divided into normal control ( NC) , FPS-ZM1 control , AGEs and FPS-ZM1 groups.By brain stereotactic techniques , the bilateral hippocampus of rats in AGEs group and FPS-ZM1 group were injected

  3. Engineering of blood vessel patterns by angio-morphogens [angiotropins]: non-mitogenic copper-ribonucleoprotein cytokins [CuRNP ribokines] with their metalloregulated constituents of RAGE-binding S100-EF-hand proteins and extracellular RNA bioaptamers in vascular remodeling of tissue and angiogenesis in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Wissler, J.H. [ARCONS Applied Research, Bad Nauheim (Germany)

    2001-12-01

    Tissue vascularization is requisite to successful cell-based therapies, biomaterial design and implant integration. Thus, known problems in ossointegration of avascular implants in connection with the generation of bone tissue reflect arrays of general problems of socio-economic relevance existing in reparative medicine still waiting for to be solved. For this purpose, morphogenesis and remodeling of endothelial angio-architectures in tissue and in vitro by isolated non-mitogenic angio-morphogens [angiotropins] are considered in terms of their structure, function and action mechanisms. Extracellular angiotropins are secreted by activated leukocytes/monocytes/macrophages. They are a family of cytokines with morphogen bioactivity selectively directed to endothelial cells. Their structure was deciphered as metalloregulated copper-ribonucleoproteins [CuRNP ribokines]. They are built up of angiotropin-related S100-EF-hand protein [ARP] and highly modified and edited 5'end-phosphorylated RNA [ARNA], complexed together by copper ions. Oxidant-sensitive ARNA and their precursors represent novel types in a RNA world: They are the first isolated and sequenced forms of extracellular RNA [eRNA], may act as cytokine and bioaptamer, contain isoguanosine [crotonoside] as modified nucleoside and show up copper as RNA-structuring transition metal ion. By metalloregulated bioaptamer functions, ARNA impart novel biofunctions to RAGE-binding S100-EF-hand proteins. Angiotropin morphogens were shown suitable for neointiation and remodeling of blood vessel patterns in different, adult, embryonal and artificial tissues. These neovascular patterns manifest regulated hemodynamics for preventing tissue necrosis, supporting tissue functions and promoting wound healing. As evaluated in skin and muscle vascularization, the neovascular patterns are integrated into homeostatic control mechanisms of tissue. Thus, the morphogens show up beneficial perspectives and are suggested useful tools

  4. Sweden: glimmer of hope for gas as nuclear debate rages

    International Nuclear Information System (INIS)

    The small market for gas in Sweden and Norway due to the use of hydroelectric power is discussed. The phasing out of nuclear power in Sweden, the broadening of the ownership of Swede-Gas, and the potential use of gas in energy efficient combined heat and power plants are highlighted. The difficult situation for Denmark's natural gas industry with the falling oil prices, and Finland's natural gas imports are considered. (UK)

  5. Rages and refusals. Managing the many faces of adolescent anxiety.

    OpenAIRE

    2001-01-01

    OBJECTIVE: To provide family physicians with a practical approach to recognition, assessment, and treatment of adolescent anxiety disorders complicated by avoidance or oppositional behaviour. QUALITY OF EVIDENCE: Current literature was searched via MEDLINE using the MeSH headings Anxiety and Anxiety Disorders, focusing on epidemiology, clinical presentations in adolescence, and both pharmacologic and nonpharmacologic treatment. In addition, internationally accepted diagnostic criteria, curren...

  6. From Rage to Rap and Prison to Print:

    Directory of Open Access Journals (Sweden)

    Josephine Metcalf

    2009-11-01

    Full Text Available 1. IntroductionBy the late 1980s, while thousands of former gang members were either dead or incarcerated, their legacy and the gang subculture was being celebrated and commodified through gangsta rap music and videos, film and fashion. In the early 1990s this lucrative cultural trend sparked interest from potential authors and publishers. Such literary attention was partially fuelled by a public fascination with life in the ghettos following the 1992 Los Angeles (LA riots, resulting in a ne...

  7. Peru v. Yale: A Battle Rages over Machu Picchu

    Science.gov (United States)

    Glenn, David

    2009-01-01

    In early 1916, the legendary Yale University archaeologist Hiram Bingham III completed his third and final expedition in southern Peru. He shipped home 74 boxes of artifacts from Machu Picchu, a spectacular site in the Andes that is believed to have been the last major settlement of the Inca empire. Those boxes were supposed to be on temporary…

  8. Could Germ from Cat Poop Trigger Rage Disorder in People?

    Science.gov (United States)

    ... for toxoplasmosis. But they had similar aggression and impulsivity scores to the healthy control group. IED-diagnosed ... be treated with a combination of an antimalaria drug and antibiotics, the CDC notes. The study appears ...

  9. Between anger and resignation; Zwischen Rage und Resignation

    Energy Technology Data Exchange (ETDEWEB)

    Roepcke, I.

    2008-07-21

    Wind power in Bavaria and Baden-Wuerttemberg is overshadowed by hydroelectric power, biomass, and solar energy. Regional development plans are obstacles to the construction of new wind power systems. (orig.)

  10. New Rage on Campus: E-Commerce Degrees.

    Science.gov (United States)

    Dobbs, Kevin

    1999-01-01

    As electronic commerce expands, higher education attempts to keep up with the demand for instruction. Some universities have added a concentration in e-commerce to their master of business administration program and others are adding majors, certifications, or degrees. (JOW)

  11. From Rage to Rap and Prison to Print:

    OpenAIRE

    Josephine Metcalf

    2009-01-01

    1. IntroductionBy the late 1980s, while thousands of former gang members were either dead or incarcerated, their legacy and the gang subculture was being celebrated and commodified through gangsta rap music and videos, film and fashion. In the early 1990s this lucrative cultural trend sparked interest from potential authors and publishers. Such literary attention was partially fuelled by a public fascination with life in the ghettos following the 1992 Los Angeles (LA) riots, resulting in a ne...

  12. Induction of IFNT-Stimulated Genes by Conceptus-Derived Exosomes during the Attachment Period

    Science.gov (United States)

    Nakamura, Keigo; Kusama, Kazuya; Bai, Rulan; Sakurai, Toshihiro; Isuzugawa, Kazuto; Godkin, James D.; Suda, Yoshihito; Imakawa, Kazuhiko

    2016-01-01

    Biochemical and/or physical communication between the conceptus and the uterine endometrium is required for conceptus implantation to the maternal endometrium, leading to placentation and the establishment of pregnancy. We previously reported that in vitro co-culture system with bovine trophoblast CT-1 cells, primary uterine endometrial epithelial cells (EECs), and uterine flushings (UFs) mimics in vivo conceptus attachment process. To identify molecules in UFs responsible for this change, we first characterized protein contents of UFs from day 17 cyclic (C17) and pregnant (P17) ewes through the use of two dimensional-Polyacrylamide Gel Electrophoresis (2D-PAGE), followed by Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) analysis. These analyses identified 266 proteins specific for P17 UFs, from which 172 proteins were identified as exosomal proteins. Among 172 exosomal proteins, 8 proteins that had been identified as exosomal proteins were chosen for further analysis, including macrophage-capping protein (CAPG), aldo-keto reductase family 1, member B1 protein (AKR1B1), bcl-2-like protein 15 (BCL2L15), carbonic anhydrase 2 (CA2), isocitrate dehydrogenase 2 (IDH2), eukaryotic translation elongation factor 2 (EEF2), moesin (MSN), and ezrin (EZR). CAPG and AKR1B1 were again confirmed in P15 and P17 UFs, and more importantly CAPG and AKR1B1, mRNA and protein, were found only in P15 and P17 conceptuses. Moreover, exosomes were isolated from C15, C17, P15, or P17 UFs. Only P15 and P17 exosomes, originated from the conceptus, contained interferon tau (IFNT) as well as CAPG and AKR1B1, and up-regulated STAT1, STAT2, MX1, MX2, BST2, and ISG15 transcripts in EECs. These observations indicate that in addition to endometrial derived exosomes previously described, conceptus-derived exosomes are present in UFs and could function to modify endometrial response. These results suggest that exosomes secreted from conceptuses as well as endometria are involved in cell to

  13. Paper de les Aldo-Ceto reductases en el metabolisme de retinoides: estudi funcional i estructural de l'AKR1B10

    OpenAIRE

    Gallego Moli, Oriol

    2006-01-01

    Per primer cop, el nostre grup va identificar un enzim de la superfamilia de les aldo-ceto reductases (AKR) actiu amb retinoides. Atès que l'AKR1B12 presenta una identitat seqüencial pròxima al 70% amb l'AKR1B1 i l'AKR1B10 humanes, es va decidir ampliar l'estudi de l'activitat retinoide oxidoreductasa entre les AKR. En la present Tesi Doctoral, hem aprofundit en l'estudi de l'activitat retinal reductasa de membres de la superfamilia de les aldo-ceto reductases (AKR). El treball es va iniciar ...

  14. Induction of IFNT-Stimulated Genes by Conceptus-Derived Exosomes during the Attachment Period.

    Science.gov (United States)

    Nakamura, Keigo; Kusama, Kazuya; Bai, Rulan; Sakurai, Toshihiro; Isuzugawa, Kazuto; Godkin, James D; Suda, Yoshihito; Imakawa, Kazuhiko

    2016-01-01

    Biochemical and/or physical communication between the conceptus and the uterine endometrium is required for conceptus implantation to the maternal endometrium, leading to placentation and the establishment of pregnancy. We previously reported that in vitro co-culture system with bovine trophoblast CT-1 cells, primary uterine endometrial epithelial cells (EECs), and uterine flushings (UFs) mimics in vivo conceptus attachment process. To identify molecules in UFs responsible for this change, we first characterized protein contents of UFs from day 17 cyclic (C17) and pregnant (P17) ewes through the use of two dimensional-Polyacrylamide Gel Electrophoresis (2D-PAGE), followed by Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) analysis. These analyses identified 266 proteins specific for P17 UFs, from which 172 proteins were identified as exosomal proteins. Among 172 exosomal proteins, 8 proteins that had been identified as exosomal proteins were chosen for further analysis, including macrophage-capping protein (CAPG), aldo-keto reductase family 1, member B1 protein (AKR1B1), bcl-2-like protein 15 (BCL2L15), carbonic anhydrase 2 (CA2), isocitrate dehydrogenase 2 (IDH2), eukaryotic translation elongation factor 2 (EEF2), moesin (MSN), and ezrin (EZR). CAPG and AKR1B1 were again confirmed in P15 and P17 UFs, and more importantly CAPG and AKR1B1, mRNA and protein, were found only in P15 and P17 conceptuses. Moreover, exosomes were isolated from C15, C17, P15, or P17 UFs. Only P15 and P17 exosomes, originated from the conceptus, contained interferon tau (IFNT) as well as CAPG and AKR1B1, and up-regulated STAT1, STAT2, MX1, MX2, BST2, and ISG15 transcripts in EECs. These observations indicate that in addition to endometrial derived exosomes previously described, conceptus-derived exosomes are present in UFs and could function to modify endometrial response. These results suggest that exosomes secreted from conceptuses as well as endometria are involved in cell to

  15. Genetics of diabetes complications.

    Science.gov (United States)

    Alkayyali, Sami; Lyssenko, Valeriya

    2014-10-01

    Chronic hyperglycemia and duration of diabetes are the major risk factors associated with development of micro- and macrovascular complications of diabetes. Although it is believed that hyperglycemia induces damage to the particular cell subtypes, e.g., mesangial cells in the renal glomerulus, capillary endothelial cells in the retina, and neurons and Schwann cells in peripheral nerves, the exact mechanisms underlying these damaging defects are not yet well understood. Clustering of micro- and macrovascular complications in families of patients with diabetes suggests a strong genetic susceptibility. However, until now only a handful number of genetic variants were reported to be associated with either nephropathy (ACE, ELMO1, FRMD3, and AKR1B1) or retinopathy (VEGF, AKR1B1, and EPO), and only a few studies were carried out for genetic susceptibility to cardiovascular diseases (ADIPOQ, GLUL) in patients with diabetes. It is, therefore, obvious that the accumulation of more data from larger studies and better phenotypically characterized cohorts is needed to facilitate genetic discoveries and unravel novel insights into the pathogenesis of diabetic complications. PMID:25169573

  16. Tendency to Aggressive Driving and Road Rage : Identifying Drivers Prone to Aggressive Driving and Road Rage in Motor Vehicle Traffic in Sweden

    OpenAIRE

    Teräsvirta, Jukka

    2011-01-01

    In the present study possible associations between driver characteristics and aggressive driving were examined. 210 participants responded to a questionnaire consisting of self-report measures of emotion regulation ability, personality traits, and attitudes towards traffic behaviours in a Swedish translation of the Propensity for Angry Driving Scale (PADS). The main results showed that females, older age, agreeableness, openness, and social desirability were negatively correlated with angry d...

  17. Misplaced Populist Rage: Congressional Missteps With Executive Compensation Limitations In The Bailout Legislation

    Directory of Open Access Journals (Sweden)

    Joseph Filloy

    2009-04-01

    Full Text Available Starting in the summer of 2008, the United States and most other economies of the world began to feel the effects of the subprime mortgage crisis. In response, the federal government enacted The Emergency Economic Stabilization Act of 2008 (EESA and The American Recovery and Reinvestment Act of 2009 (ARRA to help restore stability to the U.S. economy. Ultimately this legislation, commonly referred to as “the bailout bill(s,” would result in substantial outlays of taxpayer money to financial institutions deemed systemically significant, or “too big to fail.”

  18. RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA

    OpenAIRE

    Sirois, Cherilyn M.; Jin, Tengchuan; Miller, Allison L.; Bertheloot, Damien; Nakamura, Hirotaka; Horvath, Gabor L.; Mian, Abubakar; Jiang, Jiansheng; Schrum, Jacob; Bossaller, Lukas; Pelka, Karin; Garbi, Natalio; Brewah, Yambasu; Tian, Jane; Chang, ChewShun

    2013-01-01

    Recognition of DNA and RNA molecules derived from pathogens or self-antigen is one way the mammalian immune system senses infection and tissue damage. Activation of immune signaling receptors by nucleic acids is controlled by limiting the access of DNA and RNA to intracellular receptors, but the mechanisms by which endosome-resident receptors encounter nucleic acids from the extracellular space are largely undefined. In this study, we show that the receptor for advanced glycation end-products...

  19. MicroRNA in radiotherapy: miRage or miRador?

    Science.gov (United States)

    Korpela, E; Vesprini, D; Liu, S K

    2015-03-01

    At least half of all cancer patients will receive radiation therapy. Tumour radioresistance, or the failure to control certain tumours with this treatment, can result in locoregional recurrence; thus there is great interest in understanding the underlying biology and developing strategies to overcome this problem. The expanding investigation of microRNA in cancer suggests that these regulatory factors can influence the DNA damage response, the microenvironment and survival pathways, among other processes, and thereby may affect tumour radioresistance. As microRNA are readily detectable in tumours and biofluids, they hold promise as predictive biomarkers for therapy response and prognosis. This review highlights the current insights on the major ways that microRNA may contribute to tumour radiation response and whether their levels reflect treatment success. We conclude by applying the potential framework of future roles of miR in personalised radiotherapy using prostate cancer clinical management as an example. PMID:25611301

  20. The Wellcome Prize Lecture. Genetic imprinting: the battle of the sexes rages on.

    Science.gov (United States)

    Reik, W

    1996-03-01

    Genomic imprinting in mammals is an important genetic mechanism by which genes are expressed or repressed depending on which parent they have been inherited from. Some properties of the imprinting mechanism are already established; notably, some of the effects of imprinting on mammalian development can be explained by the phenotypic effects of a number of specific imprinted genes, which include major fetal growth factors. An evolutionary explanation of imprinting has also been suggested. Some of the molecular mechanisms of imprinting are known, and these include the modification of DNA and chromosomes in the form of DNA methylation and possibly heritable chromatin structures. Loss of imprinting or altered imprinting is implicated in a large number of genetic diseases and cancers. Many important issues remain to be resolved; these include the precise molecular mechanisms and, in particular, the nature of the primary imprints that are inherited from the parental gametes, and the genes that control the imprinting process. Isolation of the majority of imprinted genes and the elucidation of their phenotypic effects and physiology are major goals for the future. These studies will provide important insights into human genetics, and will connect evolutionary understanding with physiology, genetic disease and human behaviour. PMID:8845132

  1. Rage amongst the machines: A biological approach to reducing spatial interference in multi-robot systems

    OpenAIRE

    Zuluaga, Mauricio

    2005-01-01

    Interference is a common problem for animals, and can be characterized as a competition for different types of resources such as food, mates or territory. In the case of multi-robot systems, similar problems arise. Many species have evolved aggressive displays as a more efficient alternative to physical combat to solve conflicts over resources. This thesis considers a transportation task in which a team of robots with no centralized control frequently interfere with each other. This thesis de...

  2. Characterization of tomato germplasm through seeds through rage protein profiling by sds-page

    International Nuclear Information System (INIS)

    The 24 tomato genotypes, including 5 hybrids (Avinash-II, CKD-1092, CKD-1093, CKD-1695, CKD-1088), seven germplasm lines (07039, 09091, 27-07, 42-07, 07011, 09076, 09078) and twelve cultivars (Excellence, Nagina, Naqeeb, Advanta-1202, PTM-1431, Pakit, Rio Grande, Lyp-1, Roma, Continental, VCT-I, Peto-86), were analyzed by SDS-PAGE for total soluble seed storage proteins on 10% gels. A low level of variability was observed in protein profiles of tomato genotypes. Dendrogram based on electrophoretic data clustered the 24 genotypes in four major groups. All germplasm lines illustrated identical profiles, therefore could not be differentiated on the basis of seed storage protein profiles. However, among tomato cultivars, VCT-l found to be the most divergent and could be distinguished from others on the basis of two peptides i.e. 58 kDa and 15 kDa. Similarly, in case of hybrids, a peptide of 58 kDa was absent in Avinash while present in all other hybrids. Another peptide of 64 kDa was unique to Avinash and absent in all other hybrids. Therefore, among hybrids, Avinash can be distinguished from others based on these peptide differences. Uniprot and NCBI protein databases were searched for already reported and characterized seed storage proteins in tomato. Among 42 resolved peptides, eleven could be identified from databases. On the basis of molecular weight similarity, identified peptides were SSP-83 as Alkaline alpha-galactosidase, SSP-78 as BiP, SSP-66 as vicilin, SSP-64 as DELLA Protein, SSP-58 as SNF1, SSP-41 as SNF4, SSP-36 as putative galactinol synthase 1, SSP-33 as Xyloglucan endotransg-lycosylases, SSP-26 as expansin family, SSP-10 as Putative vicilin and SSP-8 as albumin protein. In conclusion, seed storage profiling by SDS-PAGE can economically be used to asses the genetic variation in different tomato genotypes. (author)

  3. Rage from within the Machine: Protest Music, Social Justice, and Educational Reform, a Collective Case Study

    Science.gov (United States)

    Giancola, John A., Jr.

    2009-01-01

    School reform initiatives in the United States have been occurring since the launching of Sputnik by the U.S.S.R. in 1957. These efforts have largely been internal, within school reforms, with little consideration given to external variables such as poverty that affect student achievement. Given the pervasive link between poverty and student…

  4. RAGE and activation of chondrocytes and fibroblast-like synoviocytes in joint diseases

    NARCIS (Netherlands)

    Steenvoorden, Marjan Maria Claziena

    2007-01-01

    This dissertation describes a new model in which cartilage degradation can be studied. New cartilage is formed by bovine chondrocytes obtained from the slaughterhouse and cocultured with synovial cells from rheumatoid arthritis (RA) patients to study the interaction between the chondrocytes and syno

  5. Energy efficiency - The struggle for load management is raging. The French Riviera redoubles savings

    International Nuclear Information System (INIS)

    A first article discusses the debate initiated by a decree on load management associated with the French Brottes law on energy. Load management is the possibility for consumers to reduce their consumption at peak hours. Electricity producers and suppliers are of course against, whereas new actors (load managers or aggregators) are for. The issue is then to determine who will pay this managed (and not consumed) energy. The article also evokes a controversy about the Brottes law which creates a bonus to subsidy load management, and comments the development of this load management market and its legal framework. A second article describes actions undertaken by industries of the French Riviera to manage their energy consumption

  6. Heeding the Signs: Without Help Troubled Kids Can Explode in Rage.

    Science.gov (United States)

    Blankenship, Judy

    1999-01-01

    Describes incidents of school violence in the Northwest, the young killers' personalities, characteristics of extremely aggressive children, and factors that reduce such children's potential for violence. Highlights from "Early Warning, Timely Response: A Guide to Safe Schools" (August 1998) list early warning signs, what schools can do, and what…

  7. Central Asia's raging waters the prospects of water conflict in Central Asia

    OpenAIRE

    Hartman, William B.

    2007-01-01

    This thesis examines the prospects of conflict caused by water scarcity in Central Asia. The thesis analyzes the three most recent political eras of Central Asia, Tsarist Russia, the Soviet Union and independence, utilizing indicators of water tensions including: water quality, water quantity, the management of water for multiple uses, the political divisions and geopolitical setting, state institutions and national water ethos. Although water is not likely to be the sole cause of a majo...

  8. Agresividad vial en la población general Road-rage in the general population

    OpenAIRE

    Inmaculada Fierro; Trinidad Gómez-Talegón; Francisco Javier Álvarez

    2010-01-01

    Objetivos: Analizar la prevalencia y los factores sociodemográficos asociados con la agresividad vial en la población. Métodos: Se han realizado 2.500 entrevistas a la población de Castilla y León de entre 14 y 70 años de edad. Se evaluó la agresividad vial en el año previo a la realización de la encuesta utilizando un test de ocho preguntas. Resultados: El 31,1% refirió haber vivido alguna situación de agresividad vial en el último año, y el 26,8% en más de una ocasión. El 2,6% fueron agreso...

  9. The HMGB1/RAGE axis triggers neutrophil-mediated injury amplification following necrosis

    OpenAIRE

    Huebener, Peter; Pradere, Jean-Philippe; Hernandez, Celine; Gwak, Geum-Youn; Caviglia, Jorge Matias; Mu, Xueru; Loike, John D.; Rosalind E Jenkins; Antoine, Daniel J.; Schwabe, Robert F.

    2014-01-01

    In contrast to microbially triggered inflammation, mechanisms promoting sterile inflammation remain poorly understood. Damage-associated molecular patterns (DAMPs) are considered key inducers of sterile inflammation following cell death, but the relative contribution of specific DAMPs, including high–mobility group box 1 (HMGB1), is ill defined. Due to the postnatal lethality of Hmgb1-knockout mice, the role of HMGB1 in sterile inflammation and disease processes in vivo remains controversial....

  10. 'Go! Sterilise the fertile with thy rage' envy as embittered desire.

    Science.gov (United States)

    Meredith-Owen, William

    2008-09-01

    This paper is concerned with the operation of envy: it considers its origins and their repercussions, in particular its compulsion to sterilize the evidence of fertility, exemplified by Roger Money-Kyrle's evocation of 'the parental intercourse as the supremely creative act'. The inevitable impact on the analytic relationship is considered in the context of two clinical examples of impasse. It is argued that such fundamentally negative transferences, one full of overt aggression and enactment, the other more covertly sabotaging, derive from envious retaliatory impulses originating in experiences--whether phantasied or factual--of exclusion from the anticipated 'good'. Significant recent Jungian contributions to this area are considered and the absence of references to 'envy'--so characteristic of Kleinian discourse--is noted. The ongoing value of integrating Jungian and Kleinian approaches is affirmed. PMID:18844733

  11. Rage against the Machine? Symbolic Violence in E-Learning Supported Tertiary Education

    Science.gov (United States)

    Johnson, Nicola F.; Macdonald, David; Brabazon, Tara

    2008-01-01

    The move toward online course facilitation in tertiary education has the intent of providing education at any time in any place to any person. However, the advent of blended learning and e-learning innovations has ostracised, marginalised or ignored those who cannot afford or who are unable to access the latest hardware and software to take…

  12. The quiet dangers of civilized rage: surveying the punitive aftermath of England's 2011 riots

    OpenAIRE

    Lamble, Sarah

    2013-01-01

    This article considers the state’s punitive response to the civil unrest that swept across England in August 2011. Surveying measures taken by police, courts, and politicians—including lengthy prison sentences, violent police raids, increased surveillance, and proposals for new benefit sanctions—the article highlights the targeting of disaffected young people, impoverished neighborhoods, and racialized communities. Considering these measures alongside the accompanying political rhetoric, the ...

  13. Expression of the receptor for advanced glycation end-products and frequency of polymorphism in lung cancer

    OpenAIRE

    Wang, Hongmei; Li, Yongchun; YU, WENCHENG; Ma, Liqing; Ji, Xia; Xiao, Wei

    2015-01-01

    Receptor for advanced glycation end products (RAGE) is associated with the pathogenesis of cancer progression. The pathological effects mediated through RAGE are physiologically inhibited by soluble RAGE (sRAGE). The aim of the present study was to identify the expression of the sRAGE, RAGE and RAGE ligands in serum samples and lung cancer tissue obtained from lung cancer patients. Using ELISA and immunohistochemistry, it was observed that the sRAGE levels were downregulated in the serum, the...

  14. Toward a Conceptual Model of Motive and Self-Control in Cyber-Aggression: Rage, Revenge, Reward, and Recreation

    Science.gov (United States)

    Runions, Kevin C.

    2013-01-01

    Despite widespread public attention to cyberbullying, online aggression and victimization have received scant conceptual development. This article focuses on how opportunities for aggression are distinct online from those of offline social contexts. The model developed here is informed by a recent aggression typology, which extends the…

  15. MicroRNAs in chronic lymphocytic leukemia: miRacle or miRage for prognosis and targeted therapies?

    Science.gov (United States)

    Van Roosbroeck, Katrien; Calin, George A

    2016-04-01

    Chronic lymphocytic leukemia (CLL) is a heterogeneous disease and has a highly variable clinical course with survival ranging from a couple of months to several decades. MicroRNAs (miRNAs), small non-coding RNAs that regulate transcription and translation of genes, have been found to be involved in CLL initiation, progression, and resistance to therapy. In addition, they can be used as prognostic biomarkers and as targets for novel therapies. In this review, we describe the association between miRNAs and the cytogenetic aberrations commonly found in CLL, as well as with other prognostic factors. We describe the presence of miRNAs as extracellular entities in the plasma and serum of CLL patients and discuss their role in resistance to therapy. Finally, we will explore the potential of targeted miRNA therapy for the treatment of CLL, with a special emphasis on MRX34, the first miRNA mimic that is currently being evaluated for clinical use. PMID:27040698

  16. Automatic thalamus and hippocampus segmentation from MP2RAGE - comparison of publicly available methods and implications for DTI quantification

    DEFF Research Database (Denmark)

    Næss-Schmidt, Erhard; Tietze, Anna; Blicher, Jakob Udby;

    2016-01-01

    PURPOSE: In both structural and functional MRI, there is a need for accurate and reliable automatic segmentation of brain regions. Inconsistent segmentation reduces sensitivity and may bias results in clinical studies. The current study compares the performance of publicly available segmentation ...

  17. MGA++ Analysis of Low Quantity Samples of U and Pu on an Extended-rage Gamma-ray Detector

    Energy Technology Data Exchange (ETDEWEB)

    Wang, T; Russ, G P; Williams, R W

    2007-06-04

    The IAEA has expressed a need for improved determination of gamma emitting nuclides in environmental samples collected during inspections of nuclear facilities and to use the MGA++ to determine U and Pu concentrations and isotopic compositions when those elements are present in relatively high concentrations. We are addressing the IAEA needs by evaluating the applicability of extended-range germanium detectors (ERG). In this paper we used 1g U isotopic standards and 100ug Pu liquid standards (1) to determine the performance of MGA++ on this special detector and (2) to estimate the amount of U and Pu necessary in the sample for determination of the isotopics via MGA++ within reasonable accuracy for a week of counting time using this ERG detector.

  18. "While a Storm is Raging on the Open Sea": Regional Development in a Knowledge-based Economy

    OpenAIRE

    Leydesdorff, Loet

    2009-01-01

    The Triple Helix of university-industry-government relations is elaborated into a systemic model that accounts for interactions among three dimensions. By distinguishing between the respective micro-operations, this model enables us to recombine the "Mode 2" thesis of a new production of scientific knowledge and the study of systems of innovation with the neo-classical perspective on the dynamics of the market. The mutual information in three dimensions provides us with an indicator for the s...

  19. Enzymes of the AKR1B and AKR1C subfamilies and uterine diseases

    Directory of Open Access Journals (Sweden)

    Tea eLanisnik Rizner

    2012-03-01

    Full Text Available Endometrial and cervical cancers, uterine myoma, and endometriosis are very common uterine diseases. Worldwide, more than 800,000 women are affected annually by gynecological cancers, as a result of which, more than 360,000 die. During their reproductive age, about 70% of women develop uterine myomas, 10% to 15% suffer from endometriosis, and 35% to 50% from infertility associated with endometriosis. Uterine diseases are associated with aberrant inflammatory responses and concomitant increased production of prostaglandins (PG. They are also related to decreased differentiation, due to low levels of protective progesterone and retinoic acid, and to enhanced proliferation, due to high local concentrations of estrogens. The pathogenesis of these diseases can thus be attributed to disturbed PG, estrogen and retinoid metabolism and actions. Five human members of the aldo-keto reductase 1B (AKR1B and 1C (AKR1C superfamilies, i.e., AKR1B1, AKR1B10, AKR1C1, AKR1C2 and AKR1C3, have roles in these processes and can thus be implicated in uterine diseases. AKR1B1 and AKR1C3 catalyze the formation of PGF2alpha which stimulates cell proliferation. AKR1C3 converts PGD2 to 9alpha,11beta-PGF2, and thus counteracts the formation of 15deoxy-PGJ2, which can activate pro-apoptotic peroxisome-proliferator-activated receptor beta. AKR1B10 catalyzes the reduction of retinal to retinol, and in thus lessens the formation of retinoic acid, with potential pro-differentiating actions. The AKR1C1-AKR1C3 enzymes also act as 17-keto- and 20-ketosteroid reductases to varying extents, and are implicated in increased estradiol and decreased progesterone levels. This review comprises a short introduction to uterine diseases, followed by an overview of the current literature on the AKR1B and AKR1C expression in the uterus and in uterine diseases. The potential implications of the AKR1B and AKR1C enzymes and their pathophysiologies are then discussed, followed by conclusions and

  20. Whole blood transcriptional profiling reveals deregulation of oxidative and antioxidative defence genes in myelofibrosis and related neoplasms. Potential implications of downregulation of Nrf2 for genomic instability and disease progression.

    Directory of Open Access Journals (Sweden)

    Hans Carl Hasselbalch

    Full Text Available The Philadelphia-negative chronic myeloproliferative neoplasms - essential thrombocythemia (ET, polycythemia vera (PV, and myelofibrosis (MF (MPNs - have recently been shown to be associated with chronic inflammation, oxidative stress and accumulation of reactive oxygen species (ROS. Using whole blood transcriptional profiling, we report that several oxidative stress and anti-oxidative stress genes are significantly deregulated in MPNs. Among the twenty most up- and downregulated genes, ATOX1, DEFB122, GPX8, PRDX2, PRDX6, PTGS1, and SEPP1 were progressively upregulated from ET over PV to PMF, whereas AKR1B1, CYBA, SIRT2, TTN, and UCP2 were progressively downregulated in ET, PV and PMF (all FDR <0.05. The gene Nrf2, encoding the transcription factor nuclear factor erythroid 2-related factor 2 (NFE2L2 or Nrf2 was significantly downregulated in all MPNs. Nrf2 has a key role in the regulation of the oxidative stress response and modulates both migration and retention of hematopoietic stem cells (HSCs in their niche. The patogenetic importance of Nrf2 depletion in the context of expansion of the hematopoietic progenitor pool in MPNs is discussed with particular focus upon the implications of concomitant downregulation of Nrf2 and CXCR4 for stem cell mobilization.

  1. Genome-wide DNA methylation analysis in hepatocellular carcinoma.

    Science.gov (United States)

    Yamada, Nobuhisa; Yasui, Kohichiroh; Dohi, Osamu; Gen, Yasuyuki; Tomie, Akira; Kitaichi, Tomoko; Iwai, Naoto; Mitsuyoshi, Hironori; Sumida, Yoshio; Moriguchi, Michihisa; Yamaguchi, Kanji; Nishikawa, Taichiro; Umemura, Atsushi; Naito, Yuji; Tanaka, Shinji; Arii, Shigeki; Itoh, Yoshito

    2016-04-01

    Epigenetic changes as well as genetic changes are mechanisms of tumorigenesis. We aimed to identify novel genes that are silenced by DNA hypermethylation in hepatocellular carcinoma (HCC). We screened for genes with promoter DNA hypermethylation using a genome-wide methylation microarray analysis in primary HCC (the discovery set). The microarray analysis revealed that there were 2,670 CpG sites that significantly differed in regards to the methylation level between the tumor and non-tumor liver tissues; 875 were significantly hypermethylated and 1,795 were significantly hypomethylated in the HCC tumors compared to the non‑tumor tissues. Further analyses using methylation-specific PCR, combined with expression analysis, in the validation set of primary HCC showed that, in addition to three known tumor-suppressor genes (APC, CDKN2A, and GSTP1), eight genes (AKR1B1, GRASP, MAP9, NXPE3, RSPH9, SPINT2, STEAP4, and ZNF154) were significantly hypermethylated and downregulated in the HCC tumors compared to the non-tumor liver tissues. Our results suggest that epigenetic silencing of these genes may be associated with HCC. PMID:26883180

  2. Let the Storm Rage On: Gender Portrayal and its Development in Disney's Princess Films from Snow White and the Seven Dwarfs to Frozen

    OpenAIRE

    Erna Guðmundsdóttir 1984

    2015-01-01

    This essay examines gender representation in the 11 films that constitute the official Disney Princess franchise, with the addition of the film Frozen, and how portrayal of gender has developed through the decades, from Disney’s first full-length animation, Snow White and the Seven Dwarfs in 1937. Studies have shown that television plays an important part in how children learn gender roles. With The Disney Company leading the market for children’s entertainment, their influence is extensive. ...

  3. Insertion territoriale de l'agriculture dans les espaces ruraux : Un repérage en Midi-Pyrénées

    OpenAIRE

    Triboulet, Pierre; LANGLET, Alain

    2002-01-01

    Dans une perspective d'aide aux décideurs locaux et régionaux, cet article a pour objectif d'apporter des éléments de réflexion sur les dynamiques d'évolution de l'agriculture en relation avec les dynamiques des espaces ruraux dans lesquelles elle s'insère. A cette fin, nous proposons une démarche de construction d'une base de données géographiques sur la diversité locale de l'agriculture à l'échelle régionale. L'étude porte sur la région Midi-Pyrénées. L'analyse est effectuée au niveau commu...

  4. 国内第一片ATI授权的ODM ATI显示卡联维尔ATI RAGE 128 PRO显卡

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ 显示卡市场的竞争日益激烈,nVIDIA自从推出TNT、GeForce系列显示芯片、兼并3Dfx以后,在显示卡市场的垄断地位日见巩固,这当然是多数用户特别是厂商都不愿看到的局面.目前够得上nVIDIA的对手只剩下两个--ATI与MGA.而ATI与MGA一直保持独家研发、独家生产、独家销售的模式,产量上不去,成本高昂,市场占有率也不高,在价格上根本无法同nVIDIA竞争.

  5. Effect of statins on the serum soluble form of receptor for advanced glycation end-products and its association with coronary atherosclerosis in patients with angina pectoris

    OpenAIRE

    Tsuyoshi Nozue; Sho-ichi Yamagishi; Masayoshi Takeuchi; Tsutomu Hirano; Shingo Yamamoto; Shinichi Tohyama; Kazuki Fukui; Shigeo Umezawa; Yuko Onishi; Tomoyuki Kunishima; Kiyoshi Hibi; Mitsuyasu Terashima; Ichiro Michishita

    2014-01-01

    Background: Advanced glycation end-products (AGEs) and their receptor (RAGE) play an important role in the pathogenesis of diabetic vascular complications. Recently, soluble form of RAGE (sRAGE) has been identified in mice and humans. Statins have been reported to increase serum sRAGE levels. However, whether modulation of circulating sRAGE levels has a beneficial effect on the progression of atherosclerosis is unknown. Methods: We reviewed 91 patients who had undergone percutaneous corona...

  6. Dicty_cDB: SHI546 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available : Full=Poly [ADP-ribose] polymerase; Sh... 62 2e-08 protein update 2009. 4.22 PSORT psg: 0.58 gvh: 0.23 alm...ignments: (bits) Value (Q9ZP54) RecName: Full=Poly [ADP-ribose] polymerase 1; ... 75 2e-12 ( P26446 ) RecName...EY QCKGWISGFTKCDWKGDSIER--- Frame B: liakekwqqkihllmrlnmqrvidqhvqpvkevlikkqfvlvikqnqntlme...B/CHQ835Q.Seq.d/ 1197 0.0 own update 2002.12. 7 Homology vs DNA Score E Sequences producing significant alignments: (bits) Val...1A (adprt-1A gene). 1197 0.0 1 AC025807 |AC025807.2 Homo sapiens clone RP11-657G2, WORKING DRAFT SEQUENCE, 15 unordere

  7. Dicty_cDB: SHJ389 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available nts: (bits) Value (Q9ZP54) RecName: Full=Poly [ADP-ribose] polymer...22 PSORT psg: 0.69 gvh: 0.23 alm: 0.54 top: 0.53 tms: 0.00 mit: 0.38 mip: 0.03 nuc: 0.00 erl: 0.00 erm: 0.20...ADNLKGPAIKNIIQYNKGYVDKVSPVHLLHTLSDWMLKGRPGRCPTCKNFDILFNGI EYQCKGWI--- Frame B: slliakekwqqkihllmrlnmqrvidqhvqpvkevlikkqfvlvikqnqntlme...eq.d/ 1120 0.0 own update 2002.12. 7 Homology vs DNA Score E Sequences producing significant alignme...ase-1A (adprt-1A gene). 1116 0.0 1 AC025807 |AC025807.2 Homo sapiens clone RP11-657G2, WORKING D

  8. Dicty_cDB: SHI333 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 6 7e-10 ( Q11208 ) RecName: Full=Poly [ADP-ribose] polymerase; Sh... 62 2e-08 protein update 2009. 4.21 PSORT psg: 0.69 gvh: 0.23 alm... E Sequences producing significant alignments: (bits) Value (Q9ZP54) RecName: Full=Poly [ADP-ribose] polymer...CKNFDILFNGI EYQCKGWISGFTKCDWKGDSIER--- Frame B: slliakekwqqkihllmrlnmqrvidqhvqpvkevlikkqfvlvikqnqntlme...Q) /CSM/AH/AHF4-C/AHF461Q.Seq.d/ 1203 0.0 own update 2002.12. 7 Homology vs DNA Score E Sequences producing significant alignme...ase-1A (adprt-1A gene). 1199 0.0 1 AC025807 |AC025807.2 Homo sapiens clone RP11-657G2, WORKING D

  9. Aldo keto reductases 1B in endocrinology and metabolism

    Directory of Open Access Journals (Sweden)

    AntoineMartinez

    2012-08-01

    Full Text Available The aldose reductase (human AKR1B1/mouse Akr1b3 has been the focus of many research because of its role in diabetic complications. The starting point of these alterations is the massive entry of glucose in polyol pathway where it is converted into sorbitol by this enzyme. However, the issue of aldose reductase function in non-diabetic condition remains unresolved. Aldose reductase-like enzymes (AKR1B10, Akr1b7 and Akr1b8 are highly related isoforms often co-expressed with bona fide aldose reductase, making functional analysis of one or the other isoform a challenging task. AKR1B/Akr1b members share at least 65% protein identity and the general ability to reduce many redundant substrates such as aldehydes provided from lipid peroxidation, steroids and their by-products and xenobiotics in vitro. Based on these properties, AKR1B/Akr1b are generally considered as detoxifying enzymes. Considering that divergences should be more informative than similarities to help understanding their physiological functions, we chose to review specific hallmarks of each human/mouse isoforms by focusing on tissue distribution and specific mechanisms of gene regulation. Indeed, although the aldose reductase shows ubiquitous expression, aldose reductase-like proteins exhibit tissue-specific patterns of expression. We focused on 3 organs where certain isoforms are enriched, the adrenal gland, enterohepatic and adipose tissues and tried to connect recent enzymatic and regulation data with endocrine and metabolic functions of these organs. We presented recent mouse models showing unsuspected physiological functions in the regulation of glucido-lipidic metabolism and adipose tissue homeostasis. Beyond the widely accepted idea that AKR1B/Akr1b are detoxification enzymes, these recent reports provide growing evidences that they are able to modify or generate signal molecules. This conceptually shifts this class of enzymes from unenviable status of scavenger to upper class of

  10. BVDV alters uterine prostaglandin production during pregnancy recognition in cows.

    Science.gov (United States)

    Cheng, Zhangrui; Abudureyimu, Ayimuguli; Oguejiofor, Chike F; Ellis, Rebekah; Barry, Amy Teresa; Chen, Xing; Anstaett, Olivia L; Brownlie, Joe; Wathes, D Claire

    2016-06-01

    Embryonic mortality in cows is at least in part caused by failure of pregnancy recognition (PR). Evidence has shown that bovine viral diarrhoea virus (BVDV) infection can disrupt pregnancy. Prostaglandins (PG) play important roles in many reproductive processes, such as implantation. The aim of this study was to investigate the effect of BVDV infection on uterine PG production and PR using an in vitro PR model. Bovine uterine endometrial cells isolated from ten BVDV-free cows were cultured and treated with 0 or 100ng/mL interferon-τ (IFNT) in the absence or presence of non-cytopathic BVDV (ncpBVDV). PGF2α and PGE2 concentrations in the spent medium were measured using radioimmunoassays, and in the treated cells expression of the genes associated with PG production and signalling was quantified using qPCR. The results showed that the IFNT challenge significantly stimulated PTGS1 and PTGER3 mRNA expression and PGE2 production; however, these stimulatory effects were neutralised in the presence of ncpBVDV infection. ncpBVDV infection significantly increased PTGS1 and mPGES1 mRNA expression and decreased AKR1B1 expression, leading to increased PGE2 and decreased PGF2α concentrations and an increased PGE2:PGF2α ratio. The other tested genes, including PGR, ESR1, OXTR, PTGS2, PTGER2 and PTGFR, were not significantly altered by IFNT, ncpBVDV or their combination. Our study suggests that BVDV infection may impair PR by (1) inhibiting the effect of IFNT on uterine PG production and (2) inducing an endocrine switch of PG production from PGF2α to PGE2 to decrease uterine immunity, thereby predisposing the animals to uterine disease. PMID:26952097

  11. Computational Prediction of Phylogenetically Conserved Sequence Motifs for Five Different Candidate Genes in Type II Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    P Srinivasan

    2012-07-01

    Full Text Available Background: Computational identification of phylogenetic motifs helps to understand the knowledge about known functional features that includes catalytic site, substrate binding epitopes, and protein-protein interfaces. Furthermore, they are strongly conserved among orthologs, indicating their evolutionary importance. The study aimed to analyze five candidate genes involved in type II diabetic nephropathy and to predict phylogenetic motifs from their corresponding orthologous protein sequences.Methods: AKR1B1, APOE, ENPP1, ELMO1 and IGFBP1 are the genes that have been identified as an important target for type II diabetic nephropathy through experimental studies. Their corresponding protein sequences, structures, orthologous sequences were retrieved from UniprotKB, PDB, and PHOG database respectively. Multiple sequence alignments were constructed using ClustalW and phylogenetic motifs were identified using MINER. The occurrence of amino acids in the obtained phylogenetic motifs was generated using WebLogo and false positive expectations were calculated against phylogenetic similarity.Results: In total, 17 phylogenetic motifs were identified from the five proteins and the residues such as glycine, leucine, tryptophan, aspartic acid were found in appreciable frequency whereas arginine identified in all the predicted PMs. The result implies that these residues can be important to the functional and structural role of the proteins and calculated false positive expectations implies that they were generally conserved in traditional sense.Conclusion: The prediction of phylogenetic motifs is an accurate method for detecting functionally important conserved residues. The conserved motifs can be used as a potential drug target for type II diabetic nephropathy.

  12. Effect of the bovine oviductal fluid on in vitro fertilization, development and gene expression of in vitro-produced bovine blastocysts.

    Science.gov (United States)

    Cebrian-Serrano, A; Salvador, I; García-Roselló, E; Pericuesta, E; Pérez-Cerezales, S; Gutierrez-Adán, A; Coy, P; Silvestre, M A

    2013-04-01

    Oviductal microenvironment generally provides better conditions for early embryo development than the conventional in vitro system. In an attempt to simulate the oviduct conditions or the main potentially influencing factors, the effect was studied of a bovine oviductal fluid (bOF) treatment applied prior to IVF on (i) IVF parameters, (ii) cleavage rate, (iii) blastocyst yield and (iv) blastocyst quality. Embryo quality was assessed by morphological embryo quality and relative transcript abundance of several developmental genes in bovine blastocysts. Furthermore, to study the effect of bOF without the male effect and zona-sperm interaction, artificially activated metaphase II oocytes were also treated with bOF. In vitro-matured bovine oocytes from abattoir ovaries were treated or untreated with bOF for 30 min and then washed prior to IVF or activation. Subsequently, in vitro-fertilized and parthenogenetic embryos were in vitro cultured for 7 to 8 days. The bOF treatment had no effect on fertilization parameters, cleavage, blastocyst rates both on parthenogenetic and IVF bovine embryos and neither on morphological quality of IVF blastocysts. G6PD and SOD2 genes from IVF blastocysts showed significant changes in their expression after a bOF treatment. Significant differences were found for the expression of SCL2A1, GPX1, BAX, AKR1B1 and PLAC8 genes between excellent or good blastocysts (Grade 1) and fair blastocysts (Grade 2). To our knowledge, this is the first study that evaluates the effect of bOF oocyte treatment on fertilization parameters, development and quality of bovine embryos. PMID:22908847

  13. Soluble Receptor for Advanced Glycation End Product: A Biomarker for Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Louise J. N. Jensen

    2015-01-01

    Full Text Available The receptor of advanced glycation end products (RAGE and its ligands are linked to the pathogenesis of coronary artery disease (CAD, and circulating soluble receptor of advanced glycation end products (sRAGE, reflecting the RAGE activity, is suggested as a potential biomarker. Elevated sRAGE levels are reported in relation to acute ischemia and this review focuses on the role of sRAGE as a biomarker for the acute coronary syndrome (ACS. The current studies demonstrated that sRAGE levels are elevated in relation to ACS, however during a very narrow time period, indicating that the time of sampling needs attention. Interestingly, activation of RAGE may influence the pathogenesis and reflection in sRAGE levels in acute and stable CAD differently.

  14. Vessel Ultrasound Sonographic Assessment of Soluble Receptor for Advanced Glycation End Products Efficacy in a Rat Balloon Injury Model

    Directory of Open Access Journals (Sweden)

    Hyun-Jin Tae, DVM, PhD

    2014-12-01

    Conclusions: Sonograph results are consistent with those obtained from histology; that is, sRAGE produced in Chinese hamster ovary cells has significantly higher efficacy than insect cell-originated sRAGE cells.

  15. Receptor for Advanced Glycation End Products Regulates Adipocyte Hypertrophy and Insulin Sensitivity in Mice

    OpenAIRE

    Monden, Masayo; Koyama, Hidenori; Otsuka, Yoshiko; Morioka, Tomoaki; Mori, Katsuhito; Shoji, Takuhito; Mima, Yohei; Motoyama, Koka; Fukumoto, Shinya; Shioi, Atsushi; Emoto, Masanori; Yamamoto, Yasuhiko; Yamamoto, Hiroshi; Nishizawa, Yoshiki; Kurajoh, Masafumi

    2013-01-01

    Receptor for advanced glycation end products (RAGE) has been shown to be involved in adiposity as well as atherosclerosis even in nondiabetic conditions. In this study, we examined mechanisms underlying how RAGE regulates adiposity and insulin sensitivity. RAGE overexpression in 3T3-L1 preadipocytes using adenoviral gene transfer accelerated adipocyte hypertrophy, whereas inhibitions of RAGE by small interfering RNA significantly decrease adipocyte hypertrophy. Furthermore, double knockdown o...

  16. Influence of Physical Activity Intervention on Circulating Soluble Receptor for Advanced Glycation end Products in Elderly Subjects

    OpenAIRE

    Kotani, Kazuhiko; Caccavello, Russell; Sakane, Naoki; Yamada, Toshiyuki; Taniguchi, Nobuyuki; Gugliucci, Alejandro

    2011-01-01

    Background Inflammation, often accompanied by oxidation, caused by advanced glycation end products (AGEs) may be quenched by the soluble receptor for AGEs (sRAGE). The present study aimed to investigate the influence of physical activity on circulating sRAGE, and the association between changes of circulating sRAGE and paraoxonase1 (PON1) activity (as an antioxidative enzyme) in a physical activity intervention study on an elderly subject cohort. Methods Serum sRAGE, PON1 activity and cardiom...

  17. bFGF and TGFβ1 growth factors, inflammatory markers (IL-6, TNF-α, CRP) and advanced glycation end-products (AGE, RAGE) in patients with ischemic heart disease and type 2 diabetes mellitus

    OpenAIRE

    Ekaterina Vladimirovna Ivannikova; Konstantin Vladimirovich Melkozerov; Viktor Yur'evich Kalashnikov; Sergey Anatol'evich Terekhin; Irina Vladimirovna Kononenko; Olga Mikhailovna Smirnova

    2013-01-01

    Aims. To evaluate plasma levels of transforming growth factor beta (TGFβ1), basic fibroblast growth factor (bFGF), markers for nonspecific inflammatory process (interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP)) and their putative correlation with advanced glycation end-products relative to diabetes compensation in patients with ischemic heart disease (IHD).Materials and Methods. 87 patients with IHD were enrolled in this study. All subjects underwent standar...

  18. 流感流行期大气环境特征及流感分级预报%Analysis of Atmospheric Environment Change During Flu Rage and Flu Occurrence Forecast

    Institute of Scientific and Technical Information of China (English)

    山义昌; 徐太安; 鲁丹; 郑学山; 杜恒欣

    2003-01-01

    分析了1998和2001年冬季我国北方地区流感大流行期的大气环境特征,得出冬季气温偏高,冷空气活动次数偏少且降温幅度增大;降水比上一年明显偏少且年际变化大、时间分布不均以及大气中烟尘含量高等大气环境特征与流感流行有密切关系.用1991~2001年的流感住院人数,气温、降水和能见度为因子,建立流感发生的预报方程.

  19. bFGF and TGFβ1 growth factors, inflammatory markers (IL-6, TNF-α, CRP and advanced glycation end-products (AGE, RAGE in patients with ischemic heart disease and type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ekaterina Vladimirovna Ivannikova

    2013-11-01

    Full Text Available Aims. To evaluate plasma levels of transforming growth factor beta (TGFβ1, basic fibroblast growth factor (bFGF, markers for nonspecific inflammatory process (interleukin-6 (IL-6, tumor necrosis factor alpha (TNF-α, C-reactive protein (CRP and their putative correlation with advanced glycation end-products relative to diabetes compensation in patients with ischemic heart disease (IHD.Materials and Methods. 87 patients with IHD were enrolled in this study. All subjects underwent standard clinical examination, including laboratory assessment of glycemic parameters, lipid panel and renal function, with echocardiography, supplemented with coronary angiography. Analyses for study parameters were performed on samples obtained from aorta and, separately, from cubital vein during coronary angiography.Results. Diabetes mellitus in patients with IHD is firmly associated with TGFβ1, IL-6 and CRP elevation in both arterial and venous plasma. TGFβ1 positively correlates with lipid profile parameters. Plasma concentration of inflammatory markers and advanced glycation end-products positively correlates with the extent of coronary lesions in relation to the presence of diabetes mellitus.Conclusion. Our data suggests the interplay between connective tissue growth factors and lipid metabolism in the atherosclerotic process.

  20. L'écosystème d'innovation universitaire de Aalto : une contribution au repérage des acteurs impliqués lors de la phase d'émergence

    OpenAIRE

    Froehlicher, Thomas; Barès, Franck

    2014-01-01

    The aim of this article is to better under- stand how the innovation ecosystem of Aalto University, in Helsinki, Finland, was structured in the early 2000s. Relying on an analysis of secondary data as well as on the principles of a structural analy- sis of the network, we located the actors and their connections over the emergence period of this ecosystem. The results show the coexistence of two spaces organized as socio-cognitive networks able to interact and reinforce each other. A territor...

  1. To Bleed or Not to Bleed. A Prediction Based on Individual Gene Profiling Combined With Dose-Volume Histogram Shapes in Prostate Cancer Patients Undergoing Three-Dimensional Conformal Radiation Therapy

    International Nuclear Information System (INIS)

    Purpose: The main purpose of this work was to try to elucidate why, despite excellent rectal dose-volume histograms (DVHs), some patients treated for prostate cancer exhibit late rectal bleeding (LRB) and others with poor DVHs do not. Thirty-five genes involved in DNA repair/radiation response were analyzed in patients accrued in the AIROPROS 0101 trial, which investigated the correlation between LRB and dosimetric parameters. Methods and Materials: Thirty patients undergoing conformal radiotherapy with prescription doses higher than 70 Gy (minimum follow-up, 48 months) were selected: 10 patients in the low-risk group (rectal DVH with the percent volume of rectum receiving more than 70 Gy [V70Gy] 25% and V50Gy > 60%) with G2-G3 LRB, and 10 patients in the high-risk group with no toxicity. Quantitative reverse-transcriptase polymerase chain reaction was performed on RNA from lymphoblastoid cell lines obtained from Epstein-Barr virus-immortalized peripheral-blood mononucleated cells and on peripheral blood mononucleated cells. Interexpression levels were compared by using the Kruskal-Wallis test. Results: Intergroup comparison showed many constitutive differences: nine genes were significantly down-regulated in the low-risk bleeder group vs. the high-risk bleeder and high-risk nonbleeder groups: AKR1B1 (p = 0.019), BAZ1B (p = 0.042), LSM7 (p = 0.0016), MRPL23 (p = 0.015), NUDT1 (p = 0.0031), PSMB4 (p = 0.079), PSMD1 (p = 0.062), SEC22L1 (p = 0.040), and UBB (p = 0.018). Four genes were significantly upregulated in the high-risk nonbleeder group than in the other groups: DDX17 (p = 0.048), DRAP1 (p = 0.0025), RAD23 (p = 0.015), and SRF (p = 0.024). For most of these genes, it was possible to establish a cut-off value that correctly classified most patients. Conclusions: The predictive value of sensitivity and resistance to LRB of the genes identified by the study is promising and should be tested in a larger data set.

  2. Advanced glycation end-products and receptor for advanced glycation end-products expression in patients with idiopathic pulmonary fibrosis and NSIP

    OpenAIRE

    Kyung, Sun Young; Byun, Kyung Hee; Yoon, Jin Young; Kim, Yu Jin; Lee, Sang Pyo; Park, Jeong-Woong; Lee, Bong Hee; Park, Jong Sook; Jang, An Soo; Park, Choon Sik; Jeong, Sung Hwan

    2013-01-01

    Advanced glycation end products (AGEs) are associated with the pathogenesis of various diseases. AGEs induce excess accumulation of extracellular matrix and expression of profibrotic cytokines. In addition, studies on receptor for advanced glycation end products (RAGE) have shown that the ligand-RAGE interaction activates several intracellular signaling cascades associated with several fibrotic diseases. We investigated the expression of AGEs and RAGE in samples from patients with idiopathic ...

  3. Pop / Tõnis Kahu

    Index Scriptorium Estoniae

    Kahu, Tõnis, 1962-

    2008-01-01

    Heliplaatidest: Chemical Brothers "Brotherhood", Plutonium 74 "Peittoalueen ulkopuolella", Disturbed "Indestructible", Thomas Feiner & Anywhen "The Opiates Revised", DefRage "Save Us from Religion", Kago "Mopskassi maja"

  4. Soluble receptor for advanced glycation end products mitigates vascular dysfunction in spontaneously hypertensive rats.

    Science.gov (United States)

    Liu, Yu; Yu, Manli; Zhang, Le; Cao, Qingxin; Song, Ying; Liu, Yuxiu; Gong, Jianbin

    2016-08-01

    Vascular dysfunction including vascular remodeling and endothelial dysfunction in hypertension often results in poor clinical outcomes and increased risk of vascular accidents. We investigate the effect of treatment with soluble receptor for advanced glycation end products (sRAGE) on vascular dysfunction in spontaneously hypertensive rats (SHR). Firstly, the aortic AGE/RAGE pathway was investigated in SHR. Secondly, SHR received intraperitoneal injections of sRAGE daily for 4 weeks. Effect of sRAGE against vascular dysfunction in SHR and underlying mechanism was investigated. SHR aortas exhibited enhanced activity of aldose reductase, reduced activity of glyoxalase 1, accumulation of methylglyoxal and AGE, and upregulated expression of RAGE. Treatment of SHR with sRAGE had no significant effect on blood pressure, but alleviated aortic hypertrophy and endothelial dysfunction. In vitro, treatment with sRAGE reversed the effect of incubation with AGE on proliferation of smooth muscle cells and endothelial function. Treatment of SHR with sRAGE abated oxidative stress, suppressed inflammation and NF-κB activation, improved the balance between Ang II and Ang-(1-7) through reducing angiotensin-converting enzyme (ACE) activity and enhancing ACE2 expression, and upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in aortas. In conclusion, treatment with sRAGE alleviated vascular adverse remodeling in SHR, possibly via suppression of oxidative stress and inflammation, improvement in RAS balance, and activation of PPAR-γ pathway. PMID:27426491

  5. Determinants of concentrations of N(ε)-carboxymethyl-lysine and soluble receptor for advanced glycation end products and their associations with risk of pancreatic cancer.

    Science.gov (United States)

    Duan, Zhigang; Chen, Guoqing; Chen, Liang; Stolzenberg-Solomon, Rachael; Weinstein, Stephanie J; Mannisto, Satu; White, Donna L; Albanes, Demetrius; Jiao, Li

    2014-01-01

    The soluble receptor for advanced glycation end-products (sRAGE) is shown to mitigate pro-inflammatory effects triggered by ligation of RAGE with N(ε)-carboxymethyl-lysine (CML)-AGE or other ligands. We examined the associations among host, lifestyle, and genetic determinants of CML-AGE or sRAGE and risk of pancreatic cancer in the prospective ATBC Study. We obtained baseline exposure information, data on serological and genetic biomarkers from 141 patients with pancreatic cancer and 141 subcohort controls. Stepwise linear and logistic regression models were used for data analysis. Multiple linear regression analyses showed that CML-AGE concentrations were independently inversely correlated with the minor allele of rs640742 of DDOST, physical activity, alcohol consumption, diastolic blood pressure (BP), and positively correlated with heart rate, serum sRAGE and HDL concentrations (P RAGE, age, body mass index, heart rate, and serum HDL; and positively correlated with serum CML-AGE, sucrose consumption, and diastolic BP (P RAGE was associated with reduced risk of pancreatic cancer (any T compared with CC: multivariate OR = 0.61, 95% CI: 0.38-0.98). We identified host metabolic profile, lifestyle and genetic factors that explained approximately 50% of variability of CML-AGE or sRAGE in Finnish men smokers. The association between RAGE SNPs and pancreatic cancer risk warrants further investigation. PMID:25379135

  6. Do Not Go Gentle into That Good Night

    Institute of Scientific and Technical Information of China (English)

    Dylan; Thomas

    2008-01-01

    Do not go gentle into that good night,Old age should burn and rave at close of day;Rage, rage against the dying of the light.Though wise men at their end know dark is right,Because their words had forked no lightning theyDo not go gentle into that good night.

  7. Status of LANL Efforts to Effectively Use Sequoia

    Energy Technology Data Exchange (ETDEWEB)

    Nystrom, William David [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-05-14

    Los Alamos National Laboratory (LANL) is currently working on 3 new production applications, VPC, xRage, and Pagosa. VPIC was designed to be a 3D relativist, electromagnetic Particle-In-Cell code for plasma simulation. xRage, a 3D AMR mesh amd multi physics hydro code. Pagosa, is a 3D structured mesh and multi physics hydro code.

  8. Advanced glycation end product ligands for the receptor for advanced glycation end products: Biochemical characterization and formation kinetics

    NARCIS (Netherlands)

    Valencia, J.V.; Weldon, S.C.; Quinn, D.; Kiers, G.H.; Groot, J. de; TeKoppele, J.M.; Hughes, T.E.

    2004-01-01

    Advanced glycation end products (AGEs) accumulate with age and at an accelerated rate in diabetes. AGEs bind cell-surface receptors including the receptor for advanced glycation end products (RAGE). The dependence of RAGE binding on specific biochemical characteristics of AGEs is currently unknown.

  9. Beech Lodge Care Facility, Bruree, Limerick.

    LENUS (Irish Health Repository)

    Buckley, Stephen T

    2010-01-01

    The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface molecules. As a pattern-recognition receptor capable of binding a diverse range of ligands, it is typically expressed at low levels under normal physiological conditions in the majority of tissues. In contrast, the lung exhibits high basal level expression of RAGE localised primarily in alveolar type I (ATI) cells, suggesting a potentially important role for the receptor in maintaining lung homeostasis. Indeed, disruption of RAGE levels has been implicated in the pathogenesis of a variety of pulmonary disorders including cancer and fibrosis. Furthermore, its soluble isoforms, sRAGE, which act as decoy receptors, have been shown to be a useful marker of ATI cell injury. Whilst RAGE undoubtedly plays an important role in the biology of the lung, it remains unclear as to the exact nature of this contribution under both physiological and pathological conditions.

  10. The distribution of advanced glycation end products and their receptor in the gastrointestinal tract in the rats

    DEFF Research Database (Denmark)

    Chen, Pengmin; Zhao, Jingbo; Gregersen, Hans

    2012-01-01

    and squamous epithelial cells. In the stomach, AGEs were mainly distributed in parietal cells, and RAGE was strongly expressed in chief cells, mast cells and neurons in ganglia, moderately in parietal cells, and mildly in surface mucous cells. In the intestine, colon and rectum, AGEs and RAGE were distributed...... in mucosal epithelial cells, and RAGE was also distributed in neurons in the myenteric and submucosal plexuses. CONCLUSION: AGEs and RAGE are widely distributed in epithelial cells of the GI tract as well as striated muscle cells in the esophagus. AGEs are also distributed in parietal cells in the stomach....... RAGE is also distributed in chief cells, mast cells, parietal cells and surface mucous cells in the stomach and neurons in the whole GI tract....

  11. Soluble receptor for advanced glycation end products in COPD: relationship with emphysema and chronic cor pulmonale: a case-control study

    Directory of Open Access Journals (Sweden)

    Cocci Franca

    2011-03-01

    Full Text Available Abstract Background The receptor for advanced glycation end products (RAGE is a multiligand signal transduction receptor that can initiate and perpetuate inflammation. Its soluble isoform (sRAGE acts as a decoy receptor for RAGE ligands, and is thought to afford protection against inflammation. With the present study, we aimed at determining whether circulating sRAGE is correlated with emphysema and chronic cor pulmonale in chronic obstructive pulmonary disease (COPD. Methods In 200 COPD patients and 201 age- and sex-matched controls, we measured lung function by spirometry, and sRAGE by ELISA method. We also measured the plasma levels of two RAGE ligands, N-epsilon-carboxymethyl lysine and S100A12, by ELISA method. In the COPD patients, we assessed the prevalence and severity of emphysema by computed tomography (CT, and the prevalence of chronic cor pulmonale by echocardiography. Multiple quantile regression was used to assess the effects of emphysema, chronic cor pulmonale, smoking history, and comorbid conditions on the three quartiles of sRAGE. Results sRAGE was significantly lower (p = 0.007 in COPD patients (median 652 pg/mL, interquartile range 484 to 1076 pg/mL than in controls (median 869 pg/mL, interquartile range 601 to 1240 pg/mL, and was correlated with the severity of emphysema (p Conclusions sRAGE is significantly lower in patients with COPD than in age- and sex-matched individuals without airflow obstruction. Emphysema and chronic cor pulmonale are independent predictors of reduced sRAGE in COPD.

  12. Garlic decreases liver and kidney receptor for advanced glycation end products expression in experimental diabetes.

    Science.gov (United States)

    Al-Qattan, Khaled K; Mansour, Mohamed H; Thomson, Martha; Ali, Muslim

    2016-06-01

    The up-regulation of the receptor for advanced glycation end products (RAGE) has been implicated as a major mediator in the development and progression of diabetic nephropathy and hepatic fibrogenesis. The present study was designed to investigate the potential of garlic (Allium sativum L.) to modulate the level of expression of RAGE in renal and hepatic tissues of diabetic rats. Three groups of rats were studied after 8 weeks following diabetes induction: normal, streptozotocin-induced diabetic (control diabetic), and garlic-treated diabetic rats. A polyclonal antibody of proven specificity to RAGE indicated in immunohistochemical assays that RAGE labeling was significantly increased in renal and hepatic tissues of control diabetic rats compared to the normal group. The increased RAGE labeling involved mesangial cells in glomeruli exhibiting signs of mesangial expansion, mesangial nodule formation and glomerulosclerosis. In the liver, a significant up-regulation of RAGE was observed in hepatocytes and bile ducts and vessels in portal tracts. In 2-dimensional Western blots, RAGE expression in both tissues was dominated by heterogeneous charge variants, represented by 46-50kDa isoforms with more basic pIs compared to their counterparts in normal rats. Compared to control diabetic rats, RAGE labeling in the garlic-treated diabetic group was significantly reduced throughout renal and hepatic regions and was marked by the expression of 43-50kDa acidic charge variants comparable to those observed in normal rats. The capacity of garlic to modulate diabetes-induced up-regulation of selective RAGE polymorphic variants may be implicated in attenuating the detrimental consequences of excessive RAGE signaling manifested by diabetes-associated disorders. PMID:26968224

  13. Overexpression of Receptor for Advanced Glycation End Products and High-Mobility Group Box 1 in Human Dental Pulp Inflammation

    Directory of Open Access Journals (Sweden)

    Salunya Tancharoen

    2014-01-01

    Full Text Available High mobility group box 1 (HMGB1, a nonhistone DNA-binding protein, is released into the extracellular space and promotes inflammation. HMGB1 binds to related cell signaling transduction receptors, including receptor for advanced glycation end products (RAGE, which actively participate in vascular and inflammatory diseases. The aim of this study was to examine whether RAGE and HMGB1 are involved in the pathogenesis of pulpitis and investigate the effect of Prevotella intermedia (P. intermedia lipopolysaccharide (LPS on RAGE and HMGB1 expression in odontoblast-like cells (OLC-1. RAGE and HMGB1 expression levels in clinically inflamed dental pulp were higher than those in healthy dental pulp. Upregulated expression of RAGE was observed in odontoblasts, stromal pulp fibroblasts-like cells, and endothelial-like cell lining human pulpitis tissue. Strong cytoplasmic HMGB1 immunoreactivity was noted in odontoblasts, whereas nuclear HMGB1 immunoreactivity was seen in stromal pulp fibroblasts-like cells in human pulpitis tissue. LPS stimulated OLC-1 cells produced HMGB1 in a dose-dependent manner through RAGE. HMGB1 translocation towards the cytoplasm and secretion from OLC-1 in response to LPS was inhibited by TPCA-1, an inhibitor of NF-κB activation. These findings suggest that RAGE and HMGB1 play an important role in the pulpal immune response to oral bacterial infection.

  14. C-reactive protein, advanced glycation end products and their receptor in type 2 diabetic, elderly patients with mild cognitive impairment

    Directory of Open Access Journals (Sweden)

    Malgorzata Gorska-Ciebiada

    2015-10-01

    Methods: 276 diabetics elders were screened for MCI (using the Montreal Cognitive Assessment: MoCA score. Data of biochemical parameters and biomarkers were collected. Results: Serum AGEs, RAGE and CRP levels were significantly increased in MCI patients compared to controls. In group of patients with MCI serum RAGE level was positively correlated with AGEs level and with CRP level. RAGE, AGEs and CRP concentrations were positively correlated with HbA1c levels and negatively correlated with MoCA score. The univariate logistic regression models revealed that variables which increased the likelihood of diagnosis of MCI in elderly patients with type 2 diabetes were: higher levels of HbA1c, RAGE, AGEs, CRP, TG, lower level of HDL cholesterol, previous CVD, HA or use of HA drugs, hiperlipidaemia, retinopathy, nephropathy, increased number of co-morbidities, older age and less years of formal education. HA or use of HA drugs, previous CVD, higher level of RAGE and CRP, older age and less years of formal education are the factors increasing the likelihood of having MCI in elderly patients with type 2 diabetes in multivariable model. Conclusions: In summary, serum AGEs, RAGE and CRP are increased in the circulation of MCI elderly diabetic patients compared to controls. A larger population-based prospective study needs to be performed to further confirm the relationship between AGEs, RAGE and the cognitive decline or progress to dementia.

  15. Soluble and Endogenous Secretory Receptors for Advanced Glycation End Products in Threatened Preterm Labor and Preterm Premature Rupture of Fetal Membranes

    Directory of Open Access Journals (Sweden)

    Rafał Rzepka

    2015-01-01

    Full Text Available The aim of the study was to compare sRAGE and esRAGE plasma levels in pregnant women with (A threatened premature labor (n=41, (B preterm premature rupture of membranes (n=49, and (C preterm rupture of membranes at term (n=48. The relationship between these and classic intrauterine infection markers and the latent time from symptoms up to delivery depending on RAGE’s concentration were investigated. In groups A and B, a positive correlation was found between plasma sRAGE and latent time (r = 0,422; p = 0,001; r = 0,413, p = 0,004, resp.. High prognostic values were found in both groups for plasma sRAGE concentration and the latent time from symptoms up to delivery. Groups B and C presented higher levels of esRAGE than group A (526,315 ± 129,453 pg/mL and 576,212 ± 136,237 pg/mL versus 485,918 ± 133,127 pg/mL, p< 0,05. The conclusion is that sRAGE concentration can be a favorable prognostic factor in the presence of symptoms of threatened premature labor. Higher esRAGE plasma level in case of the rupture of membranes in mature and premature pregnancy suggests its participation in fetal membranes destruction.

  16. Receptor for Advanced Glycation End-Products Signaling Interferes with the Vascular Smooth Muscle Cell Contractile Phenotype and Function.

    Directory of Open Access Journals (Sweden)

    Elie Simard

    Full Text Available Increased blood glucose concentrations promote reactions between glucose and proteins to form advanced glycation end-products (AGE. Circulating AGE in the blood plasma can activate the receptor for advanced end-products (RAGE, which is present on both endothelial and vascular smooth muscle cells (VSMC. RAGE exhibits a complex signaling that involves small G-proteins and mitogen activated protein kinases (MAPK, which lead to increased nuclear factor kappa B (NF-κB activity. While RAGE signaling has been previously addressed in endothelial cells, little is known regarding its impact on the function of VSMC. Therefore, we hypothesized that RAGE signaling leads to alterations in the mechanical and functional properties of VSMC, which could contribute to complications associated with diabetes. We demonstrated that RAGE is expressed and functional in the A7r5 VSMC model, and its activation by AGE significantly increased NF-κB activity, which is known to interfere with the contractile phenotype of VSMC. The protein levels of the contraction-related transcription factor myocardin were also decreased by RAGE activation with a concomitant decrease in the mRNA and protein levels of transgelin (SM-22α, a regulator of VSMC contraction. Interestingly, we demonstrated that RAGE activation increased the overall cell rigidity, an effect that can be related to an increase in myosin activity. Finally, although RAGE stimulation amplified calcium signaling and slightly myosin activity in VSMC challenged with vasopressin, their contractile capacity was negatively affected. Overall, RAGE activation in VSMC could represent a keystone in the development of vascular diseases associated with diabetes by interfering with the contractile phenotype of VSMC through the modification of their mechanical and functional properties.

  17. Intra-coronary administration of soluble receptor for advanced glycation end-products attenuates cardiac remodeling with decreased myocardial transforming growth factor-β1 expression and fibrosis in minipigs with ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    LU Lin; SHEN Wei-feng; ZHANG Qi; XU Yan; ZHU Zheng-bin; GENG Liang; WANG Ling-jie; JIN Cao; CHEN Qiu-jing; Ann Marie Schmidt

    2010-01-01

    Background The cardioprotective effects of soluble receptor for advanced glycation end-products (sRAGE) have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aimed to evaluate the effects of intra-coronary administration of sRAGE on left ventricular function and myocardial remodeling in a porcine model of ischemia-reperfusion (I/R) injury. Methods Ten male minipigs with I/R injury were randomly allocated to receive intra-coronary administration of sRAGE (sRAGE group, n=5) or saline (control group, n=5). Echocardiography was performed before and 2 months after infarction. Myocardial expression of transforming growth factor (TGF)-β1was determined by immunohistochemistry and fibrosis was evaluated by Sirius red staining. Results As compared with the baseline values in the control animals, left ventricular end-diastolic volume (from (19.5 5.1) to (32.3 5.6) ml, P <0.05) and end-systolic volume (from (8.3 3.2) to (15.2 4.1) ml, P <0.05) were significantly increased, whereas ejection fraction was decreased (from (61.6 13.3)% to (50.2 11.9)%, P<0.05). No obvious change in these parameters was observed in the sRAGE group. Myocardial expression of TGF-β1 was significantly elevated in the infarct and non-infarct regions in the control group, as compared with sRAGE group (both P<0.01). Fibrotic lesions were consistently more prominent in the infarct region of the myocardium in the control animals (P<0.05). Conclusion Intra-coronary sRAGE administration attenuates RAGE-mediated myocardial fibrosis and I/R injury through a TGF-β1-dependent mechanism, suggesting a clinical potential in treating RAGE/ligand-associated cardiovascular diseases.

  18. Shame and suicide in Sophocles' Ajax.

    Science.gov (United States)

    Lansky, M R

    1996-10-01

    This paper explores the vicissitudes of shame and its relation to narcissistic rage and escalation of conflict in Sophocles' Ajax. The plot is set in motion by Ajax's shame over losing the competition with Odysseus for Achilles' armor. His shame leads to narcissistic, rage and propels him to vengeance against the social order. Misidentification, an aspect of narcissistic rage, compounds his disgrace by escalating his shame to suicidal proportions when his madness leaves him. His defenses all fail, and his suicide becomes inevitable. Forces that bind him to the social order lose out to those that make of him a humiliated outcast and drive him to kill himself. PMID:8933616

  19. Narcissistic personality disorder

    Science.gov (United States)

    Personality disorder - borderline; Narcissism ... A person with narcissistic personality disorder may: React to criticism with rage, shame, or humiliation Take advantage of other people to achieve his or her ...

  20. Uusi plaate / Marko T. Lepp

    Index Scriptorium Estoniae

    Lepp, Marko T.

    1999-01-01

    Uutest plaatidest Enrique Iglesias "Enrique", Will Smith "Willennium", Celine Dion "All The Way... A Decade Of Song". Korn "Issues", Rage Agains The Machine "The Battle Of Los Angeles", Sevendust "Home"

  1. Subcontracting in electronics : from contract manufacturers to providers of electronic manufacturing services (EMS)

    OpenAIRE

    Liemt, Gijsbert van

    2007-01-01

    Discusses how the top contract manufacturers in the electronics industry try to become providers of electronic manufacturing services by deepening and broadening the rage of services that they offer and by diversifying into markets other than computing and telecommunications.

  2. A very brief history of relativity

    Science.gov (United States)

    O'Raifeartaigh, Cormac

    2015-08-01

    On 25 November 1915, as devastating war raged throughout Europe, Albert Einstein presented the paper Die Feldgleichungen der Gravitation (“The field equations of gravitation”) to the Prussian Academy of Sciences.

  3. Ghana's Decentralization: Two decades and still crawling?

    OpenAIRE

    Daniel Kweku Baah Inkoom

    2011-01-01

    After more than two decades of implementation, there are still debates raging on the nature, processes, financing and operationalization of the decentralization system in Ghana. Daniel Kweku Baah Inkoom looks at the legal, administrative, financial and human resource constraints.

  4. Development of a Single-Frequency Narrow Linewidth 1.5mm Semiconductor Laser Suitable for Spaceflight Operation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Many space applications rely on the utilization of Light Detection and Raging (LIDAR) techniques. A key component of any LIDAR system is the laser source. Single...

  5. Self-Injurious Behavior in Tourette Syndrome

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-09-01

    Full Text Available Self-injurious behavior (repetitive infliction of self harm occurred in 29% of 300 subjects with Tourette syndrome and was correlated with comorbid OCD, impulsivity, episodic rages, and with tic severity.

  6. Self-Injurious Behavior in Tourette Syndrome

    OpenAIRE

    J Gordon Millichap

    2004-01-01

    Self-injurious behavior (repetitive infliction of self harm) occurred in 29% of 300 subjects with Tourette syndrome and was correlated with comorbid OCD, impulsivity, episodic rages, and with tic severity.

  7. [Analysis of the impact of heparin on the affinity of high mobility group box-1 protein and the receptor of advanced glycation end products by surface plasmon resonance technology].

    Science.gov (United States)

    Ling, Yan; Wang, Chun-You; Yang, Zhi-Yong

    2009-11-01

    To investigate the affinity constants of heparin with high mobility group protein 1(HMGB1) and HMGB1 with the receptor of advanced glycation end products (RAGE) and to analyze the impact of heparin on the affinity of HMGB1 and RAGE, the standard BIAcore amine coupling chemistry protocol using EDC and NHS was employed for immobilizing. Surface plasmon resonance biosensor technology was used to detect the affinity constants of heparin/HMGB1, HMGB1/RAGE and heparin/ RAGE. Binding analysis was used to investigate the impact of heparin on the affinity of HMGB1 and RAGE. After the immobilization, 9 000 and 5 000 RU rise of HMGB1 and RAGE respectively were obtained. These meant that the immobilized values of HMGB1 and RAGE were about 9 and 5 ng x mm(-2) respectively. The kinetic constants were k(a) = 1.78 x 10(5) L x mol(-1) x s(-1), kd = 8.02 x 10(-4) s(-1), and the affinity constants were KA = 2.22 x 10(8) L x mol(-1), the equilibrium dissociation constant K(D) = 4.5 x 10(-9) mol x L(-1) for heparin and HMGB1; while the kinetic constants were k(a) = 1.85 x 10(3) L x mol(-1) x s(-1), k(d) = 1.81 x 10(-4) s(-1), K(A) = 1.02 x 10(7) L x mol(-1), K(D) = 9.77 x 10(-8) mol x L(-1) for HMGB1 and RAGE; there was very low affinity of heparin with RAGE. The highest concentration of 10 000 u x L(-1) of heparin in this experiment did not reach the saturation with HMGB1. After 50 mg x L(-1) of HMGB1 was mixed with heparin of 50, 100, 1 000, 10 000 u x L(-1), the combining amount of HMGB1 and RAGE declined from 100 to 50 RU. But there were no significant differences between different concentrations of heparin. It was concluded that heparin can combine with HMGB1 and affect the affinity of HMGB1/RAGE. In addition, this impact was not in a dose-dependent manner. PMID:20101991

  8. The Receptor for Advanced Glycation End Products Is a Central Mediator of Asthma Pathogenesis

    OpenAIRE

    Pavle S Milutinovic; Alcorn, John F.; Englert, Judson M; Crum, Lauren T.; Oury, Tim D.

    2012-01-01

    The receptor for advanced glycation end products (RAGE) is a multiligand receptor that has been shown to contribute to the pathogenesis of diabetes, atherosclerosis, and neurodegeneration. However, its role in asthma and allergic airway disease is largely unknown. These studies use a house dust mite (HDM) mouse model of asthma/allergic airway disease. Respiratory mechanics were assessed and compared between wild-type and RAGE knockout mice. Bronchovascular architecture was assessed with quant...

  9. Paradoxical function for the receptor for advanced glycation end products in mouse models of pulmonary fibrosis

    OpenAIRE

    Englert, Judson M; Kliment, Corrine R.; Ramsgaard, Lasse; Pavle S Milutinovic; Crum, Lauren; Tobolewski, Jacob M.; Oury, Tim D.

    2011-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor survival. The identification of therapeutic targets is essential to improving outcomes. Previous studies found that expression of the receptor for advanced glycation end products (RAGE) in the lung is significantly decreased in human IPF lungs and in two animal models of pulmonary fibrosis. In addition, RAGE-null mice spontaneously develop pulmonary fibrosis with age and more severe fibrosis when challenged with asbestos. ...

  10. The Associations of Advanced Glycation End Products and Its Soluble Receptor with Pancreatic Cancer Risk: A Case-Control Study within the Prospective EPIC Cohort

    OpenAIRE

    Grote, Verena A; Nieters, Alexandra; Kaaks, Rudolf; Tjønneland, Anne; Roswall, Nina; Overvad, Kim; Nielsen, Michael R Skjelbo; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie Christine; Racine, Antoine; Teucher, Birgit; Lukanova, Annekatrin; Boeing, Heiner; Drogan, Dagmar; Trichopoulou, Antonia

    2012-01-01

    BACKGROUND: Advanced glycation end products (AGE) and their receptors (RAGE) have been implicated in cancer development through their proinflammatory capabilities. However, prospective data on their association with cancer of specific sites, including pancreatic cancer, are limited. METHODS: Prediagnostic blood levels of the AGE product Nε-(carboxymethyl)lysine (CML) and the endogenous secreted receptor for AGE (esRAGE) were measured using ELISA in 454 patients with exocrine pancreatic ca...

  11. Brain injury requires lung protection

    OpenAIRE

    Lopez-Aguilar, Josefina; Blanch, Lluis

    2015-01-01

    The paper entitled “The high-mobility group protein B1-Receptor for advanced glycation endproducts (HMGB1-RAGE) axis mediates traumatic brain injury (TBI)-induced pulmonary dysfunction in lung transplantation” published recently in Science Translational Medicine links lung failure after transplantation with alterations in the axis HMGB1-RAGE after TBI, opening a new field for exploring indicators for the early detection of patients at risk of developing acute lung injury (ALI). The lung is on...

  12. Novel Inhibitory Effects of Glycyrrhizic Acid on the Accumulation of Advanced Glycation End Product and Its Receptor Expression

    OpenAIRE

    Cheng, Hong Sheng; Kong, Joana Magdelene Xiao Fang; Ng, Athena Xin Hui; Chan, Weng Keong; Ton, So Ha; Abdul Kadir, Khalid

    2014-01-01

    Abstract Beneficial effects of glycyrrhizic acid (GA), a bioactive extract of licorice root, in the prevention of metabolic syndrome have been consistently reported while advanced glycation end products (AGE) and receptor for advanced glycation end product (RAGE) are the leading factors in the development of diabetes mellitus. The aim of this study was to investigate the effects of GA on the AGE-RAGE axis using high-fat/high-sucrose (HF/HS) diet-induced metabolic syndrome rat models. Twenty f...

  13. Evidence for Activation of Toll-Like Receptor and Receptor for Advanced Glycation End Products in Preterm Birth

    Directory of Open Access Journals (Sweden)

    Taketoshi Noguchi

    2010-01-01

    Full Text Available Objective. Individuals with inflammation have a myriad of pregnancy aberrations including increasing their preterm birth risk. Toll-like receptors (TLRs and receptor for advanced glycation end products (RAGE and their ligands were all found to play a key role in inflammation. In the present study, we reviewed TLR and RAGE expression, their ligands, and signaling in preterm birth. Research Design and Methods. A systematic search was performed in the electronic databases PubMed and ScienceDirect up to July 2010, combining the keywords “preterm birth,” “TLR”, “RAGE”, “danger signal”, “alarmin”, “genomewide,” “microarray,” and “proteomics” with specific expression profiles of genes and proteins. Results. This paper provides data on TLR and RAGE levels and critical downstream signaling events including NF-kappaB-dependent proinflammatory cytokine expression in preterm birth. About half of the genes and proteins specifically present in preterm birth have the properties of endogenous ligands “alarmin” for receptor activation. The interactions between the TLR-mediated acute inflammation and RAGE-mediated chronic inflammation have clear implications for preterm birth via the TLR and RAGE system, which may be acting collectively. Conclusions. TLR and RAGE expression and their ligands, signaling, and functional activation are increased in preterm birth and may contribute to the proinflammatory state.

  14. Effects of candesartan cilexetil and amlodipine orotate on receptor for advanced glycation end products expression in the aortic wall of Otsuka Long-Evans Tokushima Fatty (OETFF) type 2 diabetic rats.

    Science.gov (United States)

    Kang, Min-Kyu; Chung, Woo-Baek; Hong, Seul-Ki; Kim, Ok-Ran; Ihm, Sang-Hyun; Chang, Kiyuk; Seung, Ki-Bae

    2016-04-01

    The receptor for advanced glycation end products (RAGE) plays a key role in the development of vascular inflammation and acceleration of atherosclerosis in type 2 diabetes. We investigated the effect of candesartan cilexetil (CDRT) and amlodipine orotate (AMDP) on the expression of RAGE in the aortic walls of Otsuka Long-Evans Tokushima Fatty (OLETF) rats and AGE-treated endothelial cells. Twenty five-week-old OLETF rats were randomized to 8 week treatments consisting of CDRT (n = 8), AMDP (n = 8) or saline (control, n = 8). Immunohistochemical and dihydroethidine staining revealed reduced RAGE and reactive oxygen species (ROS) signals in rats treated with CDRT or AMDP compared with control rats. Both CDRT and AMDP suppressed the expression of p22phox and p47phox NADPH oxidase subunits. However, only CDRT significantly reduced expression of phosphorylated extracellular signal regulated kinase (pERK)1/2 in the aortic wall of OLETF rats. In addition, both drugs reduced RAGE expression and total and mitochondrial ROS production in the AGE-treated endothelial cells. Both ARBs and CCBs reduced RAGE expression in the aortic walls of OLETF rats, which was attributed to decreased ROS production through inhibition of NADPH oxidase. In addition, only CDRT reduced aortic expression of RAGE via suppression of the ERK1/2 pathway unlike AMDP. PMID:26960737

  15. Children and Their Parents' Perceptions of Symptom Severity and Treatment Preference for Tourette Syndrome

    Directory of Open Access Journals (Sweden)

    Gholam Reza Dehbozorgi

    2010-08-01

    Full Text Available "n Objective: "n  "nThis study surveys children and their parents' perceptions, and their treatment preference of significant/bothersome symptoms in children with Tourette syndrome. "nMethods: "nThirty five children and adolescents who referred to an out-patient clinic of a Child Psychiatry Clinic were selected as subjects for this study. The children and their parents were interviewed about their perception of significant/bothersome symptoms of motor tics, vocal tics, learning difficulties, attention deficit disorder, hyperactivity, obsessions, compulsions, and rage attacks. "nResults: "nAbout two thirds of the subjects had symptom of rage. Inattentiveness and hyperactivity were observed in more than half of the children. There was a statistically significant difference between parents and their children in frequency of motor tics and rage attacks . Children reported the necessity for controlling and management of these symptoms less than their parents. "nDiscussion: "nThe rates of motor, vocal tics and rage attacks in the Iranian sample are similar to other studies. Rage attack is one of the most common significant/bothersome symptoms reported that should be treated. While motor tics were not rated among the most common features that should be treated in a study in Canada, it was the most common significant/bothersome symptom in Iran. Parents perceive motor tics and rage attacks as more significant/bothersome symptoms compared to children.

  16. Extract of Polygonum cuspidatum Attenuates Diabetic Retinopathy by Inhibiting the High-Mobility Group Box-1 (HMGB1 Signaling Pathway in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Eunjin Sohn

    2016-03-01

    Full Text Available High-mobility group box-1 (HMGB1 is a well-known pro-inflammatory cytokine. We aimed to investigate the effect of the ethanol extract of the root of P. cuspidatum (PCE on retinal inflammation in diabetic retinopathy. PCE (100 or 350 mg/kg/day was administered to diabetic rats for 16 weeks, and hyperglycemia and body weight loss developed in the diabetic rats. The retinal expression levels of HMGB1 and receptor for advanced glycation end products (RAGE and the activity of nuclear factor-kappa B (NF-κB in the retina were examined. Additionally, a chromatin immunoprecipitation assay was performed to analyze the binding of NF-κB binding to the RAGE promoter in the diabetic retinas. The levels of HMGB1 and RAGE expression, NF-κB activity, and NF-κB binding to the RAGE promoter were increased in the diabetic retinas. However, treatment with PCE ameliorated the increases in HMGB1 and RAGE expression, and NF-κB activity in the retina. In addition, in diabetic rats, retinal vascular permeability and the loosening of the tight junctions were inhibited by PCE. These findings suggest that PCE has a preventative effect against diabetes-induced vascular permeability by inhibiting HMGB1-RAGE-NF-κB activation in diabetic retinas. The oral administration of PCE may significantly help to suppress the development of diabetic retinopathy in patients with diabetes.

  17. Concentration of Endogenous Secretory Receptor for Advanced Glycation End Products and Matrix Gla Protein in Controlled and Uncontrolled Type 2 Diabetes Mellitus Patients

    Directory of Open Access Journals (Sweden)

    Dwi Yuniati Daulay

    2013-04-01

    Full Text Available BACKGROUND: Advanced glycation end products (AGE and their receptor (RAGE system play an important role in the development of diabetic vascular complications. Recently, an endogenous secretory RAGE (esRAGE has been identified as a novel splice variant, which lacks the transmembrane domain and is secreted in human sera. Interestingly, it was reported that esRAGE binds AGE ligands and neutralizes AGE actions. Many studies have reported that diabetes mellitus correlates with vascular calcification event and increases progressively in uncontrolled diabetes. Matrix Gla Protein (MGP is known to act as an inhibitor in vascular calcification. The aim of this study was to observe progress of vascular calcification in uncontrolled diabetes patient by biochemical markers MGP as inhibitor in vascular calcification, via mechanism of AGEs. METHODS: This study was an observational study with cross sectional design on adult type 2 diabetic male patients who were defined by the 2011 Indonesian diabetes mellitus consensus criteria. RESULTS: The results of this study showed that there was a positive significant correlation between esRAGE and HbA1C (r=0.651, p=0.009, and negative correlation between MGP and HbA1C (r=-0.465, p=0.081 in controlled diabetes group. In uncontrolled diabetes group there was a positive significant correlation between MGP and HbA1C (r=0.350, p=0.023, despite the fact esRAGE showed no significant correlation with HbA1C. There was no significant difference in level of esRAGE and MGP in controlled and uncontrolled diabetes group, but MGP showed lower level in uncontrolled diabetes group, contrary to esRAGE that had higher concentration. CONCLUSIONS: In diabetes condition, complications of vascular calcification are caused by the mechanism of increased AGE formation represented by esRAGE. In diabetes control it is very important to keep the blood vessels from complications caused by vascular calcification. KEYWORDS: type 2 diabetes mellitus

  18. Cilostazol attenuates the severity of peripheral arterial occlusive disease in patients with type 2 diabetes: the role of plasma soluble receptor for advanced glycation end-products.

    Science.gov (United States)

    Liu, Jhih-Syuan; Chuang, Tsung-Ju; Chen, Jui-Hung; Lee, Chien-Hsing; Hsieh, Chang-Hsun; Lin, Tsung-Kun; Hsiao, Fone-Ching; Hung, Yi-Jen

    2015-08-01

    Recent studies have demonstrated that the plasma soluble receptor for advanced glycation end-products (sRAGE) play a major role in developing macrovascular complications of type 2 diabetes, including peripheral arterial occlusion disease (PAOD). Cilostazol is an antiplatelet, antithrombotic agent, which has been used for the treatment of PAOD. We hypothesized that cilostazol attenuates the severity of PAOD in patients with type 2 diabetes through the augmentation of plasma sRAGE. Ninety type 2 diabetic patients with PAOD defined as intermittent claudication with ankle-brachial index (ABI) ≦0.9 were recruited for an open-labeled, placebo-controlled study for 52 weeks with oral cilostazol 100 mg twice daily (n = 45) or placebo (n = 45). Fasting plasma sRAGE, endothelial variables of E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), and inflammatory markers of high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor-α (TNF-α) were determined. After completely the 52-week treatment program, the ABI values were elevated in cilostazol group (P < 0.001). The plasma sRAGE was significantly increased (P = 0.007), and hsCRP, sVCAM, and E-selectin concentrations were significantly decreased (P = 0.028, <0.001 and <0.001, respectively) with cilostazol treatment. In a partial correlation analysis with adjustments for sex and age, the net change of sRAGE significantly correlated with the change of ABI in the cilostazol group (P = 0.043). In a stepwise multiple regression model, only the change with regards to sRAGE was significantly associated with the change of ABI (P = 0.046). Our results suggest that cilostazol may effectively attenuate the severity of PAOD in patients with type 2 diabetes. Plasma sRAGE plays a role as an independent predictor for improving the index of PAOD. PMID:25666934

  19. The Receptor for Advanced Glycation End Products Activates the AIM2 Inflammasome in Acute Pancreatitis.

    Science.gov (United States)

    Kang, Rui; Chen, Ruochan; Xie, Min; Cao, Lizhi; Lotze, Michael T; Tang, Daolin; Zeh, Herbert J

    2016-05-15

    Severe acute pancreatitis (AP) is responsible for significant human morbidity and mortality worldwide. Currently, no specific treatments for AP exist, primarily due to the lack of a mechanistic understanding of sterile inflammation and the resultant multisystem organ dysfunction, the pathologic response of AP linked to early death. In this study, we demonstrate that the class III major histocompatibility region III receptor for advanced glycation end products (RAGE) contributes to AP by modulating inflammasome activation in macrophages. RAGE mediated nucleosome-induced absent in melanoma 2 (but not NLRP3) inflammasome activation by modulating dsRNA-dependent protein kinase phosphorylation in macrophages. Pharmacological and genetic inhibition of the RAGE-dsRNA-dependent protein kinase pathway attenuated the release of inflammasome-dependent exosomal leaderless cytokines (e.g., IL-1β and high-mobility group box 1) in vitro. RAGE or absent in melanoma 2 depletion in mice limited tissue injury, reduced systemic inflammation, and protected against AP induced by l-arginine or cerulein in experimental animal models. These findings define a novel role for RAGE in the propagation of the innate immune response with activation of the nucleosome-mediated inflammasome and will help guide future development of therapeutic strategies to treat AP. PMID:27045109

  20. Metformin protects against hyperglycemia-induced cardiomyocytes injury by inhibiting the expressions of receptor for advanced glycation end products and high mobility group box 1 protein.

    Science.gov (United States)

    Zhang, Ting; Hu, Xiaorong; Cai, Yuli; Yi, Bo; Wen, Zhongyuan

    2014-03-01

    Metformin (MET), an anti-diabetic oral drug with antioxidant properties, has been proved to provide cardioprotective effects in patients with diabetic disease. However, the mechanism is unclear. This study aimd to investigate the effects of MET on the expressions of receptor for advanced glycation end products (RAGE) and high mobility group box 1 protein (HMGB1) in hyperglycemia-treated neonatal rat ventricular myocytes. Cardiocytes were prepared and cultured with high glucose and different concentrations of MET. The expressions of RAGE and HMGB1 were evaluated by Western blot analysis. The superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), lactate dehydrogenase (LDH) and creatine kinase (CK) were measured. After 12 h-incubation, MET significantly inhibited the increase of MDA, TNF-α, LDH and CK levels induced by high glucose, especially at the 5 × 10(-5) to 10(-4 )mol/L concentrations while inhibiting the decrease of SOD level. Meanwhile, RAGE and HMGB1 expression were significantly increased induced by hyperglycaemia for 24 h (P < 0.05). MET inhibited the expressions of RAGE and HMGB1 in a dose-dependent manner, especially at the 5 × 10(-5) to 10(-4 )mol/L concentrations (P < 0.05). In conclusion, our study suggested that MET could reduce hyperglycemia-induced cardiocytes injury by inhibiting the expressions of RAGE and HMGB1. PMID:24420848

  1. Exploring of protein - protein interactions at the solid - aqueous interface by means of contact angle measurements.

    Science.gov (United States)

    Grabowska, I; Dehaen, W; Radecka, H; Radecki, J

    2016-05-01

    In this article we present the results of the studies on interactions between the VC1 domain of the Receptor for Advanced Glycation End Products (RAGE) and its ligand, the S100B protein, performed by contact angle measurements. Histidine-tagged (His6) VC1-RAGE domain was covalently bonded to Cu(II) or Ni(II) complexes with dipyrromethene (DPM) self-assembled on gold surface. The method based on the theory of van Oss was used for the purpose of determining the Lifshitz-van der Waals (γ(LW)) component as well as the electron acceptor-electron donor (the Lewis acid-base, γ(+)-γ(-)) parameters of the VC1-RAGE-S100B complex. Moreover, the surface free energies of the interactions between the VC1 domain attached to the surface and the ligand present in the aqueous phase were determined. The specificity of the VC1- RAGE interactions with the ligand studied was also proved. PMID:26918510

  2. Factors Influencing Oxidative Imbalance in Pulmonary Fibrosis: An Immunohistochemical Study

    Directory of Open Access Journals (Sweden)

    Simona Inghilleri

    2011-01-01

    Full Text Available Background. Idiopathic Pulmonary Fibrosis (IPF is a fatal lung disease of unknown etiology characterized by interstitial fibrosis determining irreversible distortion of pulmonary architecture. Reactive oxygen species (ROS and markers of oxidative stress play a pivotal role in human IPF pathology, possibly through induction of epithelial-mesenchymal transition (EMT. Methods. We investigated by immunohistochemistry, in UIP and COP tissue samples, the expression of most relevant markers of the molecular interplay involving RAGE, oxidant/antioxidant balance regulation, tissue nitrosylation, and mediators of EMT. Results. In both UIP and COP, the degree of RAGE expression was similarly high, while SODs and i-NOS, diffusely present in COP endoalveolar plugs, were almost absent in UIP fibroblast foci. A lower degree of tissue nitrosilation was observed in UIP than in COP. Conclusions. Fibroblast lesions of UIP and of COP share a similar degree of activation of RAGE, while antioxidant enzyme expression markedly reduced in UIP.

  3. Skin Autofluorescence Relates to Soluble Receptor for Advanced Glycation End-Products and Albuminuria in Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    J. Škrha

    2013-01-01

    Full Text Available The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE in patients with diabetes. Skin autofluorescence (AF assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/ and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.39 ± 0.54, 2.63 ± 0.73 versus 1.96 ± 0.33 AU; P<0.0001. Positive correlation of AF with sRAGE was detected in T1DM and T2DM (r=0.37, P<0.02 and r=0.60, P<0.0001, but not in controls. Significantly higher AF values were found in patients with positive albuminuria as compared to those with normal albuminuria. Similarly, higher AF was detected in patients with endothelial dysfunction expressed by vWF, ICAM-1, and VCAM-1. Multiple regression analysis revealed independent association of skin AF with age, sRAGE, and albumin-creatinine ratio in patients with diabetes (R2=0.38. Our study confirms that AF is elevated in patients with diabetes, especially with positive albuminuria and endothelial dysfunction. The strong and independent relationship between AF and sRAGE supports the idea that AF may reflect AGEs/RAGE interactions. The exact mechanism remains to be established.

  4. Age-related accumulation of advanced glycation end-products-albumin, S100β, and the expressions of advanced glycation end product receptor differ in visceral and subcutaneous fat.

    Science.gov (United States)

    Son, Kuk Hui; Son, Myeongjoo; Ahn, Hyosang; Oh, Seyeon; Yum, Yoonji; Choi, Chang Hu; Park, Kook Yang; Byun, Kyunghee

    2016-08-19

    Visceral fat induces more inflammation by activating macrophages than subcutaneous fat, and inflammation is an underlying feature of the pathogeneses of various diseases, including cardiovascular disease and diabetes. Advanced glycation end products (AGEs), S100β, and their receptors, the receptor for advanced glycation end products (RAGE), lead to macrophage activation. However, little information is available regarding the differential accumulations of AGE-albumin (serum albumin modified by AGEs), S100β, or expressions of RAGE in different adipocyte types in fat tissues. In this study, the authors investigated whether age-related AGE-albumin accumulations S100β level, and RAGE expressions differ in subcutaneous and visceral fat tissues. Subcutaneous and visceral fat were harvested from 3- and 28-week-old rats. Macrophage activation was confirmed by Iba1 staining, and AGE-albumin accumulations and RAGE expressions were assessed by confocal microscopy. S100β were analyzed by immunoblotting. It was found that activated macrophage infiltration, AGE-albumin accumulation, and S100β in visceral fat was significantly greater in 28-week-old rats than in 3-week-old rats, but similar in subcutaneous fat. The expression of RAGE in visceral fat was much greater in 28-week-old rats, but its expression in subcutaneous fat was similar in 3- and 28-week-old rats. Furthermore, inflammatory signal pathways (NFκB, TNF-α) and proliferation pathways (FAK) in visceral fat were more activated in 28-week-old rats. These results imply that age-related AGE-albumin accumulation, S100β, and RAGE expression are more prominent in visceral than in subcutaneous fat, suggesting that visceral fat is involved in the pathogenesis of inflammation-induced diseases in the elderly. PMID:27301641

  5. Modélisation de la morphodynamique fluviale pour la recherche des relations habitat/faune aquatique

    Directory of Open Access Journals (Sweden)

    LE COARER Y.

    1995-04-01

    Full Text Available Un matériel de topographie électronique et des méthodes adaptées nous procurent rapidité, précision et souplesse dans le repérage spatial des éléments morphodynamiques et biologiques. Le traitement informatique des données fait appel à des techniques de repérage curviligne d'interpolation et de maillage. La structure numérique et topologique de cet outil de recherche offre de nombreuses possibilités de calculs et permet des visualisations conviviales des résultats.

  6. Co-morbid disorders in Tourette syndrome

    DEFF Research Database (Denmark)

    Debes, Nanette Marinette Monique

    2013-01-01

    Tourette syndrome (TS) is often accompanied by other symptoms and syndromes. The two best-known co-morbidities are Attention Deficit Hyperactivity Disorder (ADHD) and Obsessive Compulsive Disorder (OCD), but also other conditions like rage-attacks, depression, and sleeping disturbances are frequent......-morbid disorders, like rage, anxiety, and conduct disorders. The symptoms of a co-morbid disorder might appear prior to the time that tics reach clinical attention. The TS phenotype probably changes during the course of the disease. The exact aetiology of the co-occurrence of co-morbid disorders and TS is not...

  7. “Entre a cólera e o ódio”: justiça popular e assassinatos no Sudoeste do Paraná (1920-1930 - 10.4025/dialogos.v13i2.414 “Between rage and hatred”: street justice and murders in southwestern Paraná (1920-1930 - doi: 10.4025/dialogos.v13i2.414 “Entre la cólera y el odio”: justicia popular y asesinatos en el sureste del estado de Paraná (1920-1930

    Directory of Open Access Journals (Sweden)

    Aruanã Antônio dos Passos

    2010-08-01

    Full Text Available O artigo discute a relação entre a justiça e a violência na Região Sudoeste do Paraná nos anos anteriores à “efetiva” colonização da região (1920-1930. Buscamos compreender as relações estabelecidas em um sistema punitivo-repressivo (aparelho judiciário que conviveu com a violência popular, bem como a forma e as condições dessas relações. Para tanto, a análise do processo contra um habitante da região e seu filho transcorrido em 1920 na Comarca de Clevelândia é capaz de demonstrar as dificuldades que o aparelho judiciário encontrou diante da violência no Interior do Paraná, onde a justiça e a violência mantinham uma relação ambivalente.The article discusses the relationship between justice and violence in the southwestern region of Paraná in the years prior to the “effective” colonization of the region (1920-1930. We sought to comprehend how, under what conditions and which relationships were established by a punitive-repressive system (the judiciary apparatus that dealt with street justice. To that end, an analysis of the 1920 case against an inhabitant of the region and his son in Clevelândia County demonstrates the difficulties the judiciary apparatus faced against violence in the Paraná countryside, where justice and violence had an ambiguous relationship.El artículo discute la relación entre la justicia y la violencia en el sureste del Estado de Paraná (Brasil durante los años anteriores a la “efectiva” colonización de la región (1920-1930. Buscamos comprender de qué forma y cuáles fueron las condiciones y relaciones que se establecieron entre un sistema punitivo/represivo (aparato judicial y la violencia popular. Para ello, el análisis del proceso judicial contra un habitante y su hijo, ocurrido en la comarca de Clevelândia en 1920, permite demostrar las dificultades con las que tropezó el aparato judicial frente a la violencia en el interior del Estado de Paraná, donde justicia y violencia mantenían una relación ambivalente.

  8. Altered Behavior Associated with Damage to the Ventromedial Hypothalamus: A Distinctive Syndrome

    OpenAIRE

    Flynn, Frederick G.; Cummings, Jeffrey L.; Uwamie Tomiyasu

    1988-01-01

    An adult manifested a tetrad of neurobehavioral findings consisting of episodic rage, emotional lability, hyperphagia with obesity, and memory impairment with intellectual decline following surgical removal of a craniopharyngioma. Post-mortem investigation of the topography of the lesion as well as review of previously reported cases suggest that this tetrad represents a specific neurobehavioral syndrome referable to damage to the ventromedial hypothalamus.

  9. "I Asked My Parents Why a Wall Was so Important": Teaching about the GDR and Post-Reunification Germany

    Science.gov (United States)

    Streitwieser, Bernhard; Lys, Franziska

    2008-01-01

    Fifteen years after the "peaceful revolutions" brought about the collapse of communism and the reunification of East and West Germany, a heated debate rages over the legacy of communism and the continuing impact of 1989. This paper describes a new course that explores the contentious issues in this debate through the innovative use of the course…

  10. Differences in plasma and sputum biomarkers between COPD and COPD-asthma overlap.

    Science.gov (United States)

    Iwamoto, Hiroshi; Gao, Jing; Koskela, Jukka; Kinnula, Vuokko; Kobayashi, Hideo; Laitinen, Tarja; Mazur, Witold

    2014-02-01

    The pathophysiological features of chronic obstructive pulmonary disease (COPD)-asthma overlap are poorly understood and there has been no study of plasma or sputum biomarkers in overlap patients. In order to clarify the similarity and differences between overlap and COPD or asthma, we have investigated four potential biomarkers of COPD: surfactant protein A (SP-A), soluble receptor for advanced glycation end-products (sRAGE), myeloperoxidase (MPO) and neutrophil gelatinase-associated lipocalin (NGAL). SP-A and sRAGE are pneumocyte-derived markers. MPO and NGAL are neutrophil-derived molecules, but NGAL can also be expressed by respiratory epithelial cells. Plasma levels of SP-A and sRAGE and induced sputum levels of MPO and NGAL were measured by enzyme immunoassay/ELISA in 134 subjects: nonsmokers (n=26), smokers (n=23), asthma (n=32), COPD (n=39) and COPD-asthma overlap patients (n=14). In patients with COPD-asthma overlap, sputum MPO and plasma SP-A were significantly elevated whereas plasma sRAGE levels were reduced compared with asthma patients. Only sputum NGAL was significantly elevated in COPD-asthma overlap compared with COPD (p=0.00016) and could be used to differentiate patients with overlap from those with COPD. Increased induced sputum levels of NGAL might be a characteristic feature of overlap, suggesting enhanced neutrophilic airway inflammation and/or airway epithelial injury in COPD-asthma overlap. PMID:23794464

  11. Racist-Sexist-Hate Speech on College Campuses: Free Speech v. Equal Protection.

    Science.gov (United States)

    Jahn, Karon L.

    On college campuses today, the debate rages over whether self-restraint and tolerance for nonconformity is overriding a need to protect certain individuals and groups from objectionable speech. Some administrators, students, and alumni wish to prevent "bad speech" in the form of expressions of racism, sexism, and the like. Advocates for limiting…

  12. Fiddling while the ice melts? How organizational scholars can take a more active role in the climate change debate

    NARCIS (Netherlands)

    S.M. Ansari (Shahzad); B. Gray (Barbara); F.H. Wijen (Frank)

    2011-01-01

    textabstractThe debate over anthropogenic climate change or the idea that human activities are altering the physical climate of the planet continues to rage amid seemingly irreconcilable differences, both within the developed world and between developed and less developed countries. With high uncert

  13. Landau-Zener transition in quadratic-nonlinear two-state systems

    OpenAIRE

    Ishkhanyan, A. M.

    2009-01-01

    A comprehensive theory of the Landau-Zener transition in quadratic nonlinear two-state systems is developed. A compact analytic formula involving elementary functions only is derived for the final transition probability. The formula provides a highly accurate approximation for the whole rage of the variation of the Landau-Zener parameter.

  14. HIV-1 Tat Regulates Occludin and Aβ Transfer Receptor Expression in Brain Endothelial Cells via Rho/ROCK Signaling Pathway

    Science.gov (United States)

    Chen, Yanlan; Jiang, Wenlin; Wu, Xianghong; Ye, Biao; Zhou, Xiaoting

    2016-01-01

    HIV-1 transactivator protein (Tat) has been shown to play an important role in HIV-associated neurocognitive disorders. The aim of the present study was to evaluate the relationship between occludin and amyloid-beta (Aβ) transfer receptors in human cerebral microvascular endothelial cells (hCMEC/D3) in the context of HIV-1-related pathology. The protein expressions of occludin, receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP1) in hCMEC/D3 cells were examined using western blotting and immunofluorescent staining. The mRNA levels of occludin, RAGE, and LRP1 were measured using quantitative real-time polymerase chain reaction. HIV-1 Tat at 1 µg/mL and the Rho inhibitor hydroxyfasudil (HF) at 30 µmol/L, with 24 h exposure, had no significant effect on hCMEC/D3 cell viability. Treatment with HIV-1 Tat protein decreased mRNA and protein levels of occludin and LRP1 and upregulated the expression of RAGE; however, these effects were attenuated by HF. These data suggest that the Rho/ROCK signaling pathway is involved in HIV-1 Tat-mediated changes in occludin, RAGE, and LRP1 in hCMEC/D3 cells. HF may have a beneficial influence by protecting the integrity of the blood-brain barrier and the expression of Aβ transfer receptors.

  15. 糖基化终末产物及其受体在糖尿病大鼠胃组织中的分布 (Distribution of advanced glycation end products and their receptor in the stomach of diabetic rats)

    DEFF Research Database (Denmark)

    Tian, Jia Xing; Zhao, Jingbo; Li, Min;

    2015-01-01

    AIM: To observe the distribution of advanced glycation end products (AGEs) and their receptor (RAGE) in the stomach of diabetic rats. METHODS: Diabetes mellitus (DM) and control (CON) rats were reared for eight weeks. Fasting plasma glucose (FPG), glycated serum protein (GSP) and gastric layer...... CON group (P < 0.05). The expression of AGEs and RAGE in the mucosa (5.66 ± 1.90 vs 2.25 ± 0.52, 2.79 ± 0.54 vs 1.70 ± 0.30) and muscle (37.37 ± 7.38 vs 24.32 ± 4.02, 4.26 ± 0.80 vs 3.59 ± 0.37) layers of the stomach was significantly higher in the DM group than in the CON group (P < 0.05). CONCLUSION......: The expression of AGEs and RAGE is up-regulated in the stomach of diabetic rats. The increased levels of AGE and RAGE in gastric tissue may contribute to diabetic gastrointestinal dysfunction. © 2015 Baishideng Publishing Group Inc. All rights reserved. Key Words: Diabetes mellitus; Stomach; Advanced...

  16. Effect of Creative Drama-Based Group Guidance on Male-Adolescents' Conflict Resolution Skills

    Science.gov (United States)

    Yavuzer, Yasemin

    2012-01-01

    Problem Statement: This study assumes that conflict itself is not constructive or destructive, whereas the path chosen to resolve the conflict is what leads to constructive or destructive results. When individuals resolve conflicts in a destructive manner, they instill feelings of anger, rage, hostility and violence in the people involved. On the…

  17. Dublini festival II : Külalised. Muust / Jaak Rähesoo

    Index Scriptorium Estoniae

    Rähesoo, Jaak, 1941-

    2002-01-01

    Ka Kopenhaageni Betty Nanseni Teatri näidatud Robert Wilsoni tehtud Georg Büchneri "Woyzecki" tõlgenduse ning noore inglise trupi näidatud Edward Halli lavastatud William Shakespeare "Rose Rage" ("Henry VI") etenduse lavakujundusest ja -kostüümidest.

  18. Between green and grey

    NARCIS (Netherlands)

    Jeanet Kullberg

    2016-01-01

    Taking cuttings is cool. Growing vegetables is all the rage. Green oases can now be found scattered throughout Dutch towns and cities: community gardens and roof gardens where residents can go to relax and enjoy themselves, improve the appearance of their neighbourhood and meet their fellow resident

  19. Teaching the Arts of Public Theology

    Science.gov (United States)

    Casey, Shaun

    2006-01-01

    While intense discussions are raging over the definition and status of public theology, within graduate theological education relatively little attention is being paid to the teaching of the practices of public theology. This article explores one venue in graduate theological education that attempts to equip seminary and divinity school students…

  20. Freedom, Revolt and "Citizenship": Three Pillars of Identity for Youngsters Living on the Streets of Rio de Janeiro

    Science.gov (United States)

    Butler, Udi Mandel

    2009-01-01

    This article investigates the experiences, identities and aspirations of children and adolescents living on the streets of Rio de Janeiro, formed as they are around the conditions of exclusion, violence and discrimination. Significant here are experiences of "revolta"--revolt or rage--the aspiration for freedom through life on the street and the…

  1. United Nations Day (联合国成立纪念日)

    Institute of Scientific and Technical Information of China (English)

    胡亚萍

    2002-01-01

    As World War Ⅱ raged on with no end in sight, the United Nations was conceived as a way to help prevent future world wars. As early as 1943, government officials from the United States, Great Britain, and the Soviet Union agreed to meet to discuss plans for an international peacekeeping organization.

  2. Nigeria : à qui profite le pétrole ?

    OpenAIRE

    Pérouse de Montclos, Marc-Antoine

    2015-01-01

    Le débat fait rage entre d'un côté les habitants du Sud producteur qui veulent garder pour eux les revenus de l'or noir, et de l'autre ceux qui a contrario estiment qu'il faut partager les richesses entre tous les États.

  3. Complete Genome Sequence of a Rabies Virus Strain Isolated from a Brown Bear (Ursus arctos) in Primorsky Krai, Russia (November 2014)

    Science.gov (United States)

    Deviatkin, Andrei A.; Ananiev, Vasily Y.; Dedkov, Vladimir G.; Shipulin, German A.; Sokol, Nataliya N.; Dombrovskaya, Irina E.; Galkina, Irina V.; Shmelev, Mikhail E.; Gorelikov, Vladimir N.; Kozhan, Valentina N.; Prosyannikova, Marina N.; Aramilev, Sergei V.; Fomenko, Pavel V.

    2016-01-01

    We report here the complete genome sequence (GenBank KP997032) of rabies virus strain RABV/Ursus arctos/Russia/Primorye/PO-01/2014, isolated in November 2014 from a brown bear (Ursus arctos) that attacked a person in Primorsky Krai (Russian Federation). This strain was clustered into the Eurasian genetic subgroup of genotype 1 (street rage). PMID:27389270

  4. "Their Experience Is the Immigrant Experience": Ellis Island, Documentary Film, and Rhetorically Reversible Whiteness

    Science.gov (United States)

    Irwin, Meryl J.

    2013-01-01

    Political advocates on the ideological right have long taken seriously what their counterparts on the left have not: white racialized affect. As left activists and scholars have alternately lamented and raged over the steady creep of the "middle" to the "right," they have documented in detail the outcomes of whites' refusal to engage in "genuine"…

  5. Characterization of Static/Dynamic Topological Routing For Grid Networks

    DEFF Research Database (Denmark)

    Gutierrez Lopez, Jose Manuel; Cuevas, Ruben; Riaz, M. Tahir; Pedersen, Jens Myrup; Madsen, Ole Brun

    2009-01-01

    Grid or 2D Mesh structures are becoming one of the most attractive network topologies to study. They can be used in many different fields raging from future broadband networks to multiprocessors structures. In addition, the high requirements of future services and applications demand more flexible...

  6. Neurofeedback, Affect Regulation and Attachment: A Case Study and Analysis of Anti-Social Personality

    Science.gov (United States)

    Fisher, Sebern F.

    2007-01-01

    This case study examines the effects of neurofeedback (EEG biofeedback) training on affect regulation in a fifty-five year-old man with a history marked by fear, rage, alcoholism, chronic unemployment and multiple failed treatments. He had been diagnosed with ADHD and attachment disorder and met criteria for anti-social personality disorder. The…

  7. Hard Facts and Soft Skills

    Science.gov (United States)

    Terego, Alex

    2009-01-01

    The argument now raging in academic circles pits those who espouse teaching 21st century skills against those who believe that schools should be teaching explicit and well-sequenced content. This debate has largely been framed as an either-or proposition. In this author's view, portraying this debate as one between two mutually exclusive sides…

  8. The First Amendment and the Web: The Internet Porn Panic and Restricting Indecency in Cyberspace.

    Science.gov (United States)

    Mullin, Dorothy Imrich

    In the wake of the Communications Decency Act of 1996, discussions have raged both online and in the press about free speech, online pornography, and the protection of children. This paper discusses the legal and social science issues surrounding content regulation of the World Wide Web and the Internet as a whole, with an emphasis on the…

  9. Personal Accounts and Autobiographical Memories.

    Science.gov (United States)

    Stillwell, Arlene M.; Baumeister, Roy F.

    A primary internal concern of an intimate relationship is that each partner communicates with the other. A breakdown of communication may occur when an occurrence construed as minor or negligible by one partner precipitates a major explosion of anger, rage, and hurt by the other. Both partners may be at fault for allowing a disagreement to reach…

  10. Re-weaving fragmented space-time. Notes from a mapping project in Palestine Ritessere uno spaziotempo frammentato. Note da un progetto di mappatura in Palestina

    Directory of Open Access Journals (Sweden)

    Nasser Abourahme

    2010-03-01

    Full Text Available Defeat. Failure. Loss. Archives of rage. The sedimentation of deferred dreams. Each new juncture in (postcolonial temporality, every potential opening (even those that formally ‘end’ in victory seems to bring with it – each time with seemingly equal totality – these relational figures. And yet somehow the wheel keeps turning. Each repetition feels somewhat different from the last.

  11. A Dynamic Cascade Model of the Development of Substance-Use Onset

    Science.gov (United States)

    Dodge, Kenneth A.; Malone, Patrick S.; Lansford, Jennifer E.; Miller, Shari; Pettit, Gregory S.; Bates, John E.

    2009-01-01

    Although the onset of illicit substance use during adolescence can hit parents abruptly like a raging flood, its origins likely start as a trickle in early childhood. Understanding antecedent factors and how they grow into a stream that leads to adolescent drug use is important for theories of social development as well as policy formulations to…

  12. Multiculturalism Swedish Style: Shifts and Sediments in Educational Policies and Textbooks

    Science.gov (United States)

    Gruber, Sabine; Rabo, Annika

    2014-01-01

    In the almost two decades that have passed since the Swedish parliament declared that Sweden is a multicultural society, debates about immigrants, about multiculturalism and about different ways of being a citizen have raged. So far there has been no stepping away from the declaration. In the rhetorical arena multiculturalism is still a word with…

  13. Validation of the presence of comorbidities in a Danish clinical cohort of children with tourette syndrome

    DEFF Research Database (Denmark)

    Debes, N.M.M.M.; Hjalgrim, H.; Skov, L.

    2008-01-01

    Tourette syndrome (TS) is characterized by the presence of motor and vocal tics and is often accompanied by comorbid symptoms. We assessed the frequency of the comorbid symptoms obsessive-compulsive disorder obsessive-compulsive disorder, attention-deficit hyperactivity disorder (ADHD), rage...

  14. Follow the Leaders? An Analysis of Convergence and Innovation of Faculty Recruiting Practices in US Business Schools

    Science.gov (United States)

    Finch, David; Deephouse, David L.; O'Reilly, Norm; Massie, Tyler; Hillenbrand, Carola

    2016-01-01

    The debate associated with the qualifications of business school faculty has raged since the 1959 release of the Gordon-Howell and Pierson reports, which encouraged business schools in the USA to enhance their legitimacy by increasing their faculties' doctoral qualifications and scholarly rigor. Today, the legitimacy of specific faculty…

  15. Scanning for Digitization Projects

    Science.gov (United States)

    Wentzel, Larry

    2007-01-01

    Librarians and archivists find themselves facing the prospect of digitization. Everyone is doing it, everyone needs it. Discussions rage nationally and internationally concerning what to digitize and the best means to present and retain digital objects. Digitization is the act of making something digital, expressing a physical object "in numerical…

  16. The Effects of Haloperidol on Discrimination Learning and Behavioral Symptoms in Autistic Children.

    Science.gov (United States)

    Anderson, Lowell T.; And Others

    1989-01-01

    The double-blind and placebo controlled study with 45 autistic children (ages 2-7) found that the drug, haloperidol, showed powerful therapeutic effects in reducing behavioral symptoms when administered for 4 weeks at doses raging from 0.25 to 4.0 milligrams/day. Learning effects were not found. (Author/DB)

  17. Low Endogenous Secretory Receptor for Advanced Glycation End-Products Levels Are Associated With Inflammation and Carotid Atherosclerosis in Prediabetes.

    Science.gov (United States)

    Di Pino, Antonino; Urbano, Francesca; Zagami, Rose Maria; Filippello, Agnese; Di Mauro, Stefania; Piro, Salvatore; Purrello, Francesco; Rabuazzo, Agata Maria

    2016-04-01

    Pre-diabetes is associated with advanced vascular damage. Our data shows that subjects with pre-diabetes exhibited low esRAGE plasma levels and gene expression, which are inversely related with markers of inflammation and atherosclerotic risk. PMID:26885882

  18. Massive Open Online Librarianship: Emerging Practices in Response to MOOCs

    Science.gov (United States)

    Mune, Christina

    2015-01-01

    Massive Open Online Courses, or MOOCs, have recently emerged as a disruptive pedagogy gaining rapid momentum in higher education. In some states, proposed legislations would accredit MOOCs to provide college-credit courses in the name of cost saving, efficiency and access. While debates rage regarding the place of MOOCs in higher education, some…

  19. Academic Superheroes? A Critical Analysis of Academic Job Descriptions

    Science.gov (United States)

    Pitt, Rachael; Mewburn, Inger

    2016-01-01

    For over a decade, debate has raged about the nature and purpose of the PhD, including its role as preparation for working in academia. Academic work has changed a great deal in the last 60 years, yet our doctoral curriculum has remained relatively static. While there is increasing interest in matching PhD programmes to "real world"…

  20. Advanced Glycation End-Products and Their Receptors: Related Pathologies, Recent Therapeutic Strategies, and a Potential Model for Future Neurodegeneration Studies.

    Science.gov (United States)

    Pinkas, Adi; Aschner, Michael

    2016-05-16

    Advanced glycation end products (AGEs) are the result of a nonenzymatic reaction between sugars and proteins, lipids, or nucleic acids. AGEs are both consumed and endogenously formed; their accumulation is accelerated under hyperglycemic and oxidative stress conditions, and they are associated with the onset and complication of many diseases, such as cardiovascular diseases, diabetes, and Alzheimer's disease. AGEs exert their deleterious effects by either accumulating in the circulation and tissues or by receptor-mediated signal transduction. Several receptors bind AGEs: some are specific and contribute to clearance of AGEs, whereas others, like the RAGE receptor, are nonspecific, associated with inflammation and oxidative stress, and considered to be mediators of the aforementioned AGE-related diseases. Although several anti-AGE compounds have been studied, understanding the underlying mechanisms of RAGE and targeting it as a therapeutic strategy is becoming increasingly desirable. For achieving these goals efficiently and expeditiously, the C. elegans model has been suggested. This model is already used for studying several human diseases and, by expressing RAGE, could also be used to study RAGE-related pathways and pathologies to facilitate the development of novel therapeutic strategies. PMID:27054356

  1. Danish Municipal planning in Change

    DEFF Research Database (Denmark)

    Møller, Jørgen

    2003-01-01

    are breaking up, that the fight for planning competence in the open country is raging and that the protection og nature-friendly legislation, for which the previous gouvernment was responsible, is under quick phasing-out, at the same time as the traditional professional urban planner standards are...

  2. Facing Our Future: Children in the Aftermath of Immigration Enforcement

    Science.gov (United States)

    Chaudry, Ajay; Capps, Randy; Pedroza, Juan Manuel; Castaneda, Rosa Maria; Santos, Robert; Scott, Molly M.

    2010-01-01

    The United States is engaged in an intense debate about immigration policy, particularly with regard to unauthorized immigrants. Debates rage about the economic contributions of immigrants to the U.S. economy, job competition, tax payments and fiscal costs, and the integration of immigrants in communities and the larger society. Largely absent…

  3. Dairy Sector Profit Squeeze

    Institute of Scientific and Technical Information of China (English)

    WANG PEI

    2006-01-01

    @@ Like any other industries in China,the potential in the dairy industry is huge but competition is tough,The big players such as Mengniu and Yili are happy to stay engaged in a price war that has raged for the last year,seemingly not affected by rising raw material prices.

  4. Oriana Fallaci viha ja raev / Urmas Kiil

    Index Scriptorium Estoniae

    Kiil, Urmas

    2006-01-01

    Ajakirjanik ja kirjanik Oriana Fallaci, kelle artikkel New Yorgis toimunud terrorirünnaku muljetest avaldati 29. sept. 2001. a. Itaalia juhtivas ajalehes Corriere della sera, avaldas peagi raamatu "Raev ja uhkus" (The Rage and Pride). Raamatus mõistab ta islamimaailma mööndusteta tervikuna hukka

  5. Massive and Open

    Science.gov (United States)

    Fasimpaur, Karen

    2013-01-01

    MOOCs--massive open online courses--are all the rage these days, with hundreds of thousands of participants signing up and investors plunking down millions to get a piece of the pie. Why is there so much excitement about this new disruptive form of online learning, and how does this model apply to professional learning for teachers? Traditional…

  6. A Tale of Two Continents

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Eurasian countries unite to seek a way out of the global financial crisis How should the world cope with the raging financial storm? That question topped the agenda of the Seventh Asia-Europe Meeting(ASEM), held on October 24-25 in Beijing.At the biennial summit, leaders from 45

  7. Nuclear Power on Energy Agenda

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The big debate on whether or not to use nuclear power as an energy option has raged among countries like the U.S., Britain, and Germany for decades, with not even the advent and threat of global warming forcing a conclusion. China, however, has always stressed energy diversity and been determined to develop and use this alternative energy source.

  8. Advocacy in Action: Annual 2006 DPI/NGO Conference at the United Nations

    Science.gov (United States)

    Brown, Nancy

    2007-01-01

    The Association for Childhood Education International (ACEI) was again represented at the annual 2006 DPI/NGO conference, along with 1,600 participants from around the world. The mood this year was somber and quite serious, possibly in response to the uncertainty created by the Middle East crisis that was raging while the conference was taking…

  9. The Leadership Enigma Is More than Semantics.

    Science.gov (United States)

    Achilles, C. M.

    1992-01-01

    Debate has long raged about the relative merits of leadership, management, and administration. This article questions the utility of valuing instructional leadership over management. Administrators wear both hats. The paper describes a set of definitions and relationships that could remove some "value" connotations and frames a model for relating…

  10. Green Science: Wildfires

    Science.gov (United States)

    Palliser, Janna

    2012-01-01

    Every summer, fires rage in different areas of the western United States. They are often massive, out of control, and extremely destructive. How do these fires begin and how are they controlled? What are the overall impacts of a wildfire? Are there any benefits of a wildfire? These questions will be addressed in this article. (Contains 3 online…

  11. A Delinquent Discipline: The Rise and Fall of Criminology

    Science.gov (United States)

    Adams, Mike S.

    2009-01-01

    What is the cause of crime? One can find answers in many places: in Genesis, in the plays of Sophocles and Shakespeare, in Dostoyevsky's "Crime and Punishment" and "Brothers Karamazov." The many answers include impiety, appetite, rage, and even the lure of transgression itself. For many, religious and poetic insights still offer the most…

  12. Global health in an open world requires an open mind

    DEFF Research Database (Denmark)

    Sodemann, Morten

    suddenly re-emerged in Syria, measles is popping up all over Europe, West Nile fever came from Uganda to USA and is raging in Texas, Dengue and yellow fever threatens to spread to new areas of Europe and the southern states of USA, patients with extremely drug resistant TB have been travelling freely...

  13. Access and Quality in Education in Resettlement Schools: The Case Study of Zvivingwi Secondary School in Gutu District, Masvingo Province in Zimbabwe

    Science.gov (United States)

    Jenjekwa, Vincent

    2013-01-01

    In Zimbabwe, the discourse on access and quality in education has been a raging one since the colonial days of bottlenecks and outright discrimination against black Zimbabweans in education. The doors to education were declared open to all at independence in 1980 with the new Zimbabwe government's enunciated policy of education for all. It is an…

  14. Experimental and clinical studies of fast three-dimensional MR imaging of the heart

    International Nuclear Information System (INIS)

    MRI has been utilized since its inception to study the anatomy and physiology of the heart. However, the sensitivity of MRI to motion has always posed a major challenge in imaging this organ. The purpose of this study was to develop a 3D MP-RAGE technique for the heart, and to apply it clinically. In the experimental study, data acquisition timing was discussed by normal volunteers. Changes in magnetization recovery time affected imaging contrast very little in the phantom study. Fourteen adults and 21 children were examined. In the adults, MP-RAGE images were rated as high in quality in the visual estimation. In the quantitative estimation, the images provided almost the same anatomical information as those of cine MRI. In the children, MP-RAGE was useful for cases of partial anomalous pulmonary venous drainage, particularly in the evaluation of abnormal pulmonary veins. The 3D MP-RAGE technique was useful in imaging the heart because it was possible to obtain continuous views in the same cardiac cycle and to reconstruct views from any direction after the examination. (author)

  15. A Case Study of a "Collaborative Organizational Innovation" Intervention, Combining Action Research and Design-Thinking Methodologies

    Science.gov (United States)

    Wetzler, Jeffrey Richard

    2013-01-01

    For decades, debates have raged about performance management in education. While it is essential to understand the degree of student learning and the nature of teacher impact in education systems, when attempts at managing outcomes go wrong, the consequences can be problematic. National Education Organization (a pseudonym for the organization…

  16. Toward a Sexual Ethics Curriculum: Bringing Philosophy and Society to Bear on Individual Development

    Science.gov (United States)

    Lamb, Sharon

    2010-01-01

    For over a decade, battles have raged between conservative Abstinence Only Until Marriage (AOUM) sexuality education advocates and liberal Comprehensive Sexuality Education (CSE) advocates. While these battles have focused on the inclusion of health information about contraception and whether or not a curriculum must advocate abstinence as the…

  17. Disabling Emotion in Young Children with Particular Reference to Depression and Suicide: An Overview of Current Research. Unit for Child Studies Selected Papers Number 12.

    Science.gov (United States)

    Phillips, Shelley

    A review of the literature and a survey of texts show a remarkable absence of concern and reference to depression and suicidal behavior in young children. The meaning of death, the depressive and suicidal consequences of the agony of aloneness, and the fear of parental hostility, rage and abandonment are elements of early and middle childhood…

  18. Bone marrow stromal cells inhibits HMGB1-mediated inflammation after stroke in type 2 diabetic rats.

    Science.gov (United States)

    Hu, J; Liu, B; Zhao, Q; Jin, P; Hua, F; Zhang, Z; Liu, Y; Zan, K; Cui, G; Ye, X

    2016-06-01

    High-mobility group box 1 (HMGB1), a ligand of receptor for advanced glycation endproducts (RAGE), functions as a proinflammatory factor. It is mainly involved in inflammatory activation and contributes to the initiation and progression of stroke. By using a model of transient middle cerebral artery occlusion (MCAo) in type 2 diabetic rats, we investigated the changes of pro-inflammation mediators, blood-brain barrier (BBB) leakage and functional outcome after stroke. Type 2 diabetic rats did not show an increased lesion volume, but exhibited significantly increased expression of HMGB1 and RAGE, BBB leakage, as well as decreased functional outcome after stroke compared with control rats. Injection of bone marrow stromal cells (BMSCs) into type 2 diabetic rats significantly reduced the expression of HMGB1 and RAGE, attenuated BBB leakage, and improved functional outcome after stroke. BMSCs-treated type 2 diabetic rats inhibited inflammation and improved functional outcome after stroke. Furthermore, in vitro data support the hypothesis that BMSCs-induced reduction of HMGB1 and RAGE in T2DM-MCAo rats contributed to attenuated inflammatory response in the ischemic brain, which may lead to the beneficial effects of BMSCs treatment. Further investigation of BMSCs treatment in type 2 diabetic stroke is warranted. PMID:26946264

  19. Putting Big Data to Work: Community Colleges Use Detailed Reports to Design Smarter Workforce Training and Education Programs

    Science.gov (United States)

    Woods, Bob

    2013-01-01

    In this article, Bob Woods reports that "Big data" is all the rage on college campuses, and it makes sense that administrators would use what they know to boost student outcomes. Woods points out that community colleges around the country are using the data: (1) to guide the systematic expansion of its curriculum, providing targeted…

  20. How Should the Financial Crisis Change How We Teach Economics?

    Science.gov (United States)

    Shiller, Robert J.

    2010-01-01

    Student dissatisfaction with teaching of economics--particularly with macroeconomics--during the current financial crisis mirrors dissatisfaction that was expressed during the last big crisis, the Great Depression. Then and now, a good number of students have felt that their lectures bear little relation to the economic crisis raging outside the…

  1. A Wireless World: Charles County Public Schools Makes Wireless Universal

    Science.gov (United States)

    Hoffman, Richard

    2007-01-01

    Wireless connectivity in schools is all the rage, and many school systems have at least gotten their feet wet with a wireless lab or a few portable laptop carts. But Bijaya Devkota, the chief information officer of Charles County Public Schools, has done what many school systems only dream of--implemented universal wireless access throughout his…

  2. Experimental and clinical studies of fast three-dimensional MR imaging of the heart

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Shuhei [Okayama Univ. (Japan). School of Medicine

    1999-07-01

    MRI has been utilized since its inception to study the anatomy and physiology of the heart. However, the sensitivity of MRI to motion has always posed a major challenge in imaging this organ. The purpose of this study was to develop a 3D MP-RAGE technique for the heart, and to apply it clinically. In the experimental study, data acquisition timing was discussed by normal volunteers. Changes in magnetization recovery time affected imaging contrast very little in the phantom study. Fourteen adults and 21 children were examined. In the adults, MP-RAGE images were rated as high in quality in the visual estimation. In the quantitative estimation, the images provided almost the same anatomical information as those of cine MRI. In the children, MP-RAGE was useful for cases of partial anomalous pulmonary venous drainage, particularly in the evaluation of abnormal pulmonary veins. The 3D MP-RAGE technique was useful in imaging the heart because it was possible to obtain continuous views in the same cardiac cycle and to reconstruct views from any direction after the examination. (author)

  3. Impact of Cyanidin-3-Glucoside on Glycated LDL-Induced NADPH Oxidase Activation, Mitochondrial Dysfunction and Cell Viability in Cultured Vascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Xueping Xie

    2012-11-01

    Full Text Available Elevated levels of glycated low density lipoprotein (glyLDL are frequently detected in diabetic patients. Previous studies demonstrated that glyLDL increased the production of reactive oxygen species (ROS, activated NADPH oxidase (NOX and suppressed mitochondrial electron transport chain (mETC enzyme activities in vascular endothelial cells (EC. The present study examined the effects of cyanidin-3-glucoside (C3G, a type of anthocyanin abundant in dark-skinned berries, on glyLDL-induced ROS production, NOX activation and mETC enzyme activity in porcine aortic EC (PAEC. Co-treatment of C3G prevented glyLDL-induced upregulation of NOX4 and intracellular superoxide production in EC. C3G normalized glyLDL-induced inhibition on the enzyme activities of mETC Complex I and III, as well as the abundances of NADH dehydrogenase 1 in Complex I and cytochrome b in Complex III in EC. Blocking antibody for the receptor of advanced glycation end products (RAGE prevented glyLDL-induced changes in NOX and mETC enzymes. Combination of C3G and RAGE antibody did not significantly enhance glyLDL-induced inhibition of NOX or mETC enzymes. C3G reduced glyLDL-induced RAGE expression with the presence of RAGE antibody. C3G prevented prolonged incubation with the glyLDL-induced decrease in cell viability and the imbalance between key regulators for cell viability (cleaved caspase 3 and B cell Lyphoma-2 in EC. The findings suggest that RAGE plays an important role in glyLDL-induced oxidative stress in vascular EC. C3G may prevent glyLDL-induced NOX activation, the impairment of mETC enzymes and cell viability in cultured vascular EC.

  4. Relationship between Advanced Glycation End Products and Plaque Progression in Patients with Acute Coronary Syndrome: The JAPAN-ACS Sub-study

    Directory of Open Access Journals (Sweden)

    Fukushima Yoshifumi

    2013-01-01

    Full Text Available Abstract Background The Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome (JAPAN-ACS trial demonstrated that early aggressive statin therapy in patients with ACS significantly reduces plaque volume (PV. Advanced glycation end products (AGEs and the receptors of AGEs (RAGE may lead to angiopathy in diabetes mellitus (DM and may affect on the development of coronary PV. The present sub-study of JAPAN-ACS investigates the association between AGEs and RAGE, and PV. Methods Intravascular ultrasound (IVUS-guided percutaneous coronary intervention (PCI was undertaken, followed by the initiation of statin treatment (either 4 mg/day of pitavastatin or 20 mg/day of atorvastatin, in patients with ACS. In the 208 JAPAN-ACS subjects, PV using IVUS in non-culprit segment > 5 mm proximal or distal to the culprit lesion and, serum levels of AGEs and soluble RAGE (sRAGE were measured at baseline and 8–12 months after PCI. Results At baseline, no differences in the levels of either AGEs or sRAGE were found between patients with DM and those without DM. The levels of AGEs decreased significantly with statin therapy from 8.6 ± 2.2 to 8.0 ± 2.1 U/ml (p Conclusions High baseline AGEs levels were associated with plaque progression in the JAPAN-ACS trial. This relationship was independent of DM. These findings suggest AGEs may be related to long-term glucose control and other oxidative stresses in ACS. Trial registration NCT00242944

  5. Surfactant-derived proteins as markers of alveolar membrane damage in heart failure.

    Directory of Open Access Journals (Sweden)

    Paola Gargiulo

    Full Text Available In heart failure (HF alveolar-capillary membrane is abnormal. Surfactant-derived proteins (SPs and plasma receptor for advanced-glycation-end-products (RAGE have been proposed as lung damage markers.Eighty-nine chronic HF and 17 healthy subjects were evaluated by echocardiography, blood parameters, carbon monoxide lung diffusion (DLCO and cardiopulmonary exercise test. We measured immature SP-B, mature SP-B, SP-A, SP-D and RAGE plasma levels.Immature SP-B (arbitrary units, mature SP-A (ng/ml and SP-D (ng/ml, but not mature SP-B (ng/ml and RAGE (pg/ml levels, were higher in HF than in controls [immature SP-B: 15.6 (13.1, 75th-25th interquartile range Vs. 11.1 (6.4, p<0.01; SP-A, 29.6 (20.1 Vs. 18.3 (13.5, p = 0.01; SP-D: 125 (90 Vs. 78 (58, p<0.01]. Immature SP-B, SP-A, SP-D and RAGE values were related to DLCO, peak oxygen consumption, ventilatory efficiency, and brain natriuretic peptide (BNP, whereas plasma mature SP-B was not. The DLCO Vs. immature SP-B correlation was the strongest one. At multivariate analysis, RAGE was associated to age and creatinine, SP-A to DLCO and BNP, SP-D to BNP, mature SP-B to DLCO and creatinine, and immature SP-B only but strongly to DLCO.Immature SP-B is the most reliable biological marker of alveolar-capillary membrane function in HF.

  6. Expression of Receptor for Advanced Glycation Endproduct on Peripheral Blood Mononuclear Cells in Patients with Coronary Heart Disease%冠心病患者外周血单核细胞表面晚期糖基化终末产物受体水平的表达

    Institute of Scientific and Technical Information of China (English)

    周鹤; 牛楠; 曲鹏; 解丽颖; 杨丽

    2013-01-01

    目的探讨外周血单核细胞表面晚期糖基化终末产物受体(RAGE)的表达水平与冠心病患者临床表现及冠状动脉病变严重程度的关系,并评估其对冠心病患者风险的预测价值.方法 选择因胸痛住院并行冠状动脉造影的患者80例,据其不同临床表现、冠状动脉病变的Gensini积分、病变血管支数进行相应分组,采用流式细胞学方法测定外周血单核细胞表面RAGE水平.结果 急性心肌梗死组、不稳定型心绞痛组外周血单核细胞表面RAGE表达水平均高于稳定型心绞痛组和对照组(P<0.01).RAGE水平与高敏C反应蛋白水平呈正相关(r=0.476,P=0.01);多支病变组和两支病变组外周血单核细胞表面RAGE表达水平高于单支病变组(P<0.05);多支病变组RAGE水平高于两支病变组(P<0.05);根据冠状动脉造影Gensini评分分为三组,三组间外周血单核细胞表面RAGE水平逐渐升高,且各组间差异均具有统计学差异.外周血单核细胞表面RAGE水平与冠状动脉造影评分之间呈正相关(r=0.376,P=0.007);采用Logistic回归法分析高水平的外周血单核细胞表面RAGE水平是冠心痛患者发生急性冠状动脉综合征的独立危险因素(OR=1.180,P=0.02).结论 冠心病患者外周血单核细胞表面RAGE表达水平明显增加,且随着临床表现严重程度的增加呈逐渐升高趋势,对冠心病患者的临床表现有预测价值.外周血单核细胞RAGE水平与冠状动脉病变狭窄程度相关,对冠状动脉病变严重程度有一定的预测价值.高水平外周血单核细胞RAGE的表达是冠心痛患者临床表现严重程度的独立危险因素.%Aim To analyze the relationship between the level of receptor for advanced glycation endproducts (RAGE) on peripheral blood mononuclear cells (PBMC) and the clinical manifestations of coronary heart disease and the severity of angiographic lesion. Further investigation should be made to discuss

  7. High-mobility group box 1 inhibits HCO(3)(-) absorption in medullary thick ascending limb through a basolateral receptor for advanced glycation end products pathway.

    Science.gov (United States)

    Good, David W; George, Thampi; Watts, Bruns A

    2015-10-15

    High-mobility group box 1 (HMGB1) is a damage-associated molecule implicated in mediating kidney dysfunction in sepsis and sterile inflammatory disorders. HMGB1 is a nuclear protein released extracellularly in response to infection or injury, where it interacts with Toll-like receptor 4 (TLR4) and other receptors to mediate inflammation. Previously, we demonstrated that LPS inhibits HCO(3)(-) absorption in the medullary thick ascending limb (MTAL) through a basolateral TLR4-ERK pathway (Watts BA III, George T, Sherwood ER, Good DW. Am J Physiol Cell Physiol 301: C1296-C1306, 2011). Here, we examined whether HMGB1 could inhibit HCO(3)(-) absorption through the same pathway. Adding HMGB1 to the bath decreased HCO(3)(-) absorption by 24% in isolated, perfused rat and mouse MTALs. In contrast to LPS, inhibition by HMGB1 was preserved in MTALs from TLR4(-/-) mice and was unaffected by ERK inhibitors. Inhibition by HMGB1 was eliminated by the receptor for advanced glycation end products (RAGE) antagonist FPS-ZM1 and by neutralizing anti-RAGE antibody. Confocal immunofluorescence showed expression of RAGE in the basolateral membrane domain. Inhibition of HCO(3)(-) absorption by HMGB1 through RAGE was additive to inhibition by LPS through TLR4 and to inhibition by Gram-positive bacterial molecules through TLR2. Bath amiloride, which selectively prevents inhibition of MTAL HCO(3)(-) absorption mediated through Na⁺/H⁺ exchanger 1 (NHE1), eliminated inhibition by HMGB1. We conclude that HMGB1 inhibits MTAL HCO(3)(-) absorption through a RAGE-dependent pathway distinct from TLR4-mediated inhibition by LPS. These studies provide new evidence that HMGB1-RAGE signaling acts directly to impair the transport function of renal tubules. They reveal a novel paradigm for sepsis-induced renal tubule dysfunction, whereby exogenous pathogen-associated molecules and endogenous damage-associated molecules act directly and independently to inhibit MTAL HCO(3)(-) absorption through

  8. Anti-atherosclerotic effects of sitagliptin in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Omoto S

    2015-07-01

    Full Text Available Seitaro Omoto,1 Takehito Taniura,2 Tohru Nishizawa,3 Takeshi Tamaki,3 Akira Shouzu,4 Shosaku Nomura3 1Division of Internal Medicine, Korigaoka Yukeikai Hospital, 2Division of Internal Medicine, Daiwa Hospital, 3First Department of Internal Medicine, Kansai Medical University, 4Division of Internal Medicine, Saiseikai Izuo Hospital, Osaka, Japan Background: Advanced glycation end products, selectins, and adiponectin play important roles in the development of atherosclerosis in individuals with diabetes. Sitagliptin has been shown to reduce the concentration of glycated hemoglobin in diabetic patients. However, its effects on soluble receptor for advanced glycation end products (sRAGEs, selectins, and adiponectin in these patients are poorly understood. This study was conducted to assess the effects of sitagliptin on the circulating levels of sRAGEs, monocyte chemoattractant protein-1 (MCP-1, selectins, and adiponectin in patients with type 2 diabetes. Methods: Diabetic patients eligible for sitagliptin monotherapy or combination therapy (eg, sitagliptin plus a sulfonylurea were administered sitagliptin (50 mg/day for 6 months. Levels of soluble P-selectin (sP-selectin, soluble E-selectin (sE-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1, MCP-1, sRAGEs, and adiponectin were measured by ELISA at baseline and after 3 and 6 months of treatment. Results: At baseline, the levels of MCP-1, sP-selectin, sE-selectin, and sVCAM-1 were higher and the level of adiponectin was lower in diabetic patients than in nondiabetic patients. Sitagliptin therapy for 3 and 6 months significantly reduced plasma levels of sP-selectin, sE-selectin, sVCAM-1, and MCP-1 relative to baseline, while significantly increasing adiponectin levels. sRAGEs did not exhibit a statistical significance, although there was an increasing tendency. Furthermore, the reductions in sP-selectin, sE-selectin, sVCAM-1, and MCP-1 during sitagliptin therapy were significantly greater

  9. On the Significance of New Biochemical Markers for the Diagnosis of Premature Labour

    Directory of Open Access Journals (Sweden)

    Rafał Rzepka

    2014-01-01

    Full Text Available Preterm labour is defined as a birth taking place between 22nd and 37th weeks of gestation. Despite numerous studies on the aetiology and pathogenesis of preterm labour, its very cause still remains unclear. The importance of the cytokines and acute inflammation in preterm labour aetiology is nowadays well-proven. However, chronic inflammation as an element of the pathogenesis of premature labour is still unclear. This paper presents a literature review on the damage-associated molecular patterns (DAMPs, receptors for advanced glycation end products (RAGE, negative soluble isoforms of RAGE, chemokine-stromal cell-derived factor-1 (SDF-1 and one of the adipokines, resistin, in the pathogenesis of preterm labour. We conclude that the chronic inflammatory response can play a much more important role in the pathogenesis of preterm delivery than the acute one.

  10. Short-term effects of dietary advanced glycation end products in rats

    DEFF Research Database (Denmark)

    Poulsen, Malene Wibe; Andersen, Jeanette Marker; Hedegaard, Rikke Susanne Vingborg;

    2016-01-01

    ) dietary AGE on insulin sensitivity, expression of the receptor for AGE (RAGE), the AGE receptor 1 (AGER1) and TNF-α, F2-isoprostaglandins, body composition and food intake. For 2 weeks, thirty-six Sprague-Dawley rats were fed a diet containing 20 % milk powder with different proportions of this being...... given as heated milk powder (0, 40 or 100 %), either native (HMW) or hydrolysed (LMW). Gene expression of RAGE and AGER1 in whole blood increased in the group receiving a high AGE LMW diet, which also had the highest urinary excretion of the AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1). Urinary...... excretion of N ε -carboxymethyl-lysine increased with increasing proportion of heat-treated milk powder in the HMW and LMW diets but was unrelated to gene expression. There was no difference in insulin sensitivity, F2-isoprostaglandins, food intake, water intake, body weight or body composition between...

  11. Psychohistory and Family Among Antebellum Slaveholders.

    Science.gov (United States)

    Adams, Kenneth Alan

    2016-01-01

    This article examines the macroscopic reasons for maternal rage and its injection into slaveholder children in the antebellum South. It is argued that the misogyny that infected antebellum life metastasized in southern mistresses and affected the way they felt about themselves and their children. As mothers, they were casual parents, concerned with molding the character of their charges, rearing warriors and proper ladies, but uninterested in caring for them and helping them realize their own aspirations. It is argued that the misanthropic rage that they injected into their children constituted the poison that each generation of slaveholders had to ventilate into poison containers, slaves, as a homeostatic means of psycho-emotional survival. This intergenerational process of poison injection--from father to mother, from mother to child, from child to slave, constituted the process that insured the perpetuation of the psychic structure necessary for the continuation of slavery from generation to generation. PMID:26856182

  12. Difficile compréhension de l’effet de serre : comment concevoir un parcours d’enseignement-apprentissage au lycée ?

    OpenAIRE

    Colin, Philippe; Tran Tat, Noëmie

    2013-01-01

    Cet article présente une étude exploratoire des conditions d’enseignement-apprentissage de l’effet de serre naturel en seconde. La construction d’un parcours d’enseignement-apprentissage repose sur une prise en compte imbriquée d’une analyse de contenu de la physique mise en jeu et du repérage des difficultés des élèves. Ce repérage est effectué à partir d’entretiens prenant appui sur un modèle matériel de l’effet de serre et sur des schémas de vulgarisation. Les principaux obstacles à la com...

  13. 阿托伐他汀对2型糖尿病鼠主动脉糖基化终末产物受体基因表达的影响%Effects of atorvastatin on expression of receptor for advanced glycation end products in aorta of type 2 diabetic rats

    Institute of Scientific and Technical Information of China (English)

    冯波; 李栩; 徐雷; 王华; 颜新凤; 薛俊丽

    2011-01-01

    目的 观察阿托伐他汀对2型糖尿病(GK)大鼠动脉壁糖基化终末产物受体(RAGE)基因表达的影响,探讨阿托伐他汀抗糖尿病动脉粥样硬化作用的潜在机制.方法 健康雄性Wistar大鼠5只作为正常对照组,GK大鼠随机分为糖尿病对照组(5只)和糖尿病阿托伐他汀治疗组(4只,每日1次阿托伐他汀20 mg/kg灌胃).各组均采用高脂饮食喂养.12周后,采用透射电镜观察主动脉壁超微结构,定量RT-PCR测定主动脉RAGE和单核细胞趋化蛋白-1(MCP-1)的表达.结果 与正常对照组比较,糖尿病对照组主动脉RAGE和MCP-1表达明显升高,而阿托伐他汀治疗能够降低RAGE和MCP-1的表达.主动脉RAGE表达水平与MCP-1表达水平呈显著正相关(r=0.482,P=0.031).透射电镜下糖尿病大鼠动脉可见超微结构的改变.结论 RAGE表达在2型糖尿病早期动脉粥样硬化形成过程中明显上调,阿托伐他汀可通过下调RAGE的表达抗动脉粥样硬化的形成.%Objective To investigate the effect of atorvastatin on expression of receptor for advanced glycation end products (RAGE) in the aorta of type 2 diabetic Goto-Kakisaki (GK) rats and to discuss the potential anti-atherosclerosis mechanisms of atorvastatin. Methods 5 healthy Wistar rats (normal control group) and 9 GK rats were randomly divided into two groups : diabetic control group and atorvastatin-treated diabetic group (20 mg/kg,qd) were fed with the high fat diet for 12 weeks. The expressions of RAGE mRNA and MCP-1 mRNA of aorta were detected using RT-PCR. Ultramicrostructure of aorta was observed using electron microscope. Results Compared with normal control group , the expressions of RAGE mRNA and MCP-1 mRNA in diabetic control group were significant increased . Decreases in the expressions of RAGE mRNA and MCP-1 mRNA were observed in atorvastatin -treated diabetic group compared with diabetic control group. There was significant correlation between the expression levels of RAGE m

  14. Simulation and Analysis of Converging Shock Wave Test Problems

    Energy Technology Data Exchange (ETDEWEB)

    Ramsey, Scott D. [Los Alamos National Laboratory; Shashkov, Mikhail J. [Los Alamos National Laboratory

    2012-06-21

    Results and analysis pertaining to the simulation of the Guderley converging shock wave test problem (and associated code verification hydrodynamics test problems involving converging shock waves) in the LANL ASC radiation-hydrodynamics code xRAGE are presented. One-dimensional (1D) spherical and two-dimensional (2D) axi-symmetric geometric setups are utilized and evaluated in this study, as is an instantiation of the xRAGE adaptive mesh refinement capability. For the 2D simulations, a 'Surrogate Guderley' test problem is developed and used to obviate subtleties inherent to the true Guderley solution's initialization on a square grid, while still maintaining a high degree of fidelity to the original problem, and minimally straining the general credibility of associated analysis and conclusions.

  15. A Psychoanalytic Study of Sylvia Plath.

    Science.gov (United States)

    Feirstein, Frederick

    2016-02-01

    Sylvia Plath's rage at her abandoning husband and at her late beloved father was partly a displacement of anger toward her loving but smothering mother. Her schizoid pathology resulting from the symbiosis (along with her bipolarity) helped prompt her suicide. At the same time her rage at the men represented a struggle to prevent it. The focus of this paper is to explore in the context of her life how the style as well as the content of her last book, Ariel, made for one long suicide note-albeit a beautifully written work of art. In the most accessible of her poems, such as "Daddy," "Lady Lazarus," and "Edge," her health overcomes her pathology. In others her pathology dominates. In Ariel Plath attempted and succeeded in turning herself into a tragic, mythic heroine, eventually drowning herself in a gas oven as she would have in the ocean-a key metaphor for her mother. PMID:26859176

  16. Hydrodynamic investigation and numerical simulation of intermittent and ephemeral flows in semi-arid regions: Wadi Mekerra, Algeria

    OpenAIRE

    Korichi, Khaled; Hazzab, Abdelkrim

    2012-01-01

    Semi-arid regions are characterized by important infrequent rainfall. They often occur in early autumn and give rise to devastating floods. Flooding problems at Wadi Mekerra, located in the Sidi Bel Abbes town (Northwest Algeria), was traditionally the main concern of researchers and government officials. In this work, the magnitude of raging flood wave in the studied catchment and the principal causes are discussed. After this, we present the main hydromorphometric features and the results o...

  17. Impact of Beauty Creations Among College Going Girls

    OpenAIRE

    Mr. Shinto Sebastian

    2011-01-01

    This article tries to attempt to explain the emerging beauty consciousness of present world. This would be raging from the different issues with varied perspectives. This includes media discourse, marketing strategies, psychological pluralism etc… it is an attempt to find out the current scenario of modern world which attempts dictates terms for beauty and how it is being carried out by the younger generation especially college going girls. The attempt dealt with the success and beauty as wel...

  18. Childhood leukaemia

    International Nuclear Information System (INIS)

    The debate on whether there is any link between leukaemia clusters and nuclear installations has been raging since the early eighties. A Government Inquiry found no link between childhood leukaemia and residence near Seascale, an area near British Nuclear Fuels Sellafield plant. Research in the 1980s linked childhood leukaemia to fathers' occupations prior to conception in the Seascale plant but also to workers in the iron, steel, farming and chemical industries. This article reviews research findings to date. (UK)

  19. Social justice and a distance education business education curriculum: unlikely bedfellows?

    OpenAIRE

    Slade, Sharon; Galpin, Fenella; Prinsloo, Paul

    2011-01-01

    Business schools have been accused of being the ‘academy of the apocalypse’, serving and perpetuating greed and ‘rapacious capitalism’. There are increasing calls for business schools to redefine the purpose of business and to empower students to serve broader society whilst being profitable. Social justice is not considered to be high on the agenda of the curricula of many business schools, on the contrary. While the debate rages on regarding the complicity of business schools in pursuing a ...

  20. The impact of education, rights, obligations and protection of workers against employment

    OpenAIRE

    Vujovic, Efimija

    2012-01-01

    How in the world, and here, in the last decade of last century and the beginning of this century, the educational system meet a multitude of innovations that are caused by changes in the environment. From one side comes to deep changes in humanity and social arrangements, and the other technical and technological development experienced expansion to rage boundaries. These trends dictate economic entities, that their entrepreneurs and their management. From science to seek new solutions. Usabl...

  1. China Relief to Pakistan

    Institute of Scientific and Technical Information of China (English)

    Audrey GUO

    2010-01-01

    @@ In Pakistan the rains and floods that started around July 22 have raged through Khyber Pakhtunkhwa,Balochistan,Punjab,Azad Kashmir and Gilgit Baltistan.The rain and floods are now headed towards the Southern Province of Sindh.The provincial governments are bracing for huge flood waters."These are the most massive and heaviest floods in Pakistan territory since 1929,"said the ambassador of Pakistan Masood Khan at a press conference on August 6 in Beijing.

  2. Gravitomagnetism and the significance of the curvature scalar invariants

    OpenAIRE

    Costa, L. Filipe O.; Wylleman, Lode; Natário, José

    2016-01-01

    The curvature invariants have been subject of recent interest due to the debate concerning the notions of intrinsic/extrinsic frame-dragging, the use of the electromagnetic analogy in such classification, and the question of whether there is a fundamental difference between the gravitomagnetic field arising from the translational motion of the sources, detected with Lunar Laser Raging and in the observations of binary pulsars, and the gravitomagnetic field produced by the rotation of the Eart...

  3. Tempest in a Tea Pot: How did the Public Conversation on Genetically Modified Crops Drift so far from the Facts?

    OpenAIRE

    Goldstein, Daniel A.

    2014-01-01

    The debate over genetically modified (GM) crops has raged in Europe since 1996, but had barely risen above a whisper in the USA until recent labeling debates raised public attention. This article will explain GM crops and traits discuss safety assessment provide a view on safety from authoritative organizations discuss selected issues of current debate, and provide the author’s perspective as to why the public debate has drifted so far from scientific reality. The economic and environmental b...

  4. Between green and grey

    OpenAIRE

    Jeanet Kullberg

    2016-01-01

    Taking cuttings is cool. Growing vegetables is all the rage. Green oases can now be found scattered throughout Dutch towns and cities: community gardens and roof gardens where residents can go to relax and enjoy themselves, improve the appearance of their neighbourhood and meet their fellow residents. At the same time, private gardens in the Netherlands are increasingly losing their green appearance in favour of bricks, paving slabs and gravel, making the environment harder both literally and...

  5. New Design &amp; Build Biological System through the Use of Microalgae Addressed to Sustainable Development

    OpenAIRE

    Armen B. Avagyan

    2010-01-01

    Current trends in energy consumption and biofuel manufacturing are neither secure nor sustainable, because they are not provided by necessary cost effective technologies. Further reductions of cost and technological development will be needed for biofuels to be able to compete effectively without subsidy. With the debate raging about raw material of biofuel, microalgae may offer a solution to this conundrum; creating enormous reserves of biofuels and boosting feed production. In this goal Cen...

  6. Aggressive Behaviour in Huntington’s Disease: A Cross-Sectional Study in a Nursing Home Population

    OpenAIRE

    Shiwach, R. S.; Patel, V.

    1993-01-01

    We describe a cross-sectional study of aggressive behaviour in a sample of patients suffering from Huntington's disease in a residential nursing home. Data were obtained using the RAGE, a behaviourally oriented rating scale for measuring aggressive behaviour in cognitively impaired patients. Nursing staff rated 27 patients after a 3 day observation period. A third of the sample were rated to be at least mildly aggressive; the frequencies of some specific types of aggressive behaviour were hig...

  7. EFFECT OF WORK PSYCHOLOGY ON THE ORGANIZATIONAL CYNICISM FOR EMPLOYEE PERFORMANCE

    OpenAIRE

    H. Tezcan UYSAL; Mehmet Selami YILDIZ

    2014-01-01

    Analyzing the psychological states of employees, the work psychology is a discipline that searches out the reasons and the solutions of psychic problems. This discipline evaluates the effects of mental disorders in the sense of entire organization. Organizational cynicism is also one of these effects. The organizational cynicism is employees to have negative feelings such as anger, rage and despair against the organization they worked in. When the objectives and purposes of the organization a...

  8. 仙贞片对糖尿病大鼠肾皮质终末期糖化终产物及其受体mRNA表达的影响%Effect of Xianzhen Tablet on Content of Advanced Glycosylation End Products (AGEs) and mRNA Expression of AGE-specific Cellular Receptor in Renal Cortex of Diabetic Rats

    Institute of Scientific and Technical Information of China (English)

    唐代屹; 郭赛珊; 孙仁宇

    2005-01-01

    目的观察仙贞片对糖尿病大鼠肾皮质终末期糖化终产物(advanced glycation end products,AGEs)含量及其糖化终产物特异性受体(AGE-specific cellular receptor,RAGE)信使核糖核酸(messenger ribonucleic acid,mRNA)表达的影响,探讨其对糖尿病大鼠肾保护的作用机制.方法采用链脲佐菌素(streptozotocin,STZ)复制糖尿病持续性高血糖肾损害大鼠模型,用荧光测定法和逆转录-多聚酶链式反应(reverse transcription polymerase chain reaction,RT-PCR)技术检测模型大鼠肾皮质AGEs含量及RAGEmRNA的表达,与氨基胍作对照.结果实验12周模型大鼠肾皮质AGEs相对含量及RAGE mRNA表达明显高于正常对照组(P<0.05),仙贞片及氨基胍治疗组肾皮质AGEs相对含量及RAGE mRNA表达明显低于模型组(P<0.05),仙贞片与氨基胍组比较差异无显著性(P>0.05).结论仙贞片能减轻糖尿病大鼠肾皮质内AGEs的积聚,下调RAGE mRNA的过度表达,与氨基胍相近似,具有抑制蛋白非酶糖基化的作用,可能是其肾保护作用的机制之一.

  9. TRADE PROTECTIONISM, Better Cooperate than Fight?

    Institute of Scientific and Technical Information of China (English)

    Guo Liqin

    2009-01-01

    @@ In 2009,China witnesses a rage of trade protectionism wave.According to the Ministry of Commerce,currently,35% of anti-dumping and71% of anti-subsidy cases are against Chinese products.In the first three quarters this year,there are 19 countries launching a total of 88 anti-dumping ("AD")and countervailing("CVD")investigations against China.

  10. Analyzing India’s Oil Security: MOSES Application and Evidences from Indian Economy

    OpenAIRE

    Amanpreet Singh Chopra

    2013-01-01

    Authors applied IEA model of Short Term Energy Security (MOSES) to analyze Indian energy security profile with respect to ‘Crude Oil’, the 2nd largest component in country’s energy basket. The analysis was based on 8 quantitative indicators of External and Domestic Risk and Resilience. The MOSES indicator against each parameter was calculated and later collaborated against the rage of indicators resulting in identification of crude oil security profile of the country. The subject analysis of...

  11. Development and Investigation of an Optical Power Meter Front End

    Directory of Open Access Journals (Sweden)

    Edgaras Korsakas

    2015-07-01

    Full Text Available Circuit of the classical transimpedance amplifier (TIA is revised and improved circuit is developed. Analytical solutions for the classical and improved circuits are derived. Both circuits were built and their parameters were measured. An experiment results showed that improved TIA achieves 4.5 dB greater dynamic rage than the classical TIA at +50 °C and 12 dB greater at –10 °C.

  12. An Extendable Multi-Purpose Simulation and Optimization Framework for Thermal Problems in TCAD Applications

    OpenAIRE

    Holzer, S.; Wagner, M.; A Sheikholeslami; Karner, M.; Span, G.; Grasser, T.; Selberherr, S.

    2006-01-01

    We present the capabilities of our optimization framework in conjunction with typical applications for thermal problems. Our software package supports a wide rage of simulators and optimization strategies to improve electronic devices in terms of speed, reliability, efficiency, and to reduce thermal degradation due to mechanical influences. Moreover, we show several optimization examples, where we succeeded to extract electro-thermal material and process parameters. These new material paramet...

  13. The UCSC Ebola Genome Portal

    OpenAIRE

    Haeussler, Maximilian; Karolchik, Donna; Clawson, Hiram; Raney, Brian J.; Rosenbloom, Kate R.; Fujita, Pauline A.; Hinrichs, Angie S.; Speir, Matthew L; Eisenhart, Chris; Zweig, Ann S.; Haussler, David; Kent, W. James

    2014-01-01

    Background: With the Ebola epidemic raging out of control in West Africa, there has been a flurry of research into the Ebola virus, resulting in the generation of much genomic data. Methods: In response to the clear need for tools that integrate multiple strands of research around molecular sequences, we have created the University of California Santa Cruz (UCSC) Ebola Genome Browser, an adaptation of our popular UCSC Genome Browser web tool, which can be used to view the Ebola virus genome s...

  14. Multistakeholder Initiatives in Corporate Social Responsibility: The OECD Guidance and Conflict Minerals

    OpenAIRE

    Johns, Matthew

    2010-01-01

    In recent years, war has raged in the Democratic Republic of Congo between various military bodies, bringing death and devastation to millions of innocent civilians. The conflict has been fuelled by the country‟s abundant mineral wealth, with factions exploiting state weakness and taking control of a large proportion of the mining sector. One of the largest purchasers of the Congo‟s minerals is the global electronics industry. NGOs and civil society have subsequently accused electronics compa...

  15. Pengaruh Pola Asuh Orang Tua Terhadap Perilaku Anak Autis di Yayasan Tali Kasih Medan

    OpenAIRE

    Silaban, Esther

    2014-01-01

    Child with autism are children who have behavioral disorders, autistic child's behavior is not like any other normal child as a language that is not effective, can not communicate well, are not environmentally sensitive, emotionally unstable, aggressive and raging tantrums or misplaced. The behavior of child with autism can be treated with behavioral therapy known as ABA method (Analyst Behavior Analyst). Parents are the most effective in applying this therapy in child, because the parents ar...

  16. Protective roles of pulmonary rehabilitation mixture in experimental pulmonary fibrosis in vitro and in vivo

    International Nuclear Information System (INIS)

    Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of pulmonary fibrosis. Pulmonary rehabilitation mixture (PRM), which combines extracts from eight traditional Chinese medicines, has very good lung protection in clinical use. However, it is not known if PRM has anti-fibrotic activity. In this study, we investigated the effects of PRM on transforming growth factor-β1 (TGF-β1)-mediated and bleomycin (BLM)-induced pulmonary fibrosis in vitro and in vivo. The effects of PRM on TGF-β1-mediated epithelial-mesenchymal transition (EMT) in A549 cells, on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on BLM-induced pulmonary fibrosis in vivo were investigated. PRM treatment resulted in a reduction of EMT in A549 cells that was associated with attenuating an increase of vimentin and a decrease of E-cadherin. PRM inhibited the proliferation of HLF-1 at an IC50 of 0.51 µg/mL. PRM ameliorated BLM-induced pulmonary fibrosis in rats, with reduction of histopathological scores and collagen deposition, and a decrease in α-smooth muscle actin (α-SMA) and HMGB1 expression. An increase in receptor for advanced glycation end-product (RAGE) expression was found in BLM-instilled lungs. PRM significantly decreased EMT and prevented pulmonary fibrosis through decreasing HMGB1 and regulating RAGE in vitro and in vivo. PRM inhibited TGF-β1-induced EMT via decreased HMGB1 and vimentin and increased RAGE and E-cadherin levels. In summary, PRM prevented experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway

  17. The effect of fibroblast growth factors and advanced glycation end-products on the intima-media complex thickness in patients with coronary heart disease and type 2 diabetes

    OpenAIRE

    Ekaterina Vladimirovna Ivannikova; Victor Yurievich Kalashnikov; Olga Mikhaylovna Smirnova; Alexander Borisovich Kuznetsov; Sergei Anatolievich Terekhin; Alexander Viktorovich Il'in

    2014-01-01

    ObjectiveTo determine the levels of fibroblast transforming growth factor (TGFβ1), basic fibroblast growth factor (β-FGF), markers of nonspecific inflammatory response (interleukin-6 (IL-6)), C-reactive protein (CRP), advanced glycation end-products (AGEs) and their receptors (RAGEs) and to study their effect on the intima-media complex (IMC) thickness in patients with coronary heart disease (CHD) and type 2 diabetes, depending on carbohydrate metabolism compensation.Materials and Methods37 p...

  18. Accountants and economic governance in a dependent country, : Conflicting legacies and new professional issues in Lebanon

    OpenAIRE

    Longuenesse, Elisabeth

    2006-01-01

    Purpose: The purpose of this study was to sort out what was at stake in the fierce debates that raged after 1995 among Lebanese accountants about the conditions of membership to their new association.Approach and methodology: It fits within the recent development of the sociology of professions. But because of the specific nature of accountants expertise, it is also concerned with broader societal issues and socio-political negotiation of interests, which underlie professional battles. Lastly...

  19. Some Reflections On Current Debates In Impact Evaluation

    OpenAIRE

    White, Howard

    2009-01-01

    A debate on approaches to impact evaluation has raged in development circles in recent years. This note gives some reflections on this debate through discussion of four issues. First, it is pointed out that there are two definitions of impact evaluation. Neither one is right or wrong, but they refer to completely different things. There is no point in methodological debates unless they agree a common starting point. Second, there is confusion between counterfactuals, which are implied by the ...

  20. Pathways to a universal basic pension in Greece

    OpenAIRE

    Chrysa Leventi; Manos Matsaganis

    2011-01-01

    Although basic pension had for years failed to catch the imagination of policy makers in Greece, it was suddenly brought to the agenda in the context of the severe crisis raging since November 2009. In May 2010 the government committed to a harsh austerity programme, aiming at fiscal consolidation, in return for a rescue package easing the sovereign debt crisis. The July 2010 pension reform, a key provision of the austerity programme, provided for the introduction of a near-universal basic pe...

  1. Local decay of acoustic waves in the low Mach number limits on general unbounded domains under slip boundary conditions

    Czech Academy of Sciences Publication Activity Database

    Feireisl, Eduard

    2011-01-01

    Roč. 36, č. 10 (2011), s. 1778-1796. ISSN 0360-5302 R&D Projects: GA ČR GA201/09/0917 Institutional research plan: CEZ:AV0Z10190503 Keywords : compressible Navier-Stokes equations * low Mach number limit * RAGE theorem Subject RIV: BA - General Mathematics Impact factor: 0.894, year: 2011 http://www.tandfonline.com/doi/abs/10.1080/03605302.2011.602168

  2. Feruidus Ille Canis: the Lore and Poetry of the Dog Star in Antiquity

    Science.gov (United States)

    Ceragioli, Roger Charles

    1992-01-01

    The Dog Star, Sirius, appears in many important works of classical poetry. It also appears in numerous myths and several religious rituals. A complex body of folklore surrounds it and it had a paramount importance in agriculture. Yet no one has attempted a systematic analysis of Sirius' place in Greco-Roman art and thought. This thesis begins that analysis. The introductory chapter discusses the methodology and approach that the thesis takes to the evidence, and supplies essential background information on Sirius' place among the constellations and its relation to the physical environment of the Mediterranean. Chapter one explores Sirius' role in ancient warrior traditions. Sirius embodied the principle of cosmic heat, and through heat it was thought to cause rabies in dogs. The Greek word for rabies is lussa. But lussa also named the madness of warriors such as Achilles in the Iliad. Etymologically, lussa meant "wolfishness." Rabid dogs, wolves, and raging warriors all exhibit fiery heat as an integral part of their natures. It is argued that raging warriors, wolves, and rabid dogs were largely interchangeable entities for the Greeks. Thus when Hector and Achilles in their raging are compared to Sirius, the comparison reflects more than the likeness of their surface brilliance. Chapter two explores Sirius' connection to erotic themes in ancient poetry. Because erotic experience could be represented as a conflagration that might burn the lover into a frenzy, the fiery raging Dog Star was an appropriate symbolic accompaniment. Sirius itself experienced erotic frenzy when it became passionate for Opora (the ripe fruits of summer). Chapter three turns to Sirius' involvement in viticulture. Sirius was said to ripen the grapes, but was also conceived to have once been the faithful dog of Icarius, who first introduced wine-drinking among humans. The chapter explores Sirius' role in the myth of Icarius, and the relation of that myth to the erotic and martial sides of

  3. An improved expression system for the VC1 ligand binding domain of the receptor for advanced glycation end products in Pichia pastoris.

    Science.gov (United States)

    Degani, Genny; Colzani, Mara; Tettamanzi, Alberto; Sorrentino, Luca; Aliverti, Alessandro; Fritz, Guenter; Aldini, Giancarlo; Popolo, Laura

    2015-10-01

    The receptor for the advanced glycation end products (RAGE) is a type I transmembrane glycoprotein belonging to the immunoglobulin superfamily and binds a variety of unrelated ligands sharing a negative charge. Most ligands bind to the extracellular V or VC1 domains of the receptor. In this work, V and VC1 of human RAGE were produced in the methylotrophic yeast Pichia pastoris and directed to the secretory pathway. Fusions to a removable C-terminal His-tag evidenced proteolytic processing of the tag by extracellular proteases and also intracellular degradation of the N-terminal portion of V-His. Expression of untagged forms was attempted. While the V domain was retained intracellularly, VC1 was secreted into the medium and was functionally active in binding AGEs. The glycosylation state of VC1 was analyzed by mass spectrometry and peptide-N-glycosidase F digestion. Like RAGE isolated from mammalian sources, the degree of occupancy of the N-glycosylation sites was full at Asn25 and partial at Asn81 which was also subjected to non-enzymatic deamidation. A simple procedure for the purification to homogeneity of VC1 from the medium was developed. The folded state of the purified protein was assessed by thermal shift assays. Recombinant VC1 from P. pastoris showed a remarkably high thermal stability as compared to the protein expressed in bacteria. Our in vivo approach indicates that the V and C1 domains constitute a single folding unit. The stability and solubility of the yeast-secreted VC1 may be beneficial for future in vitro studies aimed to identify new ligands or inhibitors of RAGE. PMID:26118699

  4. Current studies of biological materials using instrumental and radiochemical neutron activation analysis

    International Nuclear Information System (INIS)

    Instrumental neutron activation analysis still remains the preferred option when analysing the trace element distribution in a wide rage of materials by neutron activation analysis. However, when lower limits of detection are required or major interferences reduce the effectiveness of this technique, radiochemical neutron activation analysis is applied. This paper examines the current use of both methods and the development of rapid radiochemical techniques for analysis of the biological materials, hair, cow's milk, human's milk, milk powder, blood and blood serum

  5. Intensified CCD Image Sensor①

    Institute of Scientific and Technical Information of China (English)

    LIUJikun; ZHAOBaoyun

    1997-01-01

    Work has been done with extending the useful imaging and detection rage of CCD.This was accomplished through direct optical coupling and bonding of image intensifiers to the CCD.It has been shown that the useful range of a CCD may be extended two orders of magnitude using these techniques in coupling a microchannel plate image intensifier to the CCD array.All of these works were done with presently available CCD made by China

  6. Parent perceptions of symptom severity in Tourette's syndrome

    OpenAIRE

    Dooley, J.; Brna, P.; Gordon, K.

    1999-01-01

    The families of 66 consecutive children with Tourette's syndrome were surveyed for their perception of symptom significance using a questionnaire. Families considered attention deficit and learning difficulties to be most significant, while motor and vocal tics were least important. When present, episodic rage was the most impairing symptom. Physicians must be aware of the significance of these comorbid symptoms for patients with Tourette's syndrome.



  7. Satirising the Norwegian language conflict: Gabriel Scott's Babels taarn contextually reconsidered

    OpenAIRE

    Hale, Frederick

    2013-01-01

    Gabriel Scott’s comedy Babels taarn (Babel Tower), first performed at the National Theatre in Kristiania in 1911, satirises the language controversy that was raging in Norway at the time. The play is regarded as important in linguistic and literary terms, but has been largely forgotten. This article argues that Scott was disillusioned by the politicisation of the language controversy and regarded the advance of landsmål as an artificial and unwelcome phenomenon in the unfolding of Norwegian c...

  8. Recognizing borderline personality disorder in the family practice setting.

    Science.gov (United States)

    Hubbard, J R; Saathoff, G B; Bernardo, M J; Barnett, B L

    1995-09-01

    The first step in the management of borderline personality disorder is making the correct diagnosis. A clinical example illustrates symptoms of a patient with borderline personality disorder in a family practice setting. Major characteristics of borderline personality disorder include severe mood instability, fear of abandonment, chronic boredom, self-injury, unstable interpersonal relationships, "splitting," identity instability and borderline rage. Early diagnosis may help prevent potential management problems and possible doctor-patient conflicts. PMID:7653428

  9. Theological reflections on empire

    OpenAIRE

    Allan A. Boesak

    2009-01-01

    Since the meeting of the World Alliance of Reformed Churches in Accra, Ghana (2004), and the adoption of the Accra Declaration, a debate has been raging in the churches about globalisation, socio-economic justice, ecological responsibility, political and cultural domination and globalised war. Central to this debate is the concept of empire and the way the United States is increasingly becoming its embodiment. Is the United States a global empire? This article argues that the United States ha...

  10. 自己愛と対人距離との関連

    OpenAIRE

    内田,利広; 堀内,詩子

    2011-01-01

    To clarify how people beset with maladapted narcissism maintain distance from others, a questionnaire targeting university students and a projective method were investigated. Sub-elements of narcissism are "narcissistic rage", "fear of others", and "avoidance tendencies". The projective method was modeled after MAPS personality projection. Two illustration boards were presented―one designated as "base-life", and another as "school-life", and participants pasting clippings of their supposed se...

  11. Is behavioral economics doomed? : The ordinary versus the extraordinary

    OpenAIRE

    David K. Levine

    2012-01-01

    It is fashionable to criticize economic theory for focusing too much on rationality and ignoring the imperfect and emotional way in which real economic decisions are reached. All of us facing the global economic crisis wonder just how rational economic men and women can be. Behavioral economics - an effort to incorporate psychological ideas into economics - has become all the rage. In this book, David K. Levine questions the idea that behavioral economics is the answer to economic problems. H...

  12. Is Behavioral Economics Doomed?

    OpenAIRE

    David K. Levine

    2013-01-01

    It is fashionable to criticize economic theory for focusing too much on rationality and ignoring the imperfect and emotional way in which real economic decisions are reached. All of us facing the global economic crisis wonder just how rational economic men and women can be. Behavioral economics — an effort to incorporate psychological ideas into economics — has become all the rage. In this book, David K. Levine questions the idea that behavioral economics is the answer to economic problems. H...

  13. Simultaneous involvement of third and sixth cranial nerve in a patient with Lyme disease

    Energy Technology Data Exchange (ETDEWEB)

    Lell, M.; Schmid, A.; Tomandl, B.F. [Division of Neuroradiology, Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen (Germany); Stemper, B.; Maihoefner, C.; Heckmann, J.G. [Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen (Germany)

    2003-02-01

    We report a 57-year-old woman with neuroborreliosis presenting with headache, shoulder muscle pain and double vision. MRI demonstrated enhancement of the right third and sixth cranial nerves. A 3D MP-RAGE sequence was used to perform multiplanar reformations to show this more graphically. The patient was free of symptoms 1 month after completion of therapy, when thickening and contrast enhancement of the nerves were less pronounced. (orig.)

  14. Gambaran Tingkat Kecemasan Orang Tua Dalam Menghadapi Masalah Perilaku Sosial Anak Retardasi Mental di YPAC Medan

    OpenAIRE

    Ndraha, Fourlina Noviyani

    2015-01-01

    Mental retardation children have limited capability of cognitive and adaptive so that it can affect their ability in socializing and behave. Parents who has children with mental retardation have anxiety in dealing with their children’s social behavior such as hyperactivity, rages and loves to fight. This research aims to identify the level of anxiety of parents in dealing with problems of mental retardation children’s social behavior in Yayasan Pembinaan Anak Cacat (YPAC) Medan. The design us...

  15. Simultaneous involvement of third and sixth cranial nerve in a patient with Lyme disease

    International Nuclear Information System (INIS)

    We report a 57-year-old woman with neuroborreliosis presenting with headache, shoulder muscle pain and double vision. MRI demonstrated enhancement of the right third and sixth cranial nerves. A 3D MP-RAGE sequence was used to perform multiplanar reformations to show this more graphically. The patient was free of symptoms 1 month after completion of therapy, when thickening and contrast enhancement of the nerves were less pronounced. (orig.)

  16. To standardize or not standardize international marketing : is it still a question?

    OpenAIRE

    Soares, Ana Maria; Farhangmehr, Minoo; Shoham, Aviv

    2003-01-01

    The standardization versus adaptation argument has been raging for years and international marketing research about it has spanned some four decades, attesting to its far reaching theoretical and practical relevance. The purpose of this paper is to review the literature on this debate. Major theoretical and empirical contributions from companies’ and consumers’ points of view are presented. The importance of resolving this issue cannot be underestimated as it as an impact on segmentation i...

  17. Inroads into Equestrian Safety: Rider-Reported Factors Contributing to Horse-Related Accidents and Near Misses on Australian Roads

    OpenAIRE

    Kirrilly Thompson; Chelsea Matthews

    2015-01-01

    Simple Summary Riding horses on roads can be dangerous, but little is known about accidents and near misses. To explore road safety issues amongst Australian equestrians, we conducted an online survey. More than half of all riders (52%) reported having experienced at least one accident or near miss in the 12 months prior to the survey, mostly attributed to speed. Whilst our findings confirmed factors identified overseas, we also identified issues around road rules, hand signals and road rage....

  18. Online úskalia folkloristického výskumu

    OpenAIRE

    Šipöczová, Eva; Ústav evropské etnologie, Filozofická fakulta, Masarykova univerzita v Brně

    2012-01-01

    The problematic aspects of internet research are slowly becoming manifest in all the Humanities. The primary concern of ethnology and folkloristics is contemporary folklore – anecdotes, urban legends, rumours, conspiracy theories, all of which are abundant on the internet. Neverteless, the nature of virtual reality has given rise to new methodological problems and uncertainties. How should we collect folklore material on the internet? A conflict rages between classic face-to-face research, an...

  19. Bite Marks From The Crime Scene- An Overview

    OpenAIRE

    Sivakumar, R.; Rajeev, R.; Heera, R.; Divya Gopinath; V.T. Beena

    2012-01-01

    In mortal combat situations, such as the violence associated with life and death struggles between assailants and victims, the teeth are often used as a weapon. Indeed, using the teeth to inflict serious injury on an attacker may be the only available defensive method for a victim. Alternatively, it is well known that assailants in sexual attacks, including sexual homicide, rape and child sexual abuse, often bite their victims as an expression of dominance, rage and animalistic behaviour. The...

  20. Influence of glycated low density lipoprotein on the proliferation,expression of intercellular adhesion molecule-1,von Willebrand factor of human umbilical endothelial cells

    Institute of Scientific and Technical Information of China (English)

    LU Jun; LIU Hui-ying; ZHANG Xiu-zhen; LEI Tao

    2009-01-01

    @@ Diabetes mellitus known as its macro-and microangiopathy has caused thousands of mortality per year.Recent researches showed that hyperglycemia,advanced glycation end products(AGEs)and some other factors acted on the process of atherogenesis.AGEs can combine with receptors of AGEs(RAGEs),which exist on the vascular endothelium,smooth muscle cells,macrophage,lymphocyte and so on.

  1. A New Approach of Personality and Psychiatric Disorders: A Short Version of the Affective Neuroscience Personality Scales

    OpenAIRE

    Jean-Baptiste Pingault; Bruno Falissard; Sylvana Côté; Sylvie Berthoz

    2012-01-01

    BACKGROUND: The Affective Neuroscience Personality Scales (ANPS) is an instrument designed to assess endophenotypes related to activity in the core emotional systems that have emerged from affective neuroscience research. It operationalizes six emotional endophenotypes with empirical evidence derived from ethology, neural analyses and pharmacology: PLAYFULNESS/joy, SEEKING/interest, CARING/nurturance, ANGER/rage, FEAR/anxiety, and SADNESS/separation distress. We aimed to provide a short versi...

  2. Fiscal policy and economic growth in Kenya

    OpenAIRE

    M'Amanja, Daniel; Morrissey, Oliver

    2005-01-01

    The question of whether or not fiscal policy stimulates growth has dominated theoretical and empirical debate for a long time. One viewpoint believes that government involvement in economic activity is vital for growth, but an opposing view holds that government operations are inherently bureaucratic and inefficient and therefore stifles rather than promotes growth. In the empirical literature, results are equally mixed. The aim of this paper is not to resolve the raging debate but to add to ...

  3. Nye patologier i selvdannelsens tidsalder

    DEFF Research Database (Denmark)

    Hammershøj, Lars Geer

    2004-01-01

    pathologies: Social pathologies no longer derive from social barriers inhibiting self-realization but from self-realization itself. As a consequence, philosophy of education, rather than sociology, appears to be the relevant field of study. The article develops a social-analytical perspective on ‘sickness in...... self-Bildung', which is conceived as a ‘refusal to transcend oneself into sociality', and offers interpretations of present pathologies such as depression, anorexia, populist freedom of speech, and demonic rage....

  4. Proprietary software versus Open Source Software for Education

    OpenAIRE

    N. Pankaja

    2013-01-01

    The Internet has brought learning "online" and offers many advantages. It is convenient, available at any time of the day, and can be accessed nearly anywhere in the world. Recently, Cloud computing is all the rage. E-Learning offers tremendous potential to increase the availability and convenience of education. Today, online content is varied and can include: text on a website, digital audio, digital video, animated images, and virtual reality environments. This content can be created in a v...

  5. Protective roles of pulmonary rehabilitation mixture in experimental pulmonary fibrosis in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, L.; Ji, Y.X.; Jiang, W.L.; Lv, C.J. [School of Pharmaceutical Sciences, Binzhou Medical University, Yantai (China)

    2015-05-08

    Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of pulmonary fibrosis. Pulmonary rehabilitation mixture (PRM), which combines extracts from eight traditional Chinese medicines, has very good lung protection in clinical use. However, it is not known if PRM has anti-fibrotic activity. In this study, we investigated the effects of PRM on transforming growth factor-β1 (TGF-β1)-mediated and bleomycin (BLM)-induced pulmonary fibrosis in vitro and in vivo. The effects of PRM on TGF-β1-mediated epithelial-mesenchymal transition (EMT) in A549 cells, on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on BLM-induced pulmonary fibrosis in vivo were investigated. PRM treatment resulted in a reduction of EMT in A549 cells that was associated with attenuating an increase of vimentin and a decrease of E-cadherin. PRM inhibited the proliferation of HLF-1 at an IC{sub 50} of 0.51 µg/mL. PRM ameliorated BLM-induced pulmonary fibrosis in rats, with reduction of histopathological scores and collagen deposition, and a decrease in α-smooth muscle actin (α-SMA) and HMGB1 expression. An increase in receptor for advanced glycation end-product (RAGE) expression was found in BLM-instilled lungs. PRM significantly decreased EMT and prevented pulmonary fibrosis through decreasing HMGB1 and regulating RAGE in vitro and in vivo. PRM inhibited TGF-β1-induced EMT via decreased HMGB1 and vimentin and increased RAGE and E-cadherin levels. In summary, PRM prevented experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.

  6. Devo-max could complicate David Cameron’s plans to repeal the Human Rights Act

    OpenAIRE

    McHargh, Aileen

    2014-01-01

    The Conservative Party have recently re-committed to repealing the Human Rights Act (HRA) and replacing it with a ‘home grown’ British Bill of Rights. Meanwhile, discussion of what level of devolution will be afforded to Scotland in the wake of the ‘No’ vote in their independence referendum has been raging on. Here, Aileen McHargh argues that further devolution complicates the Conservatives withdrawal pledge.

  7. TREATMENT PLANNING, PACING, AND COUNTERTRANSFERENCE: PERSPECTIVES ON THE PSYCHOTHERAPY OF EARLY AFFECT-CONFUSION

    Directory of Open Access Journals (Sweden)

    Richard G. Erskine

    2012-12-01

    Full Text Available This article is a rejoinder and elaboration on the article “Early Affect-Confusion: The ‘Borderline’ Between Despair and Rage: Part 1 of a Case Study Trilogy” and addresses the distinction between personality style, pattern, and disorder. It describes the pacing of a time-limited psychotherapy, the use of phenomenological inquiry in resolving transferential enactments, and the psychological function of idealization.

  8. Of Maras and Mortal Doubt: Violence, Order, and Uncertainty in Guatemala City

    OpenAIRE

    Fontes, Anthony Wayne IV

    2015-01-01

    Everyday brutality in Guatemala City shocks and numbs a society that has suffered generations of war and bloodshed. Much of this violence is blamed on maras, gangs bearing transnational signs and symbols, that operate in prisons and poor urban communities. I will explore how the maras' evolution in post-war Guatemala has made them what they are today: victim-perpetrators of massive and horrifying violence, useful targets of societal rage, pivotal figures in a politics of death reigning over p...

  9. Living it Up Mid-Air

    Institute of Scientific and Technical Information of China (English)

    GREGGWYCHERLEY

    2004-01-01

    There's something surreal about boarding a plane. Apart from the fact that you are defying gravity, the feeling of being enclosed in a large flying tube for up to 12 hours, far removed from earth and surrounded by strangers in. a strange environment can induce all kinds of behavioural changes, from air-rage to irrational fear, through to out of character flirting with aircrew or other passengers.

  10. Advanced glycation end-products induce apoptosis in pancreatic islet endothelial cells via NF-κB-activated cyclooxygenase-2/prostaglandin E2 up-regulation.

    Directory of Open Access Journals (Sweden)

    Kuo-Cheng Lan

    Full Text Available Microvascular complications eventually affect nearly all patients with diabetes. Advanced glycation end-products (AGEs resulting from hyperglycemia are a complex and heterogeneous group of compounds that accumulate in the plasma and tissues in diabetic patients. They are responsible for both endothelial dysfunction and diabetic vasculopathy. The aim of this study was to investigate the cytotoxicity of AGEs on pancreatic islet microvascular endothelial cells. The mechanism underlying the apoptotic effect of AGEs in pancreatic islet endothelial cell line MS1 was explored. The results showed that AGEs significantly decreased MS1 cell viability and induced MS1 cell apoptosis in a dose-dependent manner. AGEs dose-dependently increased the expressions of cleaved caspase-3, and cleaved poly (ADP-ribose polymerase in MS1 cells. Treatment of MS1 cells with AGEs also resulted in increased nuclear factor (NF-κB-p65 phosphorylation and cyclooxygenase (COX-2 expression. However, AGEs did not affect the expressions of endoplasmic reticulum (ER stress-related molecules in MS1 cells. Pretreatment with NS398 (a COX-2 inhibitor to inhibit prostaglandin E2 (PGE2 production reversed the induction of cleaved caspase-3, cleaved PARP, and MS1 cell viability. Moreover, AGEs significantly increased the receptor for AGEs (RAGE protein expression in MS1 cells, which could be reversed by RAGE neutralizing antibody. RAGE Neutralizing antibody could also reverse the induction of cleaved caspase-3 and cleaved PARP and decreased cell viability induced by AGEs. These results implicate the involvement of NF-κB-activated COX-2/PGE2 up-regulation in AGEs/RAGE-induced islet endothelial cell apoptosis and cytotoxicity. These findings may provide insight into the pathological processes within the pancreatic islet microvasculature induced by AGEs accumulation.

  11. Ethical and legal issues in aesthetic surgery

    OpenAIRE

    Suresh Gupta

    2012-01-01

    Rapid growth and expansion of plastic surgery in general and aesthetic surgery in particular in the past decade has brought in its wake some confusions particularly raising questions for the surgeons conduct towards his colleagues and the patients in the light of ethical requirements. Some thoughts from eminent thinkers form a backdrop to consideration of theories of medical ethics. In this article raging and continuous debates on these subjects have been avoided to maintain the momentum. Apa...

  12. Paedophilia; Diagnosis, Treatment & Moral Panic

    OpenAIRE

    Sadat, Sama; Ashraf, Kashifah; Nilsson Smith, Heidi; Chemlali, Hanan; Bosboom, Chiara; Hoff, Rasmus

    2012-01-01

    Paedophilia, briefly explained, is an adult’s sexual and emotional fascination for children. This phenomenon tends to raise a lot of strong feelings of horror, disgust and rage in the general population. The mere description is seen as horrible and directly unacceptable by normative morals and values. The collection of empirical data was done through authors and researchers, who have written reports and made research in this particular field. Additionally we interviewed persons from the ...

  13. Konst Kräver Offer : En analys av Nathalia Edenmonts konstnärskap i ljuset av Pierre Bourdieus kulturteori

    OpenAIRE

    Ericsson, Kristin

    2015-01-01

    Nathalia Edenmont is a controversial and uncompromising photo artist who has caused the whole world to rage over her obscene photographs. In this thesis I have researched Edenmonts artistry with help of the sociologist Pierre Bourdieus field analysis. By using Bourdieus's different field concepts I have researched Edenmonts artistic career by concepts such as habitus, consecration and different principles. The starting point of this research has been that Nathalia Edenmont is in the autonomou...

  14. The political theology of violence in contemporary India

    OpenAIRE

    Thomas Blom Hansen

    2008-01-01

    What are we to make of the fact that most violence in India rarely has any visible or clear actors? Why is most violence represented as 'pure events' without identifiable actors - but as 'mobs', as spontaneous combustion, as spontaneous rage that arises from perceived collective grievances and insults? Why in a country saturated in political rhetoric is it that acts of violence have acquired their own semiotic register, a singular form of 'political communication'? Fire and incidents of arson...

  15. Aspectos de infraestrutura e serviços como indicadores da turistificação na Vila de Encantadas, Ilha do Mel (Brasil)

    OpenAIRE

    Daniel Hauer Queiroz Telles; José Manoel Gonçalves Gandara

    2011-01-01

    The isle of Mel represents the reality of some insular touristic destinations in the Brazilian coasts, with very special peculiarities raging from the image of an alternative destination to the fragility of social and environmental issues. It has different characteristics, (lack of automobiles and the predominance of small inns), that began since the touristic exploration almost four decades ago. The purpose of the present article is to analyze the conditions of the infrastructure and the ser...

  16. MR imaging of cranial nerve lesions using six different high-resolution T1- and T2(*)-weighted 3D and 2D sequences

    International Nuclear Information System (INIS)

    Purpose: To find a suitable high-resolution MR protocol for the visualization of lesions of all 12 cranial nerves. Material and Methods: Thirty-eight pathologically changed cranial nerves (17 patients) were studied with MR imaging at 1.5T using 3D T2*-weighted CISS, T1-weighted 3D MP-RAGE (without and with i.v. contrast medium), T2-weighted 3D TSE, T2-weighted 2D TSE and T1-weighted fat saturation 2D TSE sequences. Visibility of the 38 lesions of the 12 cranial nerves in each sequence was evaluated by consensus of two radiologists using an evaluation scale from 1 (excellently visible) to 4 (not visible). Results: The 3D CISS sequence provided the best resolution of the cranial nerves and their lesions when surrounded by CSF. In nerves which were not surrounded by CSF, the 2D T1-weighted contrast-enhanced fat suppression technique was the best sequence. Conclusions: A combination of 3D CISS, the 2D T1-weighted fat suppressed sequence and a 3D contrast-enhanced MP-RAGE proved to be the most useful sequence to visualize all lesions of the cranial nerves. For the determination of enhancement, an additional 3D MP-RAGE sequence without contrast medium is required. This sequence is also very sensitive for the detection of hemorrhage

  17. MR imaging of cranial nerve lesions using six different high-resolution T1- and T2(*)-weighted 3D and 2D sequences

    Energy Technology Data Exchange (ETDEWEB)

    Seitz, J.; Held, P.; Strotzer, M.; Voelk, M.; Nitz, W.R.; Dorenbeck, U.; Feuerbach, S. [Univ. Hospital of Regensburg (Germany). Dept. of Diagnostic Radiology; Stamato, S. [Univ. of California, San Diego, CA (United States). Dept. of Radiology

    2002-07-01

    Purpose: To find a suitable high-resolution MR protocol for the visualization of lesions of all 12 cranial nerves. Material and Methods: Thirty-eight pathologically changed cranial nerves (17 patients) were studied with MR imaging at 1.5T using 3D T2*-weighted CISS, T1-weighted 3D MP-RAGE (without and with i.v. contrast medium), T2-weighted 3D TSE, T2-weighted 2D TSE and T1-weighted fat saturation 2D TSE sequences. Visibility of the 38 lesions of the 12 cranial nerves in each sequence was evaluated by consensus of two radiologists using an evaluation scale from 1 (excellently visible) to 4 (not visible). Results: The 3D CISS sequence provided the best resolution of the cranial nerves and their lesions when surrounded by CSF. In nerves which were not surrounded by CSF, the 2D T1-weighted contrast-enhanced fat suppression technique was the best sequence. Conclusions: A combination of 3D CISS, the 2D T1-weighted fat suppressed sequence and a 3D contrast-enhanced MP-RAGE proved to be the most useful sequence to visualize all lesions of the cranial nerves. For the determination of enhancement, an additional 3D MP-RAGE sequence without contrast medium is required. This sequence is also very sensitive for the detection of hemorrhage.

  18. Ischemic preconditioning and inflammatory response syndrome after reperfusion injury: an experimental model in diabetic rats.

    Science.gov (United States)

    Grigorescu, Bianca Liana; Georgescu, Anca Meda; Cioc, Adrian-Dan; Fodor, Raluca-Ştefania; Cotoi, Ovidiu Simion; Fodor, Pal; Copotoiu, Sanda Maria; Azamfirei, Leonard

    2015-01-01

    Quantification of local ischemia and inflammatory response syndrome correlated with histological changes associated with ischemia-reperfusion injury (IRI) after revascularization techniques. We included 12 adult male Wistar rats, aged eight weeks that were randomly divided into two groups. The first group acted as the control and at the second group, we induced diabetes by intraperitoneal streptozotocin administration (60 mg/kg). After eight weeks, the rats were subject to ischemic preconditioning for 10 minutes at three regular intervals. Twenty-four hours post-preconditioning, both groups were subject to ischemia for 20 minutes, followed by 30 minutes of reperfusion. Oxygen extraction was higher in Group 1, the arterio-venous CO2 gradient was higher in the control group, but not significant. The lactate production was higher in Group 1. The second group had a higher Na+ and also a significant difference in K+ values. Receptor for Advanced Glycation End (RAGE) values were higher in the second group but with no significant difference (RAGE1=0.32 ng/mL versus RAGE2=0.40 ng/mL). The muscle samples from the control group displayed significant rhabdomyolysis, damage to the nucleus, while the preconditioned group showed almost normal morphological characteristics. The lungs and kidneys were most damaged in the control group, with damage expressed as thickened alveolar septa, neutrophil infiltrates, eosinophilic precipitates in the proximal convolute tubule. Ischemic preconditioning significantly attenuates the ischemic reperfusion injury. PMID:26743274

  19. Effect of PKC-β Signaling Pathway on Expression of MCP-1 and VCAM-1 in Different Cell Models in Response to Advanced Glycation End Products (AGEs

    Directory of Open Access Journals (Sweden)

    Lisienny C. T. Rempel

    2015-05-01

    Full Text Available Advanced glycation end products (AGEs are compounds classified as uremic toxins in patients with chronic kidney disease that have several pro-inflammatory effects and are implicated in the development of cardiovascular diseases. To explore the mechanisms of AGEs–endothelium interactions through the receptor for AGEs (RAGE in the PKC-β pathway, we evaluated the production of MCP-1 and VCAM-1 in human endothelial cells (HUVECs, monocytes, and a coculture of both. AGEs were prepared by albumin glycation and characterized by absorbance and electrophoresis. The effect of AGEs on cell viability was assessed with an MTT assay. The cells were also treated with AGEs with and without a PKC-β inhibitor. MCP-1 and VCAM-1 in the cell supernatants were estimated by ELISA, and RAGE was evaluated by immunocytochemistry. AGEs exposure did not affect cell viability, but AGEs induced RAGE, MCP-1, and VCAM-1 expression in HUVECs. When HUVECs or monocytes were incubated with AGEs and a PKC-β inhibitor, MCP-1 and VCAM-1 expression significantly decreased. However, in the coculture, exposure to AGEs and a PKC-β inhibitor produced no significant effect. This study demonstrates, in vitro, the regulatory mechanisms involved in MCP-1 production in three cellular models and VCAM-1 production in HUVECs, and thus mimics the endothelial dysfunction caused by AGEs in early atherosclerosis. Such mechanisms could serve as therapeutic targets to reduce the harmful effects of AGEs in patients with chronic kidney disease.

  20. Contrast-enhanced MR imaging of metastatic brain tumor at 3 Tesla. Utility of T1-weighted SPACE compared with 2D spin echo and 3D gradient echo sequence

    International Nuclear Information System (INIS)

    We evaluated the newly developed whole-brain, isotropic, 3-dimensional turbo spin-echo imaging with variable flip angle echo train (SPACE) for contrast-enhanced T1-weighted imaging in detecting brain metastases at 3 tesla (T). Twenty-two patients with suspected brain metastases underwent postcontrast study with SPACE, magnetization-prepared rapid gradient-echo (MP-RAGE), and 2-dimensional T1-weighted spin echo (2D-SE) imaging at 3 T. We quantitatively compared SPACE, MP-RAGE, and 2D-SE images by using signal-to-noise ratios (SNRs) for gray matter (GM) and white matter (WM) and contrast-to-noise ratios (CNRs) for GM-to-WM, lesion-to-GM, and lesion-to-WM. Two blinded radiologists evaluated the detection of brain metastases by segment-by-segment analysis and continuously-distributed test. The CNR between GM and WM was significantly higher on MP-RAGE images than on SPACE images (P1-weighted imaging. (author)

  1. Some enuretic derivatives in an adult analysis.

    Science.gov (United States)

    Browne, N D

    1986-01-01

    The paper traces the effects of early overstimulation--leading as it does to precocious erotization and rage. Together, these combine in a manic defence by denying deadness in inner psychic reality. The rage being such as the ego cannot cope with, reappears in the recurrent fugitive dream. The paper shows how the patient is most threatened in his dreams where he repeatedly protects himself from death by castration; where death means death of inner psychic reality. In life his rage is never overt but is principally mocking, putting the other in the open while he remains protected from risks. In the same way just as the patient is most threatened in sleep, so he is likewise threatened by the change of mind at the prospect of sexual arousal. The adoption of a fetish affords protection, as it serves to negate total psychic inner deadness. The fetish itself is a sort of screen against loss and grief where these affects have been previously sexualized. Likewise the earlier adoption of the phobia of spilling liquids brought the enuretic event under ego-control by making the risks more conscious and therefore more available to act as a screen against loss and grief. PMID:3804591

  2. 血清可溶性晚期糖基化终产物受体水平与系统性红斑狼疮疾病活动度的相关性%Association between Serum Levels of Soluble Receptor for Advanced Glycation End-products and Disease Activity of Systemic Lupus Erythematosus

    Institute of Scientific and Technical Information of China (English)

    菅夏楠; 郑朝晖; 于若寒; 刘升云; 刘章锁

    2015-01-01

    Objective The aim of our study was to investigate the value of serum soluble receptor for advanced glycation (sRAGE)levels in the estimation of disease activity of systemic lupus erythematosus (SLE). Methods 104 patients who suffered from SLE and who had been treated in our hospital from June 2013 to June 2014 were included into our study.Clinical and epidemiological data were collected.Results The concentration of sRAGE in the SLE group,the non-active SLE group,active SLE group,and the control group were (1 060.16 ±762.59),(912.06 ±759.98),(1 232.96 ±736.16),and(1 300.42 ±466.01) pg/ml respectively,so the difference was statistically significant (Z = -2.891,P =0.004 ).The difference was statistically significant among the non-active SLE group,active SLE group,and the control group (χ2 =17.999,P =0.000).There was higher serum sRAGE levels in patients whose SLE disease activity index(SLEDAI)≥10 (Z =-3.052,P =0.002)and whose titer of anti-dsDNA antibody≥100 (Z =-2.276,P =0.023),and there was positive correlation between serum sRAGE levels and SLEDAI≥10(r =0.373,P =0.000),the difference was statistically significant.Conclusion We can evaluate disease activity of SLE by detecting the serum sRAGE levels,which may provide information to guide the treatment.%目的:探讨可溶性晚期糖基化终产物受体(soluble receptor for advanced glycation end-products,sRAGE)在系统性红斑狼疮(systemic lupus erythematosus,SLE)疾病活动度评价中的价值。方法收集2013年6月至2014年6月郑州大学第一附属医院 SLE 患者的临床及流行病学资料,观察血清 sRAGE 浓度与 SLE 疾病活动度的相关性。结果 SLE 组、非活动SLE 组、活动 SLE 组和健康对照组 sRAGE 浓度分别为(1060.16±762.59)、(912.06±759.98)、(1232.96±736.16)、(1300.42±466.01)pg/ml;SLE 组与健康对照组 sRAGE 浓度差异有统计学意义(Z =-2.891,P =0.004),非活动 SLE

  3. Targeting AGEs Signaling Ameliorates Central Nervous System Diabetic Complications in Rats.

    Science.gov (United States)

    Zakaria, Mohamed Naguib; El-Bassossy, Hany M; Barakat, Waleed

    2015-01-01

    Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and cognitive decline. Accumulation of advanced glycation end products (AGEs) is an important mechanism that mediates diabetic complications. Upon binding to their receptor (RAGE), AGEs mediate oxidative stress and/or cause cross-linking with proteins in blood vessels and brain tissues. The current investigation was designed to investigate the effect of agents that decrease AGEs signaling, perindopril which increases soluble RAGE (sRAGE) and alagebrium which cleaves AGEs cross-links, compared to the standard antidiabetic drug, gliclazide, on the vascular and central nervous system (CNS) complications in STZ-induced (50 mg/kg, IP) diabetes in rats. Perindopril ameliorated the elevation in blood pressure seen in diabetic animals. In addition, both perindopril and alagebrium significantly inhibited memory decline (performance in the Y-maze), neuronal degeneration (Fluoro-Jade staining), AGEs accumulation in serum and brain, and brain oxidative stress (level of reduced glutathione and activities of catalase and malondialdehyde). These results suggest that blockade of AGEs signaling after diabetes induction in rats is effective in reducing diabetic CNS complications. PMID:26491434

  4. Targeting AGEs Signaling Ameliorates Central Nervous System Diabetic Complications in Rats

    Directory of Open Access Journals (Sweden)

    Mohamed Naguib Zakaria

    2015-01-01

    Full Text Available Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and cognitive decline. Accumulation of advanced glycation end products (AGEs is an important mechanism that mediates diabetic complications. Upon binding to their receptor (RAGE, AGEs mediate oxidative stress and/or cause cross-linking with proteins in blood vessels and brain tissues. The current investigation was designed to investigate the effect of agents that decrease AGEs signaling, perindopril which increases soluble RAGE (sRAGE and alagebrium which cleaves AGEs cross-links, compared to the standard antidiabetic drug, gliclazide, on the vascular and central nervous system (CNS complications in STZ-induced (50 mg/kg, IP diabetes in rats. Perindopril ameliorated the elevation in blood pressure seen in diabetic animals. In addition, both perindopril and alagebrium significantly inhibited memory decline (performance in the Y-maze, neuronal degeneration (Fluoro-Jade staining, AGEs accumulation in serum and brain, and brain oxidative stress (level of reduced glutathione and activities of catalase and malondialdehyde. These results suggest that blockade of AGEs signaling after diabetes induction in rats is effective in reducing diabetic CNS complications.

  5. Expression of high mobility group box 1 in inflamed dental pulp and its chemotactic effect on dental pulp cells

    International Nuclear Information System (INIS)

    Highlights: • HMGB1 translocated from nucleus to cytoplasm during dental pulp inflammation. • HMGB1and its receptor RAGE were up-regulated in hDPCs under LPS stimulation. • HMGB1 enhanced hDPCs migration and induces cytoskeleton reorganization. • HMGB1 may play a critical role in dental pulp repair during inflamed state. - Abstract: High mobility group box 1 protein (HMGB1) is a chromatin protein which can be released extracellularly, eliciting a pro-inflammatory response and promoting tissue repair process. This study aimed to examine the expression and distribution of HMGB1 and its receptor RAGE in inflamed dental pulp tissues, and to assess its effects on proliferation, migration and cytoskeleton of cultured human dental pulp cells (DPCs). Our data demonstrated that cytoplasmic expression of HMGB1 was observed in inflamed pulp tissues, while HMGB1 expression was confined in the nuclei in healthy dental pulp. The mRNA expression of HMGB1 and RAGE were significantly increased in inflamed pulps. In in vitro cultured DPCs, expression of HMGB1 in both protein and mRNA level was up-regulated after treated with lipopolysaccharide (LPS). Exogenous HMGB1 enhanced DPCs migration in a dose-dependent manner and induced the reorganization of f-actin in DPCs. Our results suggests that HMGB1 are not only involved in the process of dental pulp inflammation, but also play an important role in the recruitment of dental pulp stem cells, promoting pulp repair and regeneration

  6. Fuzzy neural-network-based segmentation of multispectral magnetic-resonance brain images

    Science.gov (United States)

    Blonda, Palma N.; Bennardo, A.; Satalino, Giuseppe; Pasquariello, Guido; De Blasi, Roberto A.; Milella, D.

    1996-06-01

    This study investigates the applicability of a multimodular neuro-fuzzy system in the multispectral analysis of magnetic resonance (MR) images of the human brain. The system consists of two components: an unsupervised neural module for image segmentation in tissue regions and a supervised module for tissue labeling. The former is the fuzzy Kohonen clustering network (FKCN). The latter is a feed-forward network based on the back-propagation learning rule. The results obtained with the FKCN have been compared with those extracted by a self organizing map (SOM). The system has been used to analyze the multispectral MR brain images of a healthy volunteer. The data set included the proton density (PD), T2, T1 weighted spin-echo (SE) bands and a new T1- weighted three dimensional sequence, i.e. the magnetization- prepared rapid gradient echo (MP-RAGE). One of the main objectives of this study has been to evaluate the usefulness of brain imaging with the MP-RAGE sequence in view of automatic tissue classification. To this purpose, a quantitative evaluation has been provided on the base of some labeled areas selected interactively by a neuro- radiologist from the input raw images. Quantitative results seem to indicate that the MP-RAGE sequence may provide higher tissue separability than the T1-weighted SE sequence.

  7. Expression of high mobility group box 1 in inflamed dental pulp and its chemotactic effect on dental pulp cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xufang, E-mail: xufang.zhang@student.qut.edu.au [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059 (Australia); Jiang, Hongwei, E-mail: jianghw@163.com [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Gong, Qimei, E-mail: gongqmei@gmail.com [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Fan, Chen, E-mail: c3.fan@student.qut.edu.au [Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059 (Australia); Huang, Yihua, E-mail: enu0701@163.com [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Ling, Junqi, E-mail: lingjq@mail.sysu.edu.cn [Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Guangdong Province Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China)

    2014-08-08

    Highlights: • HMGB1 translocated from nucleus to cytoplasm during dental pulp inflammation. • HMGB1and its receptor RAGE were up-regulated in hDPCs under LPS stimulation. • HMGB1 enhanced hDPCs migration and induces cytoskeleton reorganization. • HMGB1 may play a critical role in dental pulp repair during inflamed state. - Abstract: High mobility group box 1 protein (HMGB1) is a chromatin protein which can be released extracellularly, eliciting a pro-inflammatory response and promoting tissue repair process. This study aimed to examine the expression and distribution of HMGB1 and its receptor RAGE in inflamed dental pulp tissues, and to assess its effects on proliferation, migration and cytoskeleton of cultured human dental pulp cells (DPCs). Our data demonstrated that cytoplasmic expression of HMGB1 was observed in inflamed pulp tissues, while HMGB1 expression was confined in the nuclei in healthy dental pulp. The mRNA expression of HMGB1 and RAGE were significantly increased in inflamed pulps. In in vitro cultured DPCs, expression of HMGB1 in both protein and mRNA level was up-regulated after treated with lipopolysaccharide (LPS). Exogenous HMGB1 enhanced DPCs migration in a dose-dependent manner and induced the reorganization of f-actin in DPCs. Our results suggests that HMGB1 are not only involved in the process of dental pulp inflammation, but also play an important role in the recruitment of dental pulp stem cells, promoting pulp repair and regeneration.

  8. [Glycotoxins and cellular dysfunction. A new mechanism for understanding the preventive effects of lifestyle modifications].

    Science.gov (United States)

    Michalsen, A; Bierhaus, A; Nawroth, P P; Dobos, G J

    2006-08-01

    Recently the AGE-RAGE interaction was identified as a potential mechanism underlying chronic and inflammatory diseases like atherosclerosis, diabetes mellitus and kidney disease. Advanced glycation end products (AGEs) are the derivatives of glucose-protein or glucose-lipid reactions and are mainly generated from the diet (depending on intensity of heating, cooking time and oxygenation). Binding of AGEs or other ligands to the AGE receptor (RAGE) results in cellular activation, i.e. increased expression of inflammatory mediators and oxidative stress. Diet-derived AGEs thus induce deleterious effects on tissues and the cardiovascular system. Recent research also found that other lifestyle factors are associated with pronounced inflammatory activation, e.g. psychosocial stress and smoking. In addition, each intake of meals is associated with proinflammatory cellular changes. The AGE-RAGE model and investigations of the underlying cellular mechanisms thus may lead to a better understanding of the health benefits of diets (Mediterranean diet, uncooked vegetarian diets), caloric restriction and intermittent fasting. The clinical impact of low-AGE diets and fasting and the interaction between stress and food intake should be further investigated in controlled trials. PMID:16897151

  9. Microglial AGE-albumin is critical in promoting alcohol-induced neurodegeneration in rats and humans.

    Science.gov (United States)

    Byun, Kyunghee; Bayarsaikhan, Delger; Bayarsaikhan, Enkhjargal; Son, Myeongjoo; Oh, Seyeon; Lee, Jaesuk; Son, Hye-In; Won, Moo-Ho; Kim, Seung U; Song, Byoung-Joon; Lee, Bonghee

    2014-01-01

    Alcohol is a neurotoxic agent, since long-term heavy ingestion of alcohol can cause various neural diseases including fetal alcohol syndrome, cerebellar degeneracy and alcoholic dementia. However, the molecular mechanisms of alcohol-induced neurotoxicity are still poorly understood despite numerous studies. Thus, we hypothesized that activated microglial cells with elevated AGE-albumin levels play an important role in promoting alcohol-induced neurodegeneration. Our results revealed that microglial activation and neuronal damage were found in the hippocampus and entorhinal cortex following alcohol treatment in a rat model. Increased AGE-albumin synthesis and secretion were also observed in activated microglial cells after alcohol exposure. The expressed levels of receptor for AGE (RAGE)-positive neurons and RAGE-dependent neuronal death were markedly elevated by AGE-albumin through the mitogen activated protein kinase pathway. Treatment with soluble RAGE or AGE inhibitors significantly diminished neuronal damage in the animal model. Furthermore, the levels of activated microglial cells, AGE-albumin and neuronal loss were significantly elevated in human brains from alcoholic indivisuals compared to normal controls. Taken together, our data suggest that increased AGE-albumin from activated microglial cells induces neuronal death, and that efficient regulation of its synthesis and secretion is a therapeutic target for preventing alcohol-induced neurodegeneration. PMID:25140518

  10. Effect of KIOM-79 on Diabetes-Induced Myocardial Fibrosis in Zucker Diabetic Fatty Rats

    Directory of Open Access Journals (Sweden)

    Junghyun Kim

    2013-01-01

    Full Text Available KIOM-79, a herbal mixture of parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix, and Euphorbiae radix, has a strong inhibitory effect on advanced glycation end products (AGEs formation. We investigated the beneficial effects of KIOM-79 on cardiac fibrosis in Zucker diabetic fatty (ZDF rats. KIOM-79 (50 or 500 mg/kg/day was orally administered for 13 weeks. AGEs formation and collagen expression in the myocardium were assessed by immunohistochemistry. The expression levels of the receptor for AGEs (RAGE, transforming growth factor-β1 (TGF-β1, collagen IV, fibronectin, urotensin II, and urotensin II receptor were examined in the myocardial tissue of ZDF rats. KIOM-79 treatment at 500 mg/kg inhibited the accumulation of AGEs, reduced RAGE mRNA and protein expression, and reduced the upregulation of cardiac fibrogenic factors, such as fibronectin and collagen IV, in heart of ZDF rats. Additionally, KIOM-79 ameliorated urotensin II/receptor gene expression in the cardiac tissue of ZDF rats. Our findings indicate that KIOM-79 diminishes cardiac fibrosis in ZDF rats by preventing AGEs accumulation and RAGE overexpression and by modulating the cardiac urotensin II/receptor pathway, which decreases the amount of profibrotic factors, such as TGF-β1, fibronectin, and collagen in cardiac tissue.

  11. Low levels of amyloid-beta and its transporters in neonatal rats with and without hydrocephalus

    Directory of Open Access Journals (Sweden)

    Silverberg Gerald D

    2009-05-01

    Full Text Available Abstract Background Previous studies in aging animals have shown that amyloid-beta protein (Aβ accumulates and its transporters, low-density lipoprotein receptor-related protein-1 (LRP-1 and the receptor for advanced glycation end products (RAGE are impaired during hydrocephalus. Furthermore, correlations between astrocytes and Aβ have been found in human cases of normal pressure hydrocephalus (NPH and Alzheimer's disease (AD. Because hydrocephalus occurs frequently in children, we evaluated the expression of Aβ and its transporters and reactive astrocytosis in animals with neonatal hydrocephalus. Methods Hydrocephalus was induced in neonatal rats by intracisternal kaolin injections on post-natal day one, and severe ventriculomegaly developed over a three week period. MRI was performed on post-kaolin days 10 and 21 to document ventriculomegaly. Animals were sacrificed on post-kaolin day 21. For an age-related comparison, tissue was used from previous studies when hydrocephalus was induced in a group of adult animals at either 6 months or 12 months of age. Tissue was processed for immunohistochemistry to visualize LRP-1, RAGE, Aβ, and glial fibrillary acidic protein (GFAP and with quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR to quantify expression of LRP-1, RAGE, and GFAP. Results When 21-day post-kaolin neonatal hydrocephalic animals were compared to adult (6–12 month old hydrocephalic animals, immunohistochemistry demonstrated levels of Aβ, RAGE, and LRP-1 that were substantially lower in the younger animals; in contrast, GFAP levels were elevated in both young and old hydrocephalic animals. When the neonatal hydrocephalic animals were compared to age-matched controls, qRT-PCR demonstrated no significant changes in Aβ, LRP-1 and RAGE. However, immunohistochemistry showed very small increases or decreases in individual proteins. Furthermore, qRT-PCR indicated statistically significant increases in GFAP

  12. Advancements in web-database applications for rabies surveillance

    Directory of Open Access Journals (Sweden)

    Bélanger Denise

    2011-08-01

    Full Text Available Abstract Background Protection of public health from rabies is informed by the analysis of surveillance data from human and animal populations. In Canada, public health, agricultural and wildlife agencies at the provincial and federal level are responsible for rabies disease control, and this has led to multiple agency-specific data repositories. Aggregation of agency-specific data into one database application would enable more comprehensive data analyses and effective communication among participating agencies. In Québec, RageDB was developed to house surveillance data for the raccoon rabies variant, representing the next generation in web-based database applications that provide a key resource for the protection of public health. Results RageDB incorporates data from, and grants access to, all agencies responsible for the surveillance of raccoon rabies in Québec. Technological advancements of RageDB to rabies surveillance databases include 1 automatic integration of multi-agency data and diagnostic results on a daily basis; 2 a web-based data editing interface that enables authorized users to add, edit and extract data; and 3 an interactive dashboard to help visualize data simply and efficiently, in table, chart, and cartographic formats. Furthermore, RageDB stores data from citizens who voluntarily report sightings of rabies suspect animals. We also discuss how sightings data can indicate public perception to the risk of racoon rabies and thus aid in directing the allocation of disease control resources for protecting public health. Conclusions RageDB provides an example in the evolution of spatio-temporal database applications for the storage, analysis and communication of disease surveillance data. The database was fast and inexpensive to develop by using open-source technologies, simple and efficient design strategies, and shared web hosting. The database increases communication among agencies collaborating to protect human health from

  13. The Clinical Significances of Soluble Receptor for Advanced Glycation Endproducts in Bronchoscopy Alveolus Lavage Fluid among Patients with COPD%COPD纤维支气管镜肺泡灌洗液中可溶性晚期糖基化终末产物受体水平的临床意义

    Institute of Scientific and Technical Information of China (English)

    杨兴官; 雷超; 胡占升

    2014-01-01

    Objective To discuss the clinical significances of soluble receptor for advanced glycation end-products ( sRAGE)in bronchoscopy alveolus lavage fluid( BALF)in patients with COPD. Methods A total of 40 patients with COPD who were admitted to the department of intensive care unit of the First Hospital Affiliated to Liaoning Medical University from Oc-tober 2012 to May 2013,were selected as the COPD group,meanwhile 40 patients with non-COPD were selected as the non-COPD group,and these COPD patients were divided into mild group(12 cases),moderate group(10 cases),severe group (10 cases),very severe group(8 cases). The sRAGE concentrations in BALF were detected by enzyme-linked immunosor-bent assay(ELISA). Results The concentration of sRAGE in BALF of patients in the COPD group(191 ±71)ng/L was sig-nificantly higher than that in the non-COPD group(55 ±56)ng/L(t=9. 44,P<0. 001). The concentration of sRAGE in BALF of COPD patients in the mild group,moderate group,severe group and very severe group was(111 ± 44) ng/L,(184 ±45)ng/L,(226 ±34)ng/L,and(273 ±30)ng/L,respectively,there were significant differences in concentration of sRAGE among these groups(F=30. 48,P<0. 001),and the concentration of sRAGE in very severe COPD group was signifi-cantly higher than that in severe COPD group,the concentration of sRAGE in severe COPD group was significantly higher than that in moderate group,the concentration of sRAGE in moderate group was significantly higher than that in mild group( P <0. 05 ) . Linear correlation analysis results showed that the concentration of sRAGE in BALF of COPD patients were negatively cor-related with FEV1%(r= -0. 738,P <0. 05). Conclusion The concentration of sRAGE in BALF of COPD patients was higher than that of non-COPD patients;The concentration of sRAGE in BALF is related to severity of COPD,it could be used as an index of the prognosis evaluation of COPD.%目的:探讨纤维支气管镜肺泡灌洗液中可溶性晚期

  14. Effects of glucagon-like peptide-1 on advanced glycation endproduct-induced aortic endothelial dysfunction in streptozotocin-induced diabetic rats: possible roles of Rho kinase- and AMP kinase-mediated nuclear factor κB signaling pathways.

    Science.gov (United States)

    Tang, Song-Tao; Zhang, Qiu; Tang, Hai-Qin; Wang, Chang-Jiang; Su, Huan; Zhou, Qing; Wei, Wei; Zhu, Hua-Qing; Wang, Yuan

    2016-07-01

    Interaction between advanced glycation endproducts (AGEs) and receptor for AGEs (RAGE) as well as downstream pathways leads to vascular endothelial dysfunction in diabetes. Glucagon-like peptide-1 (GLP-1) has been reported to attenuate endothelial dysfunction in the models of atherosclerosis. However, whether GLP-1 exerts protective effects on aortic endothelium in diabetic animal model and the underlying mechanisms are still not well defined. Experimental diabetes was induced through administration with combination of high-fat diet and intraperitoneal injection of streptozotocin. Rats were randomly divided into four groups, including controls, diabetes, diabetes + sitagliptin (30 mg/kg/day), diabetes + exenatide (3 μg/kg/12 h). Eventually, endothelial damage, markers of inflammation and oxidative stress, were measured. After 12 weeks administration, diabetic rats received sitagliptin and exenatide showed significant elevation of serum NO level and reduction of ET-1 as well as inflammatory cytokines levels. Moreover, sitagliptin and exenatide significantly inhibited aortic oxidative stress level and improved aortic endothelial function in diabetic rats. Importantly, these drugs inhibited the protein expression level in AGE/RAGE-induced RhoA/ROCK/NF-κB/IκBα signaling pathways and activated AMPK in diabetic aorta. Finally, the target proteins of p-eNOS, iNOS, and ET-1, which reflect endothelial function, were also changed by these drugs. Our present study indicates that sitagliptin and exenatide administrations can improve endothelial function in diabetic aorta. Of note, RAGE/RhoA/ROCK and AMPK mediated NF-κB signaling pathways may be the intervention targets of these drugs to protect aortic endothelium. PMID:26758998

  15. Interaction between S100P and the anti-allergy drug cromolyn

    International Nuclear Information System (INIS)

    Highlights: • The interaction between S100P–cromolyn was investigated by fluorescence spectroscopy. • The interfacial residues on S100P and cromolyn contact surface were mapped by 1H-15N HSQC experiments. • S100P–cromolyn complex model was generated from NMR restraints using HADDOCK program. • The stability of the S100P–cromolyn complex was studied using molecular dynamics simulations. - Abstract: The S100P protein has been known to mediate cell proliferation by binding the receptor for advanced glycation end products (RAGE) to activate signaling pathways, such as the extracellular regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. S100P/RAGE signaling is involved in a variety of diseases, such as cancer, metastasis, and diabetes. Cromolyn is an anti-allergy drug that binds S100P to block the interaction between S100P and RAGE. In the present study, we characterized the properties of the binding between cromolyn and calcium-bound S100P using various biophysical techniques. The binding affinity for S100P and cromolyn was measured to be in the millimolar range by fluorescence spectroscopy. NMR-HSQC titration experiments and HADDOCK modeling was employed to determine the spatial structure of the proposed heterotetramer model of the S100P–cromolyn complex. Additional MD simulation results revealed the important properties in the complex stability and conformational flexibility of the S100P–cromolyn complex. This proposed model has provided an understanding of the molecular level interactions of S100P–cromolyn complex

  16. Plasma CC16 levels are associated with development of ALI/ARDS in patients with ventilator-associated pneumonia: a retrospective observational study

    Directory of Open Access Journals (Sweden)

    Lutter Rene

    2009-12-01

    Full Text Available Abstract Background Despite consensus criteria, diagnosing acute lung injury, or its more severe form acute respiratory distress syndrome (ALI/ARDS remains challenging. Adding objective measures, such as plasma levels of biological markers could facilitate recognition of ALI/ARDS. This study was designed to assess and compare the diagnostic accuracy of biological markers for ALI/ARDS with ventilator-associated pneumonia (VAP. Methods We performed serial measurements of Clara cell protein (CC16, soluble receptor for advanced glycation end products (sRAGE, surfactant protein D (SP-D and Krebs von den Lungen (KL-6 in plasma of patients with VAP and mechanically ventilated control patients without VAP. ALI/ARDS was diagnosed using the criteria of the North-American European consensus conference. Results Thirty-seven patients were enrolled - 22 patients with VAP and 15 control patients. Ten patients with pneumonia met the ALI/ARDS consensus criteria. Control patients never met these criteria. Plasma CC16 had a good diagnostic capacity for ALI/ARDS as shown by the receiver operating characteristic curve with an area under the curve of 0.91 (95% confidence interval (CI 0.79 - 1.00; p p = 0.02. The diagnostic accuracies of KL-6 and sRAGE were low. Conclusion Plasma CC16 seems a potential biological marker for ALI/ARDS in patients with VAP. Plasma levels of sRAGE, SP-D and KL-6 have limited discriminative power for diagnosing ALI/ARDS in VAP.

  17. High-resolution anatomy of the human brain stem using 7-T MRI: improved detection of inner structures and nerves?

    Energy Technology Data Exchange (ETDEWEB)

    Gizewski, Elke R. [Medical University Innsbruck, Department of Neuroradiology, Innsbruck (Austria); Maderwald, Stefan [University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Linn, Jennifer; Bochmann, Katja [LMU Munich, Department of Neuroradiology, Munich (Germany); Dassinger, Benjamin [Medical University Innsbruck, Department of Neuroradiology, Innsbruck (Austria); Justus-Liebig-University Giessen, Department of Neuroradiology, Giessen (Germany); Forsting, Michael [University Hospital, University Duisburg-Essen, Departments of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Ladd, Mark E. [University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); University Hospital, University Duisburg-Essen, Departments of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany)

    2014-03-15

    The purpose of this paper is to assess the value of 7 Tesla (7 T) MRI for the depiction of brain stem and cranial nerve (CN) anatomy. Six volunteers were examined at 7 T using high-resolution SWI, MPRAGE, MP2RAGE, 3D SPACE T2, T2, and PD images to establish scanning parameters targeted at optimizing spatial resolution. Direct comparisons between 3 and 7 T were performed in two additional subjects using the finalized sequences (3 T: T2, PD, MPRAGE, SWAN; 7 T: 3D T2, MPRAGE, SWI, MP2RAGE). Artifacts and the depiction of structures were evaluated by two neuroradiologists using a standardized score sheet. Sequences could be established for high-resolution 7 T imaging even in caudal cranial areas. High in-plane resolution T2, PD, and SWI images provided depiction of inner brain stem structures such as pons fibers, raphe, reticular formation, nerve roots, and periaqueductal gray. MPRAGE and MP2RAGE provided clear depiction of the CNs. 3D T2 images improved depiction of inner brain structure in comparison to T2 images at 3 T. Although the 7-T SWI sequence provided improved contrast to some inner structures, extended areas were influenced by artifacts due to image disturbances from susceptibility differences. Seven-tesla imaging of basal brain areas is feasible and might have significant impact on detection and diagnosis in patients with specific diseases, e.g., trigeminal pain related to affection of the nerve root. Some inner brain stem structures can be depicted at 3 T, but certain sequences at 7 T, in particular 3D SPACE T2, are superior in producing anatomical in vivo images of deep brain stem structures. (orig.)

  18. Glucagon-like peptide-1 counteracts the detrimental effects of Advanced Glycation End-Products in the pancreatic beta cell line HIT-T 15

    Energy Technology Data Exchange (ETDEWEB)

    Puddu, A., E-mail: alep100@hotmail.com [University of Genova, Department of Internal Medicine and Medical Specialties, Viale Benedetto XV, 16132 Genova (Italy); Storace, D.; Durante, A.; Odetti, P.; Viviani, G.L. [University of Genova, Department of Internal Medicine and Medical Specialties, Viale Benedetto XV, 16132 Genova (Italy)

    2010-07-30

    Research highlights: {yields} GLP-1 prevents AGEs-induced cell death. {yields} GLP-1 prevents AGEs-induced oxidative stress. {yields} GLP-1 ameliorated AGEs-induced cell dysfunction. {yields} GLP-1 attenuates AGEs-induced RAGE increment. {yields} GLP-1 counteracts AGEs-induced pancreatic cell death and dysfunction. -- Abstract: Advanced Glycation End-Products (AGEs), a group of compounds resulting from the non-enzymatic reaction of reducing sugars with the free amino group of proteins, are implicated in diabetic complications. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T 15 to high concentrations of AGEs significantly decreases cell proliferation and insulin secretion, and affects transcription factors regulating insulin gene transcription. The glucagon-like peptide-1 (GLP-1) is an incretin hormone that increases proinsulin biosynthesis, stimulates insulin secretion, and improves pancreatic beta-cell viability. The aim of this work was to investigate the effects of GLP-1 on the function and viability of HIT-T 15 cells cultured with AGEs. HIT-T 15 cells were cultured for 5 days in presence of AGEs alone, or supplemented with 10 nmol/l GLP-1. Cell viability, insulin secretion, redox balance, and expression of the AGEs receptor (RAGE) were then determined. The results showed that GLP-1 protected beta cell against AGEs-induced cell death preventing both apoptosis and necrosis. Moreover, addition of GLP-1 to the AGEs culture medium restored the redox balance, improved the responsiveness to glucose, and attenuated AGEs-induced RAGE expression. These findings provide evidence that GLP-1 protects beta cells from the dangerous effects of AGEs.

  19. Glucagon-like peptide-1 counteracts the detrimental effects of Advanced Glycation End-Products in the pancreatic beta cell line HIT-T 15

    International Nuclear Information System (INIS)

    Research highlights: → GLP-1 prevents AGEs-induced cell death. → GLP-1 prevents AGEs-induced oxidative stress. → GLP-1 ameliorated AGEs-induced cell dysfunction. → GLP-1 attenuates AGEs-induced RAGE increment. → GLP-1 counteracts AGEs-induced pancreatic cell death and dysfunction. -- Abstract: Advanced Glycation End-Products (AGEs), a group of compounds resulting from the non-enzymatic reaction of reducing sugars with the free amino group of proteins, are implicated in diabetic complications. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T 15 to high concentrations of AGEs significantly decreases cell proliferation and insulin secretion, and affects transcription factors regulating insulin gene transcription. The glucagon-like peptide-1 (GLP-1) is an incretin hormone that increases proinsulin biosynthesis, stimulates insulin secretion, and improves pancreatic beta-cell viability. The aim of this work was to investigate the effects of GLP-1 on the function and viability of HIT-T 15 cells cultured with AGEs. HIT-T 15 cells were cultured for 5 days in presence of AGEs alone, or supplemented with 10 nmol/l GLP-1. Cell viability, insulin secretion, redox balance, and expression of the AGEs receptor (RAGE) were then determined. The results showed that GLP-1 protected beta cell against AGEs-induced cell death preventing both apoptosis and necrosis. Moreover, addition of GLP-1 to the AGEs culture medium restored the redox balance, improved the responsiveness to glucose, and attenuated AGEs-induced RAGE expression. These findings provide evidence that GLP-1 protects beta cells from the dangerous effects of AGEs.

  20. High-resolution anatomy of the human brain stem using 7-T MRI: improved detection of inner structures and nerves?

    International Nuclear Information System (INIS)

    The purpose of this paper is to assess the value of 7 Tesla (7 T) MRI for the depiction of brain stem and cranial nerve (CN) anatomy. Six volunteers were examined at 7 T using high-resolution SWI, MPRAGE, MP2RAGE, 3D SPACE T2, T2, and PD images to establish scanning parameters targeted at optimizing spatial resolution. Direct comparisons between 3 and 7 T were performed in two additional subjects using the finalized sequences (3 T: T2, PD, MPRAGE, SWAN; 7 T: 3D T2, MPRAGE, SWI, MP2RAGE). Artifacts and the depiction of structures were evaluated by two neuroradiologists using a standardized score sheet. Sequences could be established for high-resolution 7 T imaging even in caudal cranial areas. High in-plane resolution T2, PD, and SWI images provided depiction of inner brain stem structures such as pons fibers, raphe, reticular formation, nerve roots, and periaqueductal gray. MPRAGE and MP2RAGE provided clear depiction of the CNs. 3D T2 images improved depiction of inner brain structure in comparison to T2 images at 3 T. Although the 7-T SWI sequence provided improved contrast to some inner structures, extended areas were influenced by artifacts due to image disturbances from susceptibility differences. Seven-tesla imaging of basal brain areas is feasible and might have significant impact on detection and diagnosis in patients with specific diseases, e.g., trigeminal pain related to affection of the nerve root. Some inner brain stem structures can be depicted at 3 T, but certain sequences at 7 T, in particular 3D SPACE T2, are superior in producing anatomical in vivo images of deep brain stem structures. (orig.)

  1. A Study on Affective Cognition of Children with Different Aggression/Victim Groups%不同攻击/受欺儿童的情感认知特征研究

    Institute of Scientific and Technical Information of China (English)

    李亚真; 桑标

    2012-01-01

    The study made an inquiry on affective cognition differences among different aggression/victim groups, with five kinds of emotions as cheer, rage, sad, fear and awkward mood, including three indices such as facial expression recognition, affective attribution and sensitivity to affective perception. The results indicated that scores of non-involved children's were the best or second best. There were specific characteristics in sad and rage affective cognition of pure aggressive children and victims' The overal perfor- mance of aggressive victim children was poor, especially their sensitivity to affective perception was the worst. In addition, they consistently had low level of fear and rage affective cognition in facial expression recognition, affective attribution.%本研究以喜怒哀惧尴五种情绪为代表,从表情识别、情绪归因能力、情感觉知敏感性三个方面考察不同攻击/受欺类型儿童的情感认知特征。结果表明:未卷入儿童在各类情绪的表情识别、归因和觉知上都是次高或最高的;单纯攻击和受欺负儿童对愤怒和悲伤的情感认知呈现特殊性;攻击—受欺儿童的情感认知整体表现较差,尤其是该群体的情感觉知敏感性最差,在表情识别和情绪归因上则一致地表现出对愤怒和害怕情感的低水平认知。

  2. Interaction between S100P and the anti-allergy drug cromolyn

    Energy Technology Data Exchange (ETDEWEB)

    Penumutchu, Srinivasa R. [Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Chou, Ruey-Hwang [Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan (China); Department of Biotechnology, Asia University, Taichung 413, Taiwan (China); Yu, Chin, E-mail: cyu.nthu@gmail.com [Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan (China); The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005 (China)

    2014-11-21

    Highlights: • The interaction between S100P–cromolyn was investigated by fluorescence spectroscopy. • The interfacial residues on S100P and cromolyn contact surface were mapped by {sup 1}H-{sup 15}N HSQC experiments. • S100P–cromolyn complex model was generated from NMR restraints using HADDOCK program. • The stability of the S100P–cromolyn complex was studied using molecular dynamics simulations. - Abstract: The S100P protein has been known to mediate cell proliferation by binding the receptor for advanced glycation end products (RAGE) to activate signaling pathways, such as the extracellular regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. S100P/RAGE signaling is involved in a variety of diseases, such as cancer, metastasis, and diabetes. Cromolyn is an anti-allergy drug that binds S100P to block the interaction between S100P and RAGE. In the present study, we characterized the properties of the binding between cromolyn and calcium-bound S100P using various biophysical techniques. The binding affinity for S100P and cromolyn was measured to be in the millimolar range by fluorescence spectroscopy. NMR-HSQC titration experiments and HADDOCK modeling was employed to determine the spatial structure of the proposed heterotetramer model of the S100P–cromolyn complex. Additional MD simulation results revealed the important properties in the complex stability and conformational flexibility of the S100P–cromolyn complex. This proposed model has provided an understanding of the molecular level interactions of S100P–cromolyn complex.

  3. Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease

    Directory of Open Access Journals (Sweden)

    Yii Michael

    2011-09-01

    Full Text Available Abstract Background Type 2 diabetes and the metabolic syndrome are associated with impaired diastolic function and increased heart failure risk. Animal models and autopsy studies of diabetic patients implicate myocardial fibrosis, cardiomyocyte hypertrophy, altered myocardial microvascular structure and advanced glycation end-products (AGEs in the pathogenesis of diabetic cardiomyopathy. We investigated whether type 2 diabetes and the metabolic syndrome are associated with altered myocardial structure, microvasculature, and expression of AGEs and receptor for AGEs (RAGE in men with coronary artery disease. Methods We performed histological analysis of left ventricular biopsies from 13 control, 10 diabetic and 23 metabolic syndrome men undergoing coronary artery bypass graft surgery who did not have heart failure or atrial fibrillation, had not received loop diuretic therapy, and did not have evidence of previous myocardial infarction. Results All three patient groups had similar extent of coronary artery disease and clinical characteristics, apart from differences in metabolic parameters. Diabetic and metabolic syndrome patients had higher pulmonary capillary wedge pressure than controls, and diabetic patients had reduced mitral diastolic peak velocity of the septal mitral annulus (E', consistent with impaired diastolic function. Neither diabetic nor metabolic syndrome patients had increased myocardial interstitial fibrosis (picrosirius red, or increased immunostaining for collagen I and III, the AGE Nε-(carboxymethyllysine, or RAGE. Cardiomyocyte width, capillary length density, diffusion radius, and arteriolar dimensions did not differ between the three patient groups, whereas diabetic and metabolic syndrome patients had reduced perivascular fibrosis. Conclusions Impaired diastolic function of type 2 diabetic and metabolic syndrome patients was not dependent on increased myocardial fibrosis, cardiomyocyte hypertrophy, alteration of the

  4. Pioglitazone ameliorates memory deficits in streptozotocin-induced diabetic mice by reducing brain β-amyloid through PPARY activation

    Institute of Scientific and Technical Information of China (English)

    Li-ping LIU; Tian-hua YAN; Li-ying JIANG; Wei HU; Meng HU; Chao WANG; Qian ZHANG

    2013-01-01

    Aim:To examine the effects of pioglitazone,a PPARY agonist,on memory performance and brain amyloidogenesis in streptozotocin (STZ)-induced diabetic mice.Methods:ICR male mice were injected with STZ (150 mg/kg,iv) to induce experimental diabetes.Pioglitazone (9 and 18 mg·kg1-d-1,po) was administered for 6 weeks.Passive avoidance and Morris water maze (MWM) tests were used to evaluate cognitive function.The blood glucose and serum insulin levels were detected using the glucose oxidase method and an ELISA assay,respectively.β-amyloid (Aβ),β-amyloid precursor protein (APP),β-amyloid precursor protein cleaving enzyme 1 (BACE1),NF-κB p65,the receptor for advanced glycation end products (RAGE) and PPARy in the brains were analyzed using Western blotting assays.Results:The STZ-induced diabetic mice characterized by hyperglycemia and hypoinsulinemia performed poorly in both the passive avoidance and MWM tests,accompanied by increased Aβ1-40/Aβ1-42,APP,BACE1,NF-κB p65 and RAGE levels and decreased PPARy level in the hippocampus and cortex.Chronic pioglitazone treatment significantly ameliorated the memory deficits of STZ-induced diabetic mice,and suppressed expression of APP,BACE1,RAGE and NF-κB p65,and activated PPARy in the hippocampus and cortex.However,pioglitazone did not significantly affect blood glucose and insulin levels.Conclusion:Pioglitazone ameliorates memory deficits in STZ-induced diabetic mice by reducing brain Aβ level via activation of PPARy,which is independent of its effects on blood glucose and insulin levels.The results suggest that pioglitazone may be used for treating the cognitive dysfunction in type 1 diabetes mellitus.

  5. In-vivo evidence that high mobility group box 1 exerts deleterious effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model and Parkinson's disease which can be attenuated by glycyrrhizin.

    Science.gov (United States)

    Santoro, Matteo; Maetzler, Walter; Stathakos, Petros; Martin, Heather L; Hobert, Markus A; Rattay, Tim W; Gasser, Thomas; Forrester, John V; Berg, Daniela; Tracey, Kevin J; Riedel, Gernot; Teismann, Peter

    2016-07-01

    High-mobility group box 1 (HMGB1) is a nuclear and cytosolic protein that is released during tissue damage from immune and non-immune cells - including microglia and neurons. HMGB1 can contribute to progression of numerous chronic inflammatory and autoimmune diseases which is mediated in part by interaction with the receptor for advanced glycation endproducts (RAGE). There is increasing evidence from in vitro studies that HMGB1 may link the two main pathophysiological components of Parkinson's disease (PD), i.e. progressive dopaminergic degeneration and chronic neuroinflammation which underlie the mechanistic basis of PD progression. Analysis of tissue and biofluid samples from PD patients, showed increased HMGB1 levels in human postmortem substantia nigra specimens as well as in the cerebrospinal fluid and serum of PD patients. In a mouse model of PD induced by sub-acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), systemic administration of neutralizing antibodies to HMGB1 partly inhibited the dopaminergic cell death, and reduced the increase of RAGE and tumour necrosis factor-alpha. The small natural molecule glycyrrhizin, a component from liquorice root which can directly bind to HMGB1, both suppressed MPTP-induced HMGB1 and RAGE upregulation while reducing MPTP-induced dopaminergic cell death in a dose dependent manner. These results provide first in vivo evidence that HMGB1 serves as a powerful bridge between progressive dopaminergic neurodegeneration and chronic neuroinflammation in a model of PD, suggesting that HMGB1 is a suitable target for neuroprotective trials in PD. PMID:26921471

  6. S100B as a Potential Biomarker and Therapeutic Target in Multiple Sclerosis.

    Science.gov (United States)

    Barateiro, Andreia; Afonso, Vera; Santos, Gisela; Cerqueira, João José; Brites, Dora; van Horssen, Jack; Fernandes, Adelaide

    2016-08-01

    Multiple sclerosis (MS) pathology is characterized by neuroinflammation and demyelination. Recently, the inflammatory molecule S100B was identified in cerebrospinal fluid (CSF) and serum of MS patients. Although seen as an astrogliosis marker, lower/physiological levels of S100B are involved in oligodendrocyte differentiation/maturation. Nevertheless, increased S100B levels released upon injury may induce glial reactivity and oligodendrocyte demise, exacerbating tissue damage during an MS episode or delaying the following remyelination. Here, we aimed to unravel the functional role of S100B in the pathogenesis of MS. Elevated S100B levels were detected in the CSF of relapsing-remitting MS patients at diagnosis. Active demyelinating MS lesions showed increased expression of S100B and its receptor, the receptor for advanced glycation end products (RAGE), in the lesion area, while chronic active lesions displayed increased S100B in demyelinated areas with lower expression of RAGE in the rim. Interestingly, reactive astrocytes were identified as the predominant cellular source of S100B, whereas RAGE was expressed by activated microglia/macrophages. Using an ex vivo demyelinating model, cerebral organotypic slice cultures treated with lysophosphatidylcholine (LPC), we observed a marked elevation of S100B upon demyelination, which co-localized mostly with astrocytes. Inhibition of S100B action using a directed antibody reduced LPC-induced demyelination, prevented astrocyte reactivity and abrogated the expression of inflammatory and inflammasome-related molecules. Overall, high S100B expression in MS patient samples suggests its usefulness as a diagnostic biomarker for MS, while the beneficial outcome of its inhibition in our demyelinating model indicates S100B as an emerging therapeutic target in MS. PMID:26184632

  7. The objective qualification of non-international armed conflicts: A Colombian case study

    OpenAIRE

    Sebastian Machado; Guillermo Otálora Lozano

    2012-01-01

    Armed conflict has raged in Colombia since at least the 1960’s, involving governmental forces, rebel groups, and paramilitary forces. The Uribe government (2002-2010) declared that Colombia was not in a ‘state of armed conflict’ but was rather facing a ‘terrorist threat’. This declaration was done in fear of conferring a political status to the armed groups, and most particularly, in fear that a recognition of armed conflict would open the possibility of endowing the Revolutionary Ar...

  8. A European Culture War in the Twentieth Century? Antic-Catholicism and Anti-Bolshevism between Moscow, Berlin, and the Vatican 1922 to 1933

    OpenAIRE

    Weir, Todd

    2015-01-01

    The term “culture war” has become a generic expression for secular-catholic conflicts across nineteenth-century Europe. Yet, if measured by acts of violence, anticlericalism peaked in the years between 1927 and 1939, when thousands of Catholic priests and believers were imprisoned or executed and hundreds of churches razed in Mexico, Spain and Russia. This essay argues that not only in these three countries, but indeed across Europe a culture war raged in the interwar period. It takes, as a c...

  9. 缺氧后内皮细胞早期生长反应因子-1活化的信号机制%The Signaling Mechanism Involved in Hypoxia-induced Upregulation of Early Growth Response-1 in Endothelial Cells

    Institute of Scientific and Technical Information of China (English)

    黄春; 杨明; 施晓芸; 陈晓春

    2012-01-01

    目的 观察缺氧对内皮细胞早期生长反应因子(Egr-1)表达的影响及晚期糖基化终末产物(AGEs)及其受体(RAGE)对上述效应的可能调控机制.方法 以培养小鼠主动脉内皮细胞(MAECs)为模型,根据缺氧时间和缺氧前预处理方式,分为不同缺氧时间组[缺氧0(对照组),5,10,15,30,60,120 min组]、anti-AGE预处理组、可溶性RAGE(sRAGE)预处理组和蛋白激酶C(PKC)β抑制剂组,实时定量PCR法检测缺氧后Egr-1 mRNA含量、ELISA法检测细胞裂解液中AGEs含量、蛋白印迹法检测细胞膜蛋白中PKC各异构体的活化.结果 缺氧15 min组Egr-1 mRNA表达上调,为对照组的(14.13±0.77)倍(P=0.000 0);缺氧10~60 min内皮细胞裂解液中AGEs堆积;缺氧15 min组MAECs膜蛋白中PKCβⅡ含量为(30.57±1.86),显著高于对照组的含量(9.22±1.05)(P=0.002);anti-AGE、sRAGE和PKCβ抑制剂预处理减少缺氧诱导的Egr-1 mRNA表达上调(P=0.000 0);anti-AGE和sRAGE预处理显著减少缺氧对PKCβⅡ的活化(P=0.000 0).结论 急性缺氧诱导内皮细胞AGEs堆积、PKCβⅡ活化和Egr-1mRNA高表达,AGEs-RAGE和PKCβII信号参与急性缺氧后Egr-1诱导表达的调控.%Objective To observe the impact of hypoxia on the expression of early growth response-1 (Egr-1) in mouse aortic endothelial cells(MAECs) , and to study the underlying signaling mechanism involving advanced glycation end-products (AGEs) and its receptor (receptor for AGEs, RAGE). Methods MAECs were subjected to hypoxia treatment with a (6.0+0.5)% oxygen concentration for various periods (0, 5, 10, 15, 30, 60 or 120 min) , or -were first pre-incubated -with anti-AGEs or soluble RAGE (sRAGE) for 2 h, or LY379196 for 45 min respectively, and then subsequently exposed to hypoxia for 15 min. Egr-1 mRNA levels -were detected by real time PCR (RT-PCR), AGEs in cell lysate -were monitored by ELISA, and PKC isoformates in membrane fraction were examined by western blot. MAECs cultured -with normoxia -were

  10. L'information-documentation et sa mise en scène au quotidien : la culture informationnelle en questions

    OpenAIRE

    Maury, Yolande; Etévé, Christiane

    2010-01-01

    Rapport final ERTé Culture informationnelle et curriculum documentaire, Equipe de Paris, 15 p. Cette recherche étudie les pratiques ordinaires d'information-documentation. Son objectif est de dégager " l'aire de pertinence " de la culture informationnelle, à partir du repérage des éléments structurants de cette culture, telle qu'elle est abordée, au quotidien, en contexte scolaire (élèves, enseignants-documentalistes, éventuellement enseignants ; en collège et lycée). Les savoirs en inform...

  11. The conservation and dissemination of information - A democratic issue

    Energy Technology Data Exchange (ETDEWEB)

    Torbacke, J. [Stockholm Univ. (Sweden). Dept. of History

    1996-12-01

    The societal function of the historians are pointed out, to describe and explain, in cooperation with the archives, the chain of political, economic, social and cultural events that has shaped the country`s history. The lessons of the past, whether pleasant or unpleasant, should be passed on to the posterity. Open information is an important element in a democratic society and is normally one of the criteria that distinguishes democracy from autocracy. In the closed and controlled information society all that is hushed up and covered up leads to bitterness and rage among the citizens.

  12. Set this house on fire: the self-analysis of Raymond Carver.

    Science.gov (United States)

    Tutter, Adele

    2011-10-01

    The convergence of features of Raymond Carver's short-story oeuvre and of psychoanalytic methodology suggests that Carver's writing served as the fulcrum and focus of a self-analytic experience. Within this model, his stories function as container and mirror of myriad aspects of the writer's self. Tracing the developmental arc of the contextual meanings of one motif--fire--through six stories and their ur-texts demonstrates gains comparable to certain analytic goals, including enhanced integration, accountability, and self-awareness. Over time, Carver's narratives of rage, impotence, and despair give way to a new story: of mourning, forgiveness, and the rekindling of hope. PMID:22034681

  13. Where the Runners Went: British Motivations Behind Postal Policy and Allocation in Colonial India

    OpenAIRE

    Bharat, Sheetal

    2012-01-01

    British presence has had a profound influence on economic development in British and independent India, and the debate on the nature of this influence has been raging for decades. At one end is the imperialist view that India benefitted from British rule and at the other is the nationalist view that India is still struggling from the burden of misrule. This debate has been enriched by in-depth research on the railways, among other topics; yet the closely related postal network has received ...

  14. Hitler: a neurohistorical formulation.

    Science.gov (United States)

    Martindale, C; Hasenfus, N; Hines, D

    1976-01-01

    It is hypothesized that Adolf Hitler suffered from a constitutional left-side weakness that allowed his cerebral hemisphere to exert a strong influence on his thought and behavior. Physical characteristics such as trembling of the left extremities, lack of a left testicle, and tendency to exhibit leftward eye movements are interpreted as supportive of the hypothesis. Right hemisphere dominance is consistent with a number of Hitler's personal traits such as praise of the irrational, automatic speech, auditory hallucinations, hypochondriasis, uncontrolled rages, and spatial and musical interests. Right hemisphere dominated thought may also have formed a basis for his two basic political policies: Lebensraum and anti-Semitism. PMID:798651

  15. Epidemiological characteristics of multiple sclerosis in Tomsk Region and their dynamics for last 30 years

    Directory of Open Access Journals (Sweden)

    V. M. Alifirova

    2016-03-01

    Full Text Available The Tomsk Region is a zone of average risk multiple sclerosis (MS, prevalence makes 27.1 cases on 100 000 people. During the period with 1980 for 2010 variety of morbidity from 0.4 (1992 to 4.1 (2003 on 100 000 people. The lowest morbidity was in period with 1991 for 1995 and makes 1.8 on 100 000 people, and the highest in the rage from 2001 for 2005 — 3.1 on 100 000 people. Last 5 years in the TomskRegion to increase ofmorbidityis observed.

  16. Multi-modal ultra-high resolution structural 7-Tesla MRI data repository

    OpenAIRE

    Forstmann, Birte U.; Keuken, Max C.; Schafer, Andreas; Bazin, Pierre-Louis; Alkemade, Anneke; Turner, Robert

    2014-01-01

    Structural brain data is key for the understanding of brain function and networks, i.e., connectomics. Here we present data sets available from the ‘atlasing of the basal ganglia (ATAG)’ project, which provides ultra-high resolution 7 Tesla (T) magnetic resonance imaging (MRI) scans from young, middle-aged, and elderly participants. The ATAG data set includes whole-brain and reduced field-of-view MP2RAGE and T2*-weighted scans of the subcortex and brainstem with ultra-high resolution at a sub...

  17. Search (Non-)Neutrality and Impact on Innovation

    OpenAIRE

    L'Ecuyer, Pierre; MAILLÉ, Patrick; Stier-Moses, Nicolás; Tuffin, Bruno

    2016-01-01

    The search neutrality debate, as a parallel to the network neutrality debate, is raging worldwide, with search engines accused of biasing the ranking of their organic links to provide a competitive advantage to their own content. In a recent paper, we have designed a model and determined the optimal ranking policy for a search engine as a trade-off between short-term revenue (based on the potential immediate gain from high-ranked links) and long-term revenue (based on the satisfaction of user...

  18. City under the Ice

    DEFF Research Database (Denmark)

    Nielsen, Kristian Hvidtfelt

    military conflicts are taking place. Studying the wealth of public representations of Camp Century, established 1959-60 by the US Army 128 miles east of the Thule Air Base and often referred to as the “City under the Ice”, we find a sharp contrast between the domesticated interior and the superpower...... public image of Camp Century was one of technological comfort and military-scientific control. Amidst the raging Cold War and up against the harsh environment, the construction of the camp would prove to the public that the combined forces of the US military-technology-science complex would prevail...

  19. Rabies.

    Science.gov (United States)

    Burnett, Nark

    2013-01-01

    Rabies has been a scourge of mankind since antiquity. The name itself, ?rabies? is derived from the ancient Sanskrit rabhas meaning ?to do violence? and has been found described in medical writings several thousand years old. The rabies virus is an RNA virus of the family Rhabdoviridae (Greek for ?rod-shaped virus?), genus Lyssavirus (Lyssa being the Greek God of frenzy and rage). Rabies infections have a worldwide spread, with only a few, mostly island nations laying claim to being ?rabies free.? PMID:24049000

  20. Clinical and the demographic characteristics of patients with alopecia areata

    OpenAIRE

    Mustafa Arıca; Roza Zelal Abdioğlu; Ruken Azizoğlu Anlı; Sibel Yorgancılar

    2013-01-01

    Background and Design: In this study, our aim was to determine clinical and the demographical characteristics of the patients with alopecia areata in our region.Materials and Metods: In the study, 100 patients who received alopecia areata diagnosis with ages raging from 2 to 52 and who applied to the polyclinic of ………… Medical Faculty Dermatology Department between October and November 2009 were evaluated.Results: Of 100 patients included into the study 44 (44%) were female and 56 (56%) male....

  1. The Surprising Relationship Between Weight and Mortality: A Review of Katherine Flegal’s Recent Presentation in the Gender and Body Size Faculty Curator Series

    OpenAIRE

    Nguyen, Diana; Frederick, David

    2010-01-01

    Everyone knows that there is an “obesity epidemic” raging across America, killing our children and straining our health care system. Or, at least, that is what the media, government, and medical profession have told us, and we take it as a matter of faith that what they have said about obesity is true. This fear of fat has led to billions of dollars invested in preventing or reducing obesity. Millions of men and women struggle to lose weight in order to improve their health. But is there real...

  2. Micro-Structural Brain Alterations in Aviremic HIV+ Patients with Minor Neurocognitive Disorders: A Multi-Contrast Study at High Field.

    OpenAIRE

    Cristina Granziera; Alessandro Daducci; Samanta Simioni; Matthias Cavassini; Alexis Roche; Djalel Meskaldji; Tobias Kober; Melanie Metral; Alexandra Calmy; Gunther Helms; Bernard Hirschel; François Lazeyras; Reto Meuli; Gunnar Krueger; Du Pasquier, Renaud A.

    2013-01-01

    OBJECTIVE: Mild neurocognitive disorders (MND) affect a subset of HIV+ patients under effective combination antiretroviral therapy (cART). In this study, we used an innovative multi-contrast magnetic resonance imaging (MRI) approach at high-field to assess the presence of micro-structural brain alterations in MND+ patients. METHODS: We enrolled 17 MND+ and 19 MND- patients with undetectable HIV-1 RNA and 19 healthy controls (HC). MRI acquisitions at 3T included: MP2RAGE for T1 relaxation time...

  3. The conservation and dissemination of information - A democratic issue

    International Nuclear Information System (INIS)

    The societal function of the historians are pointed out, to describe and explain, in cooperation with the archives, the chain of political, economic, social and cultural events that has shaped the country's history. The lessons of the past, whether pleasant or unpleasant, should be passed on to the posterity. Open information is an important element in a democratic society and is normally one of the criteria that distinguishes democracy from autocracy. In the closed and controlled information society all that is hushed up and covered up leads to bitterness and rage among the citizens

  4. Nuclear industry review

    International Nuclear Information System (INIS)

    This review examines the consequences of projected excess electrical generating capacity for the maintenance of an independent nuclear power capability in Canada. Although consumption of electricity will continue to grow at rages well below historical averages, significant additions to capacity will be required in all parts of Canada in the 1990s. CANDU reactors are an attractive option for meeting load growth, particularly east of Manitoba. However, the absence of domestic orders in the 1980s may threaten the maintenance of this option. Even the most optimistic projections indicate that only one supplier of each component will remain in the nuclear business in the 1990s

  5. Report of the independent review commissioned by the Royal College of Radiologists into brachial plexus neuropathy following radiotherapy for breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Bates, Thelma; Evans, R.G.B.

    1995-12-31

    Brachial plexus neuropathy (BPN) is a rare but serious side effect of radiotherapy for operable breast carcinoma. It was identified in 48 of a sample of 126 patients (38%) who agreed to cooperate out of 249 members of RAGE, who were treated during the 14 year period 1980 to 1993 at 15 cancer centres. A conservative estimate of the total number of patients with operable breast cancer receiving radiotherapy at these centres during this time is 65,000. The incidence of BPN due to radiotherapy (BPN/RT) appears to be falling. From the first 7 years we found 41 cases and from the second 7 years only 7 cases. (author).

  6. Report of the independent review commissioned by the Royal College of Radiologists into brachial plexus neuropathy following radiotherapy for breast carcinoma

    International Nuclear Information System (INIS)

    Brachial plexus neuropathy (BPN) is a rare but serious side effect of radiotherapy for operable breast carcinoma. It was identified in 48 of a sample of 126 patients (38%) who agreed to cooperate out of 249 members of RAGE, who were treated during the 14 year period 1980 to 1993 at 15 cancer centres. A conservative estimate of the total number of patients with operable breast cancer receiving radiotherapy at these centres during this time is 65,000. The incidence of BPN due to radiotherapy (BPN/RT) appears to be falling. From the first 7 years we found 41 cases and from the second 7 years only 7 cases. (author)

  7. The Obama/Pentagon War Narrative, the Real War and Where Afghan Civilian Deaths Do Matter

    Directory of Open Access Journals (Sweden)

    Marc W. Herold

    2012-06-01

    Full Text Available This essay explores upon two inter-related issues: (1 the course of America’s raging Afghan war as actually experienced on the ground as contrasted with the Pentagon and mainstream media narrative and (2 the unrelenting Obama/Pentagon efforts to control the public narrative of that war.[1] As the real war on the ground spread geographically and violence intensified, U.S. efforts to construct a positive spin re-doubled. An examination of bodies – of foreign occupation forces and innocent Afghan civilians – reveals a clear trade-off. NATO country elites understand the quagmire and have begun pulling-back.

  8. “You Killed Our Baby!”: Cristina Yang and the Breaking of the Abortion Taboo in Grey’s Anatomy

    OpenAIRE

    Levy, Elizabeth

    2015-01-01

    In 2011, a rare event occurred on American television: Cristina Yang, one of the main characters of Grey’s Anatomy, a widely popular TV show, decided to have an abortion and went through with her decision. In light of the fact that the pro-life/pro-choice debate has been raging in the United States since 1973 and has been tightly informed by religious views, this paper attempts to determine how the abortion plotline was organized in that regard. It becomes clear that Cristina’s decision is ne...

  9. Post-harvest physiological study and evaluation of the quality of Cv. Horvin plums (prunus domestica l.) in three cold-storage conditions

    OpenAIRE

    Alfonso Parra Coronado; José Eugenio Hernández Hernández; Jesús Hernán Camacho-Tamayo

    2010-01-01

    The plum cv. Horvin is a highly perishable fruit; this hampers post-harvest handling and there is currently no cold sto-rage chamber or suitable post-harvest handling infrastructure in Colombia. The present work was aimed at evalua-ting the quality of the plum cv. Horvin in three storage conditions. The plum cv. Horvin is a climacterical fruit, its res-piratory rate being influenced by storage conditions showing a direct relationship with temperature. It was found that 4°C was the best storag...

  10. The sound and the fury: tre sguardi letterari sull’11-S tra rabbia, incredulità e metaletteratura

    OpenAIRE

    Simone Cattaneo

    2011-01-01

    The aim of the article is to offer three different versions of the 11-S terrorist attacks, showing how Juan Manuel de Prada (Baracaldo, 1970), Ray Loriga (Madrid, 1967) and Enrique Vila-Matas (Barcelona, 1948) reproduce that tragic event in some of their novels – La vida invisible, El hombre que inventó Manhattan and El Mal de Montano – employing different techniques and approaches. In that way it’s possible to recognize in their pages an interesting spectrum of emotions that goes from rage t...

  11. Nurturing Prodigy Pianists

    Institute of Scientific and Technical Information of China (English)

    ZHANGJINGDE

    2005-01-01

    CHINA's piano craze has raged for 20 years and shows no sign of flagging. China has the world's biggest piano production and is also home to most prodigy pianists.French pianist Michel Rourdoncle says that it is possible to hear infants playing excellent piano in every province. This craze is apparent in cosmopolitan Beijing and Shanghai as well as far-flung Tibet and Xinjiang. Piano tuition in China is generally 100 yuan (US $ 12) per hour - not at all cheap when taking into account the average monthly income of a couole of thousand vuan It is,

  12. The Organization of Work: Changes and Their Consequences

    OpenAIRE

    Avner Ben-Ner; Fanmin Kong; Tzu-Shian Han; Nien-Chi Liu; Yong-Seung Park

    2001-01-01

    This paper documents the changes in human resource practices from the early 1980s to the middle of the 1990s, using a unique and comprehensive data set concerning a sample of about 800 firms from a wide rage of industries in the state of Minnesota. A major aspect in these changes concerns the widespread adoption of practices that emphasize employee involvement in decision-making and in firm financial returns. Focusing on cross-sectional data the paper examines the determinants of human resour...

  13. Architecting the cloud design decisions for cloud computing service models (SaaS, PaaS, and IaaS)

    CERN Document Server

    Kavis, Michael J

    2014-01-01

    An expert guide to selecting the right cloud service model for your business Cloud computing is all the rage, allowing for the delivery of computing and storage capacity to a diverse community of end-recipients. However, before you can decide on a cloud model, you need to determine what the ideal cloud service model is for your business. Helping you cut through all the haze, Architecting the Cloud is vendor neutral and guides you in making one of the most critical technology decisions that you will face: selecting the right cloud service model(s) based on a combination of both business and tec

  14. Le médicin des sauvages: le jongleur

    Directory of Open Access Journals (Sweden)

    Aldo Trucchio

    2015-06-01

    Full Text Available The term «jongleur» is currently employed in Quebequois French with reference to the shaman‐healer of the Amerindians. The authors explore the history of the peculiar conflation between a typical medieval character and the doctor of the «savages», through the texts and images that first provided its description between the XVI and XVIII Centuries. Their aim is to show how the representations of this character result from the encounter of different pre‐existing iconographic traditions and, especially, how they express the political and religious conflicts raging in Europe at the time.

  15. Numerical simulation of Cr2N age-precipitation in high nitrogen stainless steels

    International Nuclear Information System (INIS)

    At the temperature raging from 700 to 950 deg. C, the Cr2N age-precipitation in high nitrogen austenitic stainless steels Fe24Mn18Cr3Ni0.62N was investigated in this paper. A qualitative mathematical model of Cr2N age-precipitation, ln tS = f (Me,1/T), was established based on the thermodynamics and kinetics and phase transformation theories. Satisfactory results were obtained by means of the test of artificial neural network. This mathematical model can be applied to the calculation design and predication of Cr2N age-precipitation in high nitrogen stainless steels

  16. FTW (For the Win / Fuck the World)

    OpenAIRE

    Summers, Francis; Minkin, Louisa

    2012-01-01

    Participation in the group exhibition curated by Bernice Donszelmann, Tim Renshaw and Mary McLean. Exhibited the work FTW (For the Win / Fuck the World) made in collaboration with Louisa Minkin. Here we use the format of the triumphal procession to pose questions around the twinned states of glory and nihilism. FTW! (For The Win / Fuck The World) is a banner that combines a letter to a generic addressee alongside a selection of internet memes, rage comic figures and images of disaster and cel...

  17. Theological reflections on empire

    Directory of Open Access Journals (Sweden)

    Allan A. Boesak

    2009-11-01

    Full Text Available Since the meeting of the World Alliance of Reformed Churches in Accra, Ghana (2004, and the adoption of the Accra Declaration, a debate has been raging in the churches about globalisation, socio-economic justice, ecological responsibility, political and cultural domination and globalised war. Central to this debate is the concept of empire and the way the United States is increasingly becoming its embodiment. Is the United States a global empire? This article argues that the United States has indeed become the expression of a modern empire and that this reality has considerable consequences, not just for global economics and politics but for theological refl ection as well.

  18. Shock-to-Detonation Transition simulations

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-07-14

    Shock-to-detonation transition (SDT) experiments with embedded velocity gauges provide data that can be used for both calibration and validation of high explosive (HE) burn models. Typically, a series of experiments is performed for each HE in which the initial shock pressure is varied. Here we describe a methodology for automating a series of SDT simulations and comparing numerical tracer particle velocities with the experimental gauge data. Illustrative examples are shown for PBX 9502 using the HE models implemented in the xRage ASC code at LANL.

  19. 2D-vektoripohjainen tasosuunnittelu Unity 3D:llä

    OpenAIRE

    Birkström, Patrik

    2014-01-01

    Tasosuunnittelu on hyvin tärkeä osa lähes jokaista peliprojektia. Hyvä tasosuunnittelu voi pelastaa muuten huonosti suunnitellun pelin ja huono tasosuunnittelu voi taas pilata muuten hyvän pelinautinnon. Tämä opinnäytetyö keskittyy nimenomaan 2D –tasosuunnittelun perusteisiin ja testaa RageSpline–työkalun toimivuutta Unity 3D –peliprojektissa. Tarve opinnäytetyölle syntyi Kuutti Entertainment Oy:ltä, joka kehitti Moped Mania –nimistä mobiilipeliä Unity 3D:llä. Unity on pääasiassa tarkoite...

  20. Fracture of tibial tuberosity in an adult

    OpenAIRE

    Rodrigo Pires e Albuquerque; Campos, André Siqueira; de Araújo, Gabriel Costa Serrão; Gameiro, Vinícius Schott

    2013-01-01

    The fracture of tibial tuberosity is a rare lesion and still more unusual in adults. We describe a case in an adult who suffered a left knee injury due to a fall from height. No risk factors were identified. The lesion was treated with surgical reduction and internal fixation. The rehabilitation method was successful, resulting in excellent function and rage of motion of the knee. The aim of this study was to present an unusual case of direct trauma of the tibial tuberosity in an adult and th...

  1. Eleonora Pasotti, Political branding in cities. The decline of machine politics in Bogotá, Naples, and Chicago

    Directory of Open Access Journals (Sweden)

    Gilles Pinson

    2011-11-01

    Full Text Available Au travers de cet ouvrage, Eleonora Pasotti, professeure de science politique à l’Université de Californie à Santa Cruz, renoue avec la grande tradition nord-américaine des travaux de science politique qui aborde la grande ville comme lieu d’invention et de repérage des nouvelles formes d’échange politique et de lien entre gouvernants et gouvernés. Le livre articule une analyse des nouveaux comportements électoraux et des nouvelles logiques de mobilisation électorale, d’une part, et une analy...

  2. Ring of FIRE

    OpenAIRE

    Welsch, C.; Ullrich, J.; Gläßner, C.; Kühnel, K.; Schempp, A.; Schmidt-Böcking, H.; Dörner, R.

    2004-01-01

    A small electrostatic storage ring is the central machine of the Frankfurt Ion stoRage Experiments (FIRE) which will be built up at the new Stern-Gerlach-Center of Frankfurt University. With ion energies up to 50 keV it enables the analysis of complex many-particle systems from atoms to very large bio molecules. The high luminosity of the beam allows measurements with many orders of magnitude better resolution compared to traditional measurements. It will be combined with existing experiments...

  3. The Value Added of Public Private Partnership. General Overview

    OpenAIRE

    Hussien Ahmad Al-Tarawneh

    2012-01-01

    We live in a tense world. Often at the centre of these tensions is the depth of economic despair that exists in so many places in our world. While a political battle rages about the wisdom of public-private partnerships, the pioneering but controversial concept of mixing public and private is catching on like wildfire abroad. This paper discusses if public private partnerships can and should play a role in education. It provides a brief history of global public private partnerships before tou...

  4. Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion

    OpenAIRE

    Cohen, Mitchell J; Brohi, Karim; Calfee, Carolyn S.; Rahn, Pamela; Chesebro, Brian B; Christiaans, Sarah C.; Carles, Michel; Howard, Marybeth; Pittet, Jean-François

    2009-01-01

    Introduction High mobility group box nuclear protein 1 (HMGB1) is a DNA nuclear binding protein that has recently been shown to be an early trigger of sterile inflammation in animal models of trauma-hemorrhage via the activation of the Toll-like-receptor 4 (TLR4) and the receptor for the advanced glycation endproducts (RAGE). However, whether HMGB1 is released early after trauma hemorrhage in humans and is associated with the development of an inflammatory response and coagulopathy is not kno...

  5. Parenting a damaged child: mourning, regression, and disappointment.

    Science.gov (United States)

    Fajardo, B

    1987-01-01

    This paper is an examination of the long-term parenting experiences of parents who have given birth to CNS damaged infants. In particular, the focus is on the mourning, regression, rage, and depression that frequently attend these parents throughout their lives and can become pathological and pathogenic interferences with the provision of good-enough parenting. Several clinical vignettes were presented, each of which illustrated the usefulness of different psychoanalytic clinical theories about normality and pathology of parenting and parent-child interaction. The now-classical contribution of Solnit and Stark (Mourning and the Birth of a Defective Child, 1962) is reviewed along with Benedek's and others' psychoanalytic theories about normal parenting. The thinking of these writers is within the framework of structural/libidinal theory and seems to be useful in describing certain parenting problems that concern the mourning and regressive aspects of parenting. However, it was proposed that some of the adaptive coping and pathology encompassed by Solnit and Stark's explanations is not comfortably illuminated by the structural clinical theory of conflict and drives. Freud's discussion (1917) compares mourning and melancholia, which he differentiated as related but dynamically distinct clinical phenomena. This work is briefly recalled as an earlier point in theory building where structural theory was not sufficient to explain clinical depression and rage that exceeds normal mourning (as in Freud's melancholia). It is felt that an additional theoretical perspective on parenting provided by self psychology can fill in some of the gaps left by structural theory explanations. The self psychology perspective is particularly helpful with understanding the rage, ambivalence, and chronic depression often experienced by parents of damaged children. According to this perspective, the damaged child is a disappointing selfobject for the parent, and the parent's self organization

  6. Toasted forests - Evergreen rain forests in tropical Asia under drought stress

    OpenAIRE

    Werner, Wolfgang

    2003-01-01

    This paper has been written to make an enormous threat known to the public. We all know about the forest fires that raged in Indonesia and parts of Malaysia in 1997, and about the noxious haze covering the whole region, but only a few experts are aware of the threat of extinction of the last rain forest areas in Southeast Asia. As this paper will show, droughts have always been a part of these ecosystems, which normally receive plenty of rain. Mild droughts can be regarded as slight or medium...

  7. Toasted Forests - Evergreen Rain Forests of Tropical Asia under Drought Stress

    OpenAIRE

    Werner, Wolfgang

    2003-01-01

    This paper has been written to make an enormous threat known to the public. We all know about the forest fires that raged in Indonesia and parts of Malaysia in 1997, and about the noxious haze covering the whole region, but only a few experts are aware of the threat of extinction of the last rain forest areas in Southeast Asia. As this paper will show, droughts have always been a part of these ecosystems, which normally receive plenty of rain. Mild droughts can be regarded as slight or medium...

  8. 听觉耐受下降与耳鸣%Decreased sound tolerance and tinnitus

    Institute of Scientific and Technical Information of China (English)

    祝晓宇; 张剑宁; 李明

    2012-01-01

    Summary Decreased sound tolerance includes hyperacusis and/or misophonia (phonophobia). As a commonly subjective symptom, tinnitus is defined to be a sound perceived in the ear or head without corresponding sound or electrical stimulus in the surrounding environment. It is usually occured with or without hearing loss or harmful psychic reaction, which includes dyssomnia, annoy, rage, anxiety, depress, hard to concentrate, etc. Frequently, tinnitus is accompied by decreased sound tolerance, while this text is aimed to review the corelated concepts of decreased sound tolerance,and focus on the hyperacusis which is a more common symptom.

  9. Reflections

    OpenAIRE

    Kennedy, Mary B

    2008-01-01

    In the two decades after the founding of Neuron, we witnessed the unfolding of the “molecular biology revolution” and its culmination in the sequencing of individual genomes. Cloning of cDNAs and rapid nucleotide sequencing were invented in the early 1970s. By the mid-1980s, “cDNA-cloning” was all the rage. A new breed of “molecular neuroscientists” began cloning and sequencing transcripts encoding neuronal receptors, ion channels, and signaling enzymes. The wealth of molecular data they gene...

  10. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    International Nuclear Information System (INIS)

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

  11. Shock Detector for SURF model

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-01-11

    SURF and its extension SURFplus are reactive burn models aimed at shock initiation and propagation of detonation waves in high explosives. A distinctive feature of these models is that the burn rate depends on the lead shock pressure. A key part of the models is an algorithm to detect the lead shock. Typically, shock capturing hydro algorithms have small oscillations behind a shock. Here we investigate how well the shock detection algorithm works for a nearly steady propagating detonation wave in one-dimension using the Eulerian xRage code.

  12. 读物注释

    Institute of Scientific and Technical Information of China (English)

    郑绪林

    2011-01-01

    Water,Water Everywhere ( 1 )You may know how you got your name.( 2 ) But do you know how some oceans and seas got their names? (3)The Pacific Ocean was named by an explorer from Spain,Ferdinand Magellan.(4) When Magellan sailed on the ocean,it was peaceful.In Spanish,the word for peaceful is " pacifico" -pacific.But that doesn' t mean that the Pacific Ocean is always peaceful.(5) Raging typhoons and tidal waves (6) batter the coastlines of the Pacific many times during the year.(7)Magellan just didn' t see any bad storms (8) there,probably.

  13. 读物注释

    Institute of Scientific and Technical Information of China (English)

    郑绪林

    2011-01-01

    water,water everywhere ( 1 )you may know how you got your name.( 2 ) but do you know how some oceans and seas got their names? (3)the pacific ocean was named by an explorer from spain,ferdinand magellan.(4) when magellan sailed on the ocean,it was peaceful.in spanish,the word for peaceful is " pacifico" -pacific.but that doesn' t mean that the pacific ocean is always peaceful.(5) raging typhoons and tidal waves (6) batter the coastlines of the pacific many times during the year.(7)magellan just didn' t see any bad storms (8) there,probably.

  14. The Class of '34

    OpenAIRE

    Cairney, Richard

    1995-01-01

    The Great Depression raged, governments were beleaguered, the unemployment rate stood at 30%, scurvy stalked the poor and no one was immune to contagious diseases such as scarlet fever, polio and measles when the University of Alberta School of Medicine's Class of '34 graduated. For four alumni who recently gathered in Edmonton—Drs. Morley Hodgson, Melvin Gaudin, John McLurg and Edmund Cairns—their 60th-anniversary reunion was a time to recall the changes they have witnessed in medicine, incl...

  15. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Olivas-Calderón, Edgar, E-mail: edgar_olivascalderon@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico); Recio-Vega, Rogelio, E-mail: rrecio@yahoo.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gandolfi, A. Jay, E-mail: gandolfi@pharmacy.arizona.edu [Southwest Environmental Health Science Center, University of Arizona, Tucson, AZ (United States); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Lantz, R. Clark, E-mail: lantz@email.arizona.edu [Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ (United States); González-Cortes, Tania, E-mail: taniagc2201@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gonzalez-De Alba, Cesar, E-mail: cesargonzalezalba@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Froines, John R., E-mail: jfroines@ucla.edu [Center for Environmental and Occupational Health, School of Public Health, University of California at Los Angeles, Los Angeles, CA (United States); Espinosa-Fematt, Jorge A., E-mail: dr.jorge.espinosa@gmail.com [School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico)

    2015-09-01

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

  16. Privacy and Big Data

    CERN Document Server

    Craig, Terence

    2011-01-01

    Much of what constitutes Big Data is information about us. Through our online activities, we leave an easy-to-follow trail of digital footprints that reveal who we are, what we buy, where we go, and much more. This eye-opening book explores the raging privacy debate over the use of personal data, with one undeniable conclusion: once data's been collected, we have absolutely no control over who uses it or how it is used. Personal data is the hottest commodity on the market today-truly more valuable than gold. We are the asset that every company, industry, non-profit, and government wants. Pri

  17. Strategic alliances fit pattern of industry innovation

    International Nuclear Information System (INIS)

    The strategic alliance, vitally important as an isolated practice in the oil and gas business, also fits a broad pattern of innovation by which the industry is redefining itself for prosperity in a new energy age. The industry is experiencing a renaissance in almost every aspect, from technological breakthroughs to innovative business practices to new products and markets. An inevitable outgrowth of such rapid and fundamental change is an evolution in business relationships. The strategic alliance is at the forefront of this trend. Development of new relationships capitalizes on, and partly results from, enormous advances in technology and finance. The paper discusses new relationships, the outsourcing rage, integrating work flows, and technological advances

  18. The peak oil debate

    OpenAIRE

    Graefe, Laurel

    2009-01-01

    For the past half-century, a debate has raged over when "peak oil" will occur—the point at which output can no longer increase and production begins to level off or gradually decline. Determining how long the oil supply will last has become even more pressing because the world’s energy supply still relies heavily on oil, and global energy demand is expected to rise steeply over the next twenty years. ; This article seeks to bring the peak oil debate into focus. The author notes that a number ...

  19. In Search of the jüdische Typus: A Proposed Benchmark to Test the Genetic Basis of Jewishness Challenges Notions of “Jewish Biomarkers”

    OpenAIRE

    Elhaik, E.

    2016-01-01

    The debate as to whether Jewishness is a biological trait inherent from an “authentic” “Jewish type” (jüdische Typus) ancestor or a system of beliefs has been raging for over two centuries. While the accumulated biological and anthropological evidence support the latter argument, recent genetic findings, bolstered by the direct-to-consumer genetic industry, purport to identify Jews or quantify one’s Jewishness from genomic data. To test the merit of claims that Jews and non-Jews are genetical...

  20. WHO’S WHO Scientists and Thinkers of the 20th Century

    Institute of Scientific and Technical Information of China (English)

    时林

    2004-01-01

    PSYCHOANALYST Sigmund Freud He opened a window on the unconscious--where,he said,lust,rage andrepression battle for supremacy-and changed the way we view ourselves.精神分析学家——西格蒙德·弗洛伊德(1881-1939) 他打开了无意识之窗——他说,在人的无意识中,欲望、愤怒和压抑心理都在争夺着控制大权——从而改变了我们看待自己的方式。

  1. Editorial [Malta Medical Journal, Vol.26(4)

    OpenAIRE

    Grech, Victor E.

    2014-01-01

    “Man's inhumanity to man, makes countless thousands mourn!” Robert Burns, 1784. “It is a frightening thought that man also has a shadow side to him, consisting not just of little weaknesses and foibles, but of a positively demonic dynamism. The individual seldom knows anything of this; [...] a raging monster.” Carl Jung, 1912. Syria’s civil war constitutes the worst humanitarian disaster of our time and it is estimated that over four million refugees will have fled the country by the end ...

  2. Dickens’s Global Art: Cultural and Ecological Legacy in Pictures from Italy

    OpenAIRE

    John, Juliet

    2016-01-01

    In today’s Dickens Studies, “Global Dickens” is all the critical rage. Yet the landmark work on global Dickens by Nisbet, Jordan, Gagnier and others focuses on the international dissemination and reception of Dickens’s work as opposed to Dickens’s own conception of his art. There is no doubt that Dickens saw himself as a global writer from the outset, using metaphors like “the ocean of humanity” to describe his target audience (Letter to W. C. Macready (14 January 1853)). But the travelogues ...

  3. Violence at the Margins: Street Gangs, Globalized Conflict and Sri Lankan Tamil Battlefields in London, Toronto and Paris

    OpenAIRE

    Camilla Orjuela

    2011-01-01

    This article explores the global dimensions of violent conflict and the parallels and links between violence in the diaspora and the homeland. It does so by discussing Tamil street gangs in London, Toronto and Paris. The Tamil diaspora played a key role in the war between the Sri Lankan government and the Liberation Tigers of Tamil Eelam (LTTE), which raged between 1983 and 2009. In spite of being a marginal phenomenon in the Tamil diaspora, Tamil street gangs became part of a wider culture o...

  4. Expanding horizons

    OpenAIRE

    Editor

    2009-01-01

    Dear Friends, The debate of whether Stem Cell Therapy is a hype or hope has been raging for quite some time and has been rekindled in the current year. Stem Cell Scientists have been particularly enthused by the bold standard taken by Barack Obama in passing an Executive Order that lifted the ban on federal funding of Research on Embryonic Stem Cell (ESC) lines created after August 9, 2001. With the lifting of the ban more money is expected to be poured into ESC and Stem Cell Research in gene...

  5. Natural occurrence and distribution of soil borne entomopathogenic fungi in shahrood region, northeast of Iran

    OpenAIRE

    Derakhshan, Ali

    2009-01-01

    The study investigated the occurrence of soil borne entomopathogenic fungi (EPF) in potato, wheat, sugar beet, alfalfa fields and orchards. A total of 150 soil samples were collected and EPF were isolated using Galleria method. Soil pH was rages from 6.8 to 8.1 and soil texture was sandy, loam, sandy- loam, clay and sandy-loam-clay. Soil borne EPF occurred at 78% of soil samples from which 40% Beauveria bassiana, 21% Metarhizium anisopliae and 17% had both species. Occurrence and ...

  6. Swarming by Nature and by Design

    Science.gov (United States)

    Bertozzi, Andrea

    2007-03-01

    The cohesive movement of a biological population is a commonly observed natural phenomenon. With the advent of platforms of unmanned vehicles, this occurrence is attracting renewed interest from the engineering community. This talk will review recent research results on modeling and analysis of biological swarms with some connection to the design ideas for efficient algorithms to control groups of autonomous agents. For biological models we consider two kinds of systems: driven particle systems based on force laws and continuum models based on kinematic and dynamic rules. Both models involve long-rage social attraction and short range dispersal and yield patterns involving clumping, mill vortices, and surface-tension-like effects.

  7. Arab Spring and the escalation of the sectarian divide in Bahrain: An assessment

    Directory of Open Access Journals (Sweden)

    Magdalena Karolak

    2013-04-01

    Full Text Available This article assesses why the Bahraini "Day of Rage" has inflamed sectarian fear and prompted open hostility between Sunni and Shi'a inhabitants of the kingdom. The analysis approaches the subject from a psychological perspective. Using Vamik Volkan's theory, the article presents a detailed overview of the social conflict in which religious identities play a central role. Influence of large-group psychology on the unfolding events enables a more in-depth understanding of the tense situation in Bahrain. The social division engulfing Bahrain is representative of the power struggle and confessional tensions in the Gulf region.

  8. Aloneness and the Isakower phenomenon.

    Science.gov (United States)

    Peterson, C A

    1992-01-01

    Under the sway of the oedipal imperative, the Isakower phenomenon has long been regarded as a regressive perceptual defense against castration anxiety accompanying incestuous wishes, often stimulated by primal scene exposure-fantasy. Clinical material from the psychoanalytic psychotherapy of a borderline patient with object constancy deficits is offered to support a reconceptualization of the Isakower phenomenon: Following annihilatory rage and the destruction of extant inner objects, resulting in a regression to the "drive organization of memory," the face-breast imagery within the Isakower phenomenon arrives as a hallucinatory alternative to unbearable aloneness. PMID:1607306

  9. Suicide in old age: psychotherapeutic intervention.

    Science.gov (United States)

    Maltsberger, J T

    1991-09-01

    Psychotherapy with suicidal patients can best be planned and conducted after the specific narcissistic incapacities of the patient have been identified through an examination of the clinical history. To which of the suicide-inviting affects (worthlessness, aloneness, murderous rage) is the patient vulnerable? On what exterior sustaining supports has the patient relied in the past to ward them off? What exterior sustaining supports have been lost, and which remain available in the present? What maneuvers must the psychotherapist undertake in order to offset the narcissistic deficiencies of the patient? These questions are addressed as they bear on psychotherapeutic interventions with older patients, and specific problems of countertransference are reviewed. PMID:1935193

  10. Study on the Phase Behavior of Coating Matrix in Supercritical or Sub—critical Carbon Dioxide

    Institute of Scientific and Technical Information of China (English)

    曹维良; 徐金龙; 张敬畅

    2003-01-01

    The high-pressure phase behavior of coating -solvent-supercritical or sub-critical carbon dioxide system was investigated experimentally.The coating matrix used was 108-acrylic resin at concentration raging from 10% to 50%(by mass) in mixtures with n-butyl acetate ,The experiments were conducted in a high-pressure view cell for temperatures from 35℃to 65 ℃ and for pressures from 3.0 MPa to 8.0 MPa ,The effect of temperature,pressure and content of every component on the phase behavior of the systems was observed,Finally ,the ternary phase diagram for resin-solvent-CO2 was plotted.

  11. Would medical students enter an exclusion zone in an infected district with a high mortality rate? An analysis of book reports on 28 (secondary publication)

    OpenAIRE

    Kun Hwang; Hyung Sun Hong; Won Young Heo

    2014-01-01

    This study aimed to ascertain whether medical students would enter a closed area where there was a raging epidemic of an infectious disease with a high fatality rate, and includes reasons for the students entering or refusing to enter. Participants included 50 second-year medical students. They were assigned to read a novel entitled 28, written by Youjeong Jeong, and discuss it in groups. Using their book reports, their decisions of whether or not to enter Hwayang, the city from the novel, an...

  12. Who calls the tune?

    Directory of Open Access Journals (Sweden)

    Claude Chastagner

    2011-04-01

    Full Text Available The real action was taking place behind the scenes.Irwin Pincus, music publisherA couple of weeks ago, while researching for this paper, I decided to read again Chronicles, Bob Dylan’s autobiography. Chapter 4 deals with the recording in a rented New Orleans mansion of Oh Mercy, the 1989 album produced by Daniel Lanois, unanimously hailed as Dylan’s resurrection. Dylan insists on the significant impact Lanois had on his own artistry. Through conversations, flashes of rage and frustration, and...

  13. Being Blue in Hawai‘i: Politics, Affect, and the Last Queen of Hawai‘i

    OpenAIRE

    Bruce Harvey

    2011-01-01

    For Hawaiian self-rule activists, who retain ties to the land and forms of sociality emerging out of the land, the US is regarded as an occupier force, and nonnative ownership, whether white or Japanese, a blighting catastrophe justifying resentment and rage. The demise of the Kingdom of Hawai‘i, when an oligarchy of US white settler businessmen overthrew Queen Liliʻuokalani (1838–1917) in 1893, reduced aloha ‘āina (or land-cherishing) to a ghostly affect; to be blue in Hawai‘i, today, is to ...

  14. How to recognize the work of researchers in astronomy communication?

    Science.gov (United States)

    Russo, Pedro

    2015-08-01

    One of the most important current trends in astronomy communication has been “change”. The field of astronomy communication has rapidly evolved in just the past few years, as new techniques and technologies have been adopted. Research astronomy has also visibly changed, as automation of survey systems and the launch of new telescopes has produced a tsunami of big data sets. Today, scientists and communicators must work together to navigate the raging waters of this data flood as they strive to keep our tech-savvy society informed.This invited talk will be given by Rick Fienberg.

  15. What would researchers like to improve in communication initiatives?

    Science.gov (United States)

    Russo, Pedro

    2015-08-01

    One of the most important current trends in astronomy communication has been “change”. The field of astronomy communication has rapidly evolved in just the past few years, as new techniques and technologies have been adopted. Research astronomy has also visibly changed, as automation of survey systems and the launch of new telescopes has produced a tsunami of big data sets. Today, scientists and communicators must work together to navigate the raging waters of this data flood as they strive to keep our tech-savvy society informed. This invited talk will be given by Alain Doressoundiram (Observatoire de Paris, Centre National de la Recherche Scientifique, France) TBC

  16. Conducción y sustancias psicoactivas (alcohol, drogas y medicamentos): de la magnitud del problema a la intervención en seguridad vial.

    OpenAIRE

    Fierro Lorenzo, María Inmaculada

    2015-01-01

    Con la investigación realizada para el presente trabajo se analizan diferentes aspectos del “factor humano” relacionados con la conducción, como son, el consumo de sustancias por parte de los conductores (alcohol, drogas ilegales y medicamentos) y la agresividad vial (Road rage). Respecto al consumo, se ha analizado la prevalencia de sustancias en conductores y además, en el caso del alcohol y el THC, se ha analizado su relación con la prevalencia de signos de deterioro, dependiendo de la con...

  17. When aging meets microgravity: whole genome promoters and enchancers transcription landscape in zebrafish onboard ISS

    Science.gov (United States)

    Arshanovskii, Kirill; Gusev, Oleg; Sychev, Vladimir; Poddubko, Svetlana; Deviatiiarov, Ruslan

    2016-07-01

    In order to gen new insights of gene regulation changes under conditions of real spaceflight, we have conducted whole-genome analysis of dynamic of promotes and enhancers transcriptional changes in zebrafish during prolonged exposure to real spaceflight. In the frame of Russia-Japan joint experiments "Aquatic Habitat"-"Aquarium" we have conducted Cap Analysis of Gene Expression (CAGE) assay of zebrafish in the rage from 7 to 40 days of real spaceflight onboard ISS. The analysis showed that both gene expression patterns and architecture of shapes and types of the promoters are affected by spaceflight environment.

  18. Expression of receptor for advanced glycation endproducts and nuclear factor κB in brain hippocampus of rat with chronic fluorosis

    Institute of Scientific and Technical Information of China (English)

    张凯琳

    2014-01-01

    Objective To investigate the expressions of receptor for advanced glycation endproducts(RAGE)and nuclear factorκB(NF-κB)in brain hippocampus of rat with chronic fluorosis,and to reveal the mechanism of brain damage resulted from chronic fluorosis.Methods Sixty clean grade SD rats were randomly divided to three groups(20 rats in each group,10 female and 10 male)fed with different contents of fluoride,control group with normal tap-water(<0.5 mg/L fluoride),

  19. Elemental magic, v.2 the technique of special effects animation

    CERN Document Server

    Gilland, Joseph

    2012-01-01

    Design beautiful, professional-level animated effects with these detailed step-by-step tutorials from former Disney animator and animated effects expert Joseph Gilland. Filled with beautiful, full-color artwork, Elemental Magic, Volume II, breaks down the animated effect process from beginning to end-including booming explosions, gusting winds, magical incantations, and raging fires. He also breaks down the process of effects ""clean-up,"" as well as timing and frame rates. The companion website includes real-time footage of the author lecturing as he animates the drawings from the

  20. HMGB1 Induces Secretion of Matrix Vesicles by Macrophages to Enhance Ectopic Mineralization

    Science.gov (United States)

    Chen, Qiang; Bei, Jun-Jie; Liu, Chuan; Feng, Shi-Bin; Zhao, Wei-Bo; Zhou, Zhou; Yu, Zheng-Ping; Du, Xiao-Jun; Hu, Hou-Yuan

    2016-01-01

    Numerous clinical conditions have been linked to ectopic mineralization (EM). This process of pathological biomineralization is complex and not fully elucidated, but thought to be started within matrix vesicles (MVs). We hypothesized that high mobility group box 1 (HMGB1), a cytokine associated with biomineralizing process under physiological and pathological conditions, induces EM via promoting MVs secretion from macrophages. In this study, we found that HMGB1 significantly promoted secretion of MVs from macrophages and subsequently led to mineral deposition in elevated Ca/Pi medium in vitro. Transmission electron microscopy of calcifying MVs showed formation of hydroxyapatite crystals in the vesicle interior. Subcutaneous injection into mice with MVs derived from HMGB1-treated cells showed a greater potential to initiate regional mineralization. Mechanistic experiments revealed that HMGB1 activated neutral sphingomyelinase2 (nSMase2) that involved the receptor for advanced glycation end products (RAGE) and p38 MAPK (upstream of nSMase2). Inhibition of nSMase2 with GW4869 or p38 MAPK with SB-239063 prevented MVs secretion and mineral deposition. Collectively, HMGB1 induces MVs secretion from macrophages at least in part, via the RAGE/p38 MAPK/nSMase2 signaling pathway. Our findings thus reveal a novel mechanism by which HMGB1 induces ectopic mineralization. PMID:27243975